GSDME (gasdermin E)

Gene

• Entrez ID: 1687
• Gene name: Gasdermin E
• Gene symbol: GSDME
• Synonyms (NCBI Gene): DFNA5, ICERE-1
• Chromosome: 7
• Chromosome location: 7p15.3
• Summary: Hearing impairment is a heterogeneous condition with over 40 loci described. The protein encoded by this gene is expressed in fetal cochlea, however, its function is not known. Nonsyndromic hearing impairment is associated with a mutation in this gene. Th

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs138980048	G>A,C	Likely-benign, uncertain-significance, conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs149956122	T>C	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs200758965	G>A	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Coding sequence variant, stop gained
rs374353052	TCA>-	Likely-pathogenic, likely-benign, uncertain-significance	Inframe deletion, coding sequence variant
rs727505273	AAG>-	Pathogenic	Intron variant
rs1554322596	C>T	Likely-pathogenic	Splice donor variant
rs1562687295	T>C	Pathogenic	Intron variant
rs1562687726	G>C	Pathogenic	Intron variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002839	Process	Positive regulation of immune response to tumor cell	IDA	32188940
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005546	Function	Phosphatidylinositol-4,5-bisphosphate binding	IDA	28459430
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA	28459430
GO:0005886	Component	Plasma membrane	IEA
GO:0007605	Process	Sensory perception of sound	TAS	9771715
GO:0008285	Process	Negative regulation of cell population proliferation	IDA	18223688
GO:0012501	Process	Programmed cell death	IEA
GO:0012501	Process	Programmed cell death	IMP	26236191
GO:0016020	Component	Membrane	IDA	28459430
GO:0016020	Component	Membrane	IDA	28045099
GO:0016020	Component	Membrane	IEA
GO:0022829	Function	Wide pore channel activity	IDA	28459430, 32188940, 33852854, 35594856
GO:0042491	Process	Inner ear auditory receptor cell differentiation	IEA
GO:0043410	Process	Positive regulation of MAPK cascade	IMP	26236191
GO:0055085	Process	Transmembrane transport	IEA
GO:0070269	Process	Pyroptotic inflammatory response	IDA	28459430, 31953257, 32188940, 33852854, 35594856
GO:0070269	Process	Pyroptotic inflammatory response	IEA
GO:0071356	Process	Cellular response to tumor necrosis factor	IDA	28459430
GO:0098586	Process	Cellular response to virus	IDA	28045099
GO:0098586	Process	Cellular response to virus	IEA
GO:0140507	Process	Granzyme-mediated programmed cell death signaling pathway	IDA	31953257, 32188940
GO:0141201	Process	Pyroptotic cell death	IDA	37198476, 38614101
GO:0141201	Process	Pyroptotic cell death	IDA	32188940, 33852854, 35594856
GO:1901612	Function	Cardiolipin binding	IDA	28459430
GO:1901612	Function	Cardiolipin binding	IEA
GO:2001244	Process	Positive regulation of intrinsic apoptotic signaling pathway	IDA	21522185

Other IDs

• MIM: 608798
• HGNC: 2810
• e!Ensembl: ENSG00000105928

Protein

• UniProt ID: O60443
• Protein name: Gasdermin-E (Inversely correlated with estrogen receptor expression 1) (ICERE-1) (Non-syndromic hearing impairment protein 5) [Cleaved into: Gasdermin-E, N-terminal (GSDME-NT); Gasdermin-E, C-terminal (GSDME-CT)]
• Protein function: [Gasdermin-E]: Precursor of a pore-forming protein that converts non-inflammatory apoptosis to pyroptosis (PubMed:27281216, PubMed:28459430, PubMed:33852854, PubMed:35594856, PubMed:36607699). This form constitutes the precursor of the pore-form
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF04598	Gasdermin	1 → 246	Gasdermin pore forming domain	Domain
  PF17708	Gasdermin_C	279 → 468	Gasdermin PUB domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in cochlea (PubMed:9771715). Low level of expression in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas, with highest expression in placenta (PubMed:9771715). {ECO:0000269|PubMed:9771715}.
• Sequence:

  MFAKATRNFLREVDADGDLIAVSNLNDSDKLQLLSLVTKKKRFWCWQRPKYQFLSLTLGD
  VLIEDQFPSPVVVESDFVKYEGKFANHVSGTLETALGKVKLNLGGSSRVESQSSFGTLRK
  QEVDLQQLIRDSAERTINLRNPVLQQVLEGRNEVLCVLTQKITTMQKCVISEHMQVEEKC
  GGIVGIQTKTVQVSATEDGNVTKDSNVVLEIPAATTIAYGVIELYVKLDGQFEFCLLRGK
  QGGFENKKRIDSVYLDPLVFREFAFIDMPDAAHGISSQDGPLSVLKQATLLLERNFHPFA
  ELPEPQQTALSDIFQAVLFDDELLMVLEPVCDDLVSGLSPTVAVLGELKPRQQQDLVAFL
  QLVGCSLQGGCPGPEDAGSKQLFMTAYFLVSALAEMPDSAAALLGTCCKLQIIPTLCHLL
  RALSDDGVSDLEDPTLTPLKDTERFGIVQRLFASADISLERLKSSVKAVILKDSKVFPLL
  LCITLNGLCALGREHS

• Sequence length: 496

Pathways

KEGG:

Cytosolic DNA-sensing pathway

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Autosomal dominant nonsyndromic hearing loss 5	Pathogenic	rs2128047712, rs1562687726, rs1562687295, rs727505273, rs2534973457	RCV001726686 RCV000002173 RCV000002174 RCV001808425 RCV003221318	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Monogenic hearing loss	Pathogenic	rs727505273	RCV006250169	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Rare genetic deafness	Pathogenic	rs727505273	RCV000156800	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ANOREXIA NERVOSA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ARTHRITIS, RHEUMATOID	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATTENTION DEFICIT HYPERACTIVITY DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL DOMINANT ISOLATED SENSORINEURAL DEAFNESS TYPE DFNA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL DOMINANT NONSYNDROMIC HEARING LOSS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEAFNESS, AUTOSOMAL DOMINANT 5	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GOUT	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GSDME-related disorder	Conflicting classifications of pathogenicity; Benign; Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hearing impairment	Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
HEARING LOSS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEUROTIC DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonsyndromic genetic hearing loss	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonsyndromic Hearing Loss, Mixed	Uncertain significance; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBSESSIVE-COMPULSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RHEUMATOID ARTHRITIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SENSORINEURAL HEARING LOSS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sensorineural hearing loss disorder	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SENSORINEURAL HEARING LOSS OF BILATERAL EARS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TOURETTE SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma	Adenocarcinoma	BEFREE	30061362		★☆☆☆☆ Found in Text Mining only
Autoimmune Diseases	Autoimmune Diseases	BEFREE	31548300		★☆☆☆☆ Found in Text Mining only
Autosomal dominant non-syndromic sensorineural deafness type DFNA	Non-Syndromic Sensorineural Deafness	Orphanet			★☆☆☆☆ Found in Text Mining only
Bipolar Disorder	Bipolar Disorder	GWASCAT_DG	31043756		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Breast Carcinoma	Breast Carcinoma	BEFREE	18346456, 28404884, 9523727		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	18346456, 28404884, 29682089, 9523727	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	30091681	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	30061362		★☆☆☆☆ Found in Text Mining only
Cerebrovascular accident	Stroke	GWASDB_DG	23422753		★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	18223688		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	18223688, 22493364, 30993897		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	35923131	Inhibit	★☆☆☆☆ Found in Text Mining only
Deafness	Deafness	Pubtator	17083569, 17616391, 26365971, 29266521, 32486382, 34997062	Associate	★☆☆☆☆ Found in Text Mining only
