CMC1

Chr 3

C-X9-C motif containing 1

Also known as: C3orf68, cmc1p

NCBI Gene: 152100ENSG00000187118UniProt: Q7Z7K0OMIM: 615166

CMC1 encodes a component of the MITRAC complex that regulates cytochrome c oxidase assembly in mitochondria and enables metal ion binding. Mutations cause autosomal recessive mitochondrial complex IV deficiency, typically presenting in infancy with severe neurological dysfunction, cardiomyopathy, and metabolic acidosis. The gene shows low constraint to loss-of-function variation in the population.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.24
Clinical Summary— CMC1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.11) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
17 unique Pathogenic / Likely Pathogenic· 45 VUS of 75 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.24LOEUF
pLI 0.107
Z-score 1.26
OE 0.40 (0.16–1.24)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.03Z-score
OE missense 0.99 (0.78–1.25)
49 obs / 49.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.40 (0.16–1.24)
0≤0.351.4
Missense OE0.99 (0.78–1.25)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 2 / 5.0Missense obs/exp: 49 / 49.7Syn Z: 0.21
DN
0.91top 5%
GOF
0.6932th %ile
LOF
0.08100th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

75 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic1
VUS45
Likely Benign1
16
Pathogenic
1
Likely Pathogenic
45
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
0
1
0
1
VUS
0
38
7
0
45
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total03825063

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

View in ClinVar →

Protein Context — Lollipop Plot

CMC1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Is multimodal occupational therapy in addition to usual care cost-effective in people with thumb carpometacarpal osteoarthritis? A cost-utility analysis of a randomised controlled trial
Tveter AT et al.·BMJ Open
2023
Effectiveness of Ultrasound-guided versus Landmark-based Glucocorticoid Injection in the Treatment of First Carpometacarpal Joint Osteoarthritis
Al-Nokhatha SA et al.·POCUS J
2023
Study on Antibacterial Activities of Croton macrostachyus and Pycnostachys abyssinica Leaf Extracts Against Some Human Pathogens
Yemata G et al.·ScientificWorldJournal
2025
Novel Targets in a High-Altitude Pulmonary Hypertension Rat Model Based on RNA-seq and Proteomics
Xu X et al.·Front Med (Lausanne)
2021Functional
Design, Synthesis, and Molecular Docking Studies of Curcumin Hybrid Conjugates as Potential Therapeutics for Breast Cancer
Panda SS et al.·Pharmaceuticals (Basel)
2022
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients