Pure mitochondrial myopathy

Summary

Pure mitochondrial myopathy (MONDO:0016807) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 33

Clinical features

Signs & symptoms

Clinical features (HPO)

33 HPO clinical features (Orphanet curated; top 33 by frequency):

HPO ID	Term	Frequency
HP:0003546	Exercise intolerance	Very frequent (80-99%)
HP:0003551	Difficulty climbing stairs	Very frequent (80-99%)
HP:0003701	Proximal muscle weakness	Very frequent (80-99%)
HP:0009046	Difficulty running	Very frequent (80-99%)
HP:0002359	Frequent falls	Frequent (30-79%)
HP:0002460	Distal muscle weakness	Frequent (30-79%)
HP:0002515	Waddling gait	Frequent (30-79%)
HP:0002600	Hyporeflexia of lower limbs	Frequent (30-79%)
HP:0003391	Gowers sign	Frequent (30-79%)
HP:0003547	Shoulder girdle muscle weakness	Frequent (30-79%)
HP:0003722	Neck flexor weakness	Frequent (30-79%)
HP:0003749	Pelvic girdle muscle weakness	Frequent (30-79%)
HP:0007126	Proximal amyotrophy	Frequent (30-79%)
HP:0009020	Exercise-induced muscle fatigue	Frequent (30-79%)
HP:0030199	Fatigable weakness of neck muscles	Frequent (30-79%)
HP:0000590	Progressive external ophthalmoplegia	Occasional (5-29%)
HP:0001260	Dysarthria	Occasional (5-29%)
HP:0001488	Bilateral ptosis	Occasional (5-29%)
HP:0002505	Loss of ambulation	Occasional (5-29%)
HP:0002938	Lumbar hyperlordosis	Occasional (5-29%)
HP:0003326	Myalgia	Occasional (5-29%)
HP:0003327	Axial muscle weakness	Occasional (5-29%)
HP:0003394	Muscle spasm	Occasional (5-29%)
HP:0003731	Quadriceps muscle weakness	Occasional (5-29%)
HP:0030192	Fatigable weakness of bulbar muscles	Occasional (5-29%)
HP:0030195	Fatigable weakness of swallowing muscles	Occasional (5-29%)
HP:0000651	Diplopia	Very rare (<1-4%)
HP:0001252	Hypotonia	Very rare (<1-4%)
HP:0001270	Motor delay	Very rare (<1-4%)
HP:0002650	Scoliosis	Very rare (<1-4%)
HP:0003201	Rhabdomyolysis	Very rare (<1-4%)
HP:0003652	Recurrent myoglobinuria	Very rare (<1-4%)
HP:0003691	Scapular winging	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	pure mitochondrial myopathy
Mondo ID	MONDO:0016807
Orphanet	254854
ICD-11	141365898
SNOMED CT	732245008
UMLS	C4517289
MedGen	1375079
GARD	0020768
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › mitochondrial disease › pure mitochondrial myopathy

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, maternally-inherited cardiomyopathy and hearing loss, 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

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3338063	NC_012920.1(MT-TN):m.5698G>A	MT-TN	Likely pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MT-TN	Orphanet:663	Mitochondrial DNA-related progressive external ophthalmoplegia

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-TN	HGNC:7493	ENSG00000210135		mitochondrially encoded tRNA-Asn (AAU/C)	clinvar

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-TN	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
duodenum	1
skeletal muscle tissue	1
vermiform appendix	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MT-TN	118	tissue_specific	yes	duodenum, skeletal muscle tissue, vermiform appendix

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MT-TN	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-TN	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-TN

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-TN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.