Maternally-inherited cardiomyopathy and hearing loss

Summary

Maternally-inherited cardiomyopathy and hearing loss (MONDO:0015283) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• Phenotypes (HPO): 30

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		2	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

30 HPO clinical features (Orphanet curated; top 30 by frequency):

HPO ID	Term	Frequency
HP:0000407	Sensorineural hearing impairment	Very frequent (80-99%)
HP:0001251	Ataxia	Very frequent (80-99%)
HP:0001288	Gait disturbance	Very frequent (80-99%)
HP:0001324	Muscle weakness	Very frequent (80-99%)
HP:0001350	Slurred speech	Very frequent (80-99%)
HP:0001639	Hypertrophic cardiomyopathy	Very frequent (80-99%)
HP:0011342	Mild global developmental delay	Very frequent (80-99%)
HP:0000590	Progressive external ophthalmoplegia	Frequent (30-79%)
HP:0000597	Ophthalmoparesis	Frequent (30-79%)
HP:0001268	Mental deterioration	Frequent (30-79%)
HP:0001298	Encephalopathy	Frequent (30-79%)
HP:0001635	Congestive heart failure	Frequent (30-79%)
HP:0001644	Dilated cardiomyopathy	Frequent (30-79%)
HP:0002094	Dyspnea	Frequent (30-79%)
HP:0002151	Increased circulating lactate concentration	Frequent (30-79%)
HP:0003200	Ragged-red muscle fibers	Frequent (30-79%)
HP:0003457	EMG abnormality	Frequent (30-79%)
HP:0003542	Increased serum pyruvate	Frequent (30-79%)
HP:0003546	Exercise intolerance	Frequent (30-79%)
HP:0012514	Lower limb pain	Frequent (30-79%)
HP:0030680	Abnormal cardiovascular system morphology	Frequent (30-79%)
HP:0000822	Hypertension	Occasional (5-29%)
HP:0001012	Multiple lipomas	Occasional (5-29%)
HP:0001347	Hyperreflexia	Occasional (5-29%)
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)	Occasional (5-29%)
HP:0003326	Myalgia	Occasional (5-29%)
HP:0009126	Increased adipose tissue	Occasional (5-29%)
HP:0009830	Peripheral neuropathy	Occasional (5-29%)
HP:0012378	Fatigue	Occasional (5-29%)
HP:0100749	Chest pain	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	maternally-inherited cardiomyopathy and hearing loss
Mondo ID	MONDO:0015283
Orphanet	1349
UMLS	C4510409
MedGen	1376897
GARD	0018719
Is cancer (heuristic)	no

Also known as: maternally-inherited cardiomyopathy and deafness · tRNA-LYS-related cardiomyopathy-hearing loss syndrome

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › mitochondrial disease › maternally-inherited cardiomyopathy and hearing loss

Related subtypes (11): inborn mitochondrial metabolism disorder, hereditary myopathy with lactic acidosis due to ISCU deficiency, Bjornstad syndrome, X-linked sideroblastic anemia with ataxia, ethylmalonic encephalopathy, GRACILE syndrome, mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency, autosomal dominant optic atrophy plus syndrome, pure mitochondrial myopathy, FDXR-related optic atrophy mitochondrial dysfunction syndrome, ACO2-related optic atrophy with or without extraocular features

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
MT-TK	Supportive	Mitochondrial	maternally-inherited cardiomyopathy and hearing loss	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MT-TK	Orphanet:1349	Mitochondrial DNA-related cardiomyopathy and hearing loss
MT-TK	Orphanet:255210	Mitochondrial DNA-associated Leigh syndrome
MT-TK	Orphanet:551	MERRF

Cohort genes → proteins

1 cohort genes, 0 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MT-TK	HGNC:7489	ENSG00000210156		mitochondrially encoded tRNA-Lys (AAA/G)	gencc

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MT-TK	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

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
caudate nucleus	1
skeletal muscle tissue	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MT-TK	118		yes	sural nerve, skeletal muscle tissue, caudate nucleus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MT-TK	0

Structural data

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

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MT-TK	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	1	MT-TK

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MT-TK	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.