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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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GSDMC
gasdermin C
Chromosome 8 · 8q24.21
NCBI Gene: 56169Ensembl: ENSG00000147697.10HGNC: HGNC:7151UniProt: Q9BYG8
29PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytoplasmphosphatidylinositol-4,5-bisphosphate bindingphosphatidylinositol-4-phosphate bindingdefense response to bacteriumBack painosteoarthritis, hipvertebral column disordervertebral disorder
✦AI Summary

GSDMC (gasdermin C) is a pore-forming protein that executes pyroptosis, a programmed necrotic cell death critical for immune defense 1. GSDMC is activated through proteolytic cleavage by caspase-8 in response to death signals 23. Following cleavage, the N-terminal domain translocates to the plasma membrane where it binds phosphoinositide lipids and forms 10-15 nm diameter pores through homooligomerization, triggering pyroptotic cell lysis 42. GSDMC participates in multiple inflammatory pathways: the caspase-8/GSDMC axis operates in both cancer cells and intestinal epithelial cells during inflammation 25. In pancreatic cancer, GSDMC promotes stemness and immune evasion through a pyroptosis-independent mechanism involving ADAM17-mediated cleavage and nuclear translocation 6. In intestinal immunity, cathepsin S-cleaved GSDMC targets Rab7+ vesicles rather than the plasma membrane, modulating lipid metabolism and promoting anti-helminth type 2 responses 7. Dysregulated pyroptosis involving GSDMC contributes to disease pathogenesis in sepsis, atherosclerosis, respiratory disease, and inflammatory bowel disease 185. High GSDMC expression correlates with poor cancer survival, suggesting therapeutic potential for targeting this pathway in cancer and inflammatory diseases.

Sources cited
1
Gasdermin-N domains form pores of 10-14 nm diameter containing 16 symmetric protomers and bind membrane lipids including phosphoinositides
PMID: 27281216
2
GSDMC is cleaved by caspase-8 with TNFα treatment, forms membrane pores, induces pyroptosis in cancer cells, and high GSDMC expression correlates with poor survival
PMID: 32929201
3
GSDMC is activated by inflammasome-independent mechanisms and dysregulated pyroptosis contributes to sepsis, atherosclerosis, ARDS, and neurodegenerative disorders
PMID: 37352727
4
Caspase-8/GSDMC pathway is involved in pyroptosis and plays a role in respiratory diseases
PMID: 35819638
5
Type III interferons induce ZBP1-mediated caspase-8 activation and GSDMC cleavage in intestinal epithelial cells, driving pyroptosis and delaying tissue repair in IBD
PMID: 39500322
6
GSDMC promotes stemness and immune evasion through pyroptosis-independent mechanism via ADAM17 cleavage and nuclear translocation in pancreatic cancer
PMID: 39297408
7
Cathepsin S cleaves GSDMC in intestinal epithelial cells; cleaved GSDMC targets Rab7+ vesicles to modulate lipid metabolism and promote anti-helminth immunity independent of cell death
PMID: 40701157
Disease Associationsⓘ20
Back painOpen Targets
0.49Moderate
osteoarthritis, hipOpen Targets
0.49Moderate
vertebral column disorderOpen Targets
0.46Moderate
vertebral disorderOpen Targets
0.43Moderate
total hip arthroplastyOpen Targets
0.42Moderate
musculoskeletal system diseaseOpen Targets
0.42Moderate
atrial fibrillationOpen Targets
0.41Moderate
prostate carcinomaOpen Targets
0.40Moderate
central nervous system cancerOpen Targets
0.40Moderate
osteoarthritisOpen Targets
0.39Weak
smoking behaviorOpen Targets
0.38Weak
skin agingOpen Targets
0.38Weak
vertebral joint diseaseOpen Targets
0.37Weak
spondylosisOpen Targets
0.36Weak
gliomaOpen Targets
0.34Weak
rheumatic diseaseOpen Targets
0.31Weak
osteoarthritis, kneeOpen Targets
0.30Weak
total joint arthroplastyOpen Targets
0.30Weak
androgenetic alopeciaOpen Targets
0.30Weak
medical procedureOpen Targets
0.30Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GSDMEProtein interaction90%GSDMBProtein interaction85%PJVKProtein interaction84%GSDMAShared pathway68%LEAP2Shared pathway50%EPPINShared pathway33%
Tissue Expression6 tissues
Lung
100%
Heart
68%
Brain
50%
Liver
22%
Ovary
15%
Bone Marrow
6%
Gene Interaction Network
Click a node to explore
GSDMCGSDMEGSDMBPJVKGSDMALEAP2EPPIN
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9BYG8
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.15LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.88 [0.68–1.15]
RankingsWhere GSDMC stands among ~20K protein-coding genes
  • #12,160of 20,598
    Most Researched29
  • #11,986of 17,882
    Most Constrained (LOEUF)1.15
Genes detectedGSDMC
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Pyroptosis-induced inflammation and tissue damage.
PMID: 37352727
Semin Immunol · 2023
1.00
2
Pyroptosis in inflammation-related respiratory disease.
PMID: 35819638
J Physiol Biochem · 2022
0.90
3
PD-L1-mediated gasdermin C expression switches apoptosis to pyroptosis in cancer cells and facilitates tumour necrosis.
PMID: 32929201
Nat Cell Biol · 2020
0.80
4
Type III interferons induce pyroptosis in gut epithelial cells and impair mucosal repair.
PMID: 39500322
Cell · 2024
0.70
5
Pore-forming activity and structural autoinhibition of the gasdermin family.
PMID: 27281216
Nature · 2016
0.60