C8ORF76

Chr 8

chromosome 8 open reading frame 76

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.

0
Active trials
4
Pubs (1 yr)
49
P/LP submissions
P/LP missense
1.61
LOEUF
Mechanism
Clinical SummaryC8ORF76
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
49 unique Pathogenic / Likely Pathogenic· 3 VUS of 55 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.61LOEUF
pLI 0.000
Z-score -0.45
OE 1.11 (0.781.61)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.00Z-score
OE missense 1.00 (0.891.13)
187 obs / 187.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.11 (0.781.61)
00.351.4
Missense OE1.00 (0.891.13)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 20 / 18.0Missense obs/exp: 187 / 187.1Syn Z: 0.12

ClinVar Variant Classifications

55 submitted variants in ClinVar

Classification Summary

Pathogenic49
VUS3
49
Pathogenic
3
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
49
Likely Pathogenic
0
VUS
3
Likely Benign
0
Benign
0
Total52

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

C8ORF76 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →