HSD3B7

Chr 16AR

hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 7

Also known as: CBAS1, PFIC4, SDR11E3

NCBI Gene: 80270 ENSG00000099377 UniProt: Q9H2F3 OMIM: 607764

The protein functions as a 3-beta-hydroxysteroid dehydrogenase that catalyzes early steps in bile acid synthesis from cholesterol and is localized to the endoplasmic reticulum membrane. Mutations cause congenital bile acid synthesis defect, which presents as neonatal cholestasis and progressive liver disease in early infancy. The condition follows autosomal recessive inheritance and the gene shows low constraint to loss-of-function variation.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

This gene encodes an enzyme which is involved in the initial stages of the synthesis of bile acids from cholesterol and a member of the short-chain dehydrogenase/reductase superfamily. The encoded protein is a membrane-associated endoplasmic reticulum protein which is active against 7-alpha hydrosylated sterol substrates. Mutations in this gene are associated with a congenital bile acid synthesis defect which leads to neonatal cholestasis, a form of progressive liver disease. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.331 OMIM phenotype

Clinical Summary— HSD3B7

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Gene-Disease Validity (ClinGen)

congenital bile acid synthesis defect 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

28 unique Pathogenic / Likely Pathogenic· 108 VUS of 213 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — HSD3B7

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.33LOEUF

pLI 0.000

Z-score 0.59

OE 0.84 (0.55–1.33)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.77Z-score

OE missense 0.86 (0.77–0.96)

202 obs / 235.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.84 (0.55–1.33)

0≤0.351.4

Missense OE?0.86 (0.77–0.96)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 13 / 15.5Missense obs/exp: 202 / 235.1Syn Z: 1.10

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveHSD3B7-related bile acid synthesis defect, congenitalLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6939th %ile

GOF

0.6149th %ile

LOF

0.2871th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

213 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17

Likely Pathogenic11

VUS108

Likely Benign47

Benign16

Conflicting11

Pathogenic

Likely Pathogenic

108

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	15	1	1	0	17
Likely Pathogenic	11	0	0	0	11
VUS	3	96	5	4	108
Likely Benign	0	5	9	33	47
Benign	0	4	8	4	16
Conflicting	—				11
Total	29	106	23	41	210

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

14 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap HSD3B7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →