GSDMA (gasdermin A)

2010-11-01   Norihisa Saeki , Hiroki Sasaki 

Genetics Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan

Identity

HGNC
LOCATION
17q21.1
LOCUSID
ALIAS
FKSG9,GSDM,GSDM1
FUSION GENES

DNA/RNA

Atlas Image
Genomic organization of the GSDMA gene.

Description

12 exons, spans approximately 13 kb of genomic DNA in the centromere-to-telomere orientation. The translation initiation codon is located to exon 2, and the stop codon to exon 12.

Transcription

mRNA of approximately 1.5 kb.

Pseudogene

Not reported.

Proteins

Atlas Image
GSDMA is involved in TGF-beta signaling which regulates apoptosis induction in pit cells of the gastric epithelium. Signaling from TGF-beta receptor up-regulates LMO1, a transcription factor. LMO1 binds to the promoter of GSDMA gene and enhances its expression, that results in the apoptosis induction in the pit cells.

Description

The GSDMA gene encodes a 445 amino acid protein with estimated molecular weight of 49377.95 Da. The Gasdermin family proteins have 9 conserved motifs but no known functional motif.

Expression

GSDMA protein is expressed in pit cells of the gastric epithelium, where it is involved in maintenance of homeostasis by its apoptosis induction ability under TGF-beta signaling. Its expression was also observed in epithelial cells of the esophagus, skin and mammary gland.

Localisation

Cytoplasm.

Function

Apoptosis induction, but detail is unknown.

Homology

Human genome possesses its three paralogues, GSDMB, GSDMC and GSDMD. Both N- and C-terminal amino acids are conserved among them.

Mutations

Germinal

Not reported.

Somatic

Not reported.

Implicated in

Entity name
Gastric cancer
Note
GSDMA gene is frequently silenced in gastric adenocarcinoma (16 in 18 cases examined including both diffuse and intestinal types), whose relation to prognosis is unknown.
Entity name
Esophageal cancer
Note
GSDMA gene is frequently silenced in esophageal squamous cell carcinoma (41 in 42 cases examined).

Bibliography

Pubmed IDLast YearTitleAuthors
157372032005Mutations in gasdermin 3 cause aberrant differentiation of the hair follicle and sebaceous gland.Lunny DP et al
174712402007GASDERMIN, suppressed frequently in gastric cancer, is a target of LMO1 in TGF-beta-dependent apoptotic signalling.Saeki N et al
109671282000Gasdermin (Gsdm) localizing to mouse Chromosome 11 is predominantly expressed in upper gastrointestinal tract but significantly suppressed in human gastric cancer cells.Saeki N et al
190513102009Distinctive expression and function of four GSDM family genes (GSDMA-D) in normal and malignant upper gastrointestinal epithelium.Saeki N et al
173507982007Members of a novel gene family, Gsdm, are expressed exclusively in the epithelium of the skin and gastrointestinal tract in a highly tissue-specific manner.Tamura M et al

Other Information

Locus ID:

NCBI: 284110
MIM: 611218
HGNC: 13311
Ensembl: ENSG00000167914

Variants:

dbSNP: 284110
ClinVar: 284110
TCGA: ENSG00000167914
COSMIC: GSDMA

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000167914ENST00000301659Q96QA5
ENSG00000167914ENST00000577447J3KRG2
ENSG00000167914ENST00000635792Q96QA5

Expression (GTEx)

0
10
20
30
40
50
60
70
80
90

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
220379032012Genetic variants associated with the white blood cell count in 13,923 subjects in the eMERGE Network.68
190513102009Distinctive expression and function of four GSDM family genes (GSDMA-D) in normal and malignant upper gastrointestinal epithelium.40
215460692011Asthma-associated polymorphisms in 17q21 influence cord blood ORMDL3 and GSDMA gene expression and IL-17 secretion.33
174712402007GASDERMIN, suppressed frequently in gastric cancer, is a target of LMO1 in TGF-beta-dependent apoptotic signalling.22
150108122004Evolutionary recombination hotspot around GSDML-GSDM locus is closely linked to the oncogenomic recombination hotspot around the PPP1R1B-ERBB2-GRB7 amplicon.16
213377302011Polymorphisms in GSDMA and GSDMB are associated with asthma susceptibility, atopy and BHR.15
283147532017Transethnic meta-analysis identifies GSDMA and PRDM1 as susceptibility genes to systemic sclerosis.8
264843542015Gene Expression-Genotype Analysis Implicates GSDMA, GSDMB, and LRRC3C as Contributors to Inflammatory Bowel Disease Susceptibility.7
266719132016Local genotype influences DNA methylation at two asthma-associated regions, 5q31 and 17q21, in a founder effect population.3
268862402016Association Between Gasdermin A and Gasdermin B Polymorphisms and Susceptibility to Adult and Childhood Asthma Among Jordanians.3

Citation

Norihisa Saeki ; Hiroki Sasaki

GSDMA (gasdermin A)

Atlas Genet Cytogenet Oncol Haematol. 2010-11-01

Online version: http://atlasgeneticsoncology.org/gene/45650/gsdma-(gasdermin-a)