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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.
C9
complement C9
Chromosome 5 Β· 5p13.1
NCBI Gene: 735Ensembl: ENSG00000113600.13HGNC: HGNC:1358UniProt: P02748
95PubMed Papers
22Diseases
0Drugs
47Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
wide pore channel activityprotein bindingcell killingother organism cell membraneImmunodeficiency due to a late component of complements deficiencyage-related macular degenerationmacular degenerationcomplement deficiency
✦AI Summary

C9 (complement C9) is the pore-forming component of the membrane attack complex (MAC), a critical effector of the complement cascade 12345678. During complement activation triggered by classical, alternative, lectin, and GZMK pathways, C5 is cleaved into C5b, which initiates MAC assembly 91078. C9 associates with the C5b8 intermediate complex and polymerizes to complete the pore structure, inserting into target cell membranes to cause lysis 311512136. This mechanism enables pathogen elimination and strengthens adaptive immunity through signaling cascades 78. CD59, an abundant immune regulator, protects human cells by binding C8 and deflecting C9 Ξ²-hairpins to prevent membrane perforation and MAC polymerization 14. Similarly, disulfide-locked C9 variants and horse C9 inhibit MAC assembly through competitive binding mechanisms 15. Clinically, C9 deficiency impairs complement-mediated immunity, while dysregulation contributes to age-related macular degeneration. C9 represents a validated therapeutic target for conditions where MAC-mediated tissue damage occurs.

Sources cited
1
C9 is pore-forming component of MAC
PMID: 22832194
2
C9 inserts into target cell membrane forming pore
PMID: 26841837
3
C9 polymerizes with C5b8 to complete MAC pore
PMID: 26841934
4
C9 role in membrane rupture and cell lysis
PMID: 27052168
5
C9 pore-forming function in MAC
PMID: 30552328
6
C9 polymerization in MAC assembly
PMID: 6177822
7
Complement cascade leading to MAC formation and pathogen clearance
PMID: 9212048
8
MAC cascade and adaptive immune signaling
PMID: 9634479
9
C5 cleavage initiates MAC by multiple complement pathways
PMID: 39914456
10
C5 proteolytic activation in complement pathways
PMID: 39814882
11
C9 assembly with C5b8 intermediate
PMID: 30111885
12
C9 polymerization in MAC pore formation
PMID: 34752492
13
C9 polymerization mechanism
PMID: 4055801
14
CD59 inhibits MAC by preventing C9 insertion and polymerization
PMID: 36797260
15
CD59 and C9 variants inhibit MAC assembly through competitive binding
PMID: 40523671
Disease Associationsβ“˜22
Immunodeficiency due to a late component of complements deficiencyOpen Targets
0.76Strong
age-related macular degenerationOpen Targets
0.61Moderate
macular degenerationOpen Targets
0.53Moderate
complement deficiencyOpen Targets
0.46Moderate
immunodeficiency due to a late component of complement deficiencyOpen Targets
0.37Weak
wet macular degenerationOpen Targets
0.36Weak
degeneration of macula and posterior poleOpen Targets
0.36Weak
atrophic macular degenerationOpen Targets
0.35Weak
neurodegenerative diseaseOpen Targets
0.34Weak
Abruptio PlacentaeOpen Targets
0.31Weak
chronic kidney diseaseOpen Targets
0.28Weak
circadian rhythm sleep disorderOpen Targets
0.26Weak
goutOpen Targets
0.22Weak
genetic disorderOpen Targets
0.19Weak
amyotrophic lateral sclerosisOpen Targets
0.12Weak
frontotemporal dementiaOpen Targets
0.10Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
esophageal adenocarcinomaOpen Targets
0.08Suggestive
Pick diseaseOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.06Suggestive
Complement component 9 deficiencyUniProt
Macular degeneration, age-related, 15UniProt
Pathogenic Variants47
NM_001737.5(C9):c.721del (p.Ser240_Leu241insTer)Pathogenic
not provided|Complement component 9 deficiency;Age related macular degeneration 15
β˜…β˜…β˜†β˜†2026β†’ Residue 240
NM_001737.5(C9):c.162C>A (p.Cys54Ter)Pathogenic
Complement component 9 deficiency|not provided|Complement component 9 deficiency;Age related macular degeneration 15|C9-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 54
NM_001737.5(C9):c.1039_1042del (p.Ser347fs)Pathogenic
not provided|Age related macular degeneration 15;Complement component 9 deficiency
β˜…β˜…β˜†β˜†2026β†’ Residue 347
NM_001737.5(C9):c.577del (p.Tyr193fs)Pathogenic
Complement component 9 deficiency|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 193
NM_001737.5(C9):c.1209_1222del (p.Asp403fs)Pathogenic
not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 403
NM_001737.5(C9):c.580C>T (p.Arg194Ter)Pathogenic
Complement component 9 deficiency|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 194
NM_001737.5(C9):c.346C>T (p.Arg116Ter)Pathogenic
Complement component 9 deficiency|not provided|Age related macular degeneration 15;Complement component 9 deficiency|Gastric cancer|Thyroid cancer, nonmedullary, 1
β˜…β˜…β˜†β˜†2025β†’ Residue 116
NM_001737.5(C9):c.460C>T (p.Arg154Ter)Pathogenic
Complement component 9 deficiency|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 154
NM_001737.5(C9):c.877del (p.Met293fs)Pathogenic
not provided|C9-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 293
NM_001737.5(C9):c.1184_1185del (p.Ser395fs)Pathogenic
not provided|Age related macular degeneration 15;Complement component 9 deficiency|C9-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 395
NM_001737.5(C9):c.1038_1042delinsT (p.Ser347fs)Pathogenic
not provided|Complement component 9 deficiency;Age related macular degeneration 15
β˜…β˜…β˜†β˜†2022β†’ Residue 347
NM_001737.5(C9):c.871-2A>GLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2026
NM_001737.5(C9):c.1280C>G (p.Ser427Ter)Pathogenic
Complement component 9 deficiency|not provided
β˜…β˜†β˜†β˜†2026β†’ Residue 427
NM_001737.5(C9):c.274G>T (p.Glu92Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 92
NM_001737.5(C9):c.1416+1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_001737.5(C9):c.122_134del (p.Ile41fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 41
NM_001737.5(C9):c.256C>T (p.Arg86Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 86
NM_001737.5(C9):c.651C>G (p.Tyr217Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 217
NM_001737.5(C9):c.476+2T>CLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_001737.5(C9):c.803del (p.Gly268fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 268
View on ClinVar β†—
Related Genes
ADAM10Protein interaction100%SLC25A4Protein interaction100%SLC25A5Protein interaction100%BAK1Protein interaction100%C5Protein interaction100%APOEProtein interaction99%
Tissue Expression6 tissues
Liver
100%
Lung
0%
Ovary
0%
Bone Marrow
0%
Heart
0%
Brain
0%
Gene Interaction Network
Click a node to explore
C9ADAM10SLC25A4SLC25A5BAK1C5APOE
PROTEIN STRUCTURE
Preparing viewer…
PDB8DE6 Β· 3.20 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.22LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.93 [0.71–1.22]
RankingsWhere C9 stands among ~20K protein-coding genes
  • #5,020of 20,598
    Most Researched95 Β· top quartile
  • #1,387of 5,498
    Most Pathogenic Variants47
  • #12,878of 17,882
    Most Constrained (LOEUF)1.22
Genes detectedC9
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Disruption of nuclear speckle integrity dysregulates RNA splicing in C9ORF72-FTD/ALS.
PMID: 39181135
Neuron Β· 2024
1.00
2
Divergent single cell transcriptome and epigenome alterations in ALS and FTD patients with C9orf72 mutation.
PMID: 37714849
Nat Commun Β· 2023
0.90
3
Molecular pathology, developmental changes and synaptic dysfunction in (pre-) symptomatic human C9ORF72-ALS/FTD cerebral organoids.
PMID: 39289761
Acta Neuropathol Commun Β· 2024
0.80
4
Aberrant splicing exonizes C9orf72 repeat expansion in ALS/FTD.
PMID: 40790269
Nat Neurosci Β· 2025
0.70
5
Structural basis for membrane attack complex inhibition by CD59.
PMID: 36797260
Nat Commun Β· 2023
0.60