DEAFNESS, AUTOSOMAL DOMINANT 1 (disorder)	Deafness	CLINGEN_DG	12853124, 14559215, 14676472, 14736743, 15173223, 17868390, 21522185, 22848872, 24506266, 24933359, 26915689, 9771715		★☆☆☆☆ Found in Text Mining only
DEAFNESS, AUTOSOMAL DOMINANT 5 (disorder)	Deafness	BEFREE	11297734, 28459430		★☆☆☆☆ Found in Text Mining only
DEAFNESS, AUTOSOMAL DOMINANT 5 (disorder)	Deafness	CLINVAR_DG	30828794		★☆☆☆☆ Found in Text Mining only
DEAFNESS, AUTOSOMAL DOMINANT 5 (disorder)	Deafness	GENOMICS_ENGLAND_DG	9771715		★☆☆☆☆ Found in Text Mining only
DEAFNESS, AUTOSOMAL DOMINANT 5 (disorder)	Deafness	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Hearing Loss	Hearing loss	Pubtator	17616391, 19911014, 24164807, 26365971, 29266521, 29849037, 32486382, 34433433, 35114279	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hearing Loss Sensorineural	Hearing loss	Pubtator	19911014	Associate	★☆☆☆☆ Found in Text Mining only
Hearing Loss, High-Frequency	Hearing Loss	BEFREE	12461698		★☆☆☆☆ Found in Text Mining only
Hereditary Breast and Ovarian Cancer Syndrome	Hereditary breast and ovarian cancer syndrome	Pubtator	28404884	Associate	★☆☆☆☆ Found in Text Mining only
Intestinal Cancer	Intestinal Cancer	BEFREE	31434357		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	24154762		★☆☆☆☆ Found in Text Mining only
Lymphatic Metastasis	Lymphatic metastasis	Pubtator	18346456	Associate	★☆☆☆☆ Found in Text Mining only
Major Depressive Disorder	Mental Depression	GWASCAT_DG	29942085		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant neoplasm of breast	Breast Cancer	BEFREE	18346456, 28404884, 9523727		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	30061362, 30710195		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	BEFREE	17083569, 29183726		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	18223688, 21522185, 22530481, 24154762, 30993897, 31230091, 31501419, 31616642		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	18223688		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	LHGDN	18346456		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	BEFREE	21522185		★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	BEFREE	11297734, 30914761, 30976076		★☆☆☆☆ Found in Text Mining only
Melanoma	Melanoma	Pubtator	11297734	Associate	★☆☆☆☆ Found in Text Mining only
Mouth Neoplasms	Mouth neoplasm	Pubtator	30091681	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	18223688, 21522185, 22493364, 22530481, 24154762, 28404884, 30061362, 30993897, 31230091, 31434357, 31796433, 9523727		★☆☆☆☆ Found in Text Mining only
Nodular Sclerosis Classical Hodgkin Lymphoma	Classical Hodgkin lymphoma	BEFREE	26365971		★☆☆☆☆ Found in Text Mining only
Nonsyndromic Deafness	Nonsyndromic Deafness	BEFREE	12853124, 14559215, 15378350, 16897187, 9771715		★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	BEFREE	31535374		★☆☆☆☆ Found in Text Mining only
Rheumatoid Arthritis	Rheumatoid arthritis	CTD_human_DG	17379860		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	GWASCAT_DG	29483656, 31268507		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sensorineural Hearing Loss (disorder)	Hearing Loss	BEFREE	17427029, 19911014, 26496673, 29849037		★☆☆☆☆ Found in Text Mining only
Sensorineural hearing loss, bilateral	Sensorineural hearing loss	CLINGEN_DG	12853124, 14559215, 14676472, 14736743, 15173223, 17868390, 21522185, 22848872, 24506266, 24933359, 26915689, 9771715		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma	Carcinoma	BEFREE	30091681		★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	30091681, 34433433	Associate	★☆☆☆☆ Found in Text Mining only
Stomach Carcinoma	Stomach Carcinoma	BEFREE	17083569, 29183726		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	17083569, 33407483	Associate	★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	17616391	Inhibit	★☆☆☆☆ Found in Text Mining only