C8G

Chr 9

complement C8 gamma chain

Also known as: C8C

The C8G protein is the gamma subunit of complement component 8 (C8), which forms part of the membrane attack complex that creates pores in bacterial cell membranes to eliminate pathogens through the complement cascade. Mutations cause complement component 8 deficiency, which follows autosomal recessive inheritance and results in increased susceptibility to recurrent Neisseria infections, particularly meningococcal and gonococcal disease. The gene shows low constraint to loss-of-function variation, consistent with the recessive inheritance pattern of complement deficiencies.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.93
Clinical SummaryC8G
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
83 unique Pathogenic / Likely Pathogenic· 52 VUS of 164 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.93LOEUF
pLI 0.000
Z-score -1.86
OE 1.54 (1.081.93)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.36Z-score
OE missense 1.09 (0.951.25)
141 obs / 129.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.54 (1.081.93)
00.351.4
Missense OE1.09 (0.951.25)
00.61.4
Synonymous OE1.43
01.21.6
LoF obs/exp: 21 / 13.6Missense obs/exp: 141 / 129.4Syn Z: -2.49
DN
0.6356th %ile
GOF
0.6149th %ile
LOF
0.2872th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

164 submitted variants in ClinVar

Classification Summary

Pathogenic79
Likely Pathogenic4
VUS52
Likely Benign12
Benign3
Conflicting2
79
Pathogenic
4
Likely Pathogenic
52
VUS
12
Likely Benign
3
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
79
0
79
Likely Pathogenic
0
0
4
0
4
VUS
2
42
8
0
52
Likely Benign
1
3
3
5
12
Benign
0
1
1
1
3
Conflicting
2
Total346956152

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

View in ClinVar →

Protein Context — Lollipop Plot

C8G · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC