HSD10 mitochondrial disease

disease

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Also known as 17 beta-hydroxysteroid dehydrogenase type 10 deficiency17-beta-hydroxysteroid dehydrogenase 10 deficiency17-beta-hydroxysteroid dehydrogenase X deficiency2-methyl-3-hydroxybutyric aciduria2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency2M3HBA3-hydroxy-2-methylbutyryl-CoA dehydrogenase deficiency3-hydroxyacyl-CoA dehydrogenase 2 deficiency3H2MBD deficiencychorioathetosis with mental retardation and abnormal behaviorchorioathetosis with mental retardation and abnormal behaviourHSD10 deficiencyHSD10 deficiency, atypical typeHSD10 mitochondrial disease, X-linked dominantHSD10MDHSD17B10 deficiencyhydroxyacyl-CoA dehydrogenase II deficiencymental retardation with chorioathetosis and abnormal behaviormental retardation with chorioathetosis and abnormal behaviour

Summary

HSD10 mitochondrial disease (MONDO:0010327) is a disease caused by HSD17B10 (GenCC Definitive), with 1 cohort gene.

At a glance

Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
Causal gene: HSD17B10 (GenCC Definitive)
Cohort genes: 1
ClinVar variants: 30
Phenotypes (HPO): 37

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		37	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

37 HPO clinical features (Orphanet curated; top 37 by frequency):

HPO ID	Term	Frequency
HP:0012073	Abnormal urinary acylglycine profile	Very frequent (80-99%)
HP:0000529	Progressive visual loss	Frequent (30-79%)
HP:0000750	Delayed speech and language development	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001328	Specific learning disability	Frequent (30-79%)
HP:0002342	Intellectual disability, moderate	Frequent (30-79%)
HP:0002376	Developmental regression	Frequent (30-79%)
HP:0040155	Elevated urinary 3-hydroxybutyric acid	Frequent (30-79%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000648	Optic atrophy	Occasional (5-29%)
HP:0000708	Atypical behavior	Occasional (5-29%)
HP:0000729	Autistic behavior	Occasional (5-29%)
HP:0000736	Short attention span	Occasional (5-29%)
HP:0001251	Ataxia	Occasional (5-29%)
HP:0001260	Dysarthria	Occasional (5-29%)
HP:0001266	Choreoathetosis	Occasional (5-29%)
HP:0001288	Gait disturbance	Occasional (5-29%)
HP:0001336	Myoclonus	Occasional (5-29%)
HP:0004925	Chronic lactic acidosis	Occasional (5-29%)
HP:0006892	Frontotemporal cerebral atrophy	Occasional (5-29%)
HP:0007042	Focal white matter lesions	Occasional (5-29%)
HP:0008947	Floppy infant	Occasional (5-29%)
HP:0012433	Abnormal social behavior	Occasional (5-29%)
HP:0000252	Microcephaly	Very rare (<1-4%)
HP:0000639	Nystagmus	Very rare (<1-4%)
HP:0001337	Tremor	Very rare (<1-4%)
HP:0001347	Hyperreflexia	Very rare (<1-4%)
HP:0002015	Dysphagia	Very rare (<1-4%)
HP:0002063	Rigidity	Very rare (<1-4%)
HP:0002119	Ventriculomegaly	Very rare (<1-4%)
HP:0002307	Drooling	Very rare (<1-4%)
HP:0002313	Spastic paraparesis	Very rare (<1-4%)
HP:0002579	Gastrointestinal dysmotility	Very rare (<1-4%)
HP:0007030	Nonprogressive encephalopathy	Very rare (<1-4%)
HP:0008897	Postnatal growth retardation	Very rare (<1-4%)
HP:0011470	Nasogastric tube feeding in infancy	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	HSD10 mitochondrial disease
Mondo ID	MONDO:0010327
MeSH	C536080, C564560
OMIM	300220, 300438
Orphanet	391417
DOID	DOID:0060810
SNOMED CT	791000124107
UMLS	C3266731
MedGen	781653
GARD	0010716
Is cancer (heuristic)	no

Also known as: 17 beta-hydroxysteroid dehydrogenase type 10 deficiency · 17-beta-hydroxysteroid dehydrogenase 10 deficiency · 17-beta-hydroxysteroid dehydrogenase X deficiency · 2-methyl-3-hydroxybutyric aciduria · 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency · 2M3HBA · 3-hydroxy-2-methylbutyryl-CoA dehydrogenase deficiency · 3-hydroxyacyl-CoA dehydrogenase 2 deficiency · 3H2MBD deficiency · chorioathetosis with mental retardation and abnormal behavior · chorioathetosis with mental retardation and abnormal behaviour · HSD10 deficiency · HSD10 deficiency, atypical type · HSD10 mitochondrial disease · HSD10 mitochondrial disease, X-linked dominant · HSD10MD · HSD17B10 deficiency · hydroxyacyl-CoA dehydrogenase II deficiency · mental retardation with chorioathetosis and abnormal behavior · mental retardation with chorioathetosis and abnormal behaviour (+7 more)

Data availability: 30 ClinVar variants · 3 GenCC gene-disease records.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › inborn mitochondrial metabolism disorder › HSD10 mitochondrial disease

Subtypes (3): HSD10 disease, infantile type, HSD10 disease, neonatal type, HSD10 disease, atypical type

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

30 retrieved; paginated sample, class counts are floors:

12 uncertain significance, 7 likely pathogenic, 5 pathogenic, 4 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
11442	NM_004493.3(HSD17B10):c.388C>T (p.Arg130Cys)	HSD17B10	Pathogenic	criteria provided, multiple submitters, no conflicts
11444	NM_004493.3(HSD17B10):c.740A>G (p.Asn247Ser)	HSD17B10	Pathogenic	no assertion criteria provided
11445	NM_004493.3(HSD17B10):c.574C>A (p.Arg192=)	HSD17B10	Pathogenic	no assertion criteria provided
144033	NM_004493.3(HSD17B10):c.257A>G (p.Asp86Gly)	HSD17B10	Pathogenic	no assertion criteria provided
280839	NM_004493.3(HSD17B10):c.634A>G (p.Lys212Glu)	HSD17B10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3780972	NM_004493.3(HSD17B10):c.551G>A (p.Arg184Gln)	HSD17B10	Pathogenic	criteria provided, single submitter
496894	NM_004493.3(HSD17B10):c.677G>A (p.Arg226Gln)	HSD17B10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1028768	NM_004493.3(HSD17B10):c.85C>G (p.Arg29Gly)	HSD17B10	Likely pathogenic	criteria provided, single submitter
2502293	NM_004493.3(HSD17B10):c.706C>T (p.Leu236Phe)	HSD17B10	Likely pathogenic	criteria provided, single submitter
254239	NM_004493.3(HSD17B10):c.592C>A (p.Pro198Thr)	HSD17B10	Likely pathogenic	criteria provided, single submitter
3339520	NM_004493.3(HSD17B10):c.59C>T (p.Ser20Leu)	HSD17B10	Likely pathogenic	criteria provided, single submitter
813313	NM_004493.3(HSD17B10):c.517G>C (p.Gly173Arg)	HSD17B10	Likely pathogenic	criteria provided, single submitter
973446	NM_004493.3(HSD17B10):c.753C>G (p.Ile251Met)	HSD17B10	Likely pathogenic	criteria provided, single submitter
996911	NM_004493.3(HSD17B10):c.164G>A (p.Gly55Glu)	HSD17B10	Likely pathogenic	criteria provided, single submitter
2689225	NM_004493.3(HSD17B10):c.323C>T (p.Thr108Ile)	HSD17B10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
420778	NM_004493.3(HSD17B10):c.439C>T (p.Arg147Cys)	HSD17B10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
435470	NM_004493.3(HSD17B10):c.259G>A (p.Val87Ile)	HSD17B10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4690186	NM_004493.3(HSD17B10):c.502T>C (p.Tyr168His)	HSD17B10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1028767	NM_004493.3(HSD17B10):c.14G>A (p.Cys5Tyr)	HSD17B10	Uncertain significance	criteria provided, single submitter
11443	NM_004493.3(HSD17B10):c.364C>G (p.Leu122Val)	HSD17B10	Uncertain significance	criteria provided, single submitter
11446	NM_004493.3(HSD17B10):c.745G>C (p.Glu249Gln)	HSD17B10	Uncertain significance	criteria provided, single submitter
1327475	NM_004493.3(HSD17B10):c.660A>C (p.Gln220His)	HSD17B10	Uncertain significance	criteria provided, single submitter
1690322	NM_004493.3(HSD17B10):c.347G>A (p.Arg116Gln)	HSD17B10	Uncertain significance	criteria provided, multiple submitters, no conflicts
1878522	NM_004493.3(HSD17B10):c.113T>C (p.Val38Ala)	HSD17B10	Uncertain significance	criteria provided, single submitter
203377	NM_004493.3(HSD17B10):c.218C>G (p.Thr73Arg)	HSD17B10	Uncertain significance	no assertion criteria provided
2664886	NM_004493.3(HSD17B10):c.62G>T (p.Gly21Val)	HSD17B10	Uncertain significance	criteria provided, single submitter
3235000	NM_004493.3(HSD17B10):c.11C>G (p.Ala4Gly)	HSD17B10	Uncertain significance	criteria provided, single submitter
3779740	NM_004493.3(HSD17B10):c.486+15del	HSD17B10	Uncertain significance	criteria provided, single submitter
587599	NM_004493.3(HSD17B10):c.253G>A (p.Val85Met)	HSD17B10	Uncertain significance	criteria provided, single submitter
95101	NM_004493.3(HSD17B10):c.194T>C (p.Val65Ala)	HSD17B10	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
HSD17B10	Definitive	X-linked	HSD10 mitochondrial disease	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HSD17B10	Orphanet:391428	HSD10 disease, infantile type
HSD17B10	Orphanet:391457	HSD10 disease, neonatal type
HSD17B10	Orphanet:85295	HSD10 disease, atypical type

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
HSD17B10	HGNC:4800	ENSG00000072506	Q99714	3-hydroxyacyl-CoA dehydrogenase type-2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HSD17B10	3-hydroxyacyl-CoA dehydrogenase type-2	Mitochondrial dehydrogenase involved in pathways of fatty acid, branched-chain amino acid and steroid metabolism.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HSD17B10	Enzyme (other)	yes	1.1.1.135	SDR_fam, Sc_DH/Rdtase_CS, NAD(P)-bd_dom_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
liver	1
right adrenal gland	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HSD17B10	155	ubiquitous	marker	right lobe of liver, liver, right adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HSD17B10	2,961

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HSD17B10	Q99714	15

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
tRNA processing in the mitochondrion	1	2284.0×	0.002	HSD17B10
rRNA processing in the mitochondrion	1	1268.9×	0.002	HSD17B10
tRNA modification in the mitochondrion	1	1038.2×	0.002	HSD17B10
Branched-chain amino acid catabolism	1	475.8×	0.003	HSD17B10
Mitochondrial protein degradation	1	114.2×	0.009	HSD17B10

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
brexanolone metabolic process	1	16852.0×	8e-04	HSD17B10
mitochondrial tRNA methylation	1	5617.3×	8e-04	HSD17B10
mitochondrial tRNA 5’-end processing	1	5617.3×	8e-04	HSD17B10
mitochondrial tRNA 3’-end processing	1	4213.0×	8e-04	HSD17B10
C21-steroid hormone metabolic process	1	3370.4×	8e-04	HSD17B10
L-isoleucine catabolic process	1	2808.7×	8e-04	HSD17B10
androgen metabolic process	1	887.0×	0.002	HSD17B10
bile acid biosynthetic process	1	624.1×	0.002	HSD17B10
estrogen metabolic process	1	624.1×	0.002	HSD17B10
fatty acid beta-oxidation	1	374.5×	0.004	HSD17B10
protein homotetramerization	1	237.3×	0.005	HSD17B10
fatty acid metabolic process	1	193.7×	0.006	HSD17B10
mitochondrion organization	1	151.8×	0.007	HSD17B10
lipid metabolic process	1	91.6×	0.011	HSD17B10

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
HSD17B10	LEVODOPA

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HSD17B10	249	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LEVODOPA	4	HSD17B10
PHENYLBUTAZONE	4	HSD17B10
CANDESARTAN CILEXETIL	4	HSD17B10
TELMISARTAN	4	HSD17B10
DIENESTROL	4	HSD17B10
CHOLECALCIFEROL	4	HSD17B10
BUMETANIDE	4	HSD17B10
SALMETEROL XINAFOATE	4	HSD17B10
SULFAPHENAZOLE	4	HSD17B10
RALOXIFENE HYDROCHLORIDE	4	HSD17B10
DICYCLOMINE	4	HSD17B10
CISPLATIN	4	HSD17B10
TETRABENAZINE	4	HSD17B10
DECAMETHONIUM	4	HSD17B10
LABETALOL HYDROCHLORIDE	4	HSD17B10
DIMENHYDRINATE	4	HSD17B10
HYDROXYZINE PAMOATE	4	HSD17B10
MALATHION	4	HSD17B10
PYRITHIONE ZINC	4	HSD17B10
AVOBENZONE	4	HSD17B10
CEFOXITIN SODIUM	4	HSD17B10
OXYMETHOLONE	4	HSD17B10
FEXOFENADINE HYDROCHLORIDE	4	HSD17B10
GEMIFLOXACIN MESYLATE	4	HSD17B10
AMPICILLIN SODIUM	4	HSD17B10
CHLOROTRIANISENE	4	HSD17B10
TRAZODONE HYDROCHLORIDE	4	HSD17B10
ETHOPROPAZINE HYDROCHLORIDE	4	HSD17B10
PHENAZOPYRIDINE HYDROCHLORIDE	4	HSD17B10
ACRISORCIN	4	HSD17B10

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
HSD17B10	41	Binding:39, Functional:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HSD17B10	1.1.1.135, 1.1.1.178, 1.1.1.35, 1.1.1.62	GDP-6-deoxy-D-talose 4-dehydrogenase, 3-hydroxy-2-methylbutyryl-CoA dehydrogenase, 3-hydroxyacyl-CoA dehydrogenase, 17beta-estradiol 17-dehydrogenase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
LEVODOPA	4	HSD17B10
PHENYLBUTAZONE	4	HSD17B10
CANDESARTAN CILEXETIL	4	HSD17B10
TELMISARTAN	4	HSD17B10
DIENESTROL	4	HSD17B10
CHOLECALCIFEROL	4	HSD17B10
BUMETANIDE	4	HSD17B10
SALMETEROL XINAFOATE	4	HSD17B10
SULFAPHENAZOLE	4	HSD17B10
RALOXIFENE HYDROCHLORIDE	4	HSD17B10
DICYCLOMINE	4	HSD17B10
CISPLATIN	4	HSD17B10
TETRABENAZINE	4	HSD17B10
DECAMETHONIUM	4	HSD17B10
LABETALOL HYDROCHLORIDE	4	HSD17B10
DIMENHYDRINATE	4	HSD17B10
HYDROXYZINE PAMOATE	4	HSD17B10
MALATHION	4	HSD17B10
PYRITHIONE ZINC	4	HSD17B10
AVOBENZONE	4	HSD17B10
CEFOXITIN SODIUM	4	HSD17B10
OXYMETHOLONE	4	HSD17B10
FEXOFENADINE HYDROCHLORIDE	4	HSD17B10
GEMIFLOXACIN MESYLATE	4	HSD17B10
AMPICILLIN SODIUM	4	HSD17B10
CHLOROTRIANISENE	4	HSD17B10
TRAZODONE HYDROCHLORIDE	4	HSD17B10
ETHOPROPAZINE HYDROCHLORIDE	4	HSD17B10
PHENAZOPYRIDINE HYDROCHLORIDE	4	HSD17B10
ACRISORCIN	4	HSD17B10

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	HSD17B10
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: HSD17B10