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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
C6
complement C6
Chromosome 5 Β· 5p13.1
NCBI Gene: 729Ensembl: ENSG00000039537.17HGNC: HGNC:1339UniProt: P13671
72PubMed Papers
21Diseases
0Drugs
63Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
wide pore channel activityprotein bindingcomplement activationkilling of cells of another organismImmunodeficiency due to a late component of complements deficiencycomplement deficiencyimmunodeficiency due to a late component of complement deficiencymale reproductive organ cancer
✦AI Summary

C6 (complement component 6) is a critical component of the membrane attack complex (MAC), a multiprotein cascade activated by complement pathways 1. C6 associates with C5b at the outer leaflet of target cell membranes, reducing membrane bending energy and facilitating MAC assembly and insertion 12. This insertion creates pores in target cell membranes, leading to cell lysis and destruction of pathogens 34. The complement cascade, of which C6 is part, promotes pathogen phagocytosis and strengthens adaptive immunity 1. C6 exhibits genetic variation with common polymorphisms (C6A and C6B) maintained at similar frequencies across populations, suggesting balancing selection 5. C6 deficiency is an established disease association, impairing complement-mediated immune responses. Therapeutically, C6 inhibition shows promise for neurological diseases. A humanized monoclonal antibody against C6 (CP010) blocks the C6-C5/C5b interaction, preventing MAC formation and demonstrating efficacy in experimental autoimmune myasthenia gravis and autoimmune encephalomyelitis models 6. Animals deficient in C6 showed improved recovery after neuronal trauma, indicating that MAC inhibition may benefit neuronal regeneration 6. These findings position C6 as a potential therapeutic target for complement-mediated neuroinflammatory diseases.

Sources cited
1
C6 is a component of the MAC, involved in assembly with C5b and pathogens/complement cascade role
PMID: 30552328
2
C6 and C5b associate at target cell membrane outer leaflet and reduce membrane bending energy
PMID: 32569291
3
MAC insertion into target cell membranes forms pores and causes cell lysis
PMID: 22267737
4
MAC-mediated target cell membrane rupture and cell lysis
PMID: 22832194
5
C6 polymorphisms (C6A, C6B, C6B2) maintained by balancing selection across populations
PMID: 15845028
6
Anti-C6 monoclonal antibody prevents MAC formation and has therapeutic potential in neurological disease; C6 deficiency improves recovery after neuronal trauma
PMID: 35551129
Disease Associationsβ“˜21
Immunodeficiency due to a late component of complements deficiencyOpen Targets
0.75Strong
complement deficiencyOpen Targets
0.46Moderate
immunodeficiency due to a late component of complement deficiencyOpen Targets
0.45Moderate
male reproductive organ cancerOpen Targets
0.30Weak
genetic disorderOpen Targets
0.19Weak
Benign Brain NeoplasmOpen Targets
0.18Weak
Central Nervous System NeoplasmOpen Targets
0.18Weak
benign neoplasm of adrenal glandOpen Targets
0.14Weak
cardiomyopathyOpen Targets
0.12Weak
macular degenerationOpen Targets
0.11Weak
frozen shoulderOpen Targets
0.09Suggestive
alcohol drinkingOpen Targets
0.06Suggestive
central nervous system cancerOpen Targets
0.05Suggestive
colorectal cancerOpen Targets
0.04Suggestive
Crohn's diseaseOpen Targets
0.04Suggestive
hepatocellular carcinomaOpen Targets
0.04Suggestive
Acute hepatic failureOpen Targets
0.03Suggestive
infectionOpen Targets
0.03Suggestive
Tetralogy of FallotOpen Targets
0.03Suggestive
neoplasmOpen Targets
0.03Suggestive
Complement component 6 deficiencyUniProt
Pathogenic Variants63
NM_000065.5(C6):c.1138del (p.Gln380fs)Pathogenic
not provided|Complement component 6 deficiency|C6-related disorder|Inborn genetic diseases
β˜…β˜…β˜†β˜†2026β†’ Residue 380
NM_000065.5(C6):c.1816C>T (p.Arg606Ter)Pathogenic
not provided|Complement component 6 deficiency
β˜…β˜…β˜†β˜†2026β†’ Residue 606
NM_000065.5(C6):c.2335_2336del (p.Gln779fs)Pathogenic
not provided|Complement component 6 deficiency
β˜…β˜…β˜†β˜†2026β†’ Residue 779
NM_000065.5(C6):c.821del (p.Gln274fs)Pathogenic
not provided|Complement component 6 deficiency|C6-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 274
NM_000065.5(C6):c.2406_2407del (p.Val802_Phe803insTer)Pathogenic
Complement component 6 deficiency|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 802
NM_000065.5(C6):c.1786C>T (p.Arg596Ter)Pathogenic
Complement component 6 deficiency|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 596
NM_000065.5(C6):c.1352dup (p.Tyr451Ter)Pathogenic
not provided|Complement component 6 deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 451
NM_000065.5(C6):c.1879del (p.Asp627fs)Pathogenic
Complement component 6 deficiency|Immunodeficiency due to a late component of complement deficiency|not provided|C6-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 627
NM_000065.5(C6):c.654T>A (p.Cys218Ter)Pathogenic
not provided|Complement component 6 deficiency
β˜…β˜…β˜†β˜†2024β†’ Residue 218
NM_000065.5(C6):c.1628_1629dup (p.Gln544fs)Pathogenic
Complement component 6 deficiency|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 544
NM_000065.5(C6):c.2049C>G (p.Tyr683Ter)Pathogenic
Complement component 6 deficiency|not provided|C6-related disorder
β˜…β˜…β˜†β˜†2024β†’ Residue 683
NM_000065.5(C6):c.1563C>A (p.Cys521Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2026β†’ Residue 521
NM_000065.5(C6):c.1657G>T (p.Glu553Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 553
NM_000065.5(C6):c.1912del (p.Glu637_Ile638insTer)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 637
NM_000065.5(C6):c.1589del (p.Gly530fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 530
NM_000065.5(C6):c.1839_1840del (p.Ser614fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 614
NM_000065.5(C6):c.301-1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_000065.5(C6):c.1615_1633del (p.Cys539fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 539
NM_000065.5(C6):c.733del (p.Thr245fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 245
NM_000065.5(C6):c.723del (p.Phe241fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 241
View on ClinVar β†—
Related Genes
C8AProtein interaction100%C7Protein interaction100%C8BProtein interaction100%ADAM10Protein interaction100%SLC25A4Protein interaction100%SLC25A5Protein interaction100%
Tissue Expression6 tissues
Liver
100%
Heart
16%
Ovary
2%
Lung
0%
Brain
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
C6C8AC7C8BADAM10SLC25A4SLC25A5
PROTEIN STRUCTURE
Preparing viewer…
PDB7Q6C Β· 2.29 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.01LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.85 [0.72–1.01]
RankingsWhere C6 stands among ~20K protein-coding genes
  • #6,530of 20,598
    Most Researched72
  • #1,129of 5,498
    Most Pathogenic Variants63 Β· top quartile
  • #9,790of 17,882
    Most Constrained (LOEUF)1.01
Genes detectedC6
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Nucleotide sequence analyses of human complement 6 (C6) gene suggest balancing selection.
PMID: 15845028
Ann Hum Genet Β· 2005
1.00
2
Development, Characterization, and in vivo Validation of a Humanized C6 Monoclonal Antibody that Inhibits the Membrane Attack Complex.
PMID: 35551129
J Innate Immun Β· 2023
0.90
3
Inhibition of chikungunya virus replication by N-Ο‰-Chloroacetyl-L-Ornithine in C6/36, Vero cells and human fibroblast BJ.
PMID: 36724136
Antivir Ther Β· 2023
0.80
4
Apamin binding sites in human C6 cell line and their accessibility to monoclonal antibodies.
PMID: 1966607
Neuroreport Β· 1990
0.70
5
Domain-specific distribution of carbohydrates in human fibronectins and the transformation-dependent translocation of branched type 2 chain defined by monoclonal antibody C6.
PMID: 2426270
J Biol Chem Β· 1986
0.60