Charcot-Marie-Tooth disease, axonal, mitochondrial form, 1

Summary

Charcot-Marie-Tooth disease, axonal, mitochondrial form, 1 (MONDO:0025622) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Charcot-Marie-Tooth disease, axonal, mitochondrial form, 1
Mondo ID	MONDO:0025622
OMIM	500013
DOID	DOID:0061168
UMLS	C5435765
MedGen	1731194
GARD	0025478
Is cancer (heuristic)	no

Also known as: CMTMA1

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › peripheral nervous system disorder › peripheral neuropathy › hereditary peripheral neuropathy › Charcot-Marie-Tooth disease › Charcot-Marie-Tooth disease, axonal, mitochondrial form, 1

Related subtypes (23): Charcot-Marie-Tooth disease, Guadalajara neuronal type, Charcot-Marie-Tooth disease with ptosis and parkinsonism, Charcot-Marie-Tooth disease type 3, neuronopathy, distal hereditary motor, autosomal dominant 1, neuropathy, hereditary motor and sensory, type 6A, Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b;, demyelinating hereditary motor and sensory neuropathy, intermediate Charcot-Marie-Tooth disease, Charcot-Marie-Tooth disease type 2, Charcot-Marie-Tooth disease type X, Charcot-Marie-Tooth disease type 4, Charcot-Marie-Tooth disease type 1, Charcot-Marie-Tooth disease, axonal, type 2FF, Charcot-Marie-Tooth disease, axonal, Type 2HH, Charcot-Marie-Tooth disease, demyelinating, IIA 1I, Charcot-Marie-Tooth disease, demyelinating, IIA 1H, Charcot-Marie-Tooth disease, axonal, IIa 2II, Charcot-Marie-Tooth disease, demyelinating, type 1G, Charcot-Marie-Tooth disease, demyelinating, type 1J, Charcot-Marie-tooth disease, axonal, type 2JJ, Charcot-Marie-Tooth disease, axonal, type 2KK, Charcot-Marie-Tooth disease, axonal, type 2LL, charcot-marie-tooth disease, axonal, type 2MM

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 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
370043	NC_012920.1(MT-TV):m.1661A>G	MT-CO1	Uncertain significance	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MT-CO1	Orphanet:104	Leber hereditary optic neuropathy
MT-CO1	Orphanet:254905	Isolated cytochrome C oxidase deficiency
MT-CO1	Orphanet:550	MELAS
MT-CO1	Orphanet:90641	Rare mitochondrial non-syndromic sensorineural deafness
MT-CO1	Orphanet:99845	Genetic recurrent myoglobinuria

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
MT-CO1	HGNC:7419	ENSG00000198804	P00395	Cytochrome c oxidase subunit 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MT-CO1	Cytochrome c oxidase subunit 1	Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation.

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)
MT-CO1	Enzyme (other)	yes	7.1.1.9	Cyt_C_Oxase_1, Cyt_c_Oxase_su1_BS, Cyt_c_oxase-like_su1_dom

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
granulocyte	1
rectum	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MT-CO1	134	ubiquitous	marker	granulocyte, stromal cell of endometrium, rectum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MT-CO1	3,547

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MT-CO1	P00395	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Complex IV assembly	1	228.4×	0.011	MT-CO1
Cytoprotection by HMOX1	1	184.2×	0.011	MT-CO1
TP53 Regulates Metabolic Genes	1	129.8×	0.011	MT-CO1
Mitochondrial protein degradation	1	114.2×	0.011	MT-CO1
Mitochondrial translation termination	1	109.8×	0.011	MT-CO1
Respiratory electron transport	1	95.2×	0.011	MT-CO1

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
response to copper ion	1	1532.0×	0.003	MT-CO1
respiratory electron transport chain	1	842.6×	0.003	MT-CO1
mitochondrial electron transport, cytochrome c to oxygen	1	766.0×	0.003	MT-CO1
response to electrical stimulus	1	648.1×	0.003	MT-CO1
cellular respiration	1	432.1×	0.004	MT-CO1
cerebellum development	1	358.6×	0.004	MT-CO1
aerobic respiration	1	247.8×	0.005	MT-CO1
response to oxidative stress	1	130.6×	0.009	MT-CO1
response to hypoxia	1	95.8×	0.010	MT-CO1

Therapeutics

Drug target analysis

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

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MT-CO1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
MT-CO1	19	Binding:12, Functional:4, ADMET:2, Toxicity:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MT-CO1	7.1.1.9	cytochrome-c oxidase

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	1	MT-CO1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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-CO1	19	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.