HSD3B7

Chr 16AR

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

Also known as: CBAS1, PFIC4, SDR11E3

NCBI Gene: 80270ENSG00000099377UniProt: Q9H2F3

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]

Primary Disease Associations & Inheritance

Bile acid synthesis defect, congenital, 1MIM #607765
AR
UniProtCongenital bile acid synthesis defect 1
233
ClinVar variants
42
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— HSD3B7
🧬
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 Pathogenic / Likely Pathogenic· 116 VUS of 233 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.77Z-score
OE missense 0.86 (0.77–0.96)
202 obs / 235.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.84 (0.55–1.33)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.77–0.96)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.86
0≤1.21.6
LoF obs/exp: 13 / 15.5Missense obs/exp: 202 / 235.1Syn Z: 1.10

ClinVar Variant Classifications

233 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic14
VUS116
Likely Benign48
Benign16
Conflicting11
28
Pathogenic
14
Likely Pathogenic
116
VUS
48
Likely Benign
16
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
1
16
0
28
Likely Pathogenic
8
0
6
0
14
VUS
2
96
14
4
116
Likely Benign
0
5
10
33
48
Benign
0
4
8
4
16
Conflicting
—11
Total211065441233

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.

Gene2Phenotype Curations

HSD3B7-related bile acid synthesis defect, congenital

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Bile acid synthesis defect, congenital, 1

MIM #607765

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — HSD3B7
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Integrated Analysis of Single-Cell and Bulk RNA Sequencing Reveals HSD3B7 as a Prognostic Biomarker and Potential Therapeutic Target in ccRCC.
Liu G et al.·Int J Mol Sci
2024
Genetic spectrum and clinical characteristics of 3β-hydroxy-Δ(5)-C(27)-steroid oxidoreductase (HSD3B7) deficiency in China.
Zhao J et al.·Orphanet J Rare Dis
2021
The association between HSD3B7 gene variant and Parkinson's disease in ethnic Chinese.
Lu ZJ et al.·Brain Behav
2018
Expanding the genotypic spectrum of 3β-hydroxy-δ5-C27-steroid dehydrogenase (HSD3B7) deficiency: novel mutations and clinical outcomes.
Yoldaş Çelik M et al.·J Pediatr Endocrinol Metab
2025Case report
Neonatal Cholestasis: Exploring Genetic Causes and Clinical Outcomes.
Gürcan Kaya N et al.·J Paediatr Child Health
2025
The Mutational Landscape Of Genetic Cholestatic Diseases In Pakistani Children.
Cheema HA et al.·J Pak Med Assoc
2023
Lipid metabolism classification of gliomas.
Tu S et al.·Sci Rep
2026
Prognosis and clinical characteristics of patients with 3β-hydroxy-Δ5-C27-steroid dehydrogenase deficiency diagnosed in childhood: A systematic review of the literature.
Zhang Y et al.·Medicine (Baltimore)
2022Review
Dissection of shared genetic architecture and biological association between psoriasis and cardiovascular disease based on genome-wide association studies.
Zhou P et al.·Hum Immunol
2025
Genetic Variants in MicroRNAs and Their Binding Sites Are Associated with the Risk of Parkinson Disease.
Ghanbari M et al.·Hum Mutat
2016
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools