TMC8

transmembrane channel like 8, the group of Transmembrane channel like family

Basic information

Region (hg38): 17:78130770-78142968

Previous symbols: [ "EVER2" ]

Links

ENSG00000167895 ∙ NCBI:147138 ∙ OMIM:605829 ∙ HGNC:20474 ∙ Uniprot:Q8IU68 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• epidermodysplasia verruciformis, susceptibility to, 2 (Strong), mode of inheritance: AR
• epidermodysplasia verruciformis, susceptibility to, 2 (Strong), mode of inheritance: AR
• epidermodysplasia verruciformis (Supportive), mode of inheritance: AR
• epidermodysplasia verruciformis, susceptibility to, 2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epidermodysplasia verruciformis, susceptibility to, 2	AR	Oncologic	Individuals are at high-risk of developing skin cancers, and surveillance may be beneficial to allow early detection and treatment	Allergy/Immunology/Infectious; Dermatologic; Oncologic	10084299; 10844558; 12426567

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMC8 gene.

• Epidermodysplasia_verruciformis (549 variants)
• Inborn_genetic_diseases (111 variants)
• not_provided (33 variants)
• TMC8-related_disorder (17 variants)
• Epidermodysplasia_verruciformis,_susceptibility_to,_2 (16 variants)
• Epidermodysplasia_verruciformis,_susceptibility_to,_1 (12 variants)
• not_specified (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMC8 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000152468.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	138	9	149
missense			278	15	4	297
nonsense	5		1			6
start loss			1			1
frameshift	20	1	2			23
splice donor/acceptor (+/-2bp)		10	1			11
Total	25	11	285	153	13

Highest pathogenic variant AF is 0.00024659475

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMC8	protein_coding	protein_coding	ENST00000318430	15	12199

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.14e-14	0.148	125535	0	209	125744	0.000831

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.566	380	412	0.922	0.0000257	4537
Missense in Polyphen		107	113.23	0.94501		1422
Synonymous	0.257	191	196	0.977	0.0000127	1603
Loss of Function	1.01	25	31.1	0.805	0.00000147	344

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000619	0.000618
Ashkenazi Jewish	0.000497	0.000496
East Asian	0.000381	0.000381
Finnish	0.00601	0.00602
European (Non-Finnish)	0.000292	0.000290
Middle Eastern	0.000381	0.000381
South Asian	0.000492	0.000490
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable ion channel. {ECO:0000250}.

Recessive Scores

• pRec: 0.102

Intolerance Scores

• loftool: 0.899
• rvis_EVS: 0.21
• rvis_percentile_EVS: 67.5

Haploinsufficiency Scores

• pHI: 0.103
• hipred: N
• hipred_score: 0.208
• ghis: 0.476

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.136

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tmc8

Gene ontology

• Biological process: regulation of cell growth;negative regulation of protein binding;negative regulation of protein oligomerization;ion transmembrane transport;zinc ion homeostasis;regulation of extrinsic apoptotic signaling pathway via death domain receptors
• Cellular component: extracellular space;cytoplasm;endoplasmic reticulum;endoplasmic reticulum membrane;Golgi apparatus;integral component of plasma membrane;nuclear membrane;extracellular exosome
• Molecular function: signaling receptor binding;ion channel activity;protein binding;mechanosensitive ion channel activity