TMC6

transmembrane channel like 6, the group of Transmembrane channel like family

Basic information

Region (hg38): 17:78107397-78132407

Previous symbols: [ "EVER1", "TNRC6C-AS1" ]

Links

ENSG00000141524

∙ NCBI:11322 ∙ OMIM:605828 ∙ HGNC:18021 ∙ Uniprot:Q7Z403 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

epidermodysplasia verruciformis (Strong), mode of inheritance: AR
epidermodysplasia verruciformis, susceptibility to, 1 (Strong), mode of inheritance: AR
epidermodysplasia verruciformis (Supportive), mode of inheritance: AR
epidermodysplasia verruciformis, susceptibility to, 1 (Definitive), mode of inheritance: AR
epidermodysplasia verruciformis, susceptibility to, 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epidermodysplasia verruciformis, susceptibility to, 1	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 TMC6 gene.

Epidermodysplasia_verruciformis (718 variants)
Inborn_genetic_diseases (137 variants)
not_provided (46 variants)
Epidermodysplasia_verruciformis,_susceptibility_to,_1 (19 variants)
TMC6-related_disorder (18 variants)
not_specified (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMC6 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001127198.5. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	185 clinvar	9 clinvar	197
missense			327 clinvar	25 clinvar	7 clinvar	359
nonsense	9 clinvar		2 clinvar			11
start loss			1			1
frameshift	13 clinvar	1 clinvar	1 clinvar			15
splice donor/acceptor (+/-2bp)	2 clinvar	5 clinvar	1 clinvar			8
Total	24	6	335	210	16

Highest pathogenic variant AF is 0.00002609104

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMC6	protein_coding	protein_coding	ENST00000590602	19	21950

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.86e-10	0.998	125699	0	44	125743	0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.231	481	495	0.971	0.0000335	5081
Missense in Polyphen		136	144.92	0.93842		1612
Synonymous	-0.892	252	235	1.07	0.0000167	1702
Loss of Function	2.83	22	41.7	0.527	0.00000199	434

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000698	0.000544
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000209	0.000193
Middle Eastern	0.000163	0.000163
South Asian	0.000165	0.000163
Other	0.000330	0.000326

dbNSFP

Source: dbNSFP

Function: FUNCTION: Probable ion channel. {ECO:0000250}.;
Pathway: Neutrophil degranulation;Innate Immune System;Immune System (Consensus)

Recessive Scores

pRec: 0.140

Intolerance Scores

loftool: 0.751
rvis_EVS: 0.5
rvis_percentile_EVS: 79.66

Haploinsufficiency Scores

pHI: 0.174
hipred: N
hipred_score: 0.198
ghis: 0.524

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.154

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Tmc6
Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype;

Gene ontology

Biological process: biological_process;ion transmembrane transport;neutrophil degranulation
Cellular component: cytoplasm;endoplasmic reticulum;endoplasmic reticulum membrane;Golgi apparatus;plasma membrane;integral component of plasma membrane;nuclear membrane;specific granule membrane;extracellular exosome;tertiary granule membrane
Molecular function: ion channel activity;protein binding;mechanosensitive ion channel activity