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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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HSD3B7
hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 7
Chromosome 16 · 16p11.2
NCBI Gene: 80270Ensembl: ENSG00000099377.15HGNC: HGNC:18324UniProt: Q9H2F3
26PubMed Papers
21Diseases
0Drugs
27Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindinglipid dropletB cell chemotaxisoxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptorcongenital bile acid synthesis defect 1Congenital bile acid synthesis defect type 1Congenital bile acid synthesis defectgenetic disorder
✦AI Summary

HSD3B7 (3β-hydroxy-Δ5-steroid dehydrogenase type 7) is a key metabolic enzyme catalyzing sequential dehydrogenation and isomerization reactions essential for bile acid synthesis 1. The enzyme converts 7α-hydroxylated oxysterols, including 7α,25-dihydroxycholesterol (7α,25-OHC), through NAD+-dependent sequential ordered bi-bi kinetics and requires membrane localization for full activity 1. Beyond steroid metabolism, HSD3B7 regulates immune cell positioning in lymphoid tissues by controlling 7α,25-OHC levels, which acts as a ligand for the chemotactic receptor GPR183/EBI2, directing B cell migration 2. Functionally, HSD3B7 maintains cholesterol homeostasis critical for cellular survival across multiple tissues 3. Clinically, biallelic HSD3B7 mutations cause congenital bile acid synthesis defect 1, manifesting as neonatal cholestasis in 82% of patients, with renal cysts occurring in 29% 4. Treatment with chenodeoxycholic acid (CDCA) normalizes liver biochemistries in 73% of patients and remarkably resolves renal lesions 4. Elevated HSD3B7 expression correlates with poor prognosis in clear cell renal cell carcinoma (ccRCC), promoting tumor proliferation and invasion, identifying it as a therapeutic target 5. Genetic variants in HSD3B7 also associate with reduced late-onset Parkinson's disease risk 6 and represent a potential hypertension drug target 7.

Sources cited
1
HSD3B7 catalyzes sequential dehydrogenation and isomerization of 7α-hydroxylated oxysterols through ordered bi-bi kinetics with NAD+ and requires membrane localization
PMID: 39505210
2
HSD3B7 regulates 7α,25-OHC levels controlling EBI2-mediated B cell positioning in lymphoid tissues and migration through blood-brain barrier
PMID: 39999050
3
HSD3B7 maintains cholesterol homeostasis and is essential for ccRCC cell survival; inhibition causes oxysterol accumulation and apoptosis
PMID: 38417134
4
Biallelic HSD3B7 mutations cause congenital bile acid synthesis defect with neonatal cholestasis (82%), renal cysts (29%), and response to CDCA therapy
PMID: 34627351
5
Elevated HSD3B7 expression associates with poor ccRCC prognosis and promotes tumor proliferation, migration, and invasion
PMID: 39684640
6
HSD3B7 rs9938550 variant reduces late-onset Parkinson's disease risk in Chinese populations
PMID: 29670816
7
HSD3B7 identified as hypertension drug target through Mendelian randomization analysis
PMID: 40109242
8
HSD3B7 mutations associated with neonatal cholestasis and bile acid synthesis defects, identified in genetic testing
PMID: 40302296
Disease Associationsⓘ21
congenital bile acid synthesis defect 1Open Targets
0.79Strong
Congenital bile acid synthesis defect type 1Open Targets
0.68Moderate
Congenital bile acid synthesis defectOpen Targets
0.45Moderate
genetic disorderOpen Targets
0.19Weak
IrritabilityOpen Targets
0.19Weak
psoriasisOpen Targets
0.18Weak
diverticular diseaseOpen Targets
0.16Weak
Parkinson diseaseOpen Targets
0.16Weak
Abnormality of the skeletal systemOpen Targets
0.15Weak
psoriasis vulgarisOpen Targets
0.10Weak
ulcerative colitisOpen Targets
0.10Suggestive
ankylosing spondylitisOpen Targets
0.10Suggestive
juvenile myoclonic epilepsyOpen Targets
0.09Suggestive
Crohn's diseaseOpen Targets
0.09Suggestive
sclerosing cholangitisOpen Targets
0.09Suggestive
asthmaOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.07Suggestive
Lewy body dementiaOpen Targets
0.06Suggestive
cardiovascular diseaseOpen Targets
0.06Suggestive
venous thromboembolismOpen Targets
0.05Suggestive
Congenital bile acid synthesis defect 1UniProt
Pathogenic Variants27
NM_025193.4(HSD3B7):c.45_46del (p.Gly17fs)Pathogenic
Congenital bile acid synthesis defect 1|not provided|HSD3B7-related disorder|Congenital bile acid synthesis defect
★★☆☆2026→ Residue 17
NM_025193.4(HSD3B7):c.294dup (p.Lys99fs)Pathogenic
Congenital bile acid synthesis defect 1|not provided
★★☆☆2026→ Residue 99
NM_025193.4(HSD3B7):c.79C>T (p.Arg27Ter)Pathogenic
HSD3B7-related disorder|not provided
★★☆☆2025→ Residue 27
NM_025193.4(HSD3B7):c.1025del (p.Phe342fs)Likely pathogenic
HSD3B7-related disorder|not provided|Congenital bile acid synthesis defect 1
★★☆☆2024→ Residue 342
NM_025193.4(HSD3B7):c.499G>T (p.Glu167Ter)Pathogenic
Congenital bile acid synthesis defect 1|not provided
★★☆☆2024→ Residue 167
NM_025193.4(HSD3B7):c.890del (p.Phe297fs)Pathogenic
not provided|HSD3B7-related disorder
★★☆☆2023→ Residue 297
NM_025193.4(HSD3B7):c.439G>A (p.Glu147Lys)Pathogenic
Congenital bile acid synthesis defect 1|not provided
★★☆☆2022→ Residue 147
NM_025193.4(HSD3B7):c.721_722insAG (p.Ala241fs)Pathogenic
not provided
★☆☆☆2026→ Residue 241
NM_025193.4(HSD3B7):c.503G>A (p.Trp168Ter)Pathogenic
not provided
★☆☆☆2025→ Residue 168
NM_025193.4(HSD3B7):c.532-2A>GLikely pathogenic
not provided
★☆☆☆2024
NM_025193.4(HSD3B7):c.323-1G>CPathogenic
not provided
★☆☆☆2024
NM_025193.4(HSD3B7):c.16C>T (p.Gln6Ter)Pathogenic
Congenital bile acid synthesis defect 1
★☆☆☆2024→ Residue 6
NM_025193.4(HSD3B7):c.551del (p.Leu184fs)Likely pathogenic
Congenital bile acid synthesis defect 1
★☆☆☆2024→ Residue 184
NM_025193.4(HSD3B7):c.322+1G>TLikely pathogenic
Congenital bile acid synthesis defect 1
★☆☆☆2024
NM_025193.4(HSD3B7):c.1039_1040del (p.Leu347fs)Pathogenic
Congenital bile acid synthesis defect 1
★☆☆☆2024→ Residue 347
NM_025193.4(HSD3B7):c.694+2delPathogenic
not provided|Congenital bile acid synthesis defect 1
★☆☆☆2024
NM_025193.4(HSD3B7):c.323-1G>ALikely pathogenic
Congenital bile acid synthesis defect 1
★☆☆☆2024
NM_025193.4(HSD3B7):c.618C>G (p.Tyr206Ter)Pathogenic
not provided
★☆☆☆2023→ Residue 206
NM_025193.4(HSD3B7):c.431+2T>CLikely pathogenic
Congenital bile acid synthesis defect 1
★☆☆☆2023
NM_025193.4(HSD3B7):c.611del (p.Asp204fs)Pathogenic
not provided
★☆☆☆2022→ Residue 204
View on ClinVar ↗
Related Genes
CYP8B1Protein interaction100%AKR1D1Protein interaction100%AMACRProtein interaction100%FAUProtein interaction95%CYP51A1Protein interaction84%DHCR7Protein interaction84%
Tissue Expression6 tissues
Liver
100%
Lung
8%
Ovary
6%
Heart
5%
Brain
4%
Bone Marrow
2%
Gene Interaction Network
Click a node to explore
HSD3B7CYP8B1AKR1D1AMACRFAUCYP51A1DHCR7
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9H2F3
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.41LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.07 [0.82–1.41]
RankingsWhere HSD3B7 stands among ~20K protein-coding genes
  • #12,809of 20,598
    Most Researched26
  • #1,920of 5,498
    Most Pathogenic Variants27
  • #14,585of 17,882
    Most Constrained (LOEUF)1.41
Genes detectedHSD3B7
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Bile Acid Metabolism Mediates Cholesterol Homeostasis and Promotes Tumorigenesis in Clear Cell Renal Cell Carcinoma.
PMID: 38417134
Cancer Res · 2024
1.00
2
Differential expression and modulation of EBI2 and 7α,25-OHC synthesizing (CH25H, CYP7B1) and degrading (HSD3B7) enzymes in mouse and human brain vascular cells.
PMID: 39999050
PLoS One · 2025
0.90
3
The association between
PMID: 29670816
Brain Behav · 2018
0.80
4
Integrated Analysis of Single-Cell and Bulk RNA Sequencing Reveals HSD3B7 as a Prognostic Biomarker and Potential Therapeutic Target in ccRCC.
PMID: 39684640
Int J Mol Sci · 2024
0.70
5
Substrate specificity and kinetic mechanism of 3β-hydroxy-Δ
PMID: 39505210
J Biol Chem · 2024
0.60