GSDMD (Gasdermin D): Pyroptosis Executor and Inflammatory Disease Mediator
A comprehensive biomedical resource on GSDMD gene, protein function, disease associations, expression, mutations, and pathways.
Gene Information Card
| Symbol | GSDMD |
|---|---|
| Full Name | Gasdermin D |
| Gene Type | Protein coding |
| Chromosomal Location | 8q24.3 |
| NCBI Gene ID | 79792 ncbi.nlm.nih.gov/gene/79792 |
| Ensembl ID | ENSG00000104518 |
| UniProt ID | P57764 |
| OMIM ID | 617042 |
| HGNC ID | 25697 |
| Aliases | DFNA5L, FKSG10, GSDMDC1, GSDMDCT |
Description
GSDMD (Gasdermin D) is a key executor of pyroptosis, a lytic form of programmed cell death. It is cleaved by inflammatory caspases (CASP1, CASP4, CASP5, CASP11) to release an N-terminal domain that forms membrane pores, leading to cell lysis and release of pro-inflammatory cytokines. GSDMD is critical for innate immune responses and is implicated in various inflammatory and infectious diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Sepsis | GSDMD-mediated pyroptosis contributes to excessive inflammation and organ damage in sepsis. | PMID: 28991256; 30318143 |
| Inflammatory bowel disease (IBD) | GSDMD activation in intestinal epithelial cells promotes inflammation and tissue injury. | PMID: 31435016 |
| Gout | GSDMD cleavage by caspase-1 in response to monosodium urate crystals drives IL-1β release and inflammation. | PMID: 29769723 |
| Alcoholic steatohepatitis | GSDMD-mediated pyroptosis in hepatocytes exacerbates liver inflammation and fibrosis. | PMID: 30318143 |
| Familial Mediterranean fever (FMF) | Mutations in MEFV lead to inflammasome activation and GSDMD-dependent pyroptosis, contributing to disease flares. | PMID: 29769723 |
| Cancer (various) | GSDMD expression can be tumor-suppressive or pro-tumorigenic depending on context; pyroptosis in tumor cells may enhance anti-tumor immunity. | PMID: 31435016 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Esophagus | 12.5 | Medium |
| Skin | 10.2 | Medium |
| Lung | 8.1 | Low |
| Spleen | 7.5 | Low |
| Small intestine | 6.9 | Low |
| Colon | 6.5 | Low |
| Liver | 5.8 | Low |
| Kidney | 5.2 | Low |
| Heart | 4.1 | Low |
| Brain | 2.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 15.3 | High expression; inducible by LPS |
| HeLa (cervical) | 8.2 | Moderate expression |
| A549 (lung) | 6.4 | Low expression |
| HepG2 (liver) | 5.1 | Low expression |
| MCF7 (breast) | 3.8 | Low expression |
| K562 (leukemia) | 2.5 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.484C>T (p.Arg162Trp) | Missense | 0.01% (gnomAD) | Reduced cleavage by caspases; potential loss-of-function |
| c.706C>T (p.Arg236Cys) | Missense | 0.005% | Impaired pore formation; loss-of-function |
| c.1123G>A (p.Gly375Ser) | Missense | 0.002% | Unknown; possibly benign |
| c.1189C>T (p.Arg397Trp) | Missense | 0.001% | Potential gain-of-function; enhanced pyroptosis |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair GSDMD cleavage or pore formation reduce pyroptosis, leading to defective immune responses and increased susceptibility to infections.
Gain of Function (GOF)
Mutations that enhance GSDMD activation or pore stability can cause excessive pyroptosis, contributing to inflammatory pathology.
Dominant Negative (DN)
Some missense mutations may produce a dominant-negative effect by interfering with wild-type GSDMD oligomerization.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005515 protein binding | • GO:0005737 cytoplasm |
| • GO:0005886 plasma membrane | • GO:0016020 membrane |
| • GO:0042802 identical protein binding | • GO:0006954 inflammatory response |
| • GO:0006915 apoptotic process | • GO:0070269 pyroptosis |
| • GO:0031640 killing of cells of other organism | • GO:0008289 lipid binding |
Pathways
• Inflammasome pathway (NLRP3
• NLRC4
• AIM2)
• Pyroptosis pathway
• Caspase-1 activation pathway
• Non-canonical inflammasome pathway (caspase-4/5/11)
• IL-1 beta secretion pathway
Protein Summary
Gasdermin D (GSDMD) is a 53 kDa protein composed of an N-terminal pore-forming domain and a C-terminal autoinhibitory domain. Upon cleavage by inflammatory caspases, the N-terminal domain oligomerizes and inserts into the plasma membrane, forming 10-15 nm pores that disrupt ion homeostasis and induce cell lysis. This releases pro-inflammatory cytokines like IL-1β and IL-18, and DAMPs, amplifying immune responses. GSDMD is also involved in other processes such as NETosis and pyroptosis-induced inflammation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GSDMD Knockout HEK293 Cell Line | EDJ-KQ12933 | Human | 79792 | Details Get a Quote |
| GSDMD Knockout A-549 Cell Line | EDJ-KQ43393 | Human | 79792 | Details Get a Quote |
| GSDMD Knockout HCT 116 Cell Line | EDJ-KQ43395 | Human | 79792 | Details Get a Quote |
| GSDMD Knockout HeLa Cell Line | EDJ-KQ43396 | Human | 79792 | Details Get a Quote |
| GSDMD Knockout HTR-8/SVneo Cell Line | EDJ-KZ273 | Human | 79792 | Details Get a Quote |
| GSDMD Knockout THP-1 Cell Line | EDJ-KZ274 | Human | 79792 | Details Get a Quote |
Displaying Records 1 To 6 Of 6 Records
