C8B

Chr 1AR

complement C8 beta chain

Also known as: C82

NCBI Gene: 732ENSG00000021852UniProt: P07358

This gene encodes one of the three subunits of the complement component 8 (C8) protein. C8 is composed of equimolar amounts of alpha, beta and gamma subunits, which are encoded by three separate genes. C8 is one component of the membrane attack complex, which mediates cell lysis, and it initiates membrane penetration of the complex. This protein mediates the interaction of C8 with the C5b-7 membrane attack complex precursor. In humans deficiency of this protein is associated with increased risk of meningococcal infections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

Primary Disease Associations & Inheritance

C8 deficiency, type IIMIM #613789
AR
UniProtComplement component 8 deficiency, 2
453
ClinVar variants
52
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— C8B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
52 Pathogenic / Likely Pathogenic· 215 VUS of 453 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.
1.33LOEUF
pLI 0.000
Z-score 0.11
OE 0.98 (0.73–1.33)
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.
-0.74Z-score
OE missense 1.12 (1.02–1.22)
351 obs / 313.9 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.0.98 (0.73–1.33)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.12 (1.02–1.22)
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.1.26
0≤1.21.6
LoF obs/exp: 29 / 29.6Missense obs/exp: 351 / 313.9Syn Z: -2.19

ClinVar Variant Classifications

453 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic13
VUS215
Likely Benign163
Benign16
Conflicting7
39
Pathogenic
13
Likely Pathogenic
215
VUS
163
Likely Benign
16
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
0
22
0
39
Likely Pathogenic
9
0
4
0
13
VUS
0
192
21
2
215
Likely Benign
0
10
49
104
163
Benign
0
3
6
7
16
Conflicting
—7
Total26205102113453

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

View in ClinVar →

Protein Context — Lollipop Plot

C8B · 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 II

MIM #613789

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
C8A and C8B polymorphisms in Norwegians and Norwegian lapps.
Rogde S et al.·Hum Hered
1989
Combined Heterozygous Genetic Variations in Complement C2 and C8B: An Explanation for Multidimensional Immune Imbalance?
Mannes M et al.·J Innate Immun
2023Case report
Inflammation Thread Runs across Medical Laboratory Specialities.
Nydegger U et al.·Mediators Inflamm
2016Review
Genetic aspects of complement component C8 in Norwegian meningococcal disease patients.
Rogde S et al.·Scand J Infect Dis
1990Cohort
Establishment of Coala: a novel 3D and 2D cancer cell line derived from colorectal cancer liver metastasis.
Mersakova S et al.·Hum Cell
2025
[Dedicated composite fillings--inlays].
Saulić S et al.·Vojnosanit Pregl
2003
Exome-based search for recurrent disease-causing alleles in Russian population.
Yanus GA et al.·Eur J Med Genet
2019
Whole-exome sequencing detects mutations in pediatric patients with atypical hemolytic uremic syndrome in Taiwan.
Tseng MH et al.·Clin Chim Acta
2019Cohort
Lupus manifestations in children with primary immunodeficiency diseases: Comprehensive phenotypic and genetic features and outcome.
Al-Mayouf SM et al.·Mod Rheumatol
2021
Proteomic Biomarkers for the Prediction of Transition to Psychosis in Individuals at Clinical High Risk: A Multi-cohort Model Development Study.
Byrne JF et al.·Schizophr Bull
2024Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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