HSD17B10
protein-codinghydroxysteroid 17-beta dehydrogenase 10, the group of Mitochondrial RNase P complex|Short chain dehydrogenase/reductase superfamily
Gene summary
This gene encodes 3-hydroxyacyl-CoA dehydrogenase type II, a member of the short-chain dehydrogenase/reductase superfamily. The gene product is a mitochondrial protein that catalyzes the oxidation of a wide variety of fatty acids and steroids, and is a subunit of mitochondrial ribonuclease P, which is involved in tRNA maturation. The protein has been implicated in the development of Alzheimer disease, and mutations in the gene are the cause of 17beta-hydroxysteroid dehydrogenase type 10 (HSD10) deficiency. Several alternatively spliced transcript variants have been identified, but the full-length nature of only two transcript variants has been determined. [provided by RefSeq, Aug 2014]
- HADH2
- MRXS10
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: XL
Disease ID:MONDO:0010327
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: XL
Disease ID:MONDO:0010327
Submitter: PanelApp Australia
Inheritance Pattern: XL
Disease ID:MONDO:0010327
Submitter: G2P
Inheritance Pattern: XL
Disease ID:MONDO:0018323
Submitter: Orphanet
Inheritance Pattern: XL
Disease ID:MONDO:0010327
Submitter: ClinGen
Inheritance Pattern: XL
Disease ID:MONDO:0010272
Submitter: Orphanet
Inheritance Pattern: XL
Disease ID:MONDO:0018322
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic; Biochemical; Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
Comments: Dietary measures (eg, isoleucine restriction) and medications (eg, benzhexol, mitochondrial cocktails), have been reported, but the overall efficacy has been decribed as ineffective
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HSD17B10 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004493.3. 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 | 1 | 8 | 52 | 61 | ||
| missense | 6 | 14 | 58 | 11 | 1 | 90 |
| nonsense | 2 | 2 | ||||
| start loss | 1 | 1 | ||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 8 | 14 | 77 | 63 | 1 | 163 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004484.1 | 6 | MANE Select | |
| Ensembl | ENSP00000168216.6 | 6 | MANE Select | |
| RefSeq | NP_001032900.1 | 6 | Standard | |
| Ensembl | ENSP00000364447.4 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Alzheimer,s disease - Homo sapiens (human)
- Valine, leucine and isoleucine degradation - Homo sapiens (human)
- 3-Methylglutaconic Aciduria Type I
- Valine, Leucine and Isoleucine Degradation
- 2-Methyl-3-Hydroxybutryl CoA Dehydrogenase Deficiency
Biological Process
- lipid metabolic process
- mitochondrion organization
- branched-chain amino acid catabolic process
- protein homotetramerization
- oxidation-reduction process
Molecular Function
- tRNA binding
- RNA binding
- 3-hydroxyacyl-CoA dehydrogenase activity
- protein binding
- cholate 7-alpha-dehydrogenase activity
Cellular Component
- cytoplasm
- mitochondrion
- mitochondrial matrix
- plasma membrane
- mitochondrial ribonuclease P complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000168216
- Coding exons
- 6
- Length
- 3115
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.59 | 35 | 112 | 0.311 | 0.00000908 | 1655 |
| Missense (PolyPhen) | 5 | 55.984 | 0.089311 | 787 | ||
| Synonymous | 0.433 | 41 | 44.7 | 0.918 | 0.00000353 | 579 |
| Loss of Function | 2.74 | 0 | 8.74 | 0.00 | 7.37e-7 | 121 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Mitochondrial dehydrogenase that catalyzes the beta- oxidation at position 17 of androgens and estrogens and has 3- alpha-hydroxysteroid dehydrogenase activity with androsterone (PubMed:9553139, PubMed:23042678, PubMed:12917011, PubMed:18996107, PubMed:25925575, PubMed:28888424). Catalyzes the third step in the beta-oxidation of fatty acids (PubMed:9553139, PubMed:12917011, PubMed:18996107, PubMed:25925575, PubMed:28888424). Carries out oxidative conversions of 7-alpha-OH and 7-beta-OH bile acids (PubMed:12917011). Also exhibits 20-beta- OH and 21-OH dehydrogenase activities with C21 steroids (PubMed:12917011). By interacting with intracellular amyloid-beta, it may contribute to the neuronal dysfunction associated with Alzheimer disease (AD) (PubMed:9338779). Essential for structural and functional integrity of mitochondria (PubMed:20077426). {ECO:0000269|PubMed:12917011, ECO:0000269|PubMed:18996107, ECO:0000269|PubMed:20077426, ECO:0000269|PubMed:23042678, ECO:0000269|PubMed:25925575, ECO:0000269|PubMed:26950678, ECO:0000269|PubMed:28888424, ECO:0000269|PubMed:9338779, ECO:0000269|PubMed:9553139}.;
- Disease
- DISEASE: Mental retardation, X-linked 17 (MRX17) [MIM:300705]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non- syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations. {ECO:0000269|PubMed:18252223}. Note=The gene represented in this entry is involved in disease pathogenesis. A chromosomal microduplication involving HSD17B10 and HUWE1 has been found in patients with mental retardation.;
Recessive Scores
- pRec
- 0.223
Intolerance Scores
- RVIS EVS
- 0.01
- RVIS percentile EVS
- 54.63
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.995
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |