id: O75881
gene_symbol: CYP7B1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  CYP7B1 (cytochrome P450 7B1) is an oxysterol 7-alpha-hydroxylase, a heme/iron
  cytochrome P450 monooxygenase anchored in the endoplasmic reticulum membrane. It
  catalyzes the 7-alpha-hydroxylation of oxysterols, chiefly 25-hydroxycholesterol
  and 27-hydroxycholesterol ((25R)-cholest-5-ene-3beta,26-diol), as well as
  24S-hydroxycholesterol, using molecular oxygen with electrons from NADPH via
  cytochrome P450 reductase. This is the committed 7-alpha-hydroxylation step of the
  acidic (alternative) bile-acid biosynthesis pathway, converting oxysterols
  generated by CH25H, CYP27A1 and CYP46A1 into 7-alpha-hydroxylated intermediates
  that are transported to the liver and converted to bile acids. CYP7B1 also
  7-alpha-hydroxylates 3-hydroxy steroids and neurosteroids such as
  dehydroepiandrosterone (DHEA) and pregnenolone, contributing to neurosteroid
  metabolism, and its product 7-alpha,25-dihydroxycholesterol is the ligand for the
  chemotactic receptor GPR183/EBI2 that guides B-cell migration. The enzyme is
  widely expressed (brain, testis, ovary, prostate, liver, intestine, kidney).
  Loss-of-function variants cause hereditary spastic paraplegia type 5A (SPG5A), a
  progressive motor-neuron degeneration associated with oxysterol accumulation, and,
  in severe biallelic cases, congenital bile acid synthesis defect type 3 (CBAS3)
  with neonatal cholestasis and liver failure.
existing_annotations:
- term:
    id: GO:0008395
    label: steroid hydroxylase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      IBA phylogenetic call that CYP7B1 has steroid hydroxylase activity. This is
      correct but a broad parent of the specific oxysterol/steroid 7-alpha-hydroxylase
      activity that is directly demonstrated. Keep as a correct-but-general MF.
    action: ACCEPT
    reason: >-
      CYP7B1 hydroxylates a range of steroids and oxysterols at the 7-alpha (and
      minor 6-alpha) position, so steroid hydroxylase activity is accurate. The more
      informative core MF is captured separately by oxysterol 7-alpha-hydroxylase
      activity (GO:0008396) and the specific 25-/24S-hydroxycholesterol 7-alpha-hydroxylase
      terms.
    supported_by:
    - reference_id: file:human/CYP7B1/CYP7B1-uniprot.txt
      supporting_text: >-
        Catalyzes the hydroxylation of carbon hydrogen bonds of steroids with a
        preference for 7-alpha position
- term:
    id: GO:0006699
    label: bile acid biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      IBA call that CYP7B1 participates in bile acid biosynthesis. This is the core
      biological process: CYP7B1 catalyzes the committed 7-alpha-hydroxylation step
      of the acidic (alternative) bile-acid pathway.
    action: ACCEPT
    reason: >-
      Directly supported by experimental human data: oxysterol 7-alpha-hydroxylase
      is active in the acidic pathway for bile acid synthesis, and loss of activity
      causes an inborn error of bile acid synthesis (CBAS3).
    supported_by:
    - reference_id: PMID:9802883
      supporting_text: >-
        7alpha-hydroxylase enzyme, active in the acidic pathway for bile acid synthesis
- term:
    id: GO:0042632
    label: cholesterol homeostasis
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      IBA call linking CYP7B1 to cholesterol homeostasis. By clearing oxysterols
      (oxygenated cholesterol derivatives) into the bile-acid pathway, CYP7B1
      contributes to cholesterol/oxysterol turnover; defective function causes
      cholesterol/oxysterol dysregulation implicated in SPG5A. Keep as a non-core
      downstream/physiological role.
    action: KEEP_AS_NON_CORE
    reason: >-
      The direct molecular activity is oxysterol 7-alpha-hydroxylation; cholesterol
      homeostasis is a broader physiological consequence rather than the enzyme's
      specific function. SPG5A studies frame CYP7B1 loss as defective cholesterol
      homeostasis, supporting the association but as a downstream role.
    supported_by:
    - reference_id: file:human/CYP7B1/CYP7B1-uniprot.txt
      supporting_text: >-
        Sequence alterations within CYP7B1 implicate defective cholesterol homeostasis
        in motor-neuron degeneration
- term:
    id: GO:0004497
    label: monooxygenase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro2GO IEA assigning monooxygenase activity from cytochrome P450 domains.
      Correct P450 chemistry; a broad parent of the specific 7-alpha-hydroxylase
      activity.
    action: ACCEPT
    reason: >-
      CYP7B1 is a cytochrome P450 monooxygenase that inserts one oxygen atom into
      the substrate and reduces the other to water, consistent with monooxygenase
      activity.
    supported_by:
    - reference_id: file:human/CYP7B1/CYP7B1-uniprot.txt
      supporting_text: >-
        A cytochrome P450 monooxygenase involved in the metabolism of endogenous
        oxysterols and steroid hormones
- term:
    id: GO:0005506
    label: iron ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro2GO IEA for iron ion binding, reflecting the heme iron of the P450
      catalytic center (axial Cys449 ligand to heme Fe). Correct and supported.
    action: ACCEPT
    reason: >-
      CYP7B1 uses a heme cofactor whose iron is essential for oxygen activation; the
      heme axial binding residue is annotated at position 449, confirming iron
      coordination.
    supported_by:
    - reference_id: file:human/CYP7B1/CYP7B1-uniprot.txt
      supporting_text: >-
        BINDING 449 /ligand="heme" /ligand_part="Fe"
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      IEA from UniProt subcellular-location mapping placing CYP7B1 in the
      endoplasmic reticulum (microsomal) membrane. This is the correct, core
      localization for this multi-pass membrane P450.
    action: ACCEPT
    reason: >-
      Experimentally established microsomal/ER-membrane localization; the enzyme has
      two predicted transmembrane helices and hepatic microsomal oxysterol
      7-alpha-hydroxylase activity is the assayed activity.
    supported_by:
    - reference_id: file:human/CYP7B1/CYP7B1-uniprot.txt
      supporting_text: >-
        SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
- term:
    id: GO:0008202
    label: steroid metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      ARBA machine-learning IEA for steroid metabolic process. Correct but a broad
      parent; CYP7B1's steroid role is specifically 7-alpha-hydroxylation of
      3-hydroxy steroids/neurosteroids (DHEA, pregnenolone) feeding steroid hormone
      biosynthesis.
    action: ACCEPT
    reason: >-
      CYP7B1 metabolizes steroids and neurosteroids; steroid metabolic process is
      accurate at a general level and is consistent with the UniProt steroid hormone
      biosynthesis pathway annotation.
    supported_by:
    - reference_id: file:human/CYP7B1/CYP7B1-uniprot.txt
      supporting_text: >-
        A cytochrome P450 monooxygenase involved in the metabolism of endogenous
        oxysterols and steroid hormones, including neurosteroids
- 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:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro2GO IEA capturing the P450 oxidoreductase mechanism (paired-donor
      monooxygenase using O2). Correct broad MF parent of the hydroxylase activity.
    action: ACCEPT
    reason: >-
      CYP7B1 uses molecular oxygen, incorporating one oxygen atom into substrate and
      reducing the other to water with electrons from NADPH-cytochrome P450
      reductase, exactly the chemistry described by this term.
    supported_by:
    - reference_id: file:human/CYP7B1/CYP7B1-uniprot.txt
      supporting_text: >-
        uses molecular oxygen inserting one oxygen atom into a substrate, and
        reducing the second into a water molecule, with two electrons provided by
        NADPH
- term:
    id: GO:0020037
    label: heme binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro2GO IEA for heme binding, reflecting the P450 heme cofactor. Correct
      and supported by the annotated heme axial ligand.
    action: ACCEPT
    reason: >-
      CYP7B1 requires heme as cofactor (ChEBI:CHEBI:30413) coordinated via Cys449;
      heme binding is a core molecular function of this cytochrome P450.
    supported_by:
    - reference_id: file:human/CYP7B1/CYP7B1-uniprot.txt
      supporting_text: >-
        COFACTOR: Name=heme
- term:
    id: GO:0033782
    label: 24S-hydroxycholesterol 7-alpha-hydroxylase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Automated IEA (RHEA/EC 1.14.14.26) for 24S-hydroxycholesterol 7-alpha-hydroxylase
      activity. Consistent with the UniProt catalytic-activity annotation for the
      (24S)-hydroxycholesterol reaction; a specific, correct MF (the human activity
      here is by similarity to mouse).
    action: ACCEPT
    reason: >-
      UniProt records the (24S)-hydroxycholesterol -> (24S)-7alpha-dihydroxycholesterol
      reaction (EC 1.14.14.26), matching this specific hydroxylase activity.
    supported_by:
    - reference_id: file:human/CYP7B1/CYP7B1-uniprot.txt
      supporting_text: >-
        24-hydroxycholesterol 7-alpha-hydroxylase
- term:
    id: GO:0033783
    label: 25-hydroxycholesterol 7-alpha-hydroxylase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Automated IEA (RHEA/EC 1.14.14.29) for 25-hydroxycholesterol 7-alpha-hydroxylase
      activity. This is a specific, experimentally supported activity (see EXP
      annotations from PMID:10588945 and PMID:9802883).
    action: ACCEPT
    reason: >-
      The 25-hydroxycholesterol -> 7alpha,25-dihydroxycholesterol reaction
      (EC 1.14.14.29) is directly demonstrated for human CYP7B1 and is a component
      of the enzyme's oxysterol 7-alpha-hydroxylase core function.
    supported_by:
    - reference_id: file:human/CYP7B1/CYP7B1-uniprot.txt
      supporting_text: >-
        Reaction=25-hydroxycholesterol + reduced [NADPH--hemoprotein reductase] + O2
        = 7alpha,25-dihydroxycholesterol
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: >-
      High-throughput affinity-capture/mass-spec interactome (BioPlex) annotation of
      CYP7B1 binding ubiquitin (UBB/UBC, P0CG47). Bare protein binding to a
      near-universal interactor is uninformative about CYP7B1's molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      GO:0005515 "protein binding" with a single, non-specific partner (ubiquitin)
      from a proteome-scale screen conveys no functional insight and is discouraged
      per curation guidance; it is not wrong but is an over-annotation. Retained
      rather than removed because it is an experimental IPI.
    supported_by:
    - reference_id: PMID:28514442
      supporting_text: >-
        Architecture of the human interactome defines protein communities and
        disease networks
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: >-
      Second BioPlex proteome-scale interactome annotation of CYP7B1 binding
      ubiquitin (UBB/UBC, P0CG47). As above, an uninformative bare protein-binding
      interaction.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Same rationale as the companion BioPlex annotation: high-throughput protein
      binding to ubiquitin does not inform CYP7B1's molecular function and is an
      over-annotation, but is kept because it is an experimental IPI.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: >-
        Dual proteome-scale networks reveal cell-specific remodeling of the human
        interactome
- term:
    id: GO:0006699
    label: bile acid biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: >-
      Automated IEA (UniPathway UPA00221 / mouse ortholog Q60991) for bile acid
      biosynthetic process. Correct and redundant with the experimentally supported
      core BP annotation.
    action: ACCEPT
    reason: >-
      CYP7B1 catalyzes the committed 7-alpha-hydroxylation step of the acidic
      bile-acid pathway; UniProt assigns the lipid metabolism; bile acid biosynthesis
      pathway.
    supported_by:
    - reference_id: file:human/CYP7B1/CYP7B1-uniprot.txt
      supporting_text: >-
        PATHWAY: Lipid metabolism; bile acid biosynthesis
- term:
    id: GO:0035754
    label: B cell chemotaxis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Ensembl-Compara IEA transferred from the mouse ortholog (Q60991): CYP7B1
      indirectly promotes B-cell chemotaxis because its product
      7-alpha,25-dihydroxycholesterol is the ligand for GPR183/EBI2 that guides
      B-cell positioning. A real but non-core, indirect/downstream role in human.
    action: KEEP_AS_NON_CORE
    reason: >-
      This is a physiological consequence of the enzyme's oxysterol product acting
      as an EBI2 ligand, not a direct molecular function of CYP7B1; the human
      evidence is by similarity to mouse. Keep as non-core.
    supported_by:
    - reference_id: file:human/CYP7B1/CYP7B1-uniprot.txt
      supporting_text: >-
        regulates B cell migration in germinal centers of lymphoid organs
- term:
    id: GO:0006699
    label: bile acid biosynthetic process
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-192105
  qualifier: involved_in
  review:
    summary: >-
      Reactome TAS (Synthesis of bile acids and bile salts) for bile acid
      biosynthetic process. Consistent with the core biological role of CYP7B1.
    action: ACCEPT
    reason: >-
      Reactome places CYP7B1 in bile acid/bile salt synthesis, matching the
      experimentally established acidic-pathway 7-alpha-hydroxylation role.
    supported_by:
    - reference_id: PMID:9802883
      supporting_text: >-
        7alpha-hydroxylase enzyme, active in the acidic pathway for bile acid synthesis
- 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 (Synthesis of bile acids and bile salts via 27-hydroxycholesterol)
      for bile acid biosynthetic process. This is precisely the acidic pathway in
      which CYP7B1 7-alpha-hydroxylates 27-hydroxycholesterol.
    action: ACCEPT
    reason: >-
      CYP7B1 7-alpha-hydroxylates 27-hydroxycholesterol ((25R)-cholest-5-ene-3beta,26-diol),
      the defining step of the 27-hydroxycholesterol (acidic) route to bile acids.
    supported_by:
    - reference_id: PMID:10588945
      supporting_text: >-
        able to catalyze 7alpha-hydroxylation of 27-hydroxycholesterol and
- 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) for sterol metabolic process. CYP7B1
      metabolizes oxysterols (oxygenated sterols), so this broad BP is correct.
    action: ACCEPT
    reason: >-
      By 7-alpha-hydroxylating oxysterols such as 25- and 27-hydroxycholesterol,
      CYP7B1 participates in endogenous sterol metabolism; a correct, somewhat broad
      biological-process term.
    supported_by:
    - reference_id: PMID:10588945
      supporting_text: >-
        Oxysterol 7alpha-hydroxylase has broad substrate specificity for sterol
        metabolites
- term:
    id: GO:0008396
    label: oxysterol 7-alpha-hydroxylase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-191972
  qualifier: enables
  review:
    summary: >-
      Reactome TAS (27-hydroxycholesterol is 7alpha-hydroxylated) for oxysterol
      7-alpha-hydroxylase activity. This is the specific, core molecular function of
      CYP7B1.
    action: ACCEPT
    reason: >-
      Oxysterol 7-alpha-hydroxylase activity is the defining catalytic function,
      experimentally demonstrated for 27-hydroxycholesterol and other oxysterols;
      the best-fit specific MF term.
    supported_by:
    - reference_id: PMID:10588945
      supporting_text: >-
        able to catalyze 7alpha-hydroxylation of 27-hydroxycholesterol and
- term:
    id: GO:0008396
    label: oxysterol 7-alpha-hydroxylase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-192065
  qualifier: enables
  review:
    summary: >-
      Reactome TAS (CYP7B1 7-hydroxylates 25OH-CHOL) for oxysterol 7-alpha-hydroxylase
      activity. Specific, core MF; consistent with the experimental 25-hydroxycholesterol
      activity.
    action: ACCEPT
    reason: >-
      CYP7B1 7-alpha-hydroxylates 25-hydroxycholesterol, an oxysterol; oxysterol
      7-alpha-hydroxylase activity is the correct specific MF.
    supported_by:
    - reference_id: file:human/CYP7B1/CYP7B1-uniprot.txt
      supporting_text: >-
        Reaction=25-hydroxycholesterol + reduced [NADPH--hemoprotein reductase] + O2
        = 7alpha,25-dihydroxycholesterol
- term:
    id: GO:0008396
    label: oxysterol 7-alpha-hydroxylase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5602885
  qualifier: enables
  review:
    summary: >-
      Reactome TAS (Defective CYP7B1 does not 7-hydroxylate 25OH-CHOL) for oxysterol
      7-alpha-hydroxylase activity, framed around the disease (SPG5A/CBAS3) loss of
      activity. Correct specific core MF.
    action: ACCEPT
    reason: >-
      The disease reaction confirms the wild-type activity: CYP7B1 normally
      7-alpha-hydroxylates 25-hydroxycholesterol; its loss underlies CBAS3/SPG5A.
    supported_by:
    - reference_id: PMID:9802883
      supporting_text: >-
        Hepatic microsomal oxysterol 7alpha-hydroxylase activity was undetectable in the
- term:
    id: GO:0033782
    label: 24S-hydroxycholesterol 7-alpha-hydroxylase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: >-
      ISS from the mouse ortholog (Q60991) for 24S-hydroxycholesterol 7-alpha-hydroxylase
      activity. Consistent with the UniProt catalytic-activity record (by similarity)
      for the (24S)-hydroxycholesterol reaction; a specific, plausible MF.
    action: ACCEPT
    reason: >-
      The (24S)-hydroxycholesterol -> (24S)-7alpha-dihydroxycholesterol reaction is
      annotated for CYP7B1 by similarity to the mouse ortholog; a component of its
      oxysterol 7-alpha-hydroxylase activity.
    supported_by:
    - reference_id: file:human/CYP7B1/CYP7B1-uniprot.txt
      supporting_text: >-
        Reaction=(24S)-hydroxycholesterol + reduced [NADPH--hemoprotein reductase] + O2
- term:
    id: GO:0033783
    label: 25-hydroxycholesterol 7-alpha-hydroxylase activity
  evidence_type: EXP
  original_reference_id: PMID:10588945
  qualifier: enables
  review:
    summary: >-
      Experimental (EXP) demonstration that recombinant human CYP7B1 7-alpha-hydroxylates
      oxysterols. This is a core, directly measured molecular function.
    action: ACCEPT
    reason: >-
      Human CYP7B1 transiently expressed in 293/T cells catalyzed 7-alpha-hydroxylation
      of 27-hydroxycholesterol and DHEA, directly demonstrating oxysterol/steroid
      7-alpha-hydroxylase activity (the 25-hydroxycholesterol activity is the closely
      related specific term).
    supported_by:
    - reference_id: PMID:10588945
      supporting_text: >-
        able to catalyze 7alpha-hydroxylation of 27-hydroxycholesterol and
- term:
    id: GO:0033783
    label: 25-hydroxycholesterol 7-alpha-hydroxylase activity
  evidence_type: EXP
  original_reference_id: PMID:9802883
  qualifier: enables
  review:
    summary: >-
      Experimental (EXP) support: patient hepatic microsomal oxysterol
      7-alpha-hydroxylase activity was undetectable and the mutant (R388X) protein
      was inactive when expressed, confirming CYP7B1 as the 7-alpha-hydroxylase of
      oxysterols including 25-hydroxycholesterol.
    action: ACCEPT
    reason: >-
      Loss of the 25/27-hydroxycholesterol 7-alpha-hydroxylase activity in a CYP7B1
      loss-of-function patient (with >4,500-fold accumulation of 27-hydroxycholesterol)
      demonstrates this catalytic activity for human CYP7B1.
    supported_by:
    - reference_id: PMID:9802883
      supporting_text: >-
        truncated protein was inactive when expressed in 293 cells
- term:
    id: GO:0035754
    label: B cell chemotaxis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: >-
      ISS from the mouse ortholog (Q60991) for B-cell chemotaxis, via the CYP7B1
      product 7-alpha,25-dihydroxycholesterol acting as the EBI2/GPR183 ligand. Real
      but indirect and non-core in human.
    action: KEEP_AS_NON_CORE
    reason: >-
      As with the Ensembl IEA, this reflects an indirect downstream role mediated by
      an oxysterol product rather than CYP7B1's direct molecular function; keep as
      non-core.
    supported_by:
    - reference_id: file:human/CYP7B1/CYP7B1-uniprot.txt
      supporting_text: >-
        regulates B cell migration in germinal centers of lymphoid organs
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5602885
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS for endoplasmic reticulum membrane localization. Correct, core
      localization for this microsomal P450.
    action: ACCEPT
    reason: >-
      CYP7B1 is a multi-pass ER/microsomal membrane protein; hepatic microsomal
      oxysterol 7-alpha-hydroxylase activity is the assayed activity.
    supported_by:
    - reference_id: file:human/CYP7B1/CYP7B1-uniprot.txt
      supporting_text: >-
        SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-191972
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS for ER membrane localization (duplicate of the core CC
      annotation). Correct.
    action: ACCEPT
    reason: >-
      Consistent with the established microsomal/ER-membrane localization of CYP7B1.
    supported_by:
    - reference_id: file:human/CYP7B1/CYP7B1-uniprot.txt
      supporting_text: >-
        Microsome membrane
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-192065
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS for ER membrane localization (duplicate of the core CC
      annotation). Correct.
    action: ACCEPT
    reason: >-
      Consistent with the established microsomal/ER-membrane localization of CYP7B1.
    supported_by:
    - reference_id: file:human/CYP7B1/CYP7B1-uniprot.txt
      supporting_text: >-
        SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
- term:
    id: GO:0006699
    label: bile acid biosynthetic process
  evidence_type: TAS
  original_reference_id: PMID:9802883
  qualifier: involved_in
  review:
    summary: >-
      TAS (from the primary CBAS3 paper) for bile acid biosynthetic process. Core
      biological role, directly supported by the human inborn-error phenotype.
    action: ACCEPT
    reason: >-
      Setchell et al. defined a new inborn error of bile acid synthesis caused by
      oxysterol 7-alpha-hydroxylase deficiency, placing CYP7B1 in the acidic bile
      acid biosynthesis pathway.
    supported_by:
    - reference_id: PMID:9802883
      supporting_text: >-
        7alpha-hydroxylase enzyme, active in the acidic pathway for bile acid synthesis
- term:
    id: GO:0008396
    label: oxysterol 7-alpha-hydroxylase activity
  evidence_type: TAS
  original_reference_id: PMID:9802883
  qualifier: enables
  review:
    summary: >-
      TAS (from the primary CBAS3 paper) for oxysterol 7-alpha-hydroxylase activity.
      This is the specific, core molecular function of CYP7B1.
    action: ACCEPT
    reason: >-
      The paper identifies CYP7B1 as the microsomal oxysterol 7-alpha-hydroxylase
      whose deficiency causes accumulation of 27-hydroxycholesterol and severe
      neonatal liver disease.
    supported_by:
    - reference_id: PMID:9802883
      supporting_text: >-
        7alpha-hydroxylation due to a mutation in the gene for the microsomal oxysterol
core_functions:
- description: >-
    Oxysterol 7-alpha-hydroxylase: 7-alpha-hydroxylation of oxysterols
    (25-hydroxycholesterol, 27-hydroxycholesterol/(25R)-cholest-5-ene-3beta,26-diol,
    24S-hydroxycholesterol) as the committed step of the acidic (alternative) bile
    acid biosynthesis pathway, in the endoplasmic reticulum membrane.
  molecular_function:
    id: GO:0008396
    label: oxysterol 7-alpha-hydroxylase activity
  directly_involved_in:
  - id: GO:0006699
    label: bile acid biosynthetic process
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  supported_by:
  - reference_id: PMID:9802883
    supporting_text: >-
      7alpha-hydroxylase enzyme, active in the acidic pathway for bile acid synthesis
  - reference_id: PMID:10588945
    supporting_text: >-
      able to catalyze 7alpha-hydroxylation of 27-hydroxycholesterol and
- description: >-
    7-alpha-hydroxylation of oxysterols and 3-hydroxy steroids/neurosteroids (e.g.
    DHEA, pregnenolone) as part of endogenous sterol and steroid metabolism,
    contributing to cholesterol/oxysterol turnover and neurosteroid metabolism.
  molecular_function:
    id: GO:0008396
    label: oxysterol 7-alpha-hydroxylase activity
  directly_involved_in:
  - id: GO:0016125
    label: sterol metabolic process
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  supported_by:
  - reference_id: PMID:10588945
    supporting_text: >-
      Oxysterol 7alpha-hydroxylase has broad substrate specificity for sterol
      metabolites
  - reference_id: file:human/CYP7B1/CYP7B1-uniprot.txt
    supporting_text: >-
      A cytochrome P450 monooxygenase involved in the metabolism of endogenous
      oxysterols and steroid hormones, including neurosteroids
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: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: PMID:10588945
  title: Structure and functions of human oxysterol 7alpha-hydroxylase cDNAs and gene
    CYP7B1.
  findings:
  - statement: >-
      Human CYP7B1 expressed in 293/T cells 7-alpha-hydroxylates 27-hydroxycholesterol
      and DHEA; the enzyme has broad substrate specificity for sterol metabolites and
      is expressed in steroidogenic and bile-acid-handling tissues.
    supporting_text: >-
      The human oxysterol 7alpha-hydroxylase transiently expressed in 293/T cells was
      able to catalyze 7alpha-hydroxylation of 27-hydroxycholesterol and
      dehydroepiandrosterone (DHEA).
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Abstract-only in cache (full_text_available:false) but directly establishes
      human CYP7B1 oxysterol/DHEA 7-alpha-hydroxylase activity and tissue expression.
      Title/PMID match the fetched record.
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease
    networks.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      BioPlex proteome-scale interactome; the CYP7B1 hit is a bare protein-binding
      interaction with ubiquitin (UBB, P0CG47), uninformative for molecular function.
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Second BioPlex interactome dataset; same uninformative ubiquitin (P0CG47)
      protein-binding interaction as PMID:28514442.
- id: PMID:9802883
  title: 'Identification of a new inborn error in bile acid synthesis: mutation of
    the oxysterol 7alpha-hydroxylase gene causes severe neonatal liver disease.'
  findings:
  - statement: >-
      Loss of microsomal oxysterol 7-alpha-hydroxylase (CYP7B1) activity causes a new
      inborn error of bile acid synthesis (CBAS3), with massive 27-hydroxycholesterol
      accumulation and severe neonatal cholestatic liver disease; establishes CYP7B1
      in the acidic bile-acid pathway.
    supporting_text: >-
      a deficiency in 7alpha-hydroxylation due to a mutation in the gene for the
      microsomal oxysterol 7alpha-hydroxylase enzyme, active in the acidic pathway
      for bile acid synthesis
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Abstract-only in cache but the primary human disease/enzyme paper; establishes
      CYP7B1 catalytic activity, ER/microsomal localization, and bile-acid-synthesis
      role. Title/PMID match.
- id: Reactome:R-HSA-191972
  title: 27-hydroxycholesterol is 7alpha-hydroxylated
  findings: []
- id: Reactome:R-HSA-192065
  title: CYP7B1 7-hydroxylates 25OH-CHOL
  findings: []
- id: Reactome:R-HSA-192105
  title: Synthesis of bile acids and bile salts
  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-5602885
  title: Defective CYP7B1 does not 7-hydroxylate 25OH-CHOL
  findings: []
- id: file:human/CYP7B1/CYP7B1-uniprot.txt
  title: UniProtKB entry O75881 (CP7B1_HUMAN), Cytochrome P450 7B1
  findings: []