GSDMD gasdermin D [Homo sapiens (human)] - Gene

Summary

Official Symbol: GSDMDprovided by HGNC
Official Full Name: gasdermin Dprovided by HGNC
Primary source: HGNC:HGNC:25697
See related: Ensembl:ENSG00000104518 MIM:617042
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DF5L; DFNA5L; FKSG10; GSDMDC1
Summary: 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]
Expression: Ubiquitous expression in spleen (RPKM 35.6), duodenum (RPKM 18.8) and 24 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 8q24.3

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
109.20190607	current	GRCh38.p13 (GCF_000001405.39)	8	NC_000008.11 (143553387..143563062)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (144635383..144645232)

Chromosome 8 - NC_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

findings suggest that NLRP3 is central to the activation/release of active caspase-1/GSDM-D encapsulated in microparticles (MP) by Francisella.
Title: Francisella induced microparticulate caspase-1/gasdermin-D activation is regulated by NLRP3 independent of Pyrin.
GSDMD is proteolytically activated by neutrophil proteases and, in turn, affects protease activation and nuclear expansion in a feed-forward loop. In addition to the central role of GSDMD in pyroptosis, we propose that GSDMD also plays an essential function in NETosis.
Title: Gasdermin D plays a vital role in the generation of neutrophil extracellular traps.
GSDMD regulates the release of microparticulate active caspase 1 from monocytes essential for induction of cell death and thereby may play a critical role in sepsis-induced endothelial cell injury.
Title: Microparticulate Caspase 1 Regulates Gasdermin D and Pulmonary Vascular Endothelial Cell Injury.
Once inserted, the N-terminal domain of GSDMD assembles arc-, slit-, and ring-shaped oligomers, each of which being able to form transmembrane pores. This assembly and pore formation process is independent on whether GSDMD has been cleaved by caspase-1, caspase-4, or caspase-5.
Title: Mechanism of membrane pore formation by human gasdermin-D.
Study reports the crystal structure of GSDMD C-terminal domain. Two interaction sites mediate the association of C and N domains. Mutations of GSDMD C-domain residues predicted to locate at its interface with the N-domain enhanced pyroptosis. Results suggest that GSDMDs may employ a distinct mode of intramolecular domain interaction and autoinhibition, which may be relevant to its unique role in pyroptosis.
Title: Structures of the Gasdermin D C-Terminal Domains Reveal Mechanisms of Autoinhibition.
lncRNA RP185F18.6 and DeltaNp63 may be considered unfavorable biomarkers, whereas GSDMD may be a favorable biomarker in colorectal cancer (CRC) ; these markers may prove valuable in the future diagnosis and prognosis of CRC
Title: Biological functions and clinical significance of the newly identified long non‑coding RNA RP1‑85F18.6 in colorectal cancer.
High GSDMD expression is associated with tumor-node-metastasis in nonsmall cell lung cancer.
Title: 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.
the gasdermin-D pore: Executor of pyroptotic cell death
Title: The gasdermin-D pore: Executor of pyroptotic cell death.
Results implicate pyroptosis induced by the CASP11/4-GSDMD pathway in the pathogenesis of alcoholic hepatitis
Title: Pyroptosis by caspase11/4-gasdermin-D pathway in alcoholic hepatitis in mice and patients.
The present study not only contributes to our understanding of GSDMD recognition by inflammatory caspases but also reports a specific inhibitor for these caspases that can serve as a tool for investigating inflammasome signaling.
Title: Mechanism of gasdermin D recognition by inflammatory caspases and their inhibition by a gasdermin D-derived peptide inhibitor.

Submit: New GeneRIF Correction See all GeneRIFs (24)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

Go to the top of the page Help

Immune System, organism-specific biosystem (from REACTOME)
Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
Innate Immune System, organism-specific biosystem (from REACTOME)
Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
NOD-like receptor signaling pathway, organism-specific biosystem (from KEGG)
NOD-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting various pathogens and generating innate immune responses. The intracellular NOD-like receptor (NLR) family contains mo...
NOD-like receptor signaling pathway, conserved biosystem (from KEGG)
NOD-like receptor signaling pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting various pathogens and generating innate immune responses. The intracellular NOD-like receptor (NLR) family contains mo...
Neutrophil degranulation, organism-specific biosystem (from REACTOME)
Neutrophil degranulation, organism-specific biosystemNeutrophils are the most abundant leukocytes (white blood cells), indispensable in defending the body against invading microorganisms. In response to infection, neutrophils leave the circulation and ...

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

WI-8705 (e-PCR)
- UniSTS:53282

D8S2072 (e-PCR)
- UniSTS:28381

Homology

Homologs of the GSDMD gene: The GSDMD gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, and rat.
Orthologs from Annotation Pipeline: 122 organisms have orthologs with human gene GSDMD
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
cardiolipin binding	ISS Inferred from Sequence or Structural Similarity more info
phosphatidic acid binding	ISS Inferred from Sequence or Structural Similarity more info
phosphatidylinositol-4,5-bisphosphate binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
phosphatidylinositol-4,5-bisphosphate binding	ISS Inferred from Sequence or Structural Similarity more info
phosphatidylinositol-4-phosphate binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
phosphatidylinositol-4-phosphate binding	ISS Inferred from Sequence or Structural Similarity more info
phosphatidylserine binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
phosphatidylserine binding	ISS Inferred from Sequence or Structural Similarity more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
cellular response to extracellular stimulus	IEA Inferred from Electronic Annotation more info
cytolysis	ISS Inferred from Sequence or Structural Similarity more info
defense response to Gram-negative bacterium	ISS Inferred from Sequence or Structural Similarity more info
defense response to Gram-positive bacterium	ISS Inferred from Sequence or Structural Similarity more info
inflammatory response	IEA Inferred from Electronic Annotation more info
innate immune response	IEA Inferred from Electronic Annotation more info
neutrophil degranulation	TAS Traceable Author Statement more info
pore complex assembly	ISS Inferred from Sequence or Structural Similarity more info
pore formation in membrane of other organism	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of interleukin-1 beta secretion	ISS Inferred from Sequence or Structural Similarity more info
protein homooligomerization	ISS Inferred from Sequence or Structural Similarity more info
pyroptosis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
pyroptosis	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
NLRP3 inflammasome complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
NLRP3 inflammasome complex	ISS Inferred from Sequence or Structural Similarity more info
cytosol	ISS Inferred from Sequence or Structural Similarity more info
extracellular region	TAS Traceable Author Statement more info
extracellular space	ISS Inferred from Sequence or Structural Similarity more info
ficolin-1-rich granule lumen	TAS Traceable Author Statement more info
nucleoplasm	IDA Inferred from Direct Assay more info
plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
specific granule lumen	TAS Traceable Author Statement more info
tertiary granule lumen	TAS Traceable Author Statement more info

General protein information

Go to the top of the page Help

Preferred Names: gasdermin-D

Names: gasdermin domain containing 1; gasdermin domain-containing protein 1

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001166237.1 → NP_001159709.1 gasdermin-D

See identical proteins and their annotated locations for NP_001159709.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same protein.

Source sequence(s)

AK291817, BC008904, BC069000

Consensus CDS

CCDS34956.1

UniProtKB/Swiss-Prot

P57764

Related

ENSP00000433209.1, ENST00000526406.5

Conserved Domains (1) summary

pfam04598
Location:4 → 456

Gasdermin; Gasdermin family
NM_024736.7 → NP_079012.3 gasdermin-D

See identical proteins and their annotated locations for NP_079012.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the shorter transcript. Both variants 1 and 2 encode the same protein.

Source sequence(s)

BC008904, BC069000

Consensus CDS

CCDS34956.1

UniProtKB/Swiss-Prot

P57764

Related

ENSP00000262580.4, ENST00000262580.9

Conserved Domains (1) summary

pfam04598
Location:4 → 456

Gasdermin; Gasdermin family