CYP27A1

UniProt ID: Q02318
Organism: Homo sapiens
Review Status: INITIALIZED
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Gene Description

CYP27A1 (sterol 27-hydroxylase / sterol 26-hydroxylase, EC 1.14.15.15) is a mitochondrial cytochrome P450 that receives electrons from the adrenodoxin (ferredoxin) / ferredoxin reductase electron-transfer system and hydroxylates the sterol side chain at C27 (C26). Acting on 5-beta-cholestane intermediates, it initiates side-chain oxidation in bile-acid biosynthesis, converting 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol through the C27 alcohol and aldehyde to the C27 acid (di-/tri-hydroxycoprostanoic acids, DHCA/THCA). It also converts cholesterol to 27-hydroxycholesterol, the first committed step of the acidic (alternative) bile-acid pathway, and can further oxidize this product to 3-beta-hydroxy-5-cholestenoic acid. Through the same terminal-methyl hydroxylase chemistry it acts on additional sterols and oxysterols, including 7-ketocholesterol (detoxification in retinal pigment epithelium) and, secondarily, vitamin D3 intermediates. The enzyme is a heme-thiolate P450 (axial cysteine ligand) that is post-translationally imported into mitochondria and associates as a membrane-extrinsic protein with the matrix face of the mitochondrial inner membrane. Loss of CYP27A1 activity causes cerebrotendinous xanthomatosis (CTX), an autosomal-recessive sterol storage disorder with cholestanol and bile-alcohol accumulation, tendon xanthomas, cataracts, and progressive neurological decline that is treatable with chenodeoxycholic acid.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005739 mitochondrion
IBA
GO_REF:0000033 		ACCEPT
Summary: Phylogenetic (PAN-GO) inference that CYP27A1 is active in the mitochondrion. Correct: CYP27A1 is a mitochondrial P450 imported into mitochondria and associated with the inner membrane. Accept as a core localization.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
associates with the inner membrane as a membrane extrinsic protein.
GO:0008203 cholesterol metabolic process
IBA
GO_REF:0000033 		ACCEPT
Summary: Phylogenetic inference that CYP27A1 is involved in cholesterol metabolism. Correct and core: CYP27A1 27-hydroxylates cholesterol and channels excess cholesterol into bile-acid pathways.
Supporting Evidence:
PMID:9660774
alternative pathways of bile acid synthesis which begin with 27-hydroxylation of cholesterol catalyzed by P450c27
GO:0030343 vitamin D 25-hydroxylase activity
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: Phylogenetic inference of vitamin D 25-hydroxylase activity. CYP27A1 has historically been considered a vitamin D3 25-hydroxylase, but PMID:15465040 shows that toward vitamin D2 CYP27A1 hydroxylates at C-24 and C-27 (not C-25) and that CYP2R1 is the physiologically important 25-hydroxylase (26-fold higher kcat/Km). This is a minor, non-core side activity rather than the enzyme's primary sterol 27-hydroxylase function; keep as non-core.
Reason: Physiological vitamin D 25-hydroxylation is attributed to CYP2R1; CYP27A1's vitamin D activity is low-efficiency and not its core function.
Supporting Evidence:
PMID:15465040
CYP2R1 hydroxylated vitamin D(2) at the C-25 position while CYP27A1 hydroxylated it at positions C-24 and C-27
GO:0031073 cholesterol 26-hydroxylase activity
IBA
GO_REF:0000033 		ACCEPT
Summary: Phylogenetic inference of cholesterol 26(27)-hydroxylase activity. This is a core molecular function of CYP27A1, directly supported by experimental IDA annotations.
Supporting Evidence:
PMID:9660774
27-hydroxylation of cholesterol catalyzed by P450c27
GO:0004497 monooxygenase activity
IEA
GO_REF:0000120 		ACCEPT
Summary: Electronic InterPro/ARBA annotation to the general monooxygenase parent. Correct but less specific than the sterol 26/27-hydroxylase activity; accept as a valid general classification of this cytochrome P450 monooxygenase.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
Cytochrome P450 monooxygenase that catalyzes regio- and
GO:0005506 iron ion binding
IEA
GO_REF:0000002 		ACCEPT
Summary: Electronic InterPro annotation for iron binding. Correct: CYP27A1 is a heme-thiolate P450 whose heme iron is ligated by an axial cysteine (residue 476). Core cofactor function.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
axial binding residue
GO:0005739 mitochondrion
IEA
GO_REF:0000117 		ACCEPT
Summary: Electronic ARBA annotation for mitochondrial localization. Correct; duplicates the IBA and HTP mitochondrion annotations.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
associates with the inner membrane as a membrane extrinsic protein.
GO:0005743 mitochondrial inner membrane
IEA
GO_REF:0000044 		ACCEPT
Summary: Electronic UniProt subcellular-location mapping to mitochondrial inner membrane. Correct and represents the specific location: CYP27A1 associates with the inner membrane as a membrane-extrinsic protein after import into the matrix. Core.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
associates with the inner membrane as a membrane extrinsic protein.
GO:0008202 steroid metabolic process
IEA
GO_REF:0000117 		ACCEPT
Summary: Electronic ARBA annotation to the broad steroid metabolic process. Correct but general; the specific processes (bile acid biosynthesis, cholesterol catabolism) are captured elsewhere. Accept as a valid parent term.
Supporting Evidence:
PMID:1708392
catalyzes the first step in the oxidation of the side chain of sterol intermediates in the bile acid synthesis pathway
GO:0008610 lipid biosynthetic process
IEA
GO_REF:0000117 		MARK AS OVER ANNOTATED
Summary: Electronic ARBA annotation to the very broad lipid biosynthetic process parent. Not wrong (bile acids and oxysterols are lipids) but uninformatively general; the specific biological processes are better captured by bile acid biosynthesis (GO:0006699). Mark as over-annotated.
Reason: Overly general; CYP27A1's biosynthetic contributions are specifically to bile acids and oxysterols, already captured by more precise terms.
GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen
IEA
GO_REF:0000120 		ACCEPT
Summary: Electronic annotation to the broad oxidoreductase/monooxygenase MF parent. Correct but general; accept as a valid higher-level classification of the P450 activity.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
Cytochrome P450 monooxygenase that catalyzes regio- and
GO:0020037 heme binding
IEA
GO_REF:0000002 		ACCEPT
Summary: Electronic InterPro annotation for heme binding. Correct: CYP27A1 is a heme-thiolate cytochrome P450 with an axial-cysteine-ligated heme. Core cofactor function; duplicates the IDA heme binding annotation.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
Name=heme; Xref=ChEBI:CHEBI:30413;
GO:0047748 cholestanetetraol 26-dehydrogenase activity
IEA
GO_REF:0000120 		ACCEPT
Summary: Electronic RHEA/EC (EC:1.14.15.15) annotation. Despite the misleading GO label, the GO definition of GO:0047748 is the sterol 26-hydroxylase reaction (5-beta-cholestane-3a,7a,12a-triol -> (25R)-THCA-26-oate; RHEA:34631), which is the core catalytic activity of CYP27A1. Accept; supported by multiple EXP/IDA annotations.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
EC=1.14.15.15
GO:0016716 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, another compound as one donor, and incorporation of one atom of oxygen
IEA
GO_REF:0000107 		ACCEPT
Summary: Ensembl-projected orthology annotation (from mouse Cyp27a1, Q9DBG1) to the specific monooxygenase MF parent. Correct as a general classification; also directly supported by an IDA (PMID:21411718). Accept.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
Cytochrome P450 monooxygenase that catalyzes regio- and
GO:0045880 positive regulation of smoothened signaling pathway
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Ensembl-projected orthology annotation (from mouse Cyp27a1). CYP27A1 produces 7-keto,27-hydroxycholesterol, an oxysterol that can activate smoothened. This is an indirect downstream consequence of an enzymatic product, not a molecular activity of CYP27A1; keep as a non-core biological-process annotation.
Reason: Effect on smoothened signaling is mediated indirectly by an oxysterol product; it is a peripheral role, not the enzyme's core hydroxylase function.
GO:1901755 vitamin D3 biosynthetic process
IDA
PMID:15465040
Metabolism of vitamin D by human microsomal CYP2R1. 		KEEP AS NON CORE
Summary: IDA from a study that concludes CYP2R1, not CYP27A1, is the physiologically important vitamin D 25-hydroxylase, and that CYP27A1 hydroxylates vitamin D2 at C-24/C-27 rather than C-25. CYP27A1 may play a redundant role in vitamin D biosynthesis, so this is a non-core, secondary process for the gene.
Reason: CYP27A1's role in vitamin D3 biosynthesis is minor/redundant relative to CYP2R1; retain but do not treat as a core function.
Supporting Evidence:
PMID:15465040
These results strongly suggest that CYP2R1 plays a physiologically important role in the vitamin D 25-hydroxylation in humans.
GO:0006699 bile acid biosynthetic process
TAS
Reactome:R-HSA-193368 		ACCEPT
Summary: Reactome TAS (bile acid/bile salt synthesis via 7alpha-hydroxycholesterol, the neutral pathway). Core biological process: CYP27A1 performs the side-chain oxidation steps of bile-acid biosynthesis. Accept.
Supporting Evidence:
PMID:1708392
catalyzes the first step in the oxidation of the side chain of sterol intermediates in the bile acid synthesis pathway
GO:0006699 bile acid biosynthetic process
TAS
Reactome:R-HSA-193775 		ACCEPT
Summary: Reactome TAS (bile acid synthesis via 24-hydroxycholesterol pathway). Core biological process for CYP27A1; accept (duplicate of the bile-acid biosynthesis annotation).
Supporting Evidence:
PMID:1708392
catalyzes the first step in the oxidation of the side chain of sterol intermediates in the bile acid synthesis pathway
GO:0006699 bile acid biosynthetic process
TAS
Reactome:R-HSA-193807 		ACCEPT
Summary: Reactome TAS (bile acid synthesis via 27-hydroxycholesterol, the acidic/alternative pathway that CYP27A1 initiates). Core biological process; accept.
Supporting Evidence:
PMID:9660774
alternative pathways of bile acid synthesis which begin with 27-hydroxylation of cholesterol catalyzed by P450c27
GO:0016125 sterol metabolic process
TAS
Reactome:R-HSA-211976 		ACCEPT
Summary: Reactome TAS (endogenous sterols) to the broad sterol metabolic process. Correct but general; the specific cholesterol/bile-acid processes are captured by more precise terms. Accept as a valid parent.
Supporting Evidence:
PMID:1708392
catalyzes the first step in the oxidation of the side chain of sterol intermediates in the bile acid synthesis pathway
GO:0006699 bile acid biosynthetic process
IEA
GO_REF:0000041 		ACCEPT
Summary: Electronic UniPathway (UPA00221, bile acid biosynthesis) mapping. Correct and core; duplicates the experimental/TAS bile-acid biosynthesis annotations. Accept.
Supporting Evidence:
PMID:1708392
catalyzes the first step in the oxidation of the side chain of sterol intermediates in the bile acid synthesis pathway
GO:0006707 cholesterol catabolic process
IEA
GO_REF:0000041 		ACCEPT
Summary: Electronic UniPathway (UPA01058, cholesterol degradation) mapping. Correct and core: 27-hydroxylation directs cholesterol into catabolic bile-acid pathways. Duplicates the IDA cholesterol catabolic process annotation. Accept.
Supporting Evidence:
PMID:9660774
alternative pathways of bile acid synthesis which begin with 27-hydroxylation of cholesterol catalyzed by P450c27
GO:0016716 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, another compound as one donor, and incorporation of one atom of oxygen
IDA
PMID:21411718
Conversion of 7-ketocholesterol to oxysterol metabolites by ... 		ACCEPT
Summary: IDA from the study of 7-ketocholesterol conversion by recombinant CYP27A1, which demonstrated CYP27A1 monooxygenase (hydroxylase) activity producing 7KCh-27OH and 7KCh-27COOH. This is a valid specific-monooxygenase MF classification; the underlying activity is core 26/27-hydroxylase chemistry acting on an oxysterol. Accept.
Supporting Evidence:
PMID:21411718
7KCh is metabolized at a 4-fold higher rate than cholesterol in the reconstituted system in vitro
GO:0045880 positive regulation of smoothened signaling pathway
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: ISS annotation transferred from mouse (MGI:88594). As with the Ensembl-projected equivalent, this reflects an indirect effect of a CYP27A1 oxysterol product on smoothened, not a core molecular activity. Keep as non-core.
Reason: Peripheral, indirect (oxysterol-mediated) effect on smoothened signaling; not the enzyme's core hydroxylase function.
GO:0005743 mitochondrial inner membrane
ISS
GO_REF:0000024 		ACCEPT
Summary: ISS annotation (from ortholog UniProtKB:P17178, rat CYP27A1) for mitochondrial inner membrane localization. Correct and core; duplicates the IEA subcellular-location annotation. Accept.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
associates with the inner membrane as a membrane extrinsic protein.
GO:0047748 cholestanetetraol 26-dehydrogenase activity
EXP
PMID:1708392
Characterization of human sterol 27-hydroxylase. A mitochond... 		ACCEPT
Summary: Experimental characterization of human sterol 27-hydroxylase showing multi-step oxidation (R-CH3 -> R-CH2OH -> R-COOH) at carbon 27 of bile-acid sterol intermediates. The GO:0047748 definition is the EC 1.14.15.15 sterol 26-hydroxylase reaction, so this is the core molecular function. Accept.
Supporting Evidence:
PMID:1708392
the expression of active enzyme capable of catalyzing multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates of the bile acid synthesis pathway
GO:0047748 cholestanetetraol 26-dehydrogenase activity
EXP
PMID:2019602
Mutations in the bile acid biosynthetic enzyme sterol 27-hyd... 		ACCEPT
Summary: Experimental annotation from the CTX study: CTX-causing CYP27 mutations produce immunoreactive sterol 27-hydroxylase protein with greatly diminished activity, confirming the sterol 26/27-hydroxylase (EC 1.14.15.15) core function. Accept.
Supporting Evidence:
PMID:2019602
the synthesis of immunoreactive sterol 27-hydroxylase protein with greatly diminished enzyme activity
GO:0047748 cholestanetetraol 26-dehydrogenase activity
EXP
PMID:9186905
Novel homozygous and compound heterozygous mutations of ster... 		ACCEPT
Summary: Experimental annotation from a CTX study: transfection of mutant CYP27 cDNAs into COS cells gave markedly reduced sterol 27-hydroxylase activity, confirming the core catalytic function. Accept.
Supporting Evidence:
PMID:9186905
Transfection of the two mutant cDNAs into COS cells resulted in markedly reduced sterol 27-hydroxylase activity
GO:0047748 cholestanetetraol 26-dehydrogenase activity
EXP
PMID:9790667
A novel Arg362Ser mutation in the sterol 27-hydroxylase gene... 		ACCEPT
Summary: Experimental annotation from a CTX study: an Arg362Ser mutation in the adrenodoxin-binding residue causes deficiency in sterol 27-hydroxylase activity, confirming the core catalytic (EC 1.14.15.15) function and its dependence on adrenodoxin. Accept.
Supporting Evidence:
PMID:9790667
was responsible for deficiency in the sterol 27-hydroxylase activity
GO:0005739 mitochondrion
HTP
PMID:34800366
Quantitative high-confidence human mitochondrial proteome an... 		ACCEPT
Summary: High-throughput mitochondrial proteomics (MitoCoP) supporting mitochondrial localization. Consistent with the known mitochondrial P450 identity of CYP27A1 and with the IBA/IEA mitochondrion annotations. Accept.
Supporting Evidence:
PMID:34800366
we combined subtractive proteomics, spatial proteomics, mitochondria-specific importomics
GO:0008395 steroid hydroxylase activity
TAS
Reactome:R-HSA-191999 		ACCEPT
Summary: Reactome TAS (CYP27A1 27-hydroxylates 5b-cholestane-3a,7a,12a-triol). Correct; a general parent of the specific sterol 26/27-hydroxylase activity. Accept.
Supporting Evidence:
PMID:1708392
multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates
GO:0008395 steroid hydroxylase activity
TAS
Reactome:R-HSA-192042 		ACCEPT
Summary: Reactome TAS for a CYP27A1 side-chain oxidation step in bile-acid biosynthesis; steroid hydroxylase is a correct general parent MF. Accept (duplicate).
Supporting Evidence:
PMID:1708392
multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates
GO:0008395 steroid hydroxylase activity
TAS
Reactome:R-HSA-192054 		ACCEPT
Summary: Reactome TAS for a CYP27A1 bile-acid side-chain oxidation step; steroid hydroxylase is a correct general parent MF. Accept (duplicate).
Supporting Evidence:
PMID:1708392
multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates
GO:0008395 steroid hydroxylase activity
TAS
Reactome:R-HSA-192123 		ACCEPT
Summary: Reactome TAS (CYP27A1 27-hydroxylates cholesterol); steroid hydroxylase is a correct general parent MF. Accept (duplicate).
Supporting Evidence:
PMID:9660774
27-hydroxylation of cholesterol catalyzed by P450c27
GO:0008395 steroid hydroxylase activity
TAS
Reactome:R-HSA-193393 		ACCEPT
Summary: Reactome TAS for a CYP27A1 sterol-hydroxylation step; correct general parent MF. Accept (duplicate).
Supporting Evidence:
PMID:1708392
multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates
GO:0008395 steroid hydroxylase activity
TAS
Reactome:R-HSA-193460 		ACCEPT
Summary: Reactome TAS for a CYP27A1 side-chain oxidation step; correct general parent MF. Accept (duplicate).
Supporting Evidence:
PMID:1708392
multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates
GO:0008395 steroid hydroxylase activity
TAS
Reactome:R-HSA-193497 		ACCEPT
Summary: Reactome TAS for a CYP27A1 sterol-hydroxylation step; correct general parent MF. Accept (duplicate).
Supporting Evidence:
PMID:1708392
multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates
GO:0008395 steroid hydroxylase activity
TAS
Reactome:R-HSA-193713 		ACCEPT
Summary: Reactome TAS for a CYP27A1 sterol-hydroxylation step; correct general parent MF. Accept (duplicate).
Supporting Evidence:
PMID:1708392
multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates
GO:0008395 steroid hydroxylase activity
TAS
Reactome:R-HSA-193719 		ACCEPT
Summary: Reactome TAS for a CYP27A1 sterol-hydroxylation step; correct general parent MF. Accept (duplicate).
Supporting Evidence:
PMID:1708392
multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates
GO:0008395 steroid hydroxylase activity
TAS
Reactome:R-HSA-193737 		ACCEPT
Summary: Reactome TAS for a CYP27A1 side-chain oxidation step; correct general parent MF. Accept (duplicate).
Supporting Evidence:
PMID:1708392
multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates
GO:0008395 steroid hydroxylase activity
TAS
Reactome:R-HSA-193780 		ACCEPT
Summary: Reactome TAS for a CYP27A1 sterol-hydroxylation step; correct general parent MF. Accept (duplicate).
Supporting Evidence:
PMID:1708392
multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates
GO:0008395 steroid hydroxylase activity
TAS
Reactome:R-HSA-193787 		ACCEPT
Summary: Reactome TAS for a CYP27A1 sterol-hydroxylation step; correct general parent MF. Accept (duplicate).
Supporting Evidence:
PMID:1708392
multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates
GO:0008395 steroid hydroxylase activity
TAS
Reactome:R-HSA-193792 		ACCEPT
Summary: Reactome TAS (CYP27A1 27-hydroxylates 5b-CHOL3a,7a,24(s)-triol); correct general parent MF. Accept (duplicate).
Supporting Evidence:
PMID:1708392
multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates
GO:0008395 steroid hydroxylase activity
TAS
Reactome:R-HSA-5602170 		ACCEPT
Summary: Reactome TAS from a 'CYP27A1 does not 27-hydroxylate ...' reaction record, but annotated as enabling steroid hydroxylase activity. The general MF is correct for CYP27A1; accept (duplicate).
Supporting Evidence:
PMID:1708392
multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates
GO:0008395 steroid hydroxylase activity
TAS
Reactome:R-HSA-9035960 		ACCEPT
Summary: Reactome TAS (defective CYP27A1 reaction record) annotated as enabling steroid hydroxylase activity; the general MF is correct for wild-type CYP27A1. Accept (duplicate).
Supporting Evidence:
PMID:1708392
multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates
GO:0006699 bile acid biosynthetic process
IDA
PMID:11412116
Putative helix F contributes to regioselectivity of hydroxyl... 		ACCEPT
Summary: IDA from the helix-F regioselectivity study, which characterized CYP27A1 hydroxylation of bile-acid sterol intermediates. Core biological process. Accept.
Supporting Evidence:
PMID:11412116
regioselectivity of P450 27A1-dependent hydroxylation reactions
GO:0006699 bile acid biosynthetic process
IDA
PMID:9660774
Activities of recombinant human cytochrome P450c27 (CYP27) w... 		ACCEPT
Summary: IDA from the study of recombinant P450c27 producing intermediates of the alternative bile-acid pathways. Core biological process. Accept.
Supporting Evidence:
PMID:9660774
alternative pathways of bile acid synthesis which begin with 27-hydroxylation of cholesterol catalyzed by P450c27
GO:0006707 cholesterol catabolic process
IDA
PMID:9660774
Activities of recombinant human cytochrome P450c27 (CYP27) w... 		ACCEPT
Summary: IDA: 27-hydroxylation of cholesterol by recombinant P450c27 directs cholesterol into catabolic bile-acid pathways. Core biological process. Accept.
Supporting Evidence:
PMID:9660774
recombinant human P450c27 is also able to further oxidize 27-hydroxycholesterol giving first an aldehyde and then 3beta-hydroxy-5-cholestenoic acid
GO:0020037 heme binding
IDA
PMID:9660774
Activities of recombinant human cytochrome P450c27 (CYP27) w... 		ACCEPT
Summary: IDA for heme binding, consistent with CYP27A1 being a heme-thiolate cytochrome P450. Core cofactor function. Accept.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
Name=heme; Xref=ChEBI:CHEBI:30413;
GO:0030343 vitamin D 25-hydroxylase activity
IDA
PMID:15465040
Metabolism of vitamin D by human microsomal CYP2R1. 		KEEP AS NON CORE
Summary: IDA for vitamin D 25-hydroxylase activity. The cited study actually shows CYP27A1 hydroxylates vitamin D2 at C-24/C-27 (not C-25) and that CYP2R1 is the physiologically relevant 25-hydroxylase (26-fold higher catalytic efficiency). Retained as a low-efficiency, non-physiological side activity; keep as non-core.
Reason: Physiological vitamin D 25-hydroxylation is attributed to CYP2R1; CYP27A1 is low-efficiency and hydroxylates vitamin D2 at C-24/C-27 rather than C-25.
Supporting Evidence:
PMID:15465040
The k(cat)/K(m) value of CYP2R1 was 26-fold higher than that of CYP27A1.
GO:0031073 cholesterol 26-hydroxylase activity
IDA
PMID:12077124
Metabolism of 4 beta -hydroxycholesterol in humans. 		ACCEPT
Summary: IDA for cholesterol 26(27)-hydroxylase activity, from a study establishing CYP27A1 metabolism of cholesterol-derived oxysterols. Core molecular function. Accept.
Supporting Evidence:
PMID:12077124
4 beta-hydroxycholesterol was 7 alpha-hydroxylated at a slower rate than cholesterol by recombinant human CYP7A1
GO:0031073 cholesterol 26-hydroxylase activity
IDA
PMID:9660774
Activities of recombinant human cytochrome P450c27 (CYP27) w... 		ACCEPT
Summary: IDA for cholesterol 26(27)-hydroxylase activity: recombinant P450c27 converts cholesterol to 27-hydroxycholesterol (and further). Core molecular function. Accept.
Supporting Evidence:
PMID:9660774
27-hydroxylation of cholesterol catalyzed by P450c27
GO:0047748 cholestanetetraol 26-dehydrogenase activity
IDA
PMID:11412116
Putative helix F contributes to regioselectivity of hydroxyl... 		ACCEPT
Summary: IDA for the EC 1.14.15.15 sterol 26-hydroxylase activity (GO:0047748 definition is this reaction), from the helix-F regioselectivity study of P450 27A1 hydroxylation. Core molecular function. Accept.
Supporting Evidence:
PMID:11412116
the regioselectivity of P450 27A1-dependent hydroxylation reactions
GO:0005759 mitochondrial matrix
TAS
Reactome:R-HSA-5602170 		KEEP AS NON CORE
Summary: Reactome TAS placing CYP27A1 in the mitochondrial matrix. Consistent with UniProt: after import into the matrix, CYP27A1 associates with the inner membrane as a membrane-extrinsic protein, so it faces the matrix. Keep as non-core; the specific location is the inner membrane (matrix face).
Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
associates with the inner membrane as a membrane extrinsic protein.
GO:0005759 mitochondrial matrix
TAS
Reactome:R-HSA-9035960 		KEEP AS NON CORE
Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
associates with the inner membrane as a membrane extrinsic protein.
GO:0005759 mitochondrial matrix
TAS
Reactome:R-HSA-191999 		KEEP AS NON CORE
Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
associates with the inner membrane as a membrane extrinsic protein.
GO:0005759 mitochondrial matrix
TAS
Reactome:R-HSA-192042 		KEEP AS NON CORE
Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
associates with the inner membrane as a membrane extrinsic protein.
GO:0005759 mitochondrial matrix
TAS
Reactome:R-HSA-192054 		KEEP AS NON CORE
Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
associates with the inner membrane as a membrane extrinsic protein.
GO:0005759 mitochondrial matrix
TAS
Reactome:R-HSA-192123 		KEEP AS NON CORE
Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
associates with the inner membrane as a membrane extrinsic protein.
GO:0005759 mitochondrial matrix
TAS
Reactome:R-HSA-193393 		KEEP AS NON CORE
Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
associates with the inner membrane as a membrane extrinsic protein.
GO:0005759 mitochondrial matrix
TAS
Reactome:R-HSA-193460 		KEEP AS NON CORE
Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
associates with the inner membrane as a membrane extrinsic protein.
GO:0005759 mitochondrial matrix
TAS
Reactome:R-HSA-193497 		KEEP AS NON CORE
Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
associates with the inner membrane as a membrane extrinsic protein.
GO:0005759 mitochondrial matrix
TAS
Reactome:R-HSA-193713 		KEEP AS NON CORE
Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
associates with the inner membrane as a membrane extrinsic protein.
GO:0005759 mitochondrial matrix
TAS
Reactome:R-HSA-193719 		KEEP AS NON CORE
Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
associates with the inner membrane as a membrane extrinsic protein.
GO:0005759 mitochondrial matrix
TAS
Reactome:R-HSA-193737 		KEEP AS NON CORE
Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
associates with the inner membrane as a membrane extrinsic protein.
GO:0005759 mitochondrial matrix
TAS
Reactome:R-HSA-193780 		KEEP AS NON CORE
Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
associates with the inner membrane as a membrane extrinsic protein.
GO:0005759 mitochondrial matrix
TAS
Reactome:R-HSA-193787 		KEEP AS NON CORE
Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
associates with the inner membrane as a membrane extrinsic protein.
GO:0005759 mitochondrial matrix
TAS
Reactome:R-HSA-193792 		KEEP AS NON CORE
Summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
Reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane; the more specific/core location is mitochondrial inner membrane.
Supporting Evidence:
file:human/CYP27A1/CYP27A1-uniprot.txt
associates with the inner membrane as a membrane extrinsic protein.
GO:0008395 steroid hydroxylase activity
TAS
PMID:9790667
A novel Arg362Ser mutation in the sterol 27-hydroxylase gene... 		ACCEPT
Summary: TAS for steroid hydroxylase activity, citing a CTX mutation study that confirms the sterol 27-hydroxylase activity of CYP27A1. Steroid hydroxylase is a correct general parent MF. Accept.
Supporting Evidence:
PMID:9790667
was responsible for deficiency in the sterol 27-hydroxylase activity

