HSD17B8
protein-codinghydroxysteroid 17-beta dehydrogenase 8, the group of Short chain dehydrogenase/reductase superfamily
Gene summary
In mice, the Ke6 protein is a 17-beta-hydroxysteroid dehydrogenase that can regulate the concentration of biologically active estrogens and androgens. It is preferentially an oxidative enzyme and inactivates estradiol, testosterone, and dihydrotestosterone. However, the enzyme has some reductive activity and can synthesize estradiol from estrone. The protein encoded by this gene is similar to Ke6 and is a member of the short-chain dehydrogenase superfamily. An alternatively spliced transcript of this gene has been detected, but the full-length nature of this variant has not been determined. [provided by RefSeq, Jul 2008]
- FABGL
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.2 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 HSD17B8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014234.5. 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 | ||||
| missense | 31 | 2 | 33 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 34 | 2 | 0 | 36 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055049.1 | 9 | MANE Select | |
| Ensembl | ENSP00000363794.3 | 9 | MANE Select | |
| Ensembl | ENSP00000529288.1 | 8 | Standard | |
| Ensembl | ENSP00000529288.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Steroid hormone biosynthesis - Homo sapiens (human)
- Metabolism of lipids
- Fatty acyl-CoA biosynthesis
- Metabolism
- Fatty acid metabolism
Biological Process
- fatty acid biosynthetic process
- estrogen biosynthetic process
- androgen metabolic process
- protein heterotetramerization
- oxidation-reduction process
Molecular Function
- 3-hydroxyacyl-CoA dehydrogenase activity
- estradiol 17-beta-dehydrogenase activity
- protein binding
- 3-oxoacyl-[acyl-carrier-protein] reductase (NADH) activity
- testosterone dehydrogenase (NAD+) activity
Cellular Component
- mitochondrial envelope
- mitochondrial matrix
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000374662
- Coding exons
- 9
- Length
- 2190
- Individuals with no LoFs
- 125259
- Homozygous LoFs
- 3
- Heterozygous LoFs
- 359
- Defined
- 125621
- p
- 0.00144
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.428 | 125 | 139 | 0.898 | 0.00000694 | 1634 |
| Missense (PolyPhen) | 60 | 56.619 | 1.0597 | 677 | ||
| Synonymous | 0.958 | 46 | 55.0 | 0.836 | 0.00000280 | 553 |
| Loss of Function | 1.32 | 9 | 14.4 | 0.624 | 7.23e-7 | 150 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00092 | 0.00087 | rare |
| Latino/Admixed American | 0.0010 | 0.00098 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0017 | 0.0017 | notable |
| Finnish | 0.0014 | 0.0014 | notable |
| European (Non-Finnish) | 0.0021 | 0.0020 | notable |
| South Asian | 0.00035 | 0.00029 | rare |
| Other | 0.0018 | 0.0018 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: NAD-dependent 17-beta-hydroxysteroid dehydrogenase with highest activity towards estradiol. Has very low activity towards testosterone (PubMed:17978863). The heterotetramer with CBR4 has NADH-dependent 3-ketoacyl-acyl carrier protein reductase activity, and thereby plays a role in mitochondrial fatty acid biosynthesis (PubMed:19571038, PubMed:25203508). Within the heterotetramer, HSD17B8 binds NADH; CBR4 binds NADPD (PubMed:25203508). {ECO:0000269|PubMed:17978863, ECO:0000269|PubMed:19571038, ECO:0000269|PubMed:25203508}.;
Intolerance Scores
- LoFtool
- 0.564
- RVIS EVS
- 0.57
- RVIS percentile EVS
- 81.89
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.895
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |