C8ORF48

Chr 8

chromosome 8 open reading frame 48

The protein encoded by this gene functions as a component of the mitochondrial respiratory chain complex I, participating in cellular energy production through oxidative phosphorylation. Mutations cause autosomal recessive mitochondrial complex I deficiency, presenting with multisystem manifestations including neurodegeneration, developmental delay, and metabolic dysfunction. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

0
Active trials
0
Pubs (1 yr)
87
P/LP submissions
P/LP missense
1.65
LOEUF
Mechanism
Clinical SummaryC8ORF48
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
87 unique Pathogenic / Likely Pathogenic· 19 VUS of 118 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.65LOEUF
pLI 0.000
Z-score 0.30
OE 0.87 (0.481.65)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.23Z-score
OE missense 1.27 (1.141.43)
204 obs / 160.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.87 (0.481.65)
00.351.4
Missense OE1.27 (1.141.43)
00.61.4
Synonymous OE1.28
01.21.6
LoF obs/exp: 6 / 6.9Missense obs/exp: 204 / 160.1Syn Z: -1.72

ClinVar Variant Classifications

118 submitted variants in ClinVar

Classification Summary

Pathogenic83
Likely Pathogenic4
VUS19
Likely Benign9
Benign1
83
Pathogenic
4
Likely Pathogenic
19
VUS
9
Likely Benign
1
Benign

Curated Variants Distribution

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

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
83
Likely Pathogenic
4
VUS
19
Likely Benign
9
Benign
1
Total116

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

C8ORF48 · 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 →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found