GSDMB

protein-coding

gasdermin B, the group of Gasdermins

Gene summary

This gene encodes a member of the gasdermin-domain containing protein family. Other gasdermin-family genes are implicated in the regulation of apoptosis in epithelial cells, and are linked to cancer. Alternative splicing and the use of alternative promoters results in multiple transcript variants. Additional variants have been described, but they are candidates for nonsense-mediated mRNA decay (NMD) and are unlikely to be protein-coding. [provided by RefSeq, Nov 2016]

Previous symbols:

GSDML

MANE transcript

NM_001165958.2

Inheritance

—

ClinVar variants

U:49B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr17:39,904,595-39,919,854

External References & Databases

Ensembl (ENSG00000073605)

Transcript & Mutation Effects

hg38 • Region Span ~15.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GSDMB variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 49

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001165958.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	3 clinvar	1 clinvar	5
missense			45 clinvar	6 clinvar		51
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	49	9	1	59

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001165958.2	RefSeq	NP_001159430.1	10	MANE Select
ENST00000418519.6	Ensembl	ENSP00000415049.1	10	MANE Select
NM_001042471.2	RefSeq	NP_001035936.1	9	Standard
NM_001165959.2	RefSeq	NP_001159431.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

biological_process
pyroptosis

Molecular Function

phosphatidylserine binding
molecular_function
phosphatidylinositol-4,5-bisphosphate binding
phosphatidylinositol-4-phosphate binding

Cellular Component

cellular_component
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000418519
Coding exons: 10
Length: 15260
Individuals with no LoFs: 125653
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125659
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.175	221	228	0.967	0.0000122	2721
Missense (PolyPhen)		48	45.446	1.0562		631
Synonymous	0.109	91	92.3	0.986	0.00000509	802
Loss of Function	1.39	13	19.6	0.663	9.79e-7	244

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000030	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: The N-terminal moiety promotes pyroptosis. May be acting by homooligomerizing within the membrane and forming pores (PubMed:27281216). The physiological relevance of this observation is unknown (Probable). {ECO:0000269|PubMed:27281216, ECO:0000305}.;

Recessive Scores

pRec: 0.0472

Intolerance Scores

LoFtool: 0.993
RVIS EVS: 1.18
RVIS percentile EVS: 92.75

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.00390

Gene Damage Prediction

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