HSD3B1
protein-codinghydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1, the group of Short chain dehydrogenase/reductase superfamily
Gene summary
The protein encoded by this gene is an enzyme that catalyzes the oxidative conversion of delta-5-3-beta-hydroxysteroid precursors into delta-4-ketosteroids, which leads to the production of all classes of steroid hormones. The encoded protein also catalyzes the interconversion of 3-beta-hydroxy- and 3-keto-5-alpha-androstane steroids. [provided by RefSeq, Jun 2016]
- HSDB3
- HSD3B
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HSD3B1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000862.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 60 | 10 | 70 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 60 | 10 | 0 | 70 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000853.1 | 3 | MANE Select | |
| Ensembl | ENSP00000358421.3 | 3 | MANE Select | |
| RefSeq | NP_001315544.1 | 3 | Standard | |
| Ensembl | ENSP00000432268.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| hsd3b1 | Danio rerio | Structure: melanocyte Quality: dispersed abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cortisol synthesis and secretion - Homo sapiens (human)
- Aldosterone synthesis and secretion - Homo sapiens (human)
- Cushing,s syndrome - Homo sapiens (human)
- Steroid hormone biosynthesis - Homo sapiens (human)
- Ovarian steroidogenesis - Homo sapiens (human)
Biological Process
- steroid biosynthetic process
- androgen biosynthetic process
- estrogen biosynthetic process
- glucocorticoid biosynthetic process
- mineralocorticoid biosynthetic process
Molecular Function
- 3-keto sterol reductase activity
- 3-beta-hydroxy-delta5-steroid dehydrogenase activity
- steroid delta-isomerase activity
- oxidoreductase activity
- oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
Cellular Component
- mitochondrial inner membrane
- mitochondrial intermembrane space
- endoplasmic reticulum membrane
- integral component of membrane
- smooth endoplasmic reticulum membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000369413
- Coding exons
- 3
- Length
- 7861
- Individuals with no LoFs
- 125705
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 41
- Defined
- 125746
- p
- 0.000163
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.01 | 242 | 202 | 1.20 | 0.0000116 | 2415 |
| Missense (PolyPhen) | 74 | 57.096 | 1.2961 | 697 | ||
| Synonymous | -3.20 | 123 | 85.4 | 1.44 | 0.00000535 | 738 |
| Loss of Function | 0.415 | 11 | 12.6 | 0.874 | 8.26e-7 | 143 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00087 | 0.00087 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00015 | 0.00015 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: 3-beta-HSD is a bifunctional enzyme, that catalyzes the oxidative conversion of Delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. The 3-beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids. Efficiently catalyzes the transformation of pregnenolone to progesterone, 17-alpha-hydroxypregnenolone to 17- alpha-hydroxyprogesterone, DHEA to 4-androstenedione, dihydrotestosterone to 5-alpha-androstane-3 beta,17 beta-diol, dehydroepiandrosterone to androstenedione and 5-alpha-androstan-3 beta,17 beta-diol to 5-alpha-dihydrotestosterone. {ECO:0000269|PubMed:1401999, ECO:0000269|PubMed:2139411}.;
Recessive Scores
- pRec
- 0.327
Intolerance Scores
- LoFtool
- 0.177
- RVIS EVS
- 0.15
- RVIS percentile EVS
- 64.74
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.676
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |