HSD17B6
protein-codinghydroxysteroid 17-beta dehydrogenase 6, the group of Short chain dehydrogenase/reductase superfamily
Gene summary
The protein encoded by this gene has both oxidoreductase and epimerase activities and is involved in androgen catabolism. The oxidoreductase activity can convert 3 alpha-adiol to dihydrotestosterone, while the epimerase activity can convert androsterone to epi-androsterone. Both reactions use NAD+ as the preferred cofactor. This gene is a member of the retinol dehydrogenase family. [provided by RefSeq, Aug 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~35.6 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 HSD17B6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003725.4. 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 | 1 | 1 | 2 | |||
| missense | 43 | 2 | 45 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 45 | 3 | 1 | 49 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003716.2 | 4 | MANE Select | |
| Ensembl | ENSP00000318631.1 | 4 | MANE Select | |
| Ensembl | ENSP00000452273.1 | 4 | Standard | |
| Ensembl | ENSP00000452273.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Retinol metabolism - Homo sapiens (human)
- Steroid hormone biosynthesis - Homo sapiens (human)
- Signaling by GPCR
- Signal Transduction
- The canonical retinoid cycle in rods (twilight vision)
Biological Process
- androgen biosynthetic process
- androgen catabolic process
- electron transport chain
Molecular Function
- catalytic activity
- estradiol 17-beta-dehydrogenase activity
- retinol dehydrogenase activity
- electron transfer activity
- oxidoreductase activity
Cellular Component
- endoplasmic reticulum
- early endosome membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000554643
- Coding exons
- 4
- Length
- 35630
- Individuals with no LoFs
- 125672
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 76
- Defined
- 125748
- p
- 0.000302
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.492 | 161 | 180 | 0.897 | 0.00000963 | 2045 |
| Missense (PolyPhen) | 58 | 57.114 | 1.0155 | 686 | ||
| Synonymous | 0.667 | 67 | 74.3 | 0.902 | 0.00000429 | 645 |
| Loss of Function | 2.59 | 3 | 13.1 | 0.229 | 8.37e-7 | 126 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.0011 | 0.0010 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00031 | 0.00029 | rare |
| South Asian | 0.000099 | 0.000098 | rare |
| Other | 0.00053 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: NAD-dependent oxidoreductase with broad substrate specificity that shows both oxidative and reductive activity (in vitro). Has 17-beta-hydroxysteroid dehydrogenase activity towards various steroids (in vitro). Converts 5-alpha-androstan-3- alpha,17-beta-diol to androsterone and estradiol to estrone (in vitro). Has 3-alpha-hydroxysteroid dehydrogenase activity towards androsterone (in vitro). Has retinol dehydrogenase activity towards all-trans-retinol (in vitro). Can convert androsterone to epi-androsterone. Androsterone is first oxidized to 5-alpha- androstane-3,17-dione and then reduced to epi-andosterone. Can act on both C-19 and C-21 3-alpha-hydroxysteroids. {ECO:0000269|PubMed:10896656, ECO:0000269|PubMed:11360992, ECO:0000269|PubMed:11513953}.;
Recessive Scores
- pRec
- 0.267
Intolerance Scores
- LoFtool
- 0.373
- RVIS EVS
- -0.03
- RVIS percentile EVS
- 51.66
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |