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…

Primary Disease Associations & Inheritance

HSD10 mitochondrial diseaseMIM #300438

XLD

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · HSD10 mitochondrial disease · XL · ClinGen 2018

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.34

LOEUF· LoF intol.

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — X-linked: males carry a single copy

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

Background carrier burden — how many people carry a rare variant somewhere in HSD17B10?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 390

120 rare PASS variants

Rare truncating (LoF)

1 in 29,000

3 rare PASS variants

Rare synonymous (reference)

1 in 1,700

100 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for HSD17B10. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~561k	1 in 740	1 in 30,000
South Asian	~36k	1 in 610	none seen
Remaining (unassigned)	~31k	1 in 540	none seen
European (Finnish)	~27k	≈ 1 in 9,000	1 in 4,500
Admixed American	~23k	1 in 510	none seen
African / African American	~21k	1 in 810	none seen
East Asian	~20k	1 in 500	none seen
Ashkenazi Jewish	~13k	≈ 1 in 13,000	none seen
Middle Eastern	~2,758	≈ 1 in 660	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