HSD3B7

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	IBA GO_REF:0000033	MODIFY	Summary: Broad phylogenetically-inferred molecular-function term correctly placing HSD3B7 as an NAD(P)-dependent dehydrogenase acting on a CH-OH group. This is accurate but general; the specific activity is the 3-beta-hydroxy-Delta5-steroid dehydrogenase reaction on 7-alpha-hydroxylated C27 sterols. Reason: The IBA term is correct at the family level but too general for a gene with a demonstrated specific catalytic activity. Retain the parent but propose the specific dehydrogenase terms already supported by experiment (GO:0003854, GO:0047016) as the core molecular function. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000041225 · 3-beta-HSD family node (GO_Central IBA) SUPPORTS TRANSFER Family-level IBA correctly assigns the general NAD(P)-dependent CH-OH dehydrogenase activity, but HSD3B7 has a demonstrated more specific 3-beta-hydroxy-Delta5-C27-steroid dehydrogenase activity (PMID:11067870). Proposed replacements: 3-beta-hydroxy-Delta5-steroid dehydrogenase (NAD+) activity cholest-5-ene-3-beta,7-alpha-diol 3-beta-dehydrogenase activity Supporting Evidence: file:human/HSD3B7/HSD3B7-uniprot.txt HSD VII is active
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: HSD3B7 is a multi-pass endoplasmic reticulum membrane (microsomal) protein; this UniProt SubCellular-mapping IEA correctly captures the primary localization. Reason: The ER membrane localization is directly stated in UniProt (SUBCELLULAR LOCATION) and consistent with the microsomal enzyme described in PMID:11067870 and with the two predicted transmembrane helices. This is a core aspect of the annotation. Supporting Evidence: file:human/HSD3B7/HSD3B7-uniprot.txt Endoplasmic reticulum membrane; Multi-pass
GO:0006694 steroid biosynthetic process	IEA GO_REF:0000120	MODIFY	Summary: Broad biosynthetic-process term. HSD3B7 participates in steroid (sterol/bile-acid) biosynthesis, so the term is not wrong, but the specific and better-supported process is bile acid biosynthesis (GO:0006699). Reason: Bile-acid precursors are C27 sterols and the enzyme is specific for the bile-acid pathway; the more informative process term GO:0006699 is preferred. The broad steroid-biosynthesis term is retained conceptually but should be specialized. Proposed replacements: bile acid biosynthetic process Supporting Evidence: file:human/HSD3B7/HSD3B7-uniprot.txt Lipid metabolism; steroid biosynthesis
GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	IEA GO_REF:0000120	MODIFY	Summary: Same broad dehydrogenase molecular-function term as the IBA annotation, here from InterPro/ARBA. Correct but general. Reason: Correct family-level assignment (NAD(P)-dependent CH-OH oxidoreductase), but a more specific term is warranted given the demonstrated 3-beta-hydroxy-Delta5-steroid dehydrogenase activity. Propose the specific MF terms. Proposed replacements: 3-beta-hydroxy-Delta5-steroid dehydrogenase (NAD+) activity cholest-5-ene-3-beta,7-alpha-diol 3-beta-dehydrogenase activity Supporting Evidence: file:human/HSD3B7/HSD3B7-uniprot.txt HSD VII is active
GO:0047016 cholest-5-ene-3-beta,7-alpha-diol 3-beta-dehydrogenase activity	IEA GO_REF:0000120	ACCEPT	Summary: Specific molecular-function term (EC 1.1.1.181) for the 3-beta-dehydrogenation of the 7-alpha-hydroxylated sterol cholest-5-ene-3-beta,7-alpha-diol (7-alpha-hydroxycholesterol). This is the demonstrated activity of HSD3B7 and is the core function; here inferred electronically but corroborated by experiment (PMID:11067870). Reason: This is exactly the biochemically characterized activity of HSD3B7 acting on 7-alpha-hydroxycholesterol, matching the UniProt catalytic-activity entry (Rhea:11896, EC 1.1.1.181). Accept as a core molecular function. Supporting Evidence: PMID:11067870 active against four 7alpha-hydroxylated sterols
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: Generic protein-binding annotation from a proteome-scale (HuRI/CCSB) binary interactome screen. The partner (SPRY2, O43597) is not part of a functionally characterized HSD3B7 complex, and the bare protein-binding term is uninformative about the enzyme's molecular function. Reason: High-throughput interactome hits assigned only the uninformative GO:0005515 term. Per curation guidance, bare protein binding does not describe HSD3B7's catalytic function; this is retained as an over-annotation rather than removed, since the interaction data itself is experimental. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Generic protein-binding annotations from the HuRI binary interactome map, covering many heterogeneous partners (keratin-associated proteins, transcription factors, etc.). None represent a defined functional HSD3B7 complex, and the term is uninformative about molecular function. Reason: These are large-scale yeast-two-hybrid/binary-screen hits annotated only to the bare GO:0005515 term. Not informative for HSD3B7's dehydrogenase function; marked as over-annotated per policy rather than removed. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome
GO:0035754 B cell chemotaxis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Biological-process annotation transferred by Ensembl Compara from the mouse ortholog (Q9EQC1), reflecting HSD3B7's role in degrading the oxysterol 7-alpha,25-dihydroxycholesterol, an EBI2/GPR183 ligand that positions B cells in lymphoid tissue. Reason: This is a genuine but downstream/physiological consequence inferred from the mouse ortholog, not HSD3B7's core catalytic role in bile-acid synthesis. The human enzyme does act on 7-alpha,25-OHC in vitro (UniProt catalytic activity Rhea:47156), supporting relevance, but the process is peripheral and evidence is by-similarity; keep as non-core. Supporting Evidence: file:human/HSD3B7/HSD3B7-uniprot.txt Plays a key role in cell positioning and
GO:0006699 bile acid biosynthetic process	TAS Reactome:R-HSA-193368	ACCEPT	Summary: HSD3B7 catalyzes the second step of the classic (neutral) bile-acid pathway via 7-alpha-hydroxycholesterol; Reactome annotates its participation in bile acid biosynthesis. This is a core biological process for HSD3B7. Reason: Bile acid biosynthesis is the central, disease-defining role of HSD3B7, established biochemically and genetically (PMID:11067870). Accept as core. Supporting Evidence: PMID:11067870 a single C(27) 3beta-HSD enzyme can participate in all known pathways of bile acid synthesis
GO:0006699 bile acid biosynthetic process	TAS Reactome:R-HSA-193775	ACCEPT	Summary: Participation in bile-acid/bile-salt synthesis via the 24-hydroxycholesterol (acidic/alternative) branch; HSD3B7 performs the 3-beta-dehydrogenation/isomerization step on the 7-alpha-hydroxylated 24-hydroxy sterol. Core bile-acid process annotation. Reason: Duplicate of the core bile-acid biosynthetic process annotation, from a different Reactome pathway branch. Correct and core; the enzyme acts across all bile-acid pathway branches. Supporting Evidence: PMID:11067870 a single C(27) 3beta-HSD enzyme can participate in all known pathways of bile acid synthesis
GO:0006699 bile acid biosynthetic process	TAS Reactome:R-HSA-193807	ACCEPT	Summary: Participation in bile-acid/bile-salt synthesis via the 27-hydroxycholesterol branch. HSD3B7 acts on the 7-alpha-hydroxylated 27-hydroxy sterol. Core bile-acid process annotation. Reason: Duplicate of the core bile-acid biosynthetic process annotation from another Reactome branch. Consistent with the enzyme's broad substrate range across bile-acid pathways. Supporting Evidence: PMID:11067870 a single C(27) 3beta-HSD enzyme can participate in all known pathways of bile acid synthesis
GO:0003854 3-beta-hydroxy-Delta5-steroid dehydrogenase (NAD+) activity	TAS Reactome:R-HSA-192097	ACCEPT	Summary: Core molecular function - NAD+-dependent 3-beta-hydroxy-Delta5-steroid dehydrogenase (with associated isomerase activity). Reactome R-HSA-192097 describes HSD3B7 oxidizing/isomerizing 7-alpha-hydroxycholesterol to 4-cholesten-7-alpha-ol-3-one. Reason: This is the defining catalytic activity of HSD3B7, supported by biochemistry (PMID:11067870) and by the Reactome reaction. Accept as a core molecular function. Supporting Evidence: Reactome:R-HSA-192097 catalyzed by HSD3B7 (3 beta-hydroxysteroid dehydrogenase type 7) in the endoplasmic reticulum membrane
GO:0003854 3-beta-hydroxy-Delta5-steroid dehydrogenase (NAD+) activity	TAS Reactome:R-HSA-193789	ACCEPT	Summary: Same core 3-beta-hydroxy-Delta5-steroid dehydrogenase activity, annotated from the Reactome reaction on cholest-5-ene-3beta,7alpha,24(S)-triol (the 24-hydroxy branch substrate). Reason: Duplicate core molecular-function annotation from another Reactome reaction; correct and central to HSD3B7 function. Supporting Evidence: Reactome:R-HSA-193789 catalyzed by HSD3B7 (3 beta-hydroxysteroid dehydrogenase type 7) in the endoplasmic reticulum membrane
GO:0003854 3-beta-hydroxy-Delta5-steroid dehydrogenase (NAD+) activity	TAS Reactome:R-HSA-193816	ACCEPT	Summary: Same core 3-beta-hydroxy-Delta5-steroid dehydrogenase activity, annotated from the Reactome reaction on cholest-5-ene-3beta,7alpha,27-triol (the 27-hydroxy branch substrate). Reason: Duplicate core molecular-function annotation from another Reactome reaction; correct and central to HSD3B7 function. Supporting Evidence: Reactome:R-HSA-193816 in a reaction catalyzed by HSD3B7 (3 beta-hydroxysteroid dehydrogenase type 7) in the endoplasmic reticulum membrane
GO:0005811 lipid droplet	IDA GO_REF:0000052	KEEP AS NON CORE	Summary: Immunofluorescence-based (HPA) localization to lipid droplets. HSD3B7's mechanistically-supported and primary compartment is the ER membrane; a lipid-droplet signal is plausible for an ER-associated lipid-metabolizing enzyme but is secondary. Reason: The IDA/HPA lipid-droplet signal is a real immunolocalization observation but is not the primary functional compartment (ER membrane, multi-pass). Lipid droplets are ER-derived and this may reflect ER continuity; retain as non-core rather than treat as a core localization. Supporting Evidence: file:human/HSD3B7/HSD3B7-uniprot.txt Endoplasmic reticulum membrane; Multi-pass
GO:0047016 cholest-5-ene-3-beta,7-alpha-diol 3-beta-dehydrogenase activity	EXP PMID:11067870 The bile acid synthetic gene 3beta-hydroxy-Delta(5)-C(27)-st...	ACCEPT	Summary: Experimentally demonstrated activity - the expression-cloned C27 3beta-HSD acts on 7-alpha-hydroxylated sterols (cholest-5-ene-3-beta,7-alpha-diol, i.e. 7-alpha-hydroxycholesterol), catalyzing the 3-beta-dehydrogenation (EC 1.1.1.181). This is the specific, disease-relevant core molecular function. Reason: Direct experimental evidence (transfection/activity assay) for this exact specific activity in the defining paper. Core molecular function. Supporting Evidence: PMID:11067870 active against four 7alpha-hydroxylated sterols
GO:0035754 B cell chemotaxis	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sequence-similarity transfer from the mouse ortholog (Q9EQC1) of the role in lymphocyte positioning via degradation of the EBI2/GPR183 ligand 7-alpha,25-dihydroxycholesterol. Reason: Same physiological role as the Ensembl IEA annotation, here as manual ISS from mouse. Genuine but peripheral relative to HSD3B7's core bile-acid catalytic function, and inferred by similarity; keep as non-core. Supporting Evidence: file:human/HSD3B7/HSD3B7-uniprot.txt Plays a key role in cell positioning and
