The C8A protein is the alpha subunit of complement component C8, which forms part of the membrane attack complex that creates pores in bacterial membranes leading to cell lysis and pathogen clearance. Mutations cause complement C8 deficiency type I, inherited in an autosomal recessive pattern, which results in increased susceptibility to recurrent Neisseria infections. This gene shows minimal constraint against loss-of-function variants in the general population.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 1.181 OMIM phenotype
Clinical SummaryC8A
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.18LOEUF
pLI 0.000
Z-score 0.75
OE 0.85 (0.631.18)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.07Z-score
OE missense 1.17 (1.071.27)
372 obs / 318.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.85 (0.631.18)
00.351.4
Missense OE1.17 (1.071.27)
00.61.4
Synonymous OE1.13
01.21.6
LoF obs/exp: 26 / 30.5Missense obs/exp: 372 / 318.1Syn Z: -1.10
DN
0.6260th %ile
GOF
0.5856th %ile
LOF
0.2969th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

C8A · 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.

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Clinical Literature
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