TMC6

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

Basic information

Region (hg38): 17:78107396-78132407

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

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 (699 variants)
• not provided (71 variants)
• Inborn genetic diseases (53 variants)
• not specified (21 variants)
• Epidermodysplasia verruciformis, susceptibility to, 1 (16 variants)
• TMC6-related condition (1 variants)
• Epidermodysplasia verruciformis, susceptibility to, 2 (1 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.

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			1	142	10	153
missense			288	12	10	310
nonsense	7		1			8
start loss			1			1
frameshift	9		1			10
inframe indel			5			5
splice donor/acceptor (+/-2bp)	1	5	1			7
splice region			17	31	7	55
non coding	2		43	109	55	209
Total	19	5	341	263	75

Highest pathogenic variant AF is 0.000105

Variants in TMC6

This is a list of pathogenic ClinVar variants found in the TMC6 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-78112904-C-T			Likely benign (Jul 09, 2018)
17-78112992-C-T			Benign (Jul 09, 2018)
17-78113158-TG-T		Epidermodysplasia verruciformis, susceptibility to, 1	Uncertain significance (Nov 01, 2018)
17-78113176-G-A		Epidermodysplasia verruciformis	Uncertain significance (Aug 10, 2023)
17-78113179-G-A		Epidermodysplasia verruciformis	Uncertain significance (May 26, 2020)
17-78113182-G-A		Epidermodysplasia verruciformis • Epidermodysplasia verruciformis, susceptibility to, 1	Conflicting classifications of pathogenicity (Dec 22, 2023)
17-78113183-G-A		Epidermodysplasia verruciformis	Uncertain significance (Dec 31, 2021)
17-78113186-C-G		Epidermodysplasia verruciformis • Inborn genetic diseases	Uncertain significance (Aug 09, 2022)
17-78113186-C-T		Epidermodysplasia verruciformis	Uncertain significance (Jul 25, 2022)
17-78113188-G-A		Epidermodysplasia verruciformis	Uncertain significance (May 27, 2022)
17-78113198-C-T		Epidermodysplasia verruciformis	Uncertain significance (Aug 23, 2022)
17-78113199-G-A		Epidermodysplasia verruciformis	Likely benign (May 12, 2022)
17-78113205-C-T		Epidermodysplasia verruciformis	Likely benign (Jan 06, 2022)
17-78113207-C-T		Epidermodysplasia verruciformis	Likely benign (May 29, 2023)
17-78113210-C-T		Inborn genetic diseases	Uncertain significance (May 24, 2023)
17-78113211-C-G		Epidermodysplasia verruciformis	Uncertain significance (Dec 07, 2021)
17-78113212-C-G		Epidermodysplasia verruciformis	Uncertain significance (Jul 07, 2020)
17-78113215-C-T		Epidermodysplasia verruciformis • TMC6-related disorder	Benign (Jan 31, 2024)
17-78113218-G-A		Epidermodysplasia verruciformis	Likely benign (Oct 27, 2022)
17-78113219-A-G		Epidermodysplasia verruciformis	Likely benign (Dec 11, 2023)
17-78113220-A-G		Epidermodysplasia verruciformis	Likely benign (Nov 27, 2023)
17-78113231-C-T		Epidermodysplasia verruciformis	Likely benign (Sep 27, 2023)
17-78113277-G-A		not specified	Benign (Jan 24, 2024)
17-78113528-A-G		Epidermodysplasia verruciformis	Likely benign (Dec 24, 2023)
17-78113530-C-G		Epidermodysplasia verruciformis	Likely benign (Nov 04, 2023)

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