HSD17B10

Chr XXLD

hydroxysteroid 17-beta dehydrogenase 10

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

NCBI Gene: 3028ENSG00000072506UniProt: Q99714

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]

Primary Disease Associations & Inheritance

HSD10 mitochondrial diseaseMIM #300438
XLD
367
ClinVar variants
98
Pathogenic / LP
0.94
pLI score· haploinsufficient
0
Active trials
Clinical Summary— HSD17B10
⚡
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.
📋
ClinVar Variants
98 Pathogenic / Likely Pathogenic· 68 VUS of 367 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.31 (0.24–0.41)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.92
0≤1.21.6
LoF obs/exp: 0 / 8.7Missense obs/exp: 35 / 112.4Syn Z: 0.43

ClinVar Variant Classifications

367 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic85
Likely Pathogenic13
VUS68
Likely Benign96
Benign5
Conflicting7
85
Pathogenic
13
Likely Pathogenic
68
VUS
96
Likely Benign
5
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
83
0
85
Likely Pathogenic
0
11
2
0
13
VUS
0
49
16
3
68
Likely Benign
0
4
42
50
96
Benign
0
1
4
0
5
Conflicting
—7
Total16614753274

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

View in ClinVar →

Protein Context — Lollipop Plot

HSD17B10 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

HSD17B10-related mitochondrial disease

definitive
Monoallelic X HemizygousUndeterminedAbsent Gene Product, Altered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

HSD10 mitochondrial disease

MIM #300438

Molecular basis of disorder known

X-linked dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Hepatic micropeptide modulates mitochondrial RNA processing machinery in hepatocellular carcinoma.
Zhu L et al.·Mol Cell
2025
A novel c.59 C > T variant of the HSD17B10 gene as a possible cause of the neonatal form of HSD10 mitochondrial disease with hepatic dysfunction: a case report and review of the literature.
Jiang T et al.·Orphanet J Rare Dis
2025Review
HSD10 disease: clinical consequences of mutations in the HSD17B10 gene.
Zschocke J·J Inherit Metab Dis
2012Review
Xp11.22 duplications in four unrelated Chinese families: delineating the genotype-phenotype relationship for HSD17B10 and FGD1.
Wang Q et al.·BMC Med Genomics
2020Case report
17β-Hydroxysteroid dehydrogenases and neurosteroid metabolism in the central nervous system.
He XY et al.·Mol Cell Endocrinol
2019Review
[Clinical analysis and genetic diagnosis of three children with Isoleucine metabolic disorders due to variants of HSD17B10 and ACAT1 genes].
Ji W et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2024Case report
Submicroscopic duplications of the hydroxysteroid dehydrogenase HSD17B10 and the E3 ubiquitin ligase HUWE1 are associated with mental retardation.
Froyen G et al.·Am J Hum Genet
2008
Clinical and molecular analysis of 6 Chinese patients with isoleucine metabolism defects: identification of 3 novel mutations in the HSD17B10 and ACAT1 gene.
Su L et al.·Metab Brain Dis
2017Cohort
HSD10 mitochondrial disease: p.Leu122Val variant, mild clinical phenotype, and founder effect in French-Canadian patients from Quebec.
Waters PJ et al.·Mol Genet Genomic Med
2019Cohort
Genotype-based databases for variants causing rare diseases.
Lanthaler B et al.·Gene
2014
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools