Gasdermins (GSDM)

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Gasdermins (GSDM)

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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There are six human genes that encode gasdermin family proteins. The proteins typically contain a N-terminal pore-forming domain (PFD) and a C-terminal repressor domain (RD) [2]. Gasdermins are cleaved by caspases to free the PFD which polymerises to create the large cell membrane pores which cause pyroptosis. As examples, gasdermins D and E are cleaved by caspase-1 and caspase-3 respectively.

Targets

3278

gasdermin D Show summary »« Hide summary

Target Id

3278

Nomenclature

gasdermin D

Genes

GSDMD (Hs), Gsdmd (Mm), Gsdmd (Rn)

Ensembl ID

ENSG00000104518 (Hs), ENSMUSG00000022575 (Mm), ENSRNOG00000007728 (Rn)

UniProtKB AC

P57764 (Hs), Q3TBD9 (Mm)

Inhibitors

disulfiram pIC₅₀ 6.4 [5] - Mouse

LDC7559 [5]

Comment

Gasdermin D is a component of inflammasomes and it is required for the secretion of IL-1β (type I interferon response) and for triggering pyroptosis [1,3]. It is cleaved by caspase-1, releasing its pore-forming domain (PFD) which acts as the pyroptosis effector. The SARS-CoV-2 nucleocapsid (N) phosphoprotein has been shown to suppress infection-induced pyroptosis through direct association with host gasdermin D [4]. All components of the NLRP3/caspase-1/GSDMD signalling pathway are targets for the development of drugs with anti-inflammatory potential.

References

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1. He WT, Wan H, Hu L, Chen P, Wang X, Huang Z, Yang ZH, Zhong CQ, Han J. (2015) Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion. Cell Res, 25 (12): 1285-98. [PMID:26611636]

2. Kovacs SB, Miao EA. (2017) Gasdermins: Effectors of Pyroptosis. Trends Cell Biol, 27 (9): 673-684. [PMID:28619472]

3. Liu X, Zhang Z, Ruan J, Pan Y, Magupalli VG, Wu H, Lieberman J. (2016) Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature, 535 (7610): 153-8. [PMID:27383986]

4. Ma J, Zhu F, Zhao M, Shao F, Yu D, Ma J, Zhang X, Li W, Qian Y, Zhang Y et al.. (2021) SARS-CoV-2 nucleocapsid suppresses host pyroptosis by blocking Gasdermin D cleavage. EMBO J, 40 (18): e108249. [PMID:34296442]

5. Pandeya A, Li L, Li Z, Wei Y. (2019) Gasdermin D (GSDMD) as a new target for the treatment of infection. Medchemcomm, 10 (5): 660-667. [PMID:31191857]

How to cite this family page

Database page citation:

Gasdermins (GSDM). Accessed on 26/03/2025. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1097.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Buneman OP, Faccenda E, Harding SD, Spedding M, Cidlowski JA, Fabbro D, Davenport AP, Striessnig J, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Introduction and Other Protein Targets. Br J Pharmacol. 180 Suppl 2:S1-22.