GO:0047016 cholest-5-ene-3-beta,7-alpha-diol 3-beta-dehydrogenase activity	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity transfer (from mouse Q9EQC1) of the specific 3-beta-dehydrogenase activity on 7-alpha-hydroxycholesterol. Corroborates the experimentally-established human activity. Reason: The specific MF is independently demonstrated experimentally for the human enzyme (PMID:11067870); the ISS transfer is consistent and correct. Accept as core molecular function. Supporting Evidence: PMID:11067870 active against four 7alpha-hydroxylated sterols
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-192097	ACCEPT	Summary: ER-membrane localization asserted by Reactome for the HSD3B7-catalyzed reaction. Consistent with UniProt (multi-pass ER membrane) and the microsomal enzyme described in PMID:11067870. Core localization. Reason: Correct and core; matches the authoritative UniProt subcellular location and the biochemistry (microsomal fraction). Supporting Evidence: Reactome:R-HSA-192097 catalyzed by HSD3B7 (3 beta-hydroxysteroid dehydrogenase type 7) in the endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-193789	ACCEPT	Summary: Duplicate ER-membrane localization from another Reactome reaction for HSD3B7. Core localization. Reason: Correct and core; consistent with UniProt subcellular location. Supporting Evidence: Reactome:R-HSA-193789 catalyzed by HSD3B7 (3 beta-hydroxysteroid dehydrogenase type 7) in the endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-193816	ACCEPT	Summary: Duplicate ER-membrane localization from another Reactome reaction for HSD3B7. Core localization. Reason: Correct and core; consistent with UniProt subcellular location. Supporting Evidence: Reactome:R-HSA-193816 in a reaction catalyzed by HSD3B7 (3 beta-hydroxysteroid dehydrogenase type 7) in the endoplasmic reticulum membrane
GO:0003854 3-beta-hydroxy-Delta5-steroid dehydrogenase (NAD+) activity	NAS PMID:11067870 The bile acid synthetic gene 3beta-hydroxy-Delta(5)-C(27)-st...	ACCEPT	Summary: Non-traceable-author-statement assignment of the general 3-beta-hydroxy-Delta5-steroid dehydrogenase (NAD+) activity, sourced to the defining paper. Consistent with the experimentally-established specific activity. Reason: The core dehydrogenase molecular function is well supported by the same paper's experiments (PMID:11067870). Accept. Supporting Evidence: PMID:11067870 active against four 7alpha-hydroxylated sterols
GO:0006699 bile acid biosynthetic process	TAS PMID:11067870 The bile acid synthetic gene 3beta-hydroxy-Delta(5)-C(27)-st...	ACCEPT	Summary: The defining paper establishes HSD3B7's central role in bile-acid biosynthesis; TAS annotation of the core biological process. Loss of activity causes a bile-acid synthesis defect (CBAS1). Reason: Central, disease-defining biological process supported directly by PMID:11067870. Accept as core. Supporting Evidence: PMID:11067870 establish the central role of C(27) 3beta-HSD in the biosynthesis of bile acids

Gene Description

Existing Annotations Review

Core Functions

NAD+-dependent 3-beta-hydroxy-Delta5-steroid dehydrogenase/isomerase that oxidizes the 3-beta-hydroxyl and isomerizes the Delta5 double bond of 7-alpha-hydroxylated C27 sterols (e.g. 7-alpha-hydroxycholesterol -> 7-alpha-hydroxy-4-cholesten-3-one), the second step of bile-acid biosynthesis.

Specific 3-beta-dehydrogenation of the 7-alpha-hydroxylated sterol cholest-5-ene-3-beta,7-alpha-diol (7-alpha-hydroxycholesterol), EC 1.1.1.181, the biochemically demonstrated bile-acid-precursor-specific activity of HSD3B7.

References

📚 Additional Documentation

Notes

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