GSDMD

gasdermin D, the group of Gasdermins

Basic information

Region (hg38): 8:143553206-143563062

Previous symbols: [ "GSDMDC1" ]

Links

ENSG00000104518 ∙ NCBI:79792 ∙ OMIM:617042 ∙ HGNC:25697 ∙ Uniprot:P57764 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GSDMD gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GSDMD gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4	1	5
missense			30	4	4	38
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	30	8	6

Variants in GSDMD

This is a list of pathogenic ClinVar variants found in the GSDMD region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-143559344-G-T			Benign (Apr 04, 2018)
8-143559354-C-A			Likely benign (Jun 01, 2022)
8-143559489-C-T		not specified	Uncertain significance (Mar 31, 2023)
8-143559508-A-G		not specified	Uncertain significance (Dec 08, 2023)
8-143559541-C-G		not specified	Uncertain significance (Feb 27, 2023)
8-143559786-G-A		not specified	Uncertain significance (Oct 25, 2023)
8-143559851-G-A		not specified	Uncertain significance (Sep 26, 2023)
8-143559924-C-T		not specified	Uncertain significance (Jan 16, 2024)
8-143559981-G-GAGGGC		not specified	Benign (Mar 28, 2016)
8-143560611-G-A		not specified	Likely benign (Oct 02, 2023)
8-143560611-G-T		not specified	Uncertain significance (Jan 10, 2022)
8-143560724-C-T		not specified	Uncertain significance (May 17, 2023)
8-143560725-G-A		not specified	Likely benign (Oct 17, 2023)
8-143560761-C-A		not specified	Uncertain significance (Jun 07, 2023)
8-143561057-G-T		not specified	Uncertain significance (Dec 18, 2023)
8-143561071-C-T		not specified	Uncertain significance (Jul 19, 2022)
8-143561101-T-G		not specified	Uncertain significance (May 09, 2023)
8-143561391-A-C		not specified	Uncertain significance (Dec 06, 2021)
8-143561418-C-T		not specified	Uncertain significance (Dec 19, 2022)
8-143561751-G-A			Benign (Jul 31, 2018)
8-143561757-C-T		not specified	Uncertain significance (May 27, 2022)
8-143561758-G-A			Likely benign (Jun 01, 2022)
8-143561762-G-A		not specified	Uncertain significance (Jun 21, 2021)
8-143561768-G-A		not specified	Uncertain significance (Jul 21, 2021)
8-143561784-C-T		not specified	Uncertain significance (Jun 17, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GSDMD	protein_coding	protein_coding	ENST00000526406	10	9856

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.08e-13	0.0221	125454	0	32	125486	0.000128

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.599	261	290	0.901	0.0000180	3039
Missense in Polyphen		74	89.647	0.82546		1062
Synonymous	-0.144	138	136	1.02	0.00000925	1009
Loss of Function	0.0190	20	20.1	0.995	9.41e-7	224

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000149	0.000149
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000552	0.0000544
Finnish	0.000125	0.0000924
European (Non-Finnish)	0.000124	0.000106
Middle Eastern	0.0000552	0.0000544
South Asian	0.000330	0.000327
Other	0.000492	0.000490

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Gasdermin-D, N-terminal: Promotes pyroptosis in response to microbial infection and danger signals. Produced by the cleavage of gasdermin-D by inflammatory caspases CASP1 or CASP4 in response to canonical, as well as non-canonical (such as cytosolic LPS) inflammasome activators (PubMed:26375003, PubMed:26375259, PubMed:27418190). After cleavage, moves to the plasma membrane where it strongly binds to inner leaflet lipids, including monophosphorylated phosphatidylinositols, such as phosphatidylinositol 4-phosphate, bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)- bisphosphate, as well as phosphatidylinositol (3,4,5)- bisphosphate, and more weakly to phosphatidic acid and phosphatidylserine (PubMed:27281216). Homooligomerizes within the membrane and forms pores of 10 - 15 nanometers (nm) of inner diameter, possibly allowing the release of mature IL1B and triggering pyroptosis (PubMed:27418190, PubMed:27281216). Exhibits bactericidal activity. Gasdermin-D, N-terminal released from pyroptotic cells into the extracellular milieu rapidly binds to and kills both Gram-negative and Gram-positive bacteria, without harming neighboring mammalian cells, as it does not disrupt the plasma membrane from the outside due to lipid-binding specificity (PubMed:27281216). Under cell culture conditions, also active against intracellular bacteria, such as Listeria monocytogenes (By similarity). Strongly binds to bacterial and mitochondrial lipids, including cardiolipin. Does not bind to unphosphorylated phosphatidylinositol, phosphatidylethanolamine nor phosphatidylcholine (PubMed:27281216). {ECO:0000250|UniProtKB:Q9D8T2, ECO:0000269|PubMed:26375003, ECO:0000269|PubMed:26375259, ECO:0000269|PubMed:27281216, ECO:0000269|PubMed:27418190}.
• Pathway: NOD-like receptor signaling pathway - Homo sapiens (human);Neutrophil degranulation;Innate Immune System;Immune System (Consensus)

Recessive Scores

• pRec: 0.0912

Intolerance Scores

• loftool: 0.839
• rvis_EVS: -0.09
• rvis_percentile_EVS: 47.12

Haploinsufficiency Scores

• pHI: 0.0655
• hipred: N
• hipred_score: 0.146
• ghis: 0.460

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.475

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gsdmd
• Phenotype: digestive/alimentary phenotype; immune system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; hematopoietic system phenotype; cellular phenotype

Gene ontology

• Biological process: inflammatory response;cytolysis;cellular response to extracellular stimulus;pore formation in membrane of other organism;neutrophil degranulation;innate immune response;pore complex assembly;positive regulation of interleukin-1 beta secretion;defense response to Gram-negative bacterium;defense response to Gram-positive bacterium;protein homooligomerization;pyroptosis
• Cellular component: extracellular region;extracellular space;nucleoplasm;cytosol;plasma membrane;specific granule lumen;NLRP3 inflammasome complex;tertiary granule lumen;ficolin-1-rich granule lumen
• Molecular function: phosphatidylserine binding;protein binding;phosphatidylinositol-4,5-bisphosphate binding;phosphatidylinositol-4-phosphate binding;phosphatidic acid binding;cardiolipin binding