C8A

Chr 1AR

complement C8 alpha chain

NCBI Gene: 731ENSG00000157131UniProt: P07357

C8 is a component of the complement system and contains three polypeptides, alpha, beta and gamma. This gene encodes the alpha subunit of C8. C8 participates in the formation of the membrane attack complex (MAC). The MAC assembles on bacterial membranes to form a pore, permitting disruption of bacterial membrane organization. Mutations in this gene cause complement C8 alpha-gamma deficiency. [provided by RefSeq, Nov 2008]

Primary Disease Associations & Inheritance

C8 deficiency, type IMIM #613790
AR
UniProtComplement component 8 deficiency, 1
466
ClinVar variants
37
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— C8A
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
37 Pathogenic / Likely Pathogenic· 204 VUS of 466 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.18LOEUF
pLI 0.000
Z-score 0.75
OE 0.85 (0.63–1.18)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-1.07Z-score
OE missense 1.17 (1.07–1.27)
372 obs / 318.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.85 (0.63–1.18)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.17 (1.07–1.27)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.13
0≤1.21.6
LoF obs/exp: 26 / 30.5Missense obs/exp: 372 / 318.1Syn Z: -1.10

ClinVar Variant Classifications

466 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic10
VUS204
Likely Benign204
Benign14
Conflicting7
27
Pathogenic
10
Likely Pathogenic
204
VUS
204
Likely Benign
14
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
22
0
27
Likely Pathogenic
5
0
5
0
10
VUS
0
183
19
2
204
Likely Benign
0
16
71
117
204
Benign
0
4
5
5
14
Conflicting
—7
Total10203122124466

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

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

C8 deficiency, type I

MIM #613790

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Rare and common single nucleotide variants in childhood-onset systemic lupus erythematosus.
Sayadi A et al.·Lupus Sci Med
2025
C8A and C8B polymorphisms in Norwegians and Norwegian lapps.
Rogde S et al.·Hum Hered
1989
Polymorphism of the complement C8A and -B genes in two families with C8 beta deficiency and neisserial infections.
Barba GM et al.·Clin Immunol Immunopathol
1994
Significance of urine complement proteins in monitoring lupus activity.
Zhao J et al.·PeerJ
2022
Combined transcriptomics and proteomics analysis reveals mechanisms underlying refractory lupus nephritis in children.
Wei Q et al.·Clin Rheumatol
2025Functional
Inflammation Thread Runs across Medical Laboratory Specialities.
Nydegger U et al.·Mediators Inflamm
2016Review
Stage-dependent proteomic alterations in aqueous humor of diabetic retinopathy patients based on data-independent acquisition and parallel reaction monitoring.
Jin Y et al.·J Transl Med
2025Cohort
Evaluation of the significance of complement-related genes mutations in atypical postinfectious glomerulonephritis: a pilot study.
Xu F et al.·Int Urol Nephrol
2024
Integrated proteomic and metabolomic analysis elucidates the effects and mechanisms of Qiziyusi decoction on IVF outcomes in advanced maternal age infertility.
Jin Q et al.·Front Endocrinol (Lausanne)
2025Functional
Novel plasma glycoprotein biomarkers predict progression-free survival in surgically resected clear cell renal cell carcinoma.
Serie DJ et al.·Urol Oncol
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Enantioselective Access to Decahydroquinolines Bearing a C4a or C8a Quaternary Stereocenter from a Common Intermediate Total Synthesis of (-)-Myrioxazine A.
Calbó A et al.·J Org Chem
2025🔓 Open Access
A Point Mutation Creating a 3' Splice Site in C8A Is a Predominant Cause of C8α-γ Deficiency in African Americans.
Densen P et al.·J Immunol
2020
Exploratory Analysis of Single-Gene Predictive Biomarkers in HERA DASL Cohort Reveals That C8A mRNA Expression Is Prognostic of Outcome and Predictive of Benefit of Trastuzumab.
Willis S et al.·JCO Precis Oncol
2018🔓 Open AccessCohort
Inactive C8A‑humanin analog is as stable as a potent S14G‑humanin analog.
Arakawa T et al.·Mol Med Rep
2014
[Detecting the DNA polymorphism of human complement component C8A by PCR-SSCP analysis].
Yang ZH et al.·Sichuan Da Xue Xue Bao Yi Xue Ban
2006
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools