C2ORF69

Chr 2AR

chromosome 2 open reading frame 69

Also known as: COXPD53

NCBI Gene: 205327ENSG00000178074UniProt: Q8N8R5

Involved in oxidative phosphorylation. Located in mitochondrion. Implicated in combined oxidative phosphorylation deficiency 53. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Combined oxidative phosphorylation deficiency 53MIM #619423
AR
67
ClinVar variants
40
Pathogenic / LP
0.02
pLI score
0
Active trials
Clinical Summary— C2ORF69
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
40 Pathogenic / Likely Pathogenic· 10 VUS of 67 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.81LOEUF
pLI 0.019
Z-score 2.07
OE 0.38 (0.20–0.81)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.15Z-score
OE missense 0.78 (0.68–0.89)
164 obs / 210.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.38 (0.20–0.81)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.68–0.89)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 5 / 13.1Missense obs/exp: 164 / 210.9Syn Z: 0.22

ClinVar Variant Classifications

67 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic3
VUS10
Likely Benign16
Benign1
37
Pathogenic
3
Likely Pathogenic
10
VUS
16
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
33
0
37
Likely Pathogenic
2
0
1
0
3
VUS
0
8
2
0
10
Likely Benign
0
6
1
9
16
Benign
0
0
0
1
1
Total614371067

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Combined oxidative phosphorylation deficiency 53

MIM #619423

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools