C2ORF69

Chr 2AR

chromosome 2 open reading frame 69

Also known as: COXPD53

NCBI Gene: 205327 ENSG00000178074 UniProt: Q8N8R5 OMIM: 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.

OMIM ResearchSummary from RefSeq, UniProt

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

OMIM ResearchGenerating clinical summary…

ARLOEUF 0.811 OMIM phenotype

Clinical Summary— C2ORF69

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Population Constraint (gnomAD)

Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

8 unique Pathogenic / Likely Pathogenic· 9 VUS of 40 total submissions

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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 OE?0.38 (0.20–0.81)

0≤0.351.4

Missense OE?0.78 (0.68–0.89)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 5 / 13.1Missense obs/exp: 164 / 210.9Syn Z: 0.22

ClinVar Variant Classifications

40 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

Likely Pathogenic2

VUS9

Likely Benign18

Benign1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	5	1	0	0	6
Likely Pathogenic	2	0	0	0	2
VUS	0	8	1	0	9
Likely Benign	0	6	1	11	18
Benign	0	0	0	1	1
Total	7	15	2	12	36

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

View in ClinVar →

32 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap C2ORF69 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →