HSD3B7

Chr 16AR

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

Also known as: CBAS1, PFIC4, SDR11E3

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.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismARLOEUF 1.331 OMIM phenotype
Clinical SummaryHSD3B7
🧬
Gene-Disease Validity (ClinGen)
congenital bile acid synthesis defect 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
42 unique Pathogenic / Likely Pathogenic· 117 VUS of 237 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.33LOEUF
pLI 0.000
Z-score 0.59
OE 0.84 (0.551.33)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.77Z-score
OE missense 0.86 (0.770.96)
202 obs / 235.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.84 (0.551.33)
00.351.4
Missense OE0.86 (0.770.96)
00.61.4
Synonymous OE0.86
01.21.6
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

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

DN
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

237 submitted variants in ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic14
VUS117
Likely Benign48
Benign16
Conflicting11
28
Pathogenic
14
Likely Pathogenic
117
VUS
48
Likely Benign
16
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
15
1
12
0
28
Likely Pathogenic
11
0
3
0
14
VUS
3
96
14
4
117
Likely Benign
0
5
10
33
48
Benign
0
4
8
4
16
Conflicting
11
Total291064741234

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

View in ClinVar →

Protein Context — Lollipop Plot

HSD3B7 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 2 full-text resultsSearch PubTator3 ↗