TMC6 (transmembrane channel like 6)

Gene

• Entrez ID: 11322
• Gene name: Transmembrane channel like 6
• Gene symbol: TMC6
• Synonyms (NCBI Gene): EV1, EVER1, EVIN1, LAK-4P, TNRC6C-AS1, lnc
• Chromosome: 17
• Chromosome location: 17q25.3
• Summary: Epidermodysplasia verruciformis (EV) is an autosomal recessive dermatosis characterized by abnormal susceptibility to human papillomaviruses (HPVs) and a high rate of progression to squamous cell carcinoma on sun-exposed skin. EV is caused by mutations in

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121908327	G>A	Risk-factor	5 prime UTR variant, upstream transcript variant, stop gained, coding sequence variant, genic upstream transcript variant, non coding transcript variant
rs121908328	C>A,T	Risk-factor	Intron variant, stop gained, coding sequence variant, non coding transcript variant, missense variant
rs121908329	G>T	Risk-factor	Coding sequence variant, intron variant, non coding transcript variant, stop gained
rs754288317	C>T	Likely-pathogenic	Splice acceptor variant, genic upstream transcript variant, upstream transcript variant
rs769471844	T>A,C	Likely-pathogenic	Splice acceptor variant
rs1555655146	->A	Pathogenic	Frameshift variant, intron variant, non coding transcript variant, coding sequence variant
rs1567989416	C>T	Likely-pathogenic	Intron variant, splice donor variant
rs1567997496	TGAATGGATGGATGAGTGGAGCTCGGAGCCTGGGTCATGAGGTGGAGGCATTACCTGTACACCAGGGTGATGCAGGTGATAAAGAAGCTCACGCCCACAGTGGAGAGGTAGGCCAGGGGCATGTTGTAGGGCAGGCCACCCACCCTGGGTGTGCACTGGCTGCCATCCAGGGGGCTGCCACACGGCTGGTTCAGCGTGGCGTTACTGTAGTGGCCGTAGTACATGACGGTGTGGGTGAAGCAACCCTGCCACAGG	Pathogenic	5 prime UTR variant, initiator codon variant, coding sequence variant, splice donor variant, splice acceptor variant, non coding transcript variant, intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017951	hsa-miR-335-5p	Microarray	18185580
MIRT044869	hsa-miR-195-5p	CLASH	23622248

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000139	Component	Golgi membrane	IEA
GO:0005515	Function	Protein binding	IPI	18158319, 30068544, 32296183, 32814053, 32917726
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IDA	12426567
GO:0005783	Component	Endoplasmic reticulum	IDA	12426567, 18158319
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005794	Component	Golgi apparatus	IDA	18158319
GO:0005794	Component	Golgi apparatus	IEA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0006882	Process	Intracellular zinc ion homeostasis	IDA	18158319
GO:0008381	Function	Mechanosensitive monoatomic ion channel activity	IBA
GO:0016020	Component	Membrane	IEA
GO:0031965	Component	Nuclear membrane	IDA	18158319
GO:0031965	Component	Nuclear membrane	IEA
GO:0034220	Process	Monoatomic ion transmembrane transport	IEA
GO:0035579	Component	Specific granule membrane	TAS
GO:0050821	Process	Protein stabilization	IMP	32917726
GO:0070062	Component	Extracellular exosome	HDA	20458337
GO:0070821	Component	Tertiary granule membrane	TAS

Other IDs

• MIM: 605828
• HGNC: 18021
• e!Ensembl: ENSG00000141524

Protein

• UniProt ID: Q7Z403
• Protein name: Transmembrane channel-like protein 6 (Epidermodysplasia verruciformis protein 1) (Protein LAK-4)
• Protein function: Acts as a regulatory protein involved in the regulation of numerous cellular processes (PubMed:18158319, PubMed:30068544, PubMed:32917726). Together with its homolog TMC8/EVER2, forms a complex with CIB1 in lymphocytes and keratynocytes where TM
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF07810	TMC	540 → 646	TMC domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in placenta, prostate, testis, activated T-lymphocytes and lymphokine-activated killer (LAK) lymphocytes. {ECO:0000269|PubMed:12906855, ECO:0000269|Ref.3}.
• Sequence:

  MAQPLAFILDVPETPGDQGQGPSPYDESEVHDSFQQLIQEQSQCTAQEGLELQQREREVT
  GSSQQTLWRPEGTQSTATLRILASMPSRTIGRSRGAIISQYYNRTVQLRCRSSRPLLGNF
  VRSAWPSLRLYDLELDPTALEEEEKQSLLVKELQSLAVAQRDHMLRGMPLSLAEKRSLRE
  KSRTPRGKWRGQPGSGGVCSCCGRLRYACVLALHSLGLALLSALQALMPWRYALKRIGGQ
  FGSSVLSYFLFLKTLLAFNALLLLLLVAFIMGPQVAFPPALPGPAPVCTGLELLTGAGCF
  THTVMYYGHYSNATLNQPCGSPLDGSQCTPRVGGLPYNMPLAYLSTVGVSFFITCITLVY
  SMAHSFGESYRVGSTSGIHAITVFCSWDYKVTQKRASRLQQDNIRTRLKELLAEWQLRHS
  PRSVCGRLRQAAVLGLVWLLCLGTALGCAVAVHVFSEFMIQSPEAAGQEAVLLVLPLVVG
  LLNLGAPYLCRVLAALEPHDSPVLEVYVAICRNLILKLAILGTLCYHWLGRRVGVLQGQC
  WEDFVGQELYRFLVMDFVLMLLDTLFGELVWRIISEKKLKRRRKPEFDIARNVLELIYGQ
  TLTWLGVLFSPLLPAVQIIKLLLVFYVKKTSLLANCQAPRRPWLASHMSTVFLTLLCFPA
  FLGAAVFLCYAVWQVKPSSTCGPFRTLDTMYEAGRVWVRHLEAAGPRVSWLPWVHRYLME
  NTFFVFLVSALLLAVIYLNIQVVRGQRKVICLLKEQISNEGEDKIFLINKLHSIYERKER
  EERSRVGTTEEAAAPPALLTDEQDA

• Sequence length: 805

Pathways

Reactome:

Neutrophil degranulation

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
Epidermodysplasia verruciformis	Pathogenic; Likely pathogenic	rs1458008918, rs2145350631, rs1296234074, rs1567995497, rs749657465, rs758514260, rs776505795, rs2510624241, rs121908327, rs121908329, rs769471844, rs2510469062, rs2510516321, rs1468619952, rs2074729420, rs2074170793, rs776860184, rs1555655146, rs1567989416, rs1392702424, rs202217062, rs371786754, rs2074414994	RCV001390017 RCV001941778 RCV001950856 RCV001999708 RCV001950983 RCV001963266 RCV001948731 RCV002621322 RCV002512791 RCV001851659 RCV002227995 RCV002839453 RCV002858642 RCV003594742 RCV003760815 RCV003759530 RCV003870568 RCV002233920 RCV002534420 RCV002235403 RCV001037260 RCV001056974 RCV001201839 RCV001238118	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Epidermodysplasia verruciformis, susceptibility to, 1	Pathogenic	rs121908327, rs121908329, rs769471844, rs1567997496	RCV000005014 RCV000005016 RCV000005017 RCV000706700	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lymphoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of urinary bladder	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TMC6-related disorder	Benign; Likely benign; Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	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
Asthma	Asthma	BEFREE	30941157		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	34136741	Associate	★☆☆☆☆ Found in Text Mining only
Cafe au lait spots, multiple	Cafe-au-lait spot	HPO_DG			★☆☆☆☆ Found in Text Mining only
Carcinoma in situ of uterine cervix	Cervical Intraepithelial Neoplasia	BEFREE	20084279		★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	30050311, 30429034		★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	37468683	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	25853559	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma, Basal Cell	Carcinoma	HPO_DG			★☆☆☆☆ Found in Text Mining only
cervical cancer	Cervical Cancer	BEFREE	21387292, 27097911, 27899077		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervix carcinoma	Cervix carcinoma	BEFREE	21387292, 27097911, 27899077		★☆☆☆☆ Found in Text Mining only
Cystic Fibrosis	Cystic Fibrosis	BEFREE	26047157		★☆☆☆☆ Found in Text Mining only
Cystic Fibrosis	Cystic fibrosis	Pubtator	26047157	Associate	★☆☆☆☆ Found in Text Mining only
Dystonic Disorders	Dystonia	Pubtator	22952854	Associate	★☆☆☆☆ Found in Text Mining only
Epidermodysplasia Verruciformis	Epidermodysplasia verruciformis	Pubtator	10084299, 10844558, 17139267, 18158319, 18224692, 21387292, 22952854, 25378492, 25853559, 30068544, 32917957, 33818984, 35154113, 36602881	Associate	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Epidermodysplasia Verruciformis	Epidermodysplasia Verruciformis	LHGDN	12426567, 15042430, 17008061		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Epidermodysplasia Verruciformis	Epidermodysplasia Verruciformis	ORPHANET_DG	12426567		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Epidermodysplasia verruciformis	Epidermodysplasia Verruciformis	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Epidermodysplasia Verruciformis	Epidermodysplasia Verruciformis	BEFREE	12906855, 15042430, 16045695, 17008061, 17139267, 19706093, 21387292, 22850876, 22903682, 22952854, 23534907, 25378492, 25853559, 28196644, 28646613, 30068544, 30068545, 30156265		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Epidermodysplasia Verruciformis	Epidermodysplasia Verruciformis	CLINVAR_DG	15042430, 17139267		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Epidermodysplasia Verruciformis	Epidermodysplasia Verruciformis	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Epidermodysplasia Verruciformis	Epidermodysplasia Verruciformis	GENOMICS_ENGLAND_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Glioblastoma	Glioblastoma	BEFREE	28830791, 30204064		★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	28830791, 30154652, 30204064		★☆☆☆☆ Found in Text Mining only
Immune System Diseases	Immune system disease	Pubtator	35154113	Associate	★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	31190421		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	30050311, 30429034		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of skin	Skin cancer	BEFREE	12906855		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of thyroid	Thyroid cancer	BEFREE	29893424		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	20084279, 30154652		★☆☆☆☆ Found in Text Mining only
Malignant tumor of cervix	Cervical Tumor	BEFREE	21387292, 27097911, 27899077		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	28830791, 29893424, 30703501, 31657132, 9864400		★☆☆☆☆ Found in Text Mining only
Papillary thyroid carcinoma	Papillary thyroid carcinoma	BEFREE	30038597		★☆☆☆☆ Found in Text Mining only
Papilloma	Papilloma	BEFREE	12906855		★☆☆☆☆ Found in Text Mining only
Psoriasis	Psoriasis	Pubtator	10084299	Associate	★☆☆☆☆ Found in Text Mining only
Seborrheic dermatitis	Seborrheic dermatitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Skin lesion	Skin Lesion	BEFREE	30068544		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma	Carcinoma	BEFREE	18224692		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma	Carcinoma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of skin	Skin carcinoma	BEFREE	24913986, 26227733		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of the head and neck	Carcinoma Of The Head And Neck	BEFREE	27097911		★☆☆☆☆ Found in Text Mining only
Thyroid carcinoma	Thyroid Carcinoma	BEFREE	29893424, 30938030, 31657132		★☆☆☆☆ Found in Text Mining only
Thyroid Neoplasm	Thyroid Neoplasm	BEFREE	29893424		★☆☆☆☆ Found in Text Mining only
Uterine Cervical Dysplasia	Uterine disease	Pubtator	20084279	Associate	★☆☆☆☆ Found in Text Mining only
Uterine Cervical Neoplasms	Uterine neoplasm	Pubtator	21387292, 25853559	Associate	★☆☆☆☆ Found in Text Mining only