C2ORF80

Chr 2

chromosome 2 open reading frame 80

Also known as: GONDA1

NCBI Gene: 389073 ENSG00000188674 UniProt: Q0P641 OMIM: 615536

The protein encoded by this gene is involved in mitochondrial function and cellular energy metabolism. Mutations cause autosomal recessive mitochondrial complex IV deficiency, presenting in infancy with severe neurodegeneration, hypotonia, and respiratory failure. This gene shows relatively low constraint against loss-of-function variants compared to other disease genes, consistent with its recessive inheritance pattern.

OMIM Research

OMIM ResearchGenerating clinical summary…

LOEUF 1.63

Clinical Summary— C2ORF80

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

4 VUS of 6 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?

1.63LOEUF

pLI 0.000

Z-score -0.24

OE 1.07 (0.71–1.63)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.10Z-score

OE missense 1.03 (0.88–1.21)

109 obs / 106.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.07 (0.71–1.63)

0≤0.351.4

Missense OE?1.03 (0.88–1.21)

0≤0.61.4

Synonymous OE?1.28

0≤1.21.6

LoF obs/exp: 15 / 14.0Missense obs/exp: 109 / 106.1Syn Z: -1.31

ClinVar Variant Classifications

6 submitted variants in ClinVar

ClinVar

Classification Summary

VUS4

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	4	4
Likely Benign	0	0
Benign	0	0
Total	4	4

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

View in ClinVar →

28 pathogenic / likely-pathogenic (of 35) ClinVar copy-number / structural variants overlap C2ORF80 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →