HSD17B10

Chr XXLD

hydroxysteroid 17-beta dehydrogenase 10

Also known as: 17b-HSD10, ABAD, CAMR, DUPXp11.22, ERAB, HADH2, HCD2, HSD10MD

NCBI Gene: 3028 ENSG00000072506 UniProt: Q99714 OMIM: 300256

The protein functions as a mitochondrial dehydrogenase that catalyzes fatty acid beta-oxidation, branched-chain amino acid catabolism, and steroid metabolism, and is essential for mitochondrial structural and functional integrity. Mutations cause HSD10 mitochondrial disease with X-linked dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI = 0.94, LOEUF = 0.34), reflecting its essential role in cellular metabolism.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

XLDLOEUF 0.341 OMIM phenotype

Clinical Summary— HSD17B10

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Gene-Disease Validity (ClinGen)

HSD10 mitochondrial disease · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

14 unique Pathogenic / Likely Pathogenic· 59 VUS of 207 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.34LOEUF

pLI 0.936

Z-score 2.74

OE 0.00 (0.00–0.34)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.59Z-score

OE missense 0.31 (0.24–0.41)

35 obs / 112.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.34)

0≤0.351.4

Missense OE?0.31 (0.24–0.41)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 0 / 8.7Missense obs/exp: 35 / 112.4Syn Z: 0.43

ClinVar Variant Classifications

207 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic11

VUS59

Likely Benign95

Benign4

Conflicting9

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	2	0	0	3
Likely Pathogenic	0	11	0	0	11
VUS	0	47	9	3	59
Likely Benign	0	4	41	50	95
Benign	0	1	3	0	4
Conflicting	—				9
Total	1	65	53	53	181

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

83 pathogenic / likely-pathogenic (of 93) ClinVar copy-number / structural variants overlap HSD17B10 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →