C2ORF69

Chr 2AR

chromosome 2 open reading frame 69

Also known as: COXPD53

NCBI Gene: 205327ENSG00000178074UniProt: Q8N8R5OMIM: 619219

The C2ORF69 protein is involved in mitochondrial oxidative phosphorylation and may function in the respiratory chain. Mutations cause combined oxidative phosphorylation deficiency 53, which follows autosomal recessive inheritance. This mitochondrial disorder affects cellular energy production and can impact multiple organ systems.

OMIMResearchSummary from RefSeq, UniProt
ARLOEUF 0.811 OMIM phenotype
Clinical Summary— C2ORF69
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
40 unique Pathogenic / Likely Pathogenic· 11 VUS of 74 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
0.81LOEUF
pLI 0.019
Z-score 2.07
OE 0.38 (0.20–0.81)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.15Z-score
OE missense 0.78 (0.68–0.89)
164 obs / 210.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.38 (0.20–0.81)
0≤0.351.4
Missense OE0.78 (0.68–0.89)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 5 / 13.1Missense obs/exp: 164 / 210.9Syn Z: 0.22

ClinVar Variant Classifications

74 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic3
VUS11
Likely Benign18
Benign1
37
Pathogenic
3
Likely Pathogenic
11
VUS
18
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
1
31
0
37
Likely Pathogenic
2
0
1
0
3
VUS
0
8
3
0
11
Likely Benign
0
6
1
11
18
Benign
0
0
0
1
1
Total715361270

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

View in ClinVar →

Protein Context — Lollipop Plot

C2ORF69 · 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.

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Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
A rare autoinflammatory syndrome associated with a C2orf69 frameshift mutation: a case report.
Türkmen Ş et al.·Immunol Res
2025Case report
Loss of C2orf69 defines a fatal autoinflammatory syndrome in humans and zebrafish that evokes a glycogen-storage-associated mitochondriopathy.
Wong HH et al.·Am J Hum Genet
2021Functional
Identification and validation of oxidative stress-related diagnostic markers for recurrent pregnancy loss: insights from machine learning and molecular analysis.
Hu H et al.·Mol Divers
2024
Genome:annotated bivariate analysis of shared heritability in autoimmune hepatitis with psychiatric comorbidity
Liu L et al.·Sci Rep
2025
Effect of Recombinant Human Growth Hormone (rhGH) Use on Genetic Methylation Patterns and Their Relationship with Body Composition in Small-for-Gestational-Age (SGA) Newborns
Velásquez JMA et al.·Biomedicines
2025
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 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