C8ORF33

Chr 8

chromosome 8 open reading frame 33

The C8ORF33 protein functions as a component of the mitochondrial respiratory chain complex I, involved in oxidative phosphorylation and cellular energy production. Mutations cause Leigh syndrome, a severe mitochondrial disorder characterized by progressive neurodegeneration typically beginning in infancy or early childhood. The condition follows autosomal recessive inheritance and primarily affects the central nervous system, though multi-organ involvement can occur.

0
Active trials
1
Pubs (1 yr)
50
P/LP submissions
P/LP missense
1.84
LOEUF
Mechanism
Clinical SummaryC8ORF33
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
50 unique Pathogenic / Likely Pathogenic· 9 VUS of 75 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.84LOEUF
pLI 0.000
Z-score -0.68
OE 1.24 (0.791.84)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.45Z-score
OE missense 1.11 (0.971.27)
151 obs / 136.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.24 (0.791.84)
00.351.4
Missense OE1.11 (0.971.27)
00.61.4
Synonymous OE1.25
01.21.6
LoF obs/exp: 12 / 9.7Missense obs/exp: 151 / 136.3Syn Z: -1.41

ClinVar Variant Classifications

75 submitted variants in ClinVar

Classification Summary

Pathogenic46
Likely Pathogenic4
VUS9
Likely Benign3
Benign3
46
Pathogenic
4
Likely Pathogenic
9
VUS
3
Likely Benign
3
Benign

Curated Variants Distribution

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

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
46
Likely Pathogenic
4
VUS
9
Likely Benign
3
Benign
3
Total65

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

C8ORF33 · 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.

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Clinical Literature
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