GSDMD Gene

Name	gasdermin D
Description	Gasdermin D is a member of the gasdermin family. Members of this family appear to play a role in regulation of epithelial proliferation. Gasdermin D has been suggested to act as a tumor suppressor. Alternatively spliced transcript variants have been described. [provided by RefSeq, Oct 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Gasdermin D (GSDMD) has emerged as a central executioner of inflammatory cell death, known as pyroptosis. In response to various danger signals and bacterial infections, inflammatory caspases (including caspase‐1, −4, −5, and −11) are activated and then cleave GSDMD at a specific linker region. This proteolysis liberates the N‐terminal fragment from its autoinhibitory C‐terminal domain, allowing the N‐terminal domain to oligomerize and insert into cellular membranes to form large, nonselective pores."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n The formation of these membrane pores is critical not only for the rapid lytic demise of the cell but also for the unconventional release of proinflammatory cytokines, such as interleukin-1β, from both dying and living cells. In this way, GSDMD-mediated pore formation establishes a direct molecular link between inflammasome activation and the amplification of inflammatory signals."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, studies have shown that GSDMD is essential for executing pyroptosis in macrophages and other immune cells, and its activity can also shape the balance between pyroptotic, apoptotic, and other forms of cell death. This dynamic interplay helps determine the outcome of both antimicrobial defenses and the progression of inflammatory diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Structural and biochemical analyses reveal that the pore-forming N-terminal fragment of GSDMD undergoes dramatic conformational changes to create oligomeric assemblies with defined diameters. These pores disrupt cellular integrity, facilitate cytokine release, and may be modulated by metabolic signals and reactive oxygen species, further underscoring the regulatory complexity of this cell death mechanism."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its fundamental role in host defense and inflammation, aberrant activation or dysregulation of GSDMD-mediated pyroptosis is implicated in a range of pathological conditions, including sepsis, autoimmune disorders, and even tumor progression. For instance, in certain cancers, loss of GSDMD function can shift cell death from pyroptosis to apoptosis, thereby affecting disease outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore GSDMD’s pivotal function as the final executor of pyroptosis—directly linking inflammasome activation to membrane permeabilization, cytokine release, and the regulation of inflammatory cell death in both protective and disease contexts.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jianjin Shi, Yue Zhao, Kun Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature15514"}], "href": "https://doi.org/10.1038/nature15514"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26375003"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26375003"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Nobuhiko Kayagaki, Irma B Stowe, Bettina L Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature15541"}], "href": "https://doi.org/10.1038/nature15541"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26375259"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26375259"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xing Liu, Zhibin Zhang, Jianbin Ruan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature18629"}], "href": "https://doi.org/10.1038/nature18629"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27383986"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27383986"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jianjin Shi, Wenqing Gao, Feng Shao "}, {"type": "b", "children": [{"type": "t", "text": "Pyroptosis: Gasdermin-Mediated Programmed Necrotic Cell Death."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Trends Biochem Sci (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.tibs.2016.10.004"}], "href": "https://doi.org/10.1016/j.tibs.2016.10.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27932073"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27932073"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jingjin Ding, Kun Wang, Wang Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pore-forming activity and structural autoinhibition of the gasdermin family."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature18590"}], "href": "https://doi.org/10.1038/nature18590"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27281216"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27281216"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Wan-ting He, Haoqiang Wan, Lichen Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cr.2015.139"}], "href": "https://doi.org/10.1038/cr.2015.139"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26611636"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26611636"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Lorenzo Sborgi, Sebastian Rühl, Estefania Mulvihill, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embj.201694696"}], "href": "https://doi.org/10.15252/embj.201694696"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27418190"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27418190"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Charles L Evavold, Jianbin Ruan, Yunhao Tan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Pore-Forming Protein Gasdermin D Regulates Interleukin-1 Secretion from Living Macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunity (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.immuni.2017.11.013"}], "href": "https://doi.org/10.1016/j.immuni.2017.11.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29195811"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29195811"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Robin A Aglietti, Alberto Estevez, Aaron Gupta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GsdmD p30 elicited by caspase-11 during pyroptosis forms pores in membranes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1607769113"}], "href": "https://doi.org/10.1073/pnas.1607769113"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27339137"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27339137"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Xin Chen, Wan-Ting He, Lichen Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pyroptosis is driven by non-selective gasdermin-D pore and its morphology is different from MLKL channel-mediated necroptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cr.2016.100"}], "href": "https://doi.org/10.1038/cr.2016.100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27573174"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27573174"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Jianbin Ruan, Shiyu Xia, Xing Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cryo-EM structure of the gasdermin A3 membrane pore."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41586-018-0058-6"}], "href": "https://doi.org/10.1038/s41586-018-0058-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29695864"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29695864"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Fiachra Humphries, Liraz Shmuel-Galia, Natalia Ketelut-Carneiro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Succination inactivates gasdermin D and blocks pyroptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.abb9818"}], "href": "https://doi.org/10.1126/science.abb9818"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32820063"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32820063"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Charles L Evavold, Iva Hafner-Bratkovič, Pascal Devant, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Control of gasdermin D oligomerization and pyroptosis by the Ragulator-Rag-mTORC1 pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2021.06.028"}], "href": "https://doi.org/10.1016/j.cell.2021.06.028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34289345"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34289345"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Jianwei Gao, Xiangyu Qiu, Guangmin Xi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of GSDMD attenuates tumor proliferation via the intrinsic mitochondrial apoptotic pathway and inhibition of EGFR/Akt signaling and predicts a good prognosis in non‑small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2018.6634"}], "href": "https://doi.org/10.3892/or.2018.6634"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30106450"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30106450"}]}]}]}
Synonyms	FKSG10, DF5L, DFNA5L, GSDMDC1
Proteins	GSDMD_HUMAN
NCBI Gene ID	79792
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

GSDMD has 8,225 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 107 datasets.

Click the + buttons to view associations for GSDMD from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

GSDMD Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of GSDMD gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of GSDMD gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of GSDMD gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of GSDMD gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of GSDMD gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of GSDMD gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of GSDMD gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of GSDMD gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of GSDMD gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of GSDMD gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of GSDMD gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of GSDMD gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with GSDMD protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with GSDMD gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of GSDMD gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of GSDMD gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of GSDMD gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing GSDMD protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of GSDMD gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing GSDMD protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with GSDMD protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of GSDMD gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with GSDMD gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with GSDMD gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by GSDMD gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with GSDMD gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with GSDMD gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with GSDMD gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with GSDMD gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with GSDMD gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at GSDMD gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of GSDMD gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of GSDMD gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing GSDMD from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of GSDMD gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with GSDMD gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing GSDMD from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of GSDMD gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of GSDMD gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Kinase Perturbations	kinase perturbations changing expression of GSDMD gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.