GSDME

gasdermin E, the group of Gasdermins

Basic information

Region (hg38): 7:24698355-24757940

Previous symbols: [ "DFNA5" ]

Links

ENSG00000105928 ∙ NCBI:1687 ∙ OMIM:608798 ∙ HGNC:2810 ∙ Uniprot:O60443 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss 5 (Strong), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 5	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic	5919633; 5919636; 9771715; 12126021; 12408063; 14559215; 14676472; 17868390; 17427029; 17868390; 19911014; 21805831
The onset of deafness has been described as postlingual

ClinVar

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

• not provided (1 variants)
• Autosomal dominant nonsyndromic hearing loss 5 (1 variants)
• Rare genetic deafness (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GSDME 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	34	5	43
missense			100	10	7	117
nonsense						0
start loss						0
frameshift			8			8
inframe indel			5			5
splice donor/acceptor (+/-2bp)		1	1			2
splice region			8		2	10
non coding	1		18	48	65	132
Total	1	1	136	92	77

Variants in GSDME

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

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

Position	Type	Phenotype	Significance	ClinVar
7-24698419-T-C		Nonsyndromic Hearing Loss, Mixed	Uncertain significance (Jun 14, 2016)
7-24698443-A-C		Autosomal dominant nonsyndromic hearing loss 5	Uncertain significance (Jan 13, 2018)
7-24698489-G-A		Autosomal dominant nonsyndromic hearing loss 5	Uncertain significance (Jan 12, 2018)
7-24698499-G-A		Autosomal dominant nonsyndromic hearing loss 5	Benign (Jan 13, 2018)
7-24698520-AT-A		Nonsyndromic Hearing Loss, Mixed	Likely benign (Jun 14, 2016)
7-24698540-A-ATACTC		Nonsyndromic Hearing Loss, Mixed	Likely benign (Jun 14, 2016)
7-24698545-C-G		Autosomal dominant nonsyndromic hearing loss 5	Benign (Jan 12, 2018)
7-24698578-A-G		Autosomal dominant nonsyndromic hearing loss 5	Benign (Jan 13, 2018)
7-24698597-A-G		Autosomal dominant nonsyndromic hearing loss 5	Likely benign (Jan 13, 2018)
7-24698680-C-G		Autosomal dominant nonsyndromic hearing loss 5	Likely benign (Jan 13, 2018)
7-24698693-A-C		Autosomal dominant nonsyndromic hearing loss 5	Uncertain significance (Jan 13, 2018)
7-24698700-G-T		Autosomal dominant nonsyndromic hearing loss 5	Uncertain significance (Jan 13, 2018)
7-24698705-A-C		Autosomal dominant nonsyndromic hearing loss 5	Likely benign (Jan 12, 2018)
7-24698727-T-C		Autosomal dominant nonsyndromic hearing loss 5	Uncertain significance (Jan 13, 2018)
7-24698753-G-A		Autosomal dominant nonsyndromic hearing loss 5	Benign (Dec 17, 2018)
7-24698766-T-C		Autosomal dominant nonsyndromic hearing loss 5	Uncertain significance (Jan 13, 2018)
7-24698787-A-G		Autosomal dominant nonsyndromic hearing loss 5	Uncertain significance (Jan 13, 2018)
7-24698798-C-CCTAA		Nonsyndromic Hearing Loss, Mixed	Uncertain significance (Jun 14, 2016)
7-24698939-T-C		Autosomal dominant nonsyndromic hearing loss 5	Benign (Jun 29, 2018)
7-24698945-A-C		Autosomal dominant nonsyndromic hearing loss 5	Likely benign (Jan 13, 2018)
7-24698954-G-A		Autosomal dominant nonsyndromic hearing loss 5	Likely benign (Apr 27, 2017)
7-24698994-C-T			Likely benign (Jul 20, 2020)
7-24698996-G-A		Autosomal dominant nonsyndromic hearing loss 5	Benign (Jun 16, 2018)
7-24699002-C-T		Autosomal dominant nonsyndromic hearing loss 5	Likely benign (Aug 19, 2020)
7-24699045-A-G			Uncertain significance (Jul 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GSDME	protein_coding	protein_coding	ENST00000342947	9	71273

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.28e-9	0.525	125082	8	658	125748	0.00265

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.842	304	265	1.15	0.0000155	3214
Missense in Polyphen		94	76.231	1.2331		1091
Synonymous	-0.866	128	116	1.10	0.00000763	1015
Loss of Function	1.12	16	21.6	0.741	0.00000110	241

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00216	0.00216
Ashkenazi Jewish	0.0321	0.0319
East Asian	0.00217	0.00218
Finnish	0.00402	0.00403
European (Non-Finnish)	0.000994	0.000994
Middle Eastern	0.00217	0.00218
South Asian	0.000491	0.000490
Other	0.00424	0.00424

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in the TP53-regulated cellular response to DNA damage probably by cooperating with TP53 (PubMed:16897187, PubMed:18223688). {ECO:0000269|PubMed:16897187, ECO:0000269|PubMed:18223688}.
• Disease: DISEASE: Deafness, autosomal dominant, 5 (DFNA5) [MIM:600994]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:19911014, ECO:0000269|PubMed:24506266, ECO:0000269|PubMed:26236191, ECO:0000269|PubMed:9771715}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Is a tumor suppressor gene with an important role in colorectal cancer (CRC). {ECO:0000303|PubMed:18223688}.

Recessive Scores

• pRec: 0.115

Intolerance Scores

• rvis_EVS: -0.13
• rvis_percentile_EVS: 44.03

Haploinsufficiency Scores

• pHI: 0.106
• hipred: N
• hipred_score: 0.112
• ghis: 0.526

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Gsdme
• Phenotype: homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype

Gene ontology

• Biological process: sensory perception of sound;cell death;negative regulation of cell population proliferation;positive regulation of MAPK cascade;inner ear receptor cell differentiation;necrotic cell death;pyroptosis;cellular response to tumor necrosis factor;cellular response to virus;positive regulation of intrinsic apoptotic signaling pathway
• Cellular component: cytosol;plasma membrane;membrane
• Molecular function: phosphatidylinositol-4,5-bisphosphate binding;cardiolipin binding