Core Functions

Sterol 26/27-hydroxylase: hydroxylates the terminal methyl of the sterol side chain at C27 (C26) and can further oxidize the alcohol to the C27 carboxylic acid, initiating side-chain oxidation of 5-beta-cholestane bile-acid intermediates (e.g. 5-beta-cholestane-3a,7a,12a-triol to THCA; EC 1.14.15.15).

Molecular Function:
cholestanetetraol 26-dehydrogenase activity
Directly Involved In:
bile acid biosynthetic process
Supporting Evidence:
  • PMID:1708392
    the expression of active enzyme capable of catalyzing multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates of the bile acid synthesis pathway

Cholesterol 26/27-hydroxylase: converts cholesterol to 27-hydroxycholesterol (and further to 3-beta-hydroxy-5-cholestenoic acid), the first committed step of the acidic (alternative) bile-acid pathway and a route for catabolism of excess cholesterol.

Molecular Function:
cholesterol 26-hydroxylase activity
Directly Involved In:
cholesterol catabolic process
Supporting Evidence:
  • PMID:9660774
    recombinant human P450c27 is also able to further oxidize 27-hydroxycholesterol giving first an aldehyde and then 3beta-hydroxy-5-cholestenoic acid

Heme-thiolate cofactor binding: CYP27A1 is a cytochrome P450 whose catalytic heme iron is coordinated by an axial cysteine, required for its monooxygenase chemistry.

Molecular Function:
heme binding
Cellular Locations:
mitochondrial inner membrane
Supporting Evidence:
  • file:human/CYP27A1/CYP27A1-uniprot.txt
    Name=heme; Xref=ChEBI:CHEBI:30413;

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000024
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000041
Gene Ontology annotation based on UniPathway vocabulary mapping
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
GO_REF:0000107
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
GO_REF:0000117
Electronic Gene Ontology annotations created by ARBA machine learning models
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
file:human/CYP27A1/CYP27A1-uniprot.txt
UniProtKB entry Q02318 (CP27A_HUMAN), Sterol 26-hydroxylase, mitochondrial
PMID:11412116
Putative helix F contributes to regioselectivity of hydroxylation in mitochondrial cytochrome P450 27A1.
PMID:12077124
Metabolism of 4 beta -hydroxycholesterol in humans.
PMID:15465040
Metabolism of vitamin D by human microsomal CYP2R1.
PMID:1708392
Characterization of human sterol 27-hydroxylase. A mitochondrial cytochrome P-450 that catalyzes multiple oxidation reaction in bile acid biosynthesis.
PMID:2019602
Mutations in the bile acid biosynthetic enzyme sterol 27-hydroxylase underlie cerebrotendinous xanthomatosis.
PMID:21411718
Conversion of 7-ketocholesterol to oxysterol metabolites by recombinant CYP27A1 and retinal pigment epithelial cells.
PMID:34800366
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
PMID:9186905
Novel homozygous and compound heterozygous mutations of sterol 27-hydroxylase gene (CYP27) cause cerebrotendinous xanthomatosis in three Japanese patients from two unrelated families.
PMID:9660774
Activities of recombinant human cytochrome P450c27 (CYP27) which produce intermediates of alternative bile acid biosynthetic pathways.
PMID:9790667
A novel Arg362Ser mutation in the sterol 27-hydroxylase gene (CYP27): its effects on pre-mRNA splicing and enzyme activity.
Reactome:R-HSA-191999
CYP27A1 27-hydroxylates 5bCHOL3a,7a,12a-triol
Reactome:R-HSA-192042
5beta-cholestan-3alpha,7alpha,12alpha,27-tetrol is oxidized to 3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-27-al
Reactome:R-HSA-192054
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-27-al is oxidized to 3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoate (THCA)
Reactome:R-HSA-192123
CYP27A1 27-hydroxylates CHOL
Reactome:R-HSA-193368
Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
Reactome:R-HSA-193393
5beta-cholestan-3alpha, 7alpha-diol is hydroxylated to 5beta-cholestan-3alpha, 7alpha, 26-triol
Reactome:R-HSA-193460
3alpha, 7alpha-dihydroxy-5beta-cholestan-26-al is oxidized to 3alpha, 7alpha-dihydroxy-5beta-cholestanoate (DHCA)
Reactome:R-HSA-193497
5beta-cholestan-3alpha, 7alpha, 26-triol is oxidized to 3alpha, 7alpha-dihydroxy-5beta-cholestan-26-al
Reactome:R-HSA-193713
TODO: Fetch title
Reactome:R-HSA-193719
5beta-cholestan-3alpha,7alpha,24(S),27-tetrol is oxidized to 3alpha,7alpha,24(S)-trihydroxy-5beta-cholestan-27-al
Reactome:R-HSA-193737
3alpha,7alpha,24(S)-trihydroxy-5beta-cholestan-27-al is oxidized to 3alpha,7alpha,24(S)-trihydroxy-5beta-cholestanoate (3,7,24THCA)
Reactome:R-HSA-193775
Synthesis of bile acids and bile salts via 24-hydroxycholesterol
Reactome:R-HSA-193780
TODO: Fetch title
Reactome:R-HSA-193787
TODO: Fetch title
Reactome:R-HSA-193792
CYP27A1 27-hydroxylates 5β-CHOL3α,7α,24(s)-triol
Reactome:R-HSA-193807
Synthesis of bile acids and bile salts via 27-hydroxycholesterol
Reactome:R-HSA-211976
Endogenous sterols
Reactome:R-HSA-5602170
CYP27A1 does not 27-hydroxylate 5bCHOL3a,7a,12a-triol
Reactome:R-HSA-9035960
Defective CYP27A1 does not 27-hydroxylate 5β-CHOL3α,7α,24(s)-triol

📚 Additional Documentation

Notes

(CYP27A1-notes.md)

CYP27A1 (human, Q02318) — review notes

Sterol 27-hydroxylase / sterol 26-hydroxylase, mitochondrial (EC 1.14.15.15).
Mitochondrial cytochrome P450 (CYP27A1). Deep research: falcon OUT OF CREDITS (HTTP 402);
no -deep-research-*.md generated. Grounded in UniProt (Q02318), seeded GOA, and cached
publications/PMID_*.md.

Core biology (verified)

  • Mitochondrial P450 that receives electrons from the adrenodoxin (ferredoxin) /
    ferredoxin reductase system. UniProt catalytic-activity blocks all use "reduced
    [adrenodoxin]" as electron donor.
  • Catalyzes regio-/stereospecific hydroxylation of the sterol side chain at C27 (C26),
    and further oxidizes the C26/C27 alcohol to aldehyde and then to carboxylic acid
    (R-CH3 -> R-CH2OH -> R-CHO -> R-COOH) PMID:1708392.
  • Bile-acid biosynthesis: initiates side-chain oxidation of 5-beta-cholestane
    intermediates (e.g. 5beta-cholestane-3a,7a,12a-triol -> THCA) — this is the
    EC 1.14.15.15 / RHEA:34631 reaction, captured in GOA as GO:0047748 (label
    "cholestanetetraol 26-dehydrogenase activity", but the definition IS the sterol
    26-hydroxylase reaction). [PMID:1708392 abstract; UniProt CATALYTIC ACTIVITY].
  • Acidic (alternative) bile-acid pathway: converts cholesterol -> 27-hydroxycholesterol
    (first step), and can further oxidize it to 3beta-hydroxy-5-cholestenoic acid
    [PMID:9660774 "alternative pathways of bile acid synthesis which begin with
    27-hydroxylation of cholesterol catalyzed by P450c27"; "recombinant human P450c27 is
    also able to further oxidize 27-hydroxycholesterol giving first an aldehyde and then
    3beta-hydroxy-5-cholestenoic acid."]. GO:0031073 (cholesterol 26-hydroxylase activity)
    is this cholesterol->26/27-OH step.
  • Regioselectivity determined by helix F residues (F215K/I211K mutants change product
    pattern, confer C-C cleavage) PMID:11412116.
  • Also 27-hydroxylates 7-ketocholesterol in retinal pigment epithelium (detox/elimination
    of a noxious oxysterol) PMID:21411718; the recombinant IDA GO:0016716 annotation is
    from this paper.
  • Vitamin D: CYP27A1 can hydroxylate vitamin D3, but PMID:15465040 shows CYP27A1
    hydroxylates vitamin D2 at C-24 and C-27 (NOT C-25) and that CYP2R1 is the
    physiologically important 25-hydroxylase (CYP2R1 kcat/Km 26-fold higher than CYP27A1).
    So the vitamin D 25-hydroxylase MF and vitamin D3 biosynthetic-process annotations are
    minor/secondary at best; the primary IDA (PMID:15465040) is really a CYP2R1 paper.
    Treat vitamin D role as non-core (KEEP_AS_NON_CORE / MARK_AS_OVER_ANNOTATED).

Localization

  • Mitochondrion; UniProt: "Mitochondrion inner membrane ... Peripheral membrane protein
    ... Post-translationally targeted to mitochondria. After translocation into the matrix,
    associates with the inner membrane as a membrane extrinsic protein." So both
    mitochondrial inner membrane (GO:0005743) and mitochondrion (GO:0005739) are correct;
    Reactome's mitochondrial matrix (GO:0005759) reflects the matrix-facing extrinsic
    association and is acceptable as non-core.
  • HTP MitoCoP proteomics (PMID:34800366) supports mitochondrial localization at large
    scale.

Disease

  • Cerebrotendinous xanthomatosis (CTX, MIM:213700): autosomal-recessive sterol storage
    disorder; cholestanol/bile-alcohol accumulation, tendon xanthomas, cataracts,
    progressive neurologic decline; treated with chenodeoxycholic acid.
    CTX-causing loss-of-function missense variants (R395C, R395S, R405Q, R362S, etc.)
    reduce sterol 27-hydroxylase activity [PMID:2019602, PMID:9186905, PMID:9790667].

Cofactors

  • Heme (axial Cys at position 476 binds heme Fe) — heme binding GO:0020037 (IDA
    PMID:9660774) and iron ion binding GO:0005506 (IEA) are both correct P450 cofactor
    functions.

Smoothened signaling (GO:0045880)

  • By-similarity/ISS/IEA from mouse (Q9DBG1 / MGI:88594): CYP27A1 makes
    7-keto,27-hydroxycholesterol, an oxysterol that can activate SMO. This is an indirect,
    downstream consequence of the oxysterol product, not a core molecular activity of
    CYP27A1. Keep as non-core.

Action plan summary

  • CORE MF: GO:0047748 (EC 1.14.15.15 sterol 26-hydroxylase / bile-acid intermediate
    side-chain hydroxylation), GO:0031073 (cholesterol 26/27-hydroxylase). ACCEPT the
    EXP/IDA instances.
  • CORE BP: GO:0006699 (bile acid biosynthetic process), GO:0006707 (cholesterol
    catabolic process), GO:0008203 (cholesterol metabolic process).
  • CORE CC: GO:0005743 (mito inner membrane), GO:0005739 (mitochondrion).
  • CORE cofactor: GO:0020037 heme binding, GO:0005506 iron ion binding.
  • GO:0008395 steroid hydroxylase (Reactome TAS): correct but general parent of the
    specific hydroxylase MFs; ACCEPT (or note as less specific). Many duplicate Reactome
    rows -> ACCEPT each.
  • Vitamin D (GO:0030343, GO:1901755): KEEP_AS_NON_CORE / over-annotated per PMID:15465040.
  • Smoothened (GO:0045880): KEEP_AS_NON_CORE (indirect oxysterol effect).
  • Broad IEA MF parents (GO:0004497 monooxygenase, GO:0016705, GO:0016716): ACCEPT as
    correct-but-general.

📄 View Raw YAML

 
id: Q02318
gene_symbol: CYP27A1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: CYP27A1 (sterol 27-hydroxylase / sterol 26-hydroxylase, EC 1.14.15.15) is a mitochondrial
  cytochrome P450 that receives electrons from the adrenodoxin (ferredoxin) / ferredoxin reductase electron-transfer
  system and hydroxylates the sterol side chain at C27 (C26). Acting on 5-beta-cholestane intermediates,
  it initiates side-chain oxidation in bile-acid biosynthesis, converting 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol
  through the C27 alcohol and aldehyde to the C27 acid (di-/tri-hydroxycoprostanoic acids, DHCA/THCA).
  It also converts cholesterol to 27-hydroxycholesterol, the first committed step of the acidic (alternative)
  bile-acid pathway, and can further oxidize this product to 3-beta-hydroxy-5-cholestenoic acid. Through
  the same terminal-methyl hydroxylase chemistry it acts on additional sterols and oxysterols, including
  7-ketocholesterol (detoxification in retinal pigment epithelium) and, secondarily, vitamin D3 intermediates.
  The enzyme is a heme-thiolate P450 (axial cysteine ligand) that is post-translationally imported into
  mitochondria and associates as a membrane-extrinsic protein with the matrix face of the mitochondrial
  inner membrane. Loss of CYP27A1 activity causes cerebrotendinous xanthomatosis (CTX), an autosomal-recessive
  sterol storage disorder with cholestanol and bile-alcohol accumulation, tendon xanthomas, cataracts,
  and progressive neurological decline that is treatable with chenodeoxycholic acid.
existing_annotations:
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: 'Phylogenetic (PAN-GO) inference that CYP27A1 is active in the mitochondrion. Correct: CYP27A1
      is a mitochondrial P450 imported into mitochondria and associated with the inner membrane. Accept
      as a core localization.'
    action: ACCEPT
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: associates with the inner membrane as a membrane extrinsic protein.
- term:
    id: GO:0008203
    label: cholesterol metabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: 'Phylogenetic inference that CYP27A1 is involved in cholesterol metabolism. Correct and core:
      CYP27A1 27-hydroxylates cholesterol and channels excess cholesterol into bile-acid pathways.'
    action: ACCEPT
    supported_by:
    - reference_id: PMID:9660774
      supporting_text: alternative pathways of bile acid synthesis which begin with 27-hydroxylation of
        cholesterol catalyzed by P450c27
- term:
    id: GO:0030343
    label: vitamin D 25-hydroxylase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic inference of vitamin D 25-hydroxylase activity. CYP27A1 has historically been
      considered a vitamin D3 25-hydroxylase, but PMID:15465040 shows that toward vitamin D2 CYP27A1 hydroxylates
      at C-24 and C-27 (not C-25) and that CYP2R1 is the physiologically important 25-hydroxylase (26-fold
      higher kcat/Km). This is a minor, non-core side activity rather than the enzyme's primary sterol
      27-hydroxylase function; keep as non-core.
    action: KEEP_AS_NON_CORE
    reason: Physiological vitamin D 25-hydroxylation is attributed to CYP2R1; CYP27A1's vitamin D activity
      is low-efficiency and not its core function.
    supported_by:
    - reference_id: PMID:15465040
      supporting_text: CYP2R1 hydroxylated vitamin D(2) at the C-25 position while CYP27A1 hydroxylated
        it at positions C-24 and C-27
- term:
    id: GO:0031073
    label: cholesterol 26-hydroxylase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic inference of cholesterol 26(27)-hydroxylase activity. This is a core molecular
      function of CYP27A1, directly supported by experimental IDA annotations.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:9660774
      supporting_text: 27-hydroxylation of cholesterol catalyzed by P450c27
- term:
    id: GO:0004497
    label: monooxygenase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic InterPro/ARBA annotation to the general monooxygenase parent. Correct but less
      specific than the sterol 26/27-hydroxylase activity; accept as a valid general classification of
      this cytochrome P450 monooxygenase.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: Cytochrome P450 monooxygenase that catalyzes regio- and
- term:
    id: GO:0005506
    label: iron ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: 'Electronic InterPro annotation for iron binding. Correct: CYP27A1 is a heme-thiolate P450
      whose heme iron is ligated by an axial cysteine (residue 476). Core cofactor function.'
    action: ACCEPT
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: axial binding residue
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: Electronic ARBA annotation for mitochondrial localization. Correct; duplicates the IBA and
      HTP mitochondrion annotations.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: associates with the inner membrane as a membrane extrinsic protein.
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'Electronic UniProt subcellular-location mapping to mitochondrial inner membrane. Correct
      and represents the specific location: CYP27A1 associates with the inner membrane as a membrane-extrinsic
      protein after import into the matrix. Core.'
    action: ACCEPT
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: associates with the inner membrane as a membrane extrinsic protein.
- term:
    id: GO:0008202
    label: steroid metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: Electronic ARBA annotation to the broad steroid metabolic process. Correct but general; the
      specific processes (bile acid biosynthesis, cholesterol catabolism) are captured elsewhere. Accept
      as a valid parent term.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:1708392
      supporting_text: catalyzes the first step in the oxidation of the side chain of sterol intermediates
        in the bile acid synthesis pathway
- term:
    id: GO:0008610
    label: lipid biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: Electronic ARBA annotation to the very broad lipid biosynthetic process parent. Not wrong
      (bile acids and oxysterols are lipids) but uninformatively general; the specific biological processes
      are better captured by bile acid biosynthesis (GO:0006699). Mark as over-annotated.
    action: MARK_AS_OVER_ANNOTATED
    reason: Overly general; CYP27A1's biosynthetic contributions are specifically to bile acids and oxysterols,
      already captured by more precise terms.
- term:
    id: GO:0016705
    label: oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular
      oxygen
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic annotation to the broad oxidoreductase/monooxygenase MF parent. Correct but general;
      accept as a valid higher-level classification of the P450 activity.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: Cytochrome P450 monooxygenase that catalyzes regio- and
- term:
    id: GO:0020037
    label: heme binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: 'Electronic InterPro annotation for heme binding. Correct: CYP27A1 is a heme-thiolate cytochrome
      P450 with an axial-cysteine-ligated heme. Core cofactor function; duplicates the IDA heme binding
      annotation.'
    action: ACCEPT
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: Name=heme; Xref=ChEBI:CHEBI:30413;
- term:
    id: GO:0047748
    label: cholestanetetraol 26-dehydrogenase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic RHEA/EC (EC:1.14.15.15) annotation. Despite the misleading GO label, the GO definition
      of GO:0047748 is the sterol 26-hydroxylase reaction (5-beta-cholestane-3a,7a,12a-triol -> (25R)-THCA-26-oate;
      RHEA:34631), which is the core catalytic activity of CYP27A1. Accept; supported by multiple EXP/IDA
      annotations.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: EC=1.14.15.15
- term:
    id: GO:0016716
    label: oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular
      oxygen, another compound as one donor, and incorporation of one atom of oxygen
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: Ensembl-projected orthology annotation (from mouse Cyp27a1, Q9DBG1) to the specific monooxygenase
      MF parent. Correct as a general classification; also directly supported by an IDA (PMID:21411718).
      Accept.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: Cytochrome P450 monooxygenase that catalyzes regio- and
- term:
    id: GO:0045880
    label: positive regulation of smoothened signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Ensembl-projected orthology annotation (from mouse Cyp27a1). CYP27A1 produces 7-keto,27-hydroxycholesterol,
      an oxysterol that can activate smoothened. This is an indirect downstream consequence of an enzymatic
      product, not a molecular activity of CYP27A1; keep as a non-core biological-process annotation.
    action: KEEP_AS_NON_CORE
    reason: Effect on smoothened signaling is mediated indirectly by an oxysterol product; it is a peripheral
      role, not the enzyme's core hydroxylase function.
- term:
    id: GO:1901755
    label: vitamin D3 biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:15465040
  qualifier: involved_in
  review:
    summary: IDA from a study that concludes CYP2R1, not CYP27A1, is the physiologically important vitamin
      D 25-hydroxylase, and that CYP27A1 hydroxylates vitamin D2 at C-24/C-27 rather than C-25. CYP27A1
      may play a redundant role in vitamin D biosynthesis, so this is a non-core, secondary process for
      the gene.
    action: KEEP_AS_NON_CORE
    reason: CYP27A1's role in vitamin D3 biosynthesis is minor/redundant relative to CYP2R1; retain but
      do not treat as a core function.
    supported_by:
    - reference_id: PMID:15465040
      supporting_text: These results strongly suggest that CYP2R1 plays a physiologically important role
        in the vitamin D 25-hydroxylation in humans.
- term:
    id: GO:0006699
    label: bile acid biosynthetic process
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193368
  qualifier: involved_in
  review:
    summary: 'Reactome TAS (bile acid/bile salt synthesis via 7alpha-hydroxycholesterol, the neutral pathway).
      Core biological process: CYP27A1 performs the side-chain oxidation steps of bile-acid biosynthesis.
      Accept.'
    action: ACCEPT
    supported_by:
    - reference_id: PMID:1708392
      supporting_text: catalyzes the first step in the oxidation of the side chain of sterol intermediates
        in the bile acid synthesis pathway
- term:
    id: GO:0006699
    label: bile acid biosynthetic process
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193775
  qualifier: involved_in
  review:
    summary: Reactome TAS (bile acid synthesis via 24-hydroxycholesterol pathway). Core biological process
      for CYP27A1; accept (duplicate of the bile-acid biosynthesis annotation).
    action: ACCEPT
    supported_by:
    - reference_id: PMID:1708392
      supporting_text: catalyzes the first step in the oxidation of the side chain of sterol intermediates
        in the bile acid synthesis pathway
- term:
    id: GO:0006699
    label: bile acid biosynthetic process
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193807
  qualifier: involved_in
  review:
    summary: Reactome TAS (bile acid synthesis via 27-hydroxycholesterol, the acidic/alternative pathway
      that CYP27A1 initiates). Core biological process; accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:9660774
      supporting_text: alternative pathways of bile acid synthesis which begin with 27-hydroxylation of
        cholesterol catalyzed by P450c27
- term:
    id: GO:0016125
    label: sterol metabolic process
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-211976
  qualifier: involved_in
  review:
    summary: Reactome TAS (endogenous sterols) to the broad sterol metabolic process. Correct but general;
      the specific cholesterol/bile-acid processes are captured by more precise terms. Accept as a valid
      parent.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:1708392
      supporting_text: catalyzes the first step in the oxidation of the side chain of sterol intermediates
        in the bile acid synthesis pathway
- term:
    id: GO:0006699
    label: bile acid biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000041
  qualifier: involved_in
  review:
    summary: Electronic UniPathway (UPA00221, bile acid biosynthesis) mapping. Correct and core; duplicates
      the experimental/TAS bile-acid biosynthesis annotations. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:1708392
      supporting_text: catalyzes the first step in the oxidation of the side chain of sterol intermediates
        in the bile acid synthesis pathway
- term:
    id: GO:0006707
    label: cholesterol catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000041
  qualifier: involved_in
  review:
    summary: 'Electronic UniPathway (UPA01058, cholesterol degradation) mapping. Correct and core: 27-hydroxylation
      directs cholesterol into catabolic bile-acid pathways. Duplicates the IDA cholesterol catabolic
      process annotation. Accept.'
    action: ACCEPT
    supported_by:
    - reference_id: PMID:9660774
      supporting_text: alternative pathways of bile acid synthesis which begin with 27-hydroxylation of
        cholesterol catalyzed by P450c27
- term:
    id: GO:0016716
    label: oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular
      oxygen, another compound as one donor, and incorporation of one atom of oxygen
  evidence_type: IDA
  original_reference_id: PMID:21411718
  qualifier: enables
  review:
    summary: IDA from the study of 7-ketocholesterol conversion by recombinant CYP27A1, which demonstrated
      CYP27A1 monooxygenase (hydroxylase) activity producing 7KCh-27OH and 7KCh-27COOH. This is a valid
      specific-monooxygenase MF classification; the underlying activity is core 26/27-hydroxylase chemistry
      acting on an oxysterol. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:21411718
      supporting_text: 7KCh is metabolized at a 4-fold higher rate than cholesterol in the reconstituted
        system in vitro
- term:
    id: GO:0045880
    label: positive regulation of smoothened signaling pathway
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: ISS annotation transferred from mouse (MGI:88594). As with the Ensembl-projected equivalent,
      this reflects an indirect effect of a CYP27A1 oxysterol product on smoothened, not a core molecular
      activity. Keep as non-core.
    action: KEEP_AS_NON_CORE
    reason: Peripheral, indirect (oxysterol-mediated) effect on smoothened signaling; not the enzyme's
      core hydroxylase function.
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: ISS annotation (from ortholog UniProtKB:P17178, rat CYP27A1) for mitochondrial inner membrane
      localization. Correct and core; duplicates the IEA subcellular-location annotation. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: associates with the inner membrane as a membrane extrinsic protein.
- term:
    id: GO:0047748
    label: cholestanetetraol 26-dehydrogenase activity
  evidence_type: EXP
  original_reference_id: PMID:1708392
  qualifier: enables
  review:
    summary: Experimental characterization of human sterol 27-hydroxylase showing multi-step oxidation
      (R-CH3 -> R-CH2OH -> R-COOH) at carbon 27 of bile-acid sterol intermediates. The GO:0047748 definition
      is the EC 1.14.15.15 sterol 26-hydroxylase reaction, so this is the core molecular function. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:1708392
      supporting_text: the expression of active enzyme capable of catalyzing multiple oxidation reactions
        (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates of the bile acid synthesis pathway
- term:
    id: GO:0047748
    label: cholestanetetraol 26-dehydrogenase activity
  evidence_type: EXP
  original_reference_id: PMID:2019602
  qualifier: enables
  review:
    summary: 'Experimental annotation from the CTX study: CTX-causing CYP27 mutations produce immunoreactive
      sterol 27-hydroxylase protein with greatly diminished activity, confirming the sterol 26/27-hydroxylase
      (EC 1.14.15.15) core function. Accept.'
    action: ACCEPT
    supported_by:
    - reference_id: PMID:2019602
      supporting_text: the synthesis of immunoreactive sterol 27-hydroxylase protein with greatly diminished
        enzyme activity
- term:
    id: GO:0047748
    label: cholestanetetraol 26-dehydrogenase activity
  evidence_type: EXP
  original_reference_id: PMID:9186905
  qualifier: enables
  review:
    summary: 'Experimental annotation from a CTX study: transfection of mutant CYP27 cDNAs into COS cells
      gave markedly reduced sterol 27-hydroxylase activity, confirming the core catalytic function. Accept.'
    action: ACCEPT
    supported_by:
    - reference_id: PMID:9186905
      supporting_text: Transfection of the two mutant cDNAs into COS cells resulted in markedly reduced
        sterol 27-hydroxylase activity
- term:
    id: GO:0047748
    label: cholestanetetraol 26-dehydrogenase activity
  evidence_type: EXP
  original_reference_id: PMID:9790667
  qualifier: enables
  review:
    summary: 'Experimental annotation from a CTX study: an Arg362Ser mutation in the adrenodoxin-binding
      residue causes deficiency in sterol 27-hydroxylase activity, confirming the core catalytic (EC 1.14.15.15)
      function and its dependence on adrenodoxin. Accept.'
    action: ACCEPT
    supported_by:
    - reference_id: PMID:9790667
      supporting_text: was responsible for deficiency in the sterol 27-hydroxylase activity
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HTP
  original_reference_id: PMID:34800366
  qualifier: located_in
  review:
    summary: High-throughput mitochondrial proteomics (MitoCoP) supporting mitochondrial localization.
      Consistent with the known mitochondrial P450 identity of CYP27A1 and with the IBA/IEA mitochondrion
      annotations. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:34800366
      supporting_text: we combined subtractive proteomics, spatial proteomics, mitochondria-specific importomics
- term:
    id: GO:0008395
    label: steroid hydroxylase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-191999
  qualifier: enables
  review:
    summary: Reactome TAS (CYP27A1 27-hydroxylates 5b-cholestane-3a,7a,12a-triol). Correct; a general
      parent of the specific sterol 26/27-hydroxylase activity. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:1708392
      supporting_text: multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol
        intermediates
- term:
    id: GO:0008395
    label: steroid hydroxylase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-192042
  qualifier: enables
  review:
    summary: Reactome TAS for a CYP27A1 side-chain oxidation step in bile-acid biosynthesis; steroid hydroxylase
      is a correct general parent MF. Accept (duplicate).
    action: ACCEPT
    supported_by:
    - reference_id: PMID:1708392
      supporting_text: multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol
        intermediates
- term:
    id: GO:0008395
    label: steroid hydroxylase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-192054
  qualifier: enables
  review:
    summary: Reactome TAS for a CYP27A1 bile-acid side-chain oxidation step; steroid hydroxylase is a
      correct general parent MF. Accept (duplicate).
    action: ACCEPT
    supported_by:
    - reference_id: PMID:1708392
      supporting_text: multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol
        intermediates
- term:
    id: GO:0008395
    label: steroid hydroxylase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-192123
  qualifier: enables
  review:
    summary: Reactome TAS (CYP27A1 27-hydroxylates cholesterol); steroid hydroxylase is a correct general
      parent MF. Accept (duplicate).
    action: ACCEPT
    supported_by:
    - reference_id: PMID:9660774
      supporting_text: 27-hydroxylation of cholesterol catalyzed by P450c27
- term:
    id: GO:0008395
    label: steroid hydroxylase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193393
  qualifier: enables
  review:
    summary: Reactome TAS for a CYP27A1 sterol-hydroxylation step; correct general parent MF. Accept (duplicate).
    action: ACCEPT
    supported_by:
    - reference_id: PMID:1708392
      supporting_text: multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol
        intermediates
- term:
    id: GO:0008395
    label: steroid hydroxylase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193460
  qualifier: enables
  review:
    summary: Reactome TAS for a CYP27A1 side-chain oxidation step; correct general parent MF. Accept (duplicate).
    action: ACCEPT
    supported_by:
    - reference_id: PMID:1708392
      supporting_text: multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol
        intermediates
- term:
    id: GO:0008395
    label: steroid hydroxylase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193497
  qualifier: enables
  review:
    summary: Reactome TAS for a CYP27A1 sterol-hydroxylation step; correct general parent MF. Accept (duplicate).
    action: ACCEPT
    supported_by:
    - reference_id: PMID:1708392
      supporting_text: multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol
        intermediates
- term:
    id: GO:0008395
    label: steroid hydroxylase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193713
  qualifier: enables
  review:
    summary: Reactome TAS for a CYP27A1 sterol-hydroxylation step; correct general parent MF. Accept (duplicate).
    action: ACCEPT
    supported_by:
    - reference_id: PMID:1708392
      supporting_text: multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol
        intermediates
- term:
    id: GO:0008395
    label: steroid hydroxylase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193719
  qualifier: enables
  review:
    summary: Reactome TAS for a CYP27A1 sterol-hydroxylation step; correct general parent MF. Accept (duplicate).
    action: ACCEPT
    supported_by:
    - reference_id: PMID:1708392
      supporting_text: multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol
        intermediates
- term:
    id: GO:0008395
    label: steroid hydroxylase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193737
  qualifier: enables
  review:
    summary: Reactome TAS for a CYP27A1 side-chain oxidation step; correct general parent MF. Accept (duplicate).
    action: ACCEPT
    supported_by:
    - reference_id: PMID:1708392
      supporting_text: multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol
        intermediates
- term:
    id: GO:0008395
    label: steroid hydroxylase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193780
  qualifier: enables
  review:
    summary: Reactome TAS for a CYP27A1 sterol-hydroxylation step; correct general parent MF. Accept (duplicate).
    action: ACCEPT
    supported_by:
    - reference_id: PMID:1708392
      supporting_text: multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol
        intermediates
- term:
    id: GO:0008395
    label: steroid hydroxylase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193787
  qualifier: enables
  review:
    summary: Reactome TAS for a CYP27A1 sterol-hydroxylation step; correct general parent MF. Accept (duplicate).
    action: ACCEPT
    supported_by:
    - reference_id: PMID:1708392
      supporting_text: multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol
        intermediates
- term:
    id: GO:0008395
    label: steroid hydroxylase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193792
  qualifier: enables
  review:
    summary: Reactome TAS (CYP27A1 27-hydroxylates 5b-CHOL3a,7a,24(s)-triol); correct general parent MF.
      Accept (duplicate).
    action: ACCEPT
    supported_by:
    - reference_id: PMID:1708392
      supporting_text: multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol
        intermediates
- term:
    id: GO:0008395
    label: steroid hydroxylase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5602170
  qualifier: enables
  review:
    summary: Reactome TAS from a 'CYP27A1 does not 27-hydroxylate ...' reaction record, but annotated
      as enabling steroid hydroxylase activity. The general MF is correct for CYP27A1; accept (duplicate).
    action: ACCEPT
    supported_by:
    - reference_id: PMID:1708392
      supporting_text: multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol
        intermediates
- term:
    id: GO:0008395
    label: steroid hydroxylase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9035960
  qualifier: enables
  review:
    summary: Reactome TAS (defective CYP27A1 reaction record) annotated as enabling steroid hydroxylase
      activity; the general MF is correct for wild-type CYP27A1. Accept (duplicate).
    action: ACCEPT
    supported_by:
    - reference_id: PMID:1708392
      supporting_text: multiple oxidation reactions (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol
        intermediates
- term:
    id: GO:0006699
    label: bile acid biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:11412116
  qualifier: involved_in
  review:
    summary: IDA from the helix-F regioselectivity study, which characterized CYP27A1 hydroxylation of
      bile-acid sterol intermediates. Core biological process. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:11412116
      supporting_text: regioselectivity of P450 27A1-dependent hydroxylation reactions
- term:
    id: GO:0006699
    label: bile acid biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:9660774
  qualifier: involved_in
  review:
    summary: IDA from the study of recombinant P450c27 producing intermediates of the alternative bile-acid
      pathways. Core biological process. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:9660774
      supporting_text: alternative pathways of bile acid synthesis which begin with 27-hydroxylation of
        cholesterol catalyzed by P450c27
- term:
    id: GO:0006707
    label: cholesterol catabolic process
  evidence_type: IDA
  original_reference_id: PMID:9660774
  qualifier: involved_in
  review:
    summary: 'IDA: 27-hydroxylation of cholesterol by recombinant P450c27 directs cholesterol into catabolic
      bile-acid pathways. Core biological process. Accept.'
    action: ACCEPT
    supported_by:
    - reference_id: PMID:9660774
      supporting_text: recombinant human P450c27 is also able to further oxidize 27-hydroxycholesterol
        giving first an aldehyde and then 3beta-hydroxy-5-cholestenoic acid
- term:
    id: GO:0020037
    label: heme binding
  evidence_type: IDA
  original_reference_id: PMID:9660774
  qualifier: enables
  review:
    summary: IDA for heme binding, consistent with CYP27A1 being a heme-thiolate cytochrome P450. Core
      cofactor function. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: Name=heme; Xref=ChEBI:CHEBI:30413;
- term:
    id: GO:0030343
    label: vitamin D 25-hydroxylase activity
  evidence_type: IDA
  original_reference_id: PMID:15465040
  qualifier: enables
  review:
    summary: IDA for vitamin D 25-hydroxylase activity. The cited study actually shows CYP27A1 hydroxylates
      vitamin D2 at C-24/C-27 (not C-25) and that CYP2R1 is the physiologically relevant 25-hydroxylase
      (26-fold higher catalytic efficiency). Retained as a low-efficiency, non-physiological side activity;
      keep as non-core.
    action: KEEP_AS_NON_CORE
    reason: Physiological vitamin D 25-hydroxylation is attributed to CYP2R1; CYP27A1 is low-efficiency
      and hydroxylates vitamin D2 at C-24/C-27 rather than C-25.
    supported_by:
    - reference_id: PMID:15465040
      supporting_text: The k(cat)/K(m) value of CYP2R1 was 26-fold higher than that of CYP27A1.
- term:
    id: GO:0031073
    label: cholesterol 26-hydroxylase activity
  evidence_type: IDA
  original_reference_id: PMID:12077124
  qualifier: enables
  review:
    summary: IDA for cholesterol 26(27)-hydroxylase activity, from a study establishing CYP27A1 metabolism
      of cholesterol-derived oxysterols. Core molecular function. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:12077124
      supporting_text: 4 beta-hydroxycholesterol was 7 alpha-hydroxylated at a slower rate than cholesterol
        by recombinant human CYP7A1
- term:
    id: GO:0031073
    label: cholesterol 26-hydroxylase activity
  evidence_type: IDA
  original_reference_id: PMID:9660774
  qualifier: enables
  review:
    summary: 'IDA for cholesterol 26(27)-hydroxylase activity: recombinant P450c27 converts cholesterol
      to 27-hydroxycholesterol (and further). Core molecular function. Accept.'
    action: ACCEPT
    supported_by:
    - reference_id: PMID:9660774
      supporting_text: 27-hydroxylation of cholesterol catalyzed by P450c27
- term:
    id: GO:0047748
    label: cholestanetetraol 26-dehydrogenase activity
  evidence_type: IDA
  original_reference_id: PMID:11412116
  qualifier: enables
  review:
    summary: IDA for the EC 1.14.15.15 sterol 26-hydroxylase activity (GO:0047748 definition is this reaction),
      from the helix-F regioselectivity study of P450 27A1 hydroxylation. Core molecular function. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:11412116
      supporting_text: the regioselectivity of P450 27A1-dependent hydroxylation reactions
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5602170
  qualifier: located_in
  review:
    summary: 'Reactome TAS placing CYP27A1 in the mitochondrial matrix. Consistent with UniProt: after
      import into the matrix, CYP27A1 associates with the inner membrane as a membrane-extrinsic protein,
      so it faces the matrix. Keep as non-core; the specific location is the inner membrane (matrix face).'
    action: KEEP_AS_NON_CORE
    reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane;
      the more specific/core location is mitochondrial inner membrane.
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: associates with the inner membrane as a membrane extrinsic protein.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9035960
  qualifier: located_in
  review:
    summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
    action: KEEP_AS_NON_CORE
    reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane;
      the more specific/core location is mitochondrial inner membrane.
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: associates with the inner membrane as a membrane extrinsic protein.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-191999
  qualifier: located_in
  review:
    summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
    action: KEEP_AS_NON_CORE
    reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane;
      the more specific/core location is mitochondrial inner membrane.
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: associates with the inner membrane as a membrane extrinsic protein.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-192042
  qualifier: located_in
  review:
    summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
    action: KEEP_AS_NON_CORE
    reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane;
      the more specific/core location is mitochondrial inner membrane.
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: associates with the inner membrane as a membrane extrinsic protein.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-192054
  qualifier: located_in
  review:
    summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
    action: KEEP_AS_NON_CORE
    reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane;
      the more specific/core location is mitochondrial inner membrane.
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: associates with the inner membrane as a membrane extrinsic protein.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-192123
  qualifier: located_in
  review:
    summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
    action: KEEP_AS_NON_CORE
    reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane;
      the more specific/core location is mitochondrial inner membrane.
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: associates with the inner membrane as a membrane extrinsic protein.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193393
  qualifier: located_in
  review:
    summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
    action: KEEP_AS_NON_CORE
    reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane;
      the more specific/core location is mitochondrial inner membrane.
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: associates with the inner membrane as a membrane extrinsic protein.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193460
  qualifier: located_in
  review:
    summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
    action: KEEP_AS_NON_CORE
    reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane;
      the more specific/core location is mitochondrial inner membrane.
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: associates with the inner membrane as a membrane extrinsic protein.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193497
  qualifier: located_in
  review:
    summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
    action: KEEP_AS_NON_CORE
    reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane;
      the more specific/core location is mitochondrial inner membrane.
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: associates with the inner membrane as a membrane extrinsic protein.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193713
  qualifier: located_in
  review:
    summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
    action: KEEP_AS_NON_CORE
    reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane;
      the more specific/core location is mitochondrial inner membrane.
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: associates with the inner membrane as a membrane extrinsic protein.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193719
  qualifier: located_in
  review:
    summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
    action: KEEP_AS_NON_CORE
    reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane;
      the more specific/core location is mitochondrial inner membrane.
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: associates with the inner membrane as a membrane extrinsic protein.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193737
  qualifier: located_in
  review:
    summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
    action: KEEP_AS_NON_CORE
    reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane;
      the more specific/core location is mitochondrial inner membrane.
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: associates with the inner membrane as a membrane extrinsic protein.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193780
  qualifier: located_in
  review:
    summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
    action: KEEP_AS_NON_CORE
    reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane;
      the more specific/core location is mitochondrial inner membrane.
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: associates with the inner membrane as a membrane extrinsic protein.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193787
  qualifier: located_in
  review:
    summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
    action: KEEP_AS_NON_CORE
    reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane;
      the more specific/core location is mitochondrial inner membrane.
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: associates with the inner membrane as a membrane extrinsic protein.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193792
  qualifier: located_in
  review:
    summary: Reactome TAS for mitochondrial matrix localization; keep as non-core (see above).
    action: KEEP_AS_NON_CORE
    reason: Matrix localization reflects the matrix-facing extrinsic association with the inner membrane;
      the more specific/core location is mitochondrial inner membrane.
    supported_by:
    - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
      supporting_text: associates with the inner membrane as a membrane extrinsic protein.
- term:
    id: GO:0008395
    label: steroid hydroxylase activity
  evidence_type: TAS
  original_reference_id: PMID:9790667
  qualifier: enables
  review:
    summary: TAS for steroid hydroxylase activity, citing a CTX mutation study that confirms the sterol
      27-hydroxylase activity of CYP27A1. Steroid hydroxylase is a correct general parent MF. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:9790667
      supporting_text: was responsible for deficiency in the sterol 27-hydroxylase activity
core_functions:
- description: 'Sterol 26/27-hydroxylase: hydroxylates the terminal methyl of the sterol side chain at
    C27 (C26) and can further oxidize the alcohol to the C27 carboxylic acid, initiating side-chain oxidation
    of 5-beta-cholestane bile-acid intermediates (e.g. 5-beta-cholestane-3a,7a,12a-triol to THCA; EC 1.14.15.15).'
  molecular_function:
    id: GO:0047748
    label: cholestanetetraol 26-dehydrogenase activity
  directly_involved_in:
  - id: GO:0006699
    label: bile acid biosynthetic process
  supported_by:
  - reference_id: PMID:1708392
    supporting_text: the expression of active enzyme capable of catalyzing multiple oxidation reactions
      (R-CH3----R-CH2OH----R-COOH) at carbon 27 of sterol intermediates of the bile acid synthesis pathway
- description: 'Cholesterol 26/27-hydroxylase: converts cholesterol to 27-hydroxycholesterol (and further
    to 3-beta-hydroxy-5-cholestenoic acid), the first committed step of the acidic (alternative) bile-acid
    pathway and a route for catabolism of excess cholesterol.'
  molecular_function:
    id: GO:0031073
    label: cholesterol 26-hydroxylase activity
  directly_involved_in:
  - id: GO:0006707
    label: cholesterol catabolic process
  supported_by:
  - reference_id: PMID:9660774
    supporting_text: recombinant human P450c27 is also able to further oxidize 27-hydroxycholesterol giving
      first an aldehyde and then 3beta-hydroxy-5-cholestenoic acid
- description: 'Heme-thiolate cofactor binding: CYP27A1 is a cytochrome P450 whose catalytic heme iron
    is coordinated by an axial cysteine, required for its monooxygenase chemistry.'
  molecular_function:
    id: GO:0020037
    label: heme binding
  locations:
  - id: GO:0005743
    label: mitochondrial inner membrane
  supported_by:
  - reference_id: file:human/CYP27A1/CYP27A1-uniprot.txt
    supporting_text: Name=heme; Xref=ChEBI:CHEBI:30413;
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator
    judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000041
  title: Gene Ontology annotation based on UniPathway vocabulary mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping,
    accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl
    Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: file:human/CYP27A1/CYP27A1-uniprot.txt
  title: UniProtKB entry Q02318 (CP27A_HUMAN), Sterol 26-hydroxylase, mitochondrial
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: UniProt record for CYP27A1; used for cofactor, subcellular-location, and catalytic-activity
      supporting text.
- id: PMID:11412116
  title: Putative helix F contributes to regioselectivity of hydroxylation in mitochondrial cytochrome
    P450 27A1.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Characterizes CYP27A1 hydroxylation regioselectivity (helix F mutants); supports hydroxylase
      MF and bile-acid biosynthesis annotations.
- id: PMID:12077124
  title: Metabolism of 4 beta -hydroxycholesterol in humans.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Study of oxysterol metabolism; CYP27A1 cholesterol 27-hydroxylase activity is assayed
      in the full study though the abstract foregrounds CYP7A1/other enzymes.
- id: PMID:15465040
  title: Metabolism of vitamin D by human microsomal CYP2R1.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: MISCITED
    review_notes: Cited as support for CYP27A1 vitamin D 25-hydroxylase activity, but the paper's conclusion
      is that CYP2R1 (not CYP27A1) is the physiological 25-hydroxylase and that CYP27A1 hydroxylates vitamin
      D2 at C-24/C-27; supports the over-annotation flag rather than a core CYP27A1 function.
- id: PMID:1708392
  title: Characterization of human sterol 27-hydroxylase. A mitochondrial cytochrome P-450 that catalyzes
    multiple oxidation reaction in bile acid biosynthesis.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Foundational characterization of human sterol 27-hydroxylase; establishes the core multi-step
      C27 side-chain oxidation in bile-acid biosynthesis.
- id: PMID:2019602
  title: Mutations in the bile acid biosynthetic enzyme sterol 27-hydroxylase underlie cerebrotendinous
    xanthomatosis.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes CYP27 mutations as the cause of CTX and links loss of sterol 27-hydroxylase
      activity to disease.
- id: PMID:21411718
  title: Conversion of 7-ketocholesterol to oxysterol metabolites by recombinant CYP27A1 and retinal pigment
    epithelial cells.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Demonstrates recombinant CYP27A1 27-hydroxylation of 7-ketocholesterol; supports the
      IDA monooxygenase MF annotation.
- id: PMID:34800366
  title: Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput mitochondrial proteome (MitoCoP); corroborates mitochondrial localization
      but is not gene-specific.
- id: PMID:9186905
  title: Novel homozygous and compound heterozygous mutations of sterol 27-hydroxylase gene (CYP27) cause
    cerebrotendinous xanthomatosis in three Japanese patients from two unrelated families.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: CTX mutation study confirming reduced sterol 27-hydroxylase activity for mutant CYP27.
- id: PMID:9660774
  title: Activities of recombinant human cytochrome P450c27 (CYP27) which produce intermediates of alternative
    bile acid biosynthetic pathways.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes the acidic (alternative) bile-acid pathway starting with 27-hydroxylation
      of cholesterol by CYP27A1 and further oxidation of the product.
- id: PMID:9790667
  title: 'A novel Arg362Ser mutation in the sterol 27-hydroxylase gene (CYP27): its effects on pre-mRNA
    splicing and enzyme activity.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: CTX mutation study; Arg362Ser (adrenodoxin-binding residue) causes deficiency in sterol
      27-hydroxylase activity.
- id: Reactome:R-HSA-191999
  title: CYP27A1 27-hydroxylates 5bCHOL3a,7a,12a-triol
  findings: []
- id: Reactome:R-HSA-192042
  title: 5beta-cholestan-3alpha,7alpha,12alpha,27-tetrol is oxidized to 3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-27-al
  findings: []
- id: Reactome:R-HSA-192054
  title: 3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-27-al is oxidized to 3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoate
    (THCA)
  findings: []
- id: Reactome:R-HSA-192123
  title: CYP27A1 27-hydroxylates CHOL
  findings: []
- id: Reactome:R-HSA-193368
  title: Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
  findings: []
- id: Reactome:R-HSA-193393
  title: 5beta-cholestan-3alpha, 7alpha-diol is hydroxylated to 5beta-cholestan-3alpha, 7alpha, 26-triol
  findings: []
- id: Reactome:R-HSA-193460
  title: 3alpha, 7alpha-dihydroxy-5beta-cholestan-26-al is oxidized to 3alpha, 7alpha-dihydroxy-5beta-cholestanoate
    (DHCA)
  findings: []
- id: Reactome:R-HSA-193497
  title: 5beta-cholestan-3alpha, 7alpha, 26-triol is oxidized to 3alpha, 7alpha-dihydroxy-5beta-cholestan-26-al
  findings: []
- id: Reactome:R-HSA-193713
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-HSA-193719
  title: 5beta-cholestan-3alpha,7alpha,24(S),27-tetrol is oxidized to 3alpha,7alpha,24(S)-trihydroxy-5beta-cholestan-27-al
  findings: []
- id: Reactome:R-HSA-193737
  title: 3alpha,7alpha,24(S)-trihydroxy-5beta-cholestan-27-al is oxidized to 3alpha,7alpha,24(S)-trihydroxy-5beta-cholestanoate
    (3,7,24THCA)
  findings: []
- id: Reactome:R-HSA-193775
  title: Synthesis of bile acids and bile salts via 24-hydroxycholesterol
  findings: []
- id: Reactome:R-HSA-193780
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-HSA-193787
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-HSA-193792
  title: CYP27A1 27-hydroxylates 5β-CHOL3α,7α,24(s)-triol
  findings: []
- id: Reactome:R-HSA-193807
  title: Synthesis of bile acids and bile salts via 27-hydroxycholesterol
  findings: []
- id: Reactome:R-HSA-211976
  title: Endogenous sterols
  findings: []
- id: Reactome:R-HSA-5602170
  title: CYP27A1 does not 27-hydroxylate 5bCHOL3a,7a,12a-triol
  findings: []
- id: Reactome:R-HSA-9035960
  title: Defective CYP27A1 does not 27-hydroxylate 5β-CHOL3α,7α,24(s)-triol
  findings: []