GSDMB (gasdermin B)

2011-11-01   Masaru Tamura , Toshihiko Shiroishi 

Mammalian Genetics Laboratory, Genetic Strains Research Center, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka, Japan

Identity

HGNC
LOCATION
17q12
LOCUSID
ALIAS
GSDMB-1,GSDML,PP4052,PRO2521
FUSION GENES

DNA/RNA

Description

GSDMB belongs to the novel gene family Gasdermin (GSDM) that consists of four genes in human: GSDMA, GSDMB, GSDMC and GSDMD (Tamura et al., 2007). The human GSDMB gene is located on chromosome 17q21 and consists of 12 exons, spanning 14 kb of genomic DNA.

Transcription

GSDMB has at least four alternatively spliced transcripts variants that range from 1578 to 1646 bp in length. These splicing variants, which lack exon 6, 7, and both, are named GSDMB transcript variant 1 (Delta exon 6), GSDMB transcript variant 2 (Delta exon 6 and exon 7), GSDMB transcript variant 3 (full length) and GSDMB transcript variant 4 (Delta exon 7). GSDMB has two different promoters, Alu-derived promoter and long-terminal-repeat (LTR)-derived promoter (Sin et al., 2006; Huh et al., 2008; Komiyama et al., 2010). These two promoters drive all GSDMB transcriptions except for those starting from exon1a and exon1b.

Pseudogene

No GSDMB pseudogene has been identified in the human genome.

Proteins

Description

The full length of GSDMB gene (GSDMB transcript variant 3) encodes a 416 amino acid protein with estimated molecular weight of 47345,44 Da. GSDM family proteins have 9 conserved and unknown function motifs (motif I to IX). GSDMB lacks motif VIII where mouse alopecia mutation Rex-denuded occurs (Runkel et al., 2004; Tamura et al., 2007).

Expression

Expression of GSDMB was observed in esophagus and gastric epithelium (Saeki et al., 2009). In addition, GSDMB was frequently expressed in several cancer tissues and cancer-derived cell lines.

Localisation

Cytoplasm (Carl-McGrath et al., 2008).

Function

The function of GSDMB is largely unknown, because GSDMB is a novel protein without characteristic domains related to known function.
Expression level of GSDMB seems to be changed along progression of several cancers. However, forced expression of GSDMB could neither promote malignant transformation of CHO cells nor confer colony formation ability or carcinogenicity to CHO cells in nude mice (Sun et al., 2008). Recent large-scale genome wide association studies (GWAS) revealed that GSDMB locus is strongly correlated with asthma (Moffatt et al., 2010).

Homology

GSDMB protein shares homology with other GSDM family members for N- and C- terminal sequences. Its N-terminal sequence is also shared by DFNA5 (deafness, autosomal dominant 5) and DFNB59 (deafness, autosomal recessive 59, also known as pejvakin), although the extent of similarity to these proteins is lower than to the other GSDM family members.
GSDMB ortholog is identified in the chimpanzee, dog and cow, but not in the rat and mouse (Katoh and Katoh, 2004; Tamura et al., 2007).

Mutations

Note

No human GSDMB mutations have been reported to date.

Germinal

Not known.

Somatic

Not known.

Implicated in

Entity name
Various cancers
Note
GSDMB is up-regulated in several cancers, such as gastric, colorectal, hepatic, cervical carcinomas, suggesting the possibility that it is used as a marker for cancer development and progression.
Entity name
Asthma
Note
The genome wide association study (GWAS) demonstrated that GSDMB locus is strongly associated with asthma (Moffatt et al., 2010).

Bibliography

Pubmed IDLast YearTitleAuthors
180383102008Differential expression and localisation of gasdermin-like (GSDML), a novel member of the cancer-associated GSDMDC protein family, in neoplastic and non-neoplastic gastric, hepatic, and colon tissues.Carl-McGrath S et al
184781802008Transcriptional regulation of GSDML gene by antisense-oriented HERV-H LTR element.Huh JW et al
150108122004Evolutionary recombination hotspot around GSDML-GSDM locus is closely linked to the oncogenomic recombination hotspot around the PPP1R1B-ERBB2-GRB7 amplicon.Katoh M et al
204106672010Alu-derived cis-element regulates tumorigenesis-dependent gastric expression of GASDERMIN B (GSDMB).Komiyama H et al
208605032010A large-scale, consortium-based genomewide association study of asthma.Moffatt MF et al
154752612004The dominant alopecia phenotypes Bareskin, Rex-denuded, and Reduced Coat 2 are caused by mutations in gasdermin 3.Runkel F et al
190513102009Distinctive expression and function of four GSDM family genes (GSDMA-D) in normal and malignant upper gastrointestinal epithelium.Saeki N et al
166253202006Transcriptional control of the HERV-H LTR element of the GSDML gene in human tissues and cancer cells.Sin HS et al
186334572008Expression of GSDML Associates with Tumor Progression in Uterine Cervix Cancer.Sun Q 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: 55876
MIM: 611221
HGNC: 23690
Ensembl: ENSG00000073605

Variants:

dbSNP: 55876
ClinVar: 55876
TCGA: ENSG00000073605
COSMIC: GSDMB

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000073605ENST00000309481Q8TAX9
ENSG00000073605ENST00000360317Q8TAX9
ENSG00000073605ENST00000394175Q8TAX9
ENSG00000073605ENST00000394179Q8TAX9
ENSG00000073605ENST00000418519Q8TAX9
ENSG00000073605ENST00000468820J3QLF0
ENSG00000073605ENST00000520542Q8TAX9
ENSG00000073605ENST00000522564B2CM73
ENSG00000073605ENST00000523371B2CM72
ENSG00000073605ENST00000524039B2CM71

Expression (GTEx)

0
10
20
30
40
50
60
70
80

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA443450AsthmaDiseaseLiterature, MultilinkAnnotationassociated24934276

References

Pubmed IDYearTitleCitations
208605032010A large-scale, consortium-based genomewide association study of asthma.610
197328642009Allele-specific chromatin remodeling in the ZPBP2/GSDMB/ORMDL3 locus associated with the risk of asthma and autoimmune disease.110
197328642009Allele-specific chromatin remodeling in the ZPBP2/GSDMB/ORMDL3 locus associated with the risk of asthma and autoimmune disease.110
190290002009Chromosome 17q21 gene variants are associated with asthma and exacerbations but not atopy in early childhood.53
190682162009Investigation of Crohn's disease risk loci in ulcerative colitis further defines their molecular relationship.53
206016762010Analysis of SNPs with an effect on gene expression identifies UBE2L3 and BCL3 as potential new risk genes for Crohn's disease.50
208161952010Analyses of shared genetic factors between asthma and obesity in children.43
191339212009Genetic variation in ORM1-like 3 (ORMDL3) and gasdermin-like (GSDML) and childhood asthma.41
191339212009Genetic variation in ORM1-like 3 (ORMDL3) and gasdermin-like (GSDML) and childhood asthma.41
190513102009Distinctive expression and function of four GSDM family genes (GSDMA-D) in normal and malignant upper gastrointestinal epithelium.40

Citation

Masaru Tamura ; Toshihiko Shiroishi

GSDMB (gasdermin B)

Atlas Genet Cytogenet Oncol Haematol. 2011-11-01

Online version: http://atlasgeneticsoncology.org/gene/43972/gsdmb