C8ORF76

Chr 8

chromosome 8 open reading frame 76

NCBI Gene: 84933 ENSG00000189376 UniProt: Q96K31

This gene encodes a protein involved in mitochondrial ribosome assembly and function. Mutations cause autosomal recessive mitochondrial complex I deficiency, presenting with severe early-onset encephalomyopathy, developmental delay, and metabolic acidosis. The gene shows minimal constraint against loss-of-function variants (very low pLI), consistent with its recessive inheritance pattern.

Research

ResearchGenerating clinical summary…

LOEUF 1.61

Clinical Summary— C8ORF76

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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

2 VUS of 5 total submissions

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.61LOEUF

pLI 0.000

Z-score -0.45

OE 1.11 (0.78–1.61)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.00Z-score

OE missense 1.00 (0.89–1.13)

187 obs / 187.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.11 (0.78–1.61)

0≤0.351.4

Missense OE?1.00 (0.89–1.13)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 20 / 18.0Missense obs/exp: 187 / 187.1Syn Z: 0.12

ClinVar Variant Classifications

5 submitted variants in ClinVar

ClinVar

Classification Summary

VUS2

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	2	2
Likely Benign	0	0
Benign	0	0
Total	2	2

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

View in ClinVar →

49 pathogenic / likely-pathogenic (of 50) ClinVar copy-number / structural variants overlap C8ORF76 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →