HSD17B10

hydroxysteroid 17-beta dehydrogenase 10, the group of Mitochondrial RNase P complex|Short chain dehydrogenase/reductase superfamily

Basic information

Region (hg38): X:53431258-53434370

Previous symbols: [ "HADH2", "MRXS10" ]

Links

ENSG00000072506 ∙ NCBI:3028 ∙ OMIM:300256 ∙ HGNC:4800 ∙ Uniprot:Q99714 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• HSD10 mitochondrial disease (Definitive), mode of inheritance: XLR
• syndromic X-linked intellectual disability type 10 (Definitive), mode of inheritance: XLR
• syndromic X-linked intellectual disability type 10 (Supportive), mode of inheritance: XL
• HSD10 disease, infantile type (Supportive), mode of inheritance: XL
• HSD10 disease, neonatal type (Supportive), mode of inheritance: XL
• HSD10 mitochondrial disease (Definitive), mode of inheritance: XL
• HSD10 mitochondrial disease (Definitive), mode of inheritance: XL
• HSD10 mitochondrial disease (Strong), mode of inheritance: XL
• HSD10 mitochondrial disease (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
HSD10 mitochondrial disease	XL	General	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	Audiologic/Otolaryngologic; Biochemical; Neurologic	10521307; 11102558; 12112118; 12555940; 12696021; 12872843; 14729408; 15059617; 16148061; 17236142; 19706438; 20664630; 22132097; 22127393
Dietary measures (eg, isoleucine restriction) and medications (eg, benzhexol, mitochondrial cocktails), have been reported, but the overall efficacy has been decribed as ineffective

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HSD17B10 gene.

• not provided (1 variants)
• HSD10 mitochondrial disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HSD17B10 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	46		49
missense	1	11	41	4	1	58
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2	12		14
non coding			1	29	2	32
Total	1	11	45	79	3

Variants in HSD17B10

This is a list of pathogenic ClinVar variants found in the HSD17B10 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-53431395-C-G		not specified	Uncertain significance (Dec 20, 2018)
X-53431418-G-A			Uncertain significance (Aug 06, 2024)
X-53431437-G-C		HSD10 mitochondrial disease	Likely pathogenic (Apr 01, 2020)
X-53431440-G-A			Likely benign (Feb 01, 2024)
X-53431445-C-G		HSD10 mitochondrial disease	Pathogenic (Sep 01, 2007)
X-53431449-A-G			Likely benign (Dec 20, 2022)
X-53431450-T-C		HSD10 mitochondrial disease	Pathogenic (Sep 01, 2005)
X-53431459-G-T			Uncertain significance (Aug 24, 2022)
X-53431467-G-A			Likely benign (Oct 15, 2023)
X-53431479-T-C			Likely benign (May 11, 2023)
X-53431481-C-T			Uncertain significance (Jul 31, 2021)
X-53431482-G-A			Likely benign (Dec 19, 2023)
X-53431484-G-A		HSD10 mitochondrial disease	Likely pathogenic (-)
X-53431497-A-T			Likely benign (Dec 01, 2023)
X-53431505-C-T		Inborn genetic diseases	Uncertain significance (Jan 08, 2024)
X-53431513-C-T		HSD10 mitochondrial disease	Pathogenic/Likely pathogenic (Oct 06, 2021)
X-53431524-G-A			Likely benign (May 29, 2022)
X-53431530-T-G		HSD10 mitochondrial disease	Uncertain significance (Jul 12, 2021)
X-53431554-T-C			Likely benign (Dec 27, 2022)
X-53431556-T-C		HSD10 mitochondrial disease	Pathogenic/Likely pathogenic (Dec 01, 2022)
X-53431562-G-C		See cases	Likely pathogenic (-)
X-53431590-C-G		not specified	Uncertain significance (Feb 18, 2016)
X-53431602-A-G			Likely benign (Mar 13, 2023)
X-53431605-T-C			Likely benign (Dec 21, 2023)
X-53431607-G-A			Likely benign (Jan 19, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HSD17B10	protein_coding	protein_coding	ENST00000168216	6	3115

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.936	0.0637	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.59	35	112	0.311	0.00000908	1655
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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.
• Pathway: 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;Long-chain-3-hydroxyacyl-coa dehydrogenase deficiency (LCHAD);Fatty Acid Elongation In Mitochondria;Isovaleric Aciduria;3-Methylcrotonyl Coa Carboxylase Deficiency Type I;Propionic Acidemia;Maple Syrup Urine Disease;Valproic Acid Metabolism Pathway;3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency;Isobutyryl-coa dehydrogenase deficiency;3-hydroxyisobutyric aciduria;3-hydroxyisobutyric acid dehydrogenase deficiency;Isovaleric acidemia;Methylmalonate Semialdehyde Dehydrogenase Deficiency;Mitochondrial Beta-Oxidation of Short Chain Saturated Fatty Acids;Short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (SCHAD);Methylmalonic Aciduria;3-Methylglutaconic Aciduria Type IV;3-Methylglutaconic Aciduria Type III;Beta-Ketothiolase Deficiency;Alzheimers Disease;Valproic acid pathway;Liver steatosis AOP;Tryptophan metabolism;tRNA processing;Butanoate metabolism;tRNA modification in the mitochondrion;Branched-chain amino acid catabolism;Metabolism of amino acids and derivatives;Metabolism of RNA;Tyrosine metabolism;3-oxo-10R-octadecatrienoate beta-oxidation;Leukotriene metabolism;Saturated fatty acids beta-oxidation;Trihydroxycoprostanoyl-CoA beta-oxidation;Metabolism;Mono-unsaturated fatty acid beta-oxidation;Omega-6 fatty acid metabolism;Valine, leucine and isoleucine degradation;Dimethyl-branched-chain fatty acid mitochondrial beta-oxidation;Di-unsaturated fatty acid beta-oxidation;Vitamin E metabolism;isoleucine degradation;fatty acid β-oxidation (peroxisome);fatty acid β-oxidation;Tryptophan degradation;Valine Leucine Isoleucine degradation (Consensus)

Recessive Scores

• pRec: 0.223

Intolerance Scores

• rvis_EVS: 0.01
• rvis_percentile_EVS: 54.63

Haploinsufficiency Scores

• pHI: 0.400
• hipred: Y
• hipred_score: 0.619
• ghis: 0.497

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.995

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Low	Medium
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Hsd17b10

Gene ontology

• Biological process: lipid metabolic process;mitochondrion organization;branched-chain amino acid catabolic process;protein homotetramerization;oxidation-reduction process;mitochondrial tRNA methylation;mitochondrial tRNA processing;mitochondrial tRNA 5'-end processing;mitochondrial tRNA 3'-end processing
• Cellular component: cytoplasm;mitochondrion;mitochondrial matrix;plasma membrane;mitochondrial ribonuclease P complex
• Molecular function: tRNA binding;RNA binding;3-hydroxyacyl-CoA dehydrogenase activity;protein binding;cholate 7-alpha-dehydrogenase activity;testosterone dehydrogenase [NAD(P)] activity;3-hydroxy-2-methylbutyryl-CoA dehydrogenase activity