DHCR7

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005789 endoplasmic reticulum membrane	IBA GO_REF:0000033	ACCEPT	Summary: DHCR7 is an integral endoplasmic reticulum membrane enzyme; this is where its terminal cholesterol-biosynthesis reaction takes place. Reason: The ER-membrane localization is well supported experimentally (subcellular fractionation/immunolocalization) and by the multi-pass transmembrane topology. The is_active_in qualifier correctly captures that catalysis occurs at the ER membrane. This is a core cellular-component annotation. Supporting Evidence: PMID:9878250 these two related proteins are in the endoplasmic reticulum file:human/DHCR7/DHCR7-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0006695 cholesterol biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: DHCR7 catalyses the last step of cholesterol biosynthesis, converting 7-dehydrocholesterol to cholesterol. Reason: This is the central biological process for DHCR7 and is supported by biochemistry, disease genetics (SLOS), and phylogenetic inference. Core biological-process annotation. Supporting Evidence: PMID:9465114 The Delta7-sterol reductase is the ultimate enzyme of cholesterol biosynthesis in vertebrates and is absent from yeast.
GO:0047598 7-dehydrocholesterol reductase activity	IBA GO_REF:0000033	ACCEPT	Summary: The specific molecular function of DHCR7 - NADPH-dependent reduction of the C7-C8 double bond of 7-dehydrocholesterol to cholesterol (EC 1.3.1.21). Reason: This is the precise, correct molecular-function term and the core function of the gene. Strongly supported by direct enzymatic characterization across orthologs and phylogenetic inference. Supporting Evidence: PMID:9465114 remove the C7-8 double bond in 7-dehydrocholesterol
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: ER membrane localization inferred from the UniProt Subcellular Location vocabulary mapping. Reason: Correct and consistent with experimental localization; this IEA mirrors the curated Swiss-Prot subcellular location. Supporting Evidence: file:human/DHCR7/DHCR7-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0016020 membrane	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Generic membrane localization from InterPro domain mapping. Reason: DHCR7 is a multi-pass membrane protein, so 'membrane' is not wrong, but it is far less informative than the specific and experimentally supported GO:0005789 endoplasmic reticulum membrane already annotated. Retain only as a generic parent. Supporting Evidence: file:human/DHCR7/DHCR7-uniprot.txt Multi-pass membrane protein
GO:0016126 sterol biosynthetic process	IEA GO_REF:0000002	ACCEPT	Summary: Sterol biosynthetic process, the broader biosynthetic category encompassing cholesterol biosynthesis. Reason: Correct-branch parent of the specific cholesterol biosynthetic process; DHCR7 acts in sterol/cholesterol biosynthesis. Reasonable broader annotation from InterPro. Supporting Evidence: file:human/DHCR7/DHCR7-uniprot.txt Belongs to the ERG4/ERG24 family
GO:0016628 oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: General oxidoreductase activity (CH-CH group donors, NAD/NADP acceptor) inferred from InterPro. Reason: This is a correct-branch but overly general parent of the specific and experimentally established GO:0047598 7-dehydrocholesterol reductase activity. DHCR7 does reduce a C-C double bond using NADPH, so the term is not wrong, but the specific term should be preferred. Proposed replacements: 7-dehydrocholesterol reductase activity Supporting Evidence: PMID:9465114 The conversion to cholesterol depends on NADPH
GO:0047598 7-dehydrocholesterol reductase activity	IEA GO_REF:0000120	ACCEPT	Summary: 7-dehydrocholesterol reductase activity (EC 1.3.1.21) from automated annotation (ARBA/RHEA/EC mapping). Reason: Correct specific molecular function, consistent with the RHEA:23984 / EC 1.3.1.21 reaction and experimental evidence. Core function. Supporting Evidence: file:human/DHCR7/DHCR7-uniprot.txt EC=1.3.1.21
GO:0006695 cholesterol biosynthetic process	TAS Reactome:R-HSA-6807047	ACCEPT	Summary: Cholesterol biosynthetic process, asserted via the Reactome Bloch-pathway (via desmosterol) module. Reason: DHCR7 participates in cholesterol biosynthesis; the Reactome pathway assertion is consistent with the enzyme's established role. Core biological process. Supporting Evidence: PMID:9465114 The Delta7-sterol reductase is the ultimate enzyme of cholesterol biosynthesis in vertebrates and is absent from yeast.
GO:0006695 cholesterol biosynthetic process	TAS Reactome:R-HSA-9969901	ACCEPT	Summary: Cholesterol biosynthetic process, asserted via the Reactome modified Kandutsch-Russell (from zymosterol) module - the arm terminated by DHCR7. Reason: Consistent with DHCR7's role as the terminal enzyme of the Kandutsch-Russell arm of cholesterol synthesis. Core biological process. Supporting Evidence: PMID:9465114 The Delta7-sterol reductase is the ultimate enzyme of cholesterol biosynthesis in vertebrates and is absent from yeast.
GO:0006695 cholesterol biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: Cholesterol biosynthetic process from automated UniPathway (UPA00063) mapping. Reason: Correct pathway assignment consistent with the curated UniProt PATHWAY annotation (cholesterol biosynthesis). Core biological process. Supporting Evidence: file:human/DHCR7/DHCR7-uniprot.txt PATHWAY: Steroid biosynthesis; cholesterol biosynthesis.
GO:0047598 7-dehydrocholesterol reductase activity	EXP PMID:9465114 Molecular cloning and expression of the human delta7-sterol ...	ACCEPT	Summary: Direct demonstration that the cloned human enzyme removes the C7-C8 double bond of 7-dehydrocholesterol, converting it to cholesterol in an NADPH-dependent manner. Reason: Experimental evidence directly establishing the core molecular function. Supporting Evidence: PMID:9465114 Microsomes from Saccharomyces cerevisiae strains heterologously expressing the human cDNA remove the C7-8 double bond in 7-dehydrocholesterol.
GO:0005783 endoplasmic reticulum	IDA GO_REF:0000052	ACCEPT	Summary: Immunofluorescence (Human Protein Atlas) localizes DHCR7 to the endoplasmic reticulum. Reason: Consistent with the more specific ER membrane localization; ER is the correct compartment. Retained as the (broader) directly observed compartment. Supporting Evidence: PMID:9878250 these two related proteins are in the endoplasmic reticulum
GO:0033963 cholesterol-5,6-oxide hydrolase activity	IMP PMID:20615952 Identification and pharmacological characterization of chole...	KEEP AS NON CORE	Summary: DHCR7, together with EBP (D8D7I), constitutes the microsomal antiestrogen binding site (AEBS) that carries cholesterol-5,6-epoxide hydrolase (ChEH) activity; co-expression of both subunits reconstitutes ChEH and double knockdown abolishes it. Reason: This is a genuine, experimentally supported (IMP) secondary/moonlighting activity in which DHCR7 acts as a subunit of the heterodimeric AEBS complex, and it is recorded by UniProt (AltName "Cholesterol-5,6-epoxide hydrolase subunit DHCR7", EC 3.3.2.11). It is not the core reductase function and DHCR7 alone confers only weak activity (the activity requires the EBP-DHCR7 dimer), so it is kept as non-core rather than accepted as a core function. Not removed, as the full-text experimental evidence supports it. Supporting Evidence: PMID:20615952 whereas their coexpression fully file:human/DHCR7/DHCR7-uniprot.txt The precise role of
GO:0006695 cholesterol biosynthetic process	IMP PMID:38297129 7-Dehydrocholesterol is an endogenous suppressor of ferropto...	ACCEPT	Summary: Genetic/functional manipulation of DHCR7 (including SLOS variants and active-site mutagenesis) confirms its role in cholesterol biosynthesis via 7-DHC reduction. Reason: Mutagenesis and variant characterization in this study confirm that DHCR7 converts 7-DHC to cholesterol, supporting its role in the cholesterol biosynthetic process. Core biological process. Supporting Evidence: PMID:38297129 we identify proferroptotic activity of 7-dehydrocholesterol reductase (DHCR7) and an unexpected prosurvival function of its substrate, 7-dehydrocholesterol (7-DHC)
GO:0006695 cholesterol biosynthetic process	IMP PMID:38297130 7-Dehydrocholesterol dictates ferroptosis sensitivity.	ACCEPT	Summary: CRISPR screening and functional analysis place DHCR7 as the enzyme that metabolizes 7-DHC for cholesterol synthesis in distal cholesterol biosynthesis. Reason: Independently confirms DHCR7's role in cholesterol biosynthesis via 7-DHC reduction. Core biological process. Supporting Evidence: PMID:38297130 metabolized by 7-DHC reductase (DHCR7) for cholesterol synthesis
GO:0047598 7-dehydrocholesterol reductase activity	IMP PMID:38297129 7-Dehydrocholesterol is an endogenous suppressor of ferropto...	ACCEPT	Summary: Active-site mutagenesis (e.g., N274K, L306R cause loss of activity) and SLOS variant characterization confirm the 7-DHC reductase activity of DHCR7. Reason: Direct functional (mutagenesis) evidence for the core molecular function. Supporting Evidence: PMID:38297129 we identify proferroptotic activity of 7-dehydrocholesterol reductase (DHCR7)
GO:0047598 7-dehydrocholesterol reductase activity	IMP PMID:38297130 7-Dehydrocholesterol dictates ferroptosis sensitivity.	ACCEPT	Summary: Functional evidence that DHCR7 is the reductase metabolizing 7-DHC in distal cholesterol biosynthesis. Reason: Supports the core molecular function through loss/gain-of-function analysis of DHCR7 and 7-DHC levels. Supporting Evidence: PMID:38297130 metabolized by 7-DHC reductase (DHCR7) for cholesterol synthesis
GO:0160020 positive regulation of ferroptosis	IMP PMID:38297129 7-Dehydrocholesterol is an endogenous suppressor of ferropto...	KEEP AS NON CORE	Summary: DHCR7 promotes ferroptosis by consuming its substrate 7-DHC, a potent radical-trapping (anti-ferroptotic) sterol; DHCR7 loss raises 7-DHC and confers ferroptosis resistance. Reason: This is a real, experimentally supported (IMP) regulatory consequence of DHCR7's enzymatic activity - by depleting the anti-ferroptotic metabolite 7-DHC, DHCR7 acts as a pro-ferroptotic factor. It is downstream of, and secondary to, the core biosynthetic function, so it is kept as non-core rather than a defining function. Supporting Evidence: PMID:38297129 we identify proferroptotic activity of 7-dehydrocholesterol reductase (DHCR7) and an unexpected prosurvival function of its substrate, 7-dehydrocholesterol (7-DHC)
GO:0160020 positive regulation of ferroptosis	IMP PMID:38297130 7-Dehydrocholesterol dictates ferroptosis sensitivity.	KEEP AS NON CORE	Summary: Genome-wide CRISPR screening identifies DHCR7 as a pro-ferroptotic gene acting by lowering the anti-ferroptotic metabolite 7-DHC. Reason: Independently supports the pro-ferroptotic regulatory role, which is a secondary consequence of DHCR7's core reductase activity. Kept as non-core. Supporting Evidence: PMID:38297130 DHCR7 functions as a pro-ferroptotic gene
GO:0005515 protein binding	IPI PMID:32694168 TMEM147 interacts with lamin B receptor, regulates its local...	MARK AS OVER ANNOTATED	Summary: DHCR7 physically interacts with the ER/nuclear-envelope transmembrane protein TMEM147 (Q9BVK8), whose depletion reduces DHCR7 protein levels and affects cholesterol homeostasis. Reason: The interaction with TMEM147 is genuine and experimentally documented, but the bare 'protein binding' (GO:0005515) term is uninformative about molecular function. The specific interaction and its regulatory relevance are recorded here rather than captured by this generic term. Per curation policy the IPI is not removed. Supporting Evidence: PMID:32694168 physically interacts with the key sterol reductase DHCR7
GO:0005515 protein binding	IPI PMID:25637936 The terminal enzymes of cholesterol synthesis, DHCR24 and DH...	MARK AS OVER ANNOTATED	Summary: DHCR7 physically and functionally interacts with the other terminal cholesterol-synthesis reductase DHCR24 (Q15392); the two enzymes co-immunoprecipitate and DHCR24 controls DHCR7 activity. Reason: The DHCR7-DHCR24 interaction is a well-established, functionally important physical interaction (a proposed cholesterol-synthesis metabolon), but 'protein binding' is too generic to convey function. The specific interacting partner and its regulatory role are documented here. IPI retained per policy. Supporting Evidence: PMID:25637936 24-Dehydrocholesterol reductase (DHCR24) and 7-dehydrocholesterol reductase (DHCR7) coimmunoprecipitate, and when the DHCR24 gene is knocked down by siRNA, DHCR7 activity is also ablated.
GO:0050661 NADP binding	ISS GO_REF:0000024	ACCEPT	Summary: DHCR7 binds NADP(H) as the redox cofactor for the reduction of 7-DHC to cholesterol. Reason: Supported by multiple predicted NADP(+) binding-site residues (UniProt BINDING features) and by the NADPH-dependence of the catalysed reaction. Consistent with the family cofactor requirement; a correct molecular-function annotation. Supporting Evidence: PMID:9465114 The conversion to cholesterol depends on NADPH file:human/DHCR7/DHCR7-uniprot.txt /ligand="NADP(+)"
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	MARK AS OVER ANNOTATED	Summary: DHCR7 identified in a high-throughput membrane proteome of an NK-like cell line. Reason: A high-throughput proteomic membrane assignment; 'membrane' is correct but generic. The specific and experimentally supported ER membrane localization is preferred and already annotated. Supporting Evidence: PMID:19946888 approximately 40% of the identified proteins were predicted as plausible membrane proteins
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-1655827	ACCEPT	Summary: ER membrane localization asserted by Reactome. Reason: Correct, specific cellular-component localization consistent with experimental data. Core cellular component. Supporting Evidence: file:human/DHCR7/DHCR7-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-196402	ACCEPT	Summary: ER membrane localization asserted by Reactome. Reason: Correct, specific cellular-component localization consistent with experimental data. Core cellular component. Supporting Evidence: file:human/DHCR7/DHCR7-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-6807055	ACCEPT	Summary: ER membrane localization asserted by the Reactome reaction 'DHCR7 reduces 7-dehydroCHOL to CHOL'. Reason: Correct, specific cellular-component localization consistent with experimental data. Core cellular component. Supporting Evidence: file:human/DHCR7/DHCR7-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0006695 cholesterol biosynthetic process	IMP PMID:9465114 Molecular cloning and expression of the human delta7-sterol ...	ACCEPT	Summary: Functional expression of the cloned enzyme, and its identification as the ultimate cholesterol-biosynthesis enzyme defective in SLOS, support its role in cholesterol biosynthesis. Reason: Supported by the reconstitution of 7-DHC-to-cholesterol conversion on expression of the human cDNA. Core biological process. Supporting Evidence: PMID:9465114 The Delta7-sterol reductase is the ultimate enzyme of cholesterol biosynthesis in vertebrates and is absent from yeast.
GO:0005640 nuclear outer membrane	IDA PMID:9878250 The human lamin B receptor/sterol reductase multigene family...	KEEP AS NON CORE	Summary: DHCR7 was localized to the endoplasmic reticulum, contiguous with the nuclear outer membrane, in the study characterizing the LBR/sterol-reductase gene family. Reason: The nuclear outer membrane is continuous with the ER membrane, so this IDA is plausible and not contradicted, but it is a peripheral aspect of the localization; the core compartment is the ER membrane. Retained as non-core. Not removed, as it is an experimental (IDA) observation whose full text we have not read. Supporting Evidence: PMID:9878250 these two related proteins are in the endoplasmic reticulum
GO:0005783 endoplasmic reticulum	IDA PMID:9878250 The human lamin B receptor/sterol reductase multigene family...	ACCEPT	Summary: Directly localizes DHCR7 to the endoplasmic reticulum in the study characterizing the human LBR/sterol-reductase multigene family. Reason: Direct experimental (IDA) localization to the ER, consistent with the more specific ER membrane annotation. Correct compartment. Supporting Evidence: PMID:9878250 these two related proteins are in the endoplasmic reticulum
GO:0047598 7-dehydrocholesterol reductase activity	IDA PMID:9465114 Molecular cloning and expression of the human delta7-sterol ...	ACCEPT	Summary: Direct assay of the heterologously expressed human enzyme demonstrating NADPH-dependent reduction of the C7-C8 double bond of 7-dehydrocholesterol. Reason: Direct experimental (IDA) evidence for the core molecular function. Supporting Evidence: PMID:9465114 Microsomes from Saccharomyces cerevisiae strains heterologously expressing the human cDNA remove the C7-8 double bond in 7-dehydrocholesterol.

Gene Description

Existing Annotations Review

Core Functions

NADPH-dependent 7-dehydrocholesterol reductase catalysing the final, terminal step of cholesterol biosynthesis - reduction of the C7-C8 double bond of 7-dehydrocholesterol to cholesterol - at the endoplasmic reticulum membrane.

References

📚 Additional Documentation

Notes

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