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 either of two adjacent genes located on chromosome 17q25.3. Both of these genes encode integral membrane proteins that local... See more...

Aliases for TMC6 Gene

Aliases for TMC6 Gene

  • Transmembrane Channel Like 6 2 3 5
  • Epidermodysplasia Verruciformis Protein 1 3 4
  • Transmembrane Channel-Like Protein 6 3 4
  • Epidermodysplasia Verruciformis 1 2 3
  • Protein LAK-4 3 4
  • EVER1 3 4
  • EVIN1 3 4
  • Expressed In Activated T/LAK Lymphocytes 3
  • LAK-4P 3
  • EV1 3

External Ids for TMC6 Gene

Previous HGNC Symbols for TMC6 Gene

  • EVER1

Previous GeneCards Identifiers for TMC6 Gene

  • GC17M073619
  • GC17M076108
  • GC17M071533

Summaries for TMC6 Gene

Entrez Gene Summary for TMC6 Gene

  • 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 either of two adjacent genes located on chromosome 17q25.3. Both of these genes encode integral membrane proteins that localize to the endoplasmic reticulum and are predicted to form transmembrane channels. This gene encodes a transmembrane channel-like protein with 10 transmembrane domains and 2 leucine zipper motifs. [provided by RefSeq, Jul 2008]

GeneCards Summary for TMC6 Gene

TMC6 (Transmembrane Channel Like 6) is a Protein Coding gene. Diseases associated with TMC6 include Epidermodysplasia Verruciformis 1 and Skin Carcinoma. Among its related pathways are Innate Immune System. An important paralog of this gene is TMC5.

UniProtKB/Swiss-Prot Summary for TMC6 Gene

Gene Wiki entry for TMC6 Gene

Additional gene information for TMC6 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TMC6 Gene

Genomics for TMC6 Gene

GeneHancer (GH) Regulatory Elements for TMC6 Gene

Promoters and enhancers for TMC6 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TMC6 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the TMC6 gene promoter:
  • c-Ets-1

Genomic Locations for TMC6 Gene

Genomic Locations for TMC6 Gene
chr17:78,110,458-78,132,407
(GRCh38/hg38)
Size:
21,950 bases
Orientation:
Minus strand
chr17:76,106,539-76,128,488
(GRCh37/hg19)
Size:
21,950 bases
Orientation:
Minus strand

Genomic View for TMC6 Gene

Genes around TMC6 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TMC6 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TMC6 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TMC6 Gene

Proteins for TMC6 Gene

  • Protein details for TMC6 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q7Z403-TMC6_HUMAN
    Recommended name:
    Transmembrane channel-like protein 6
    Protein Accession:
    Q7Z403
    Secondary Accessions:
    • O43284
    • Q45VJ2
    • Q8IU98
    • Q8IUI7
    • Q8IWU8
    • Q8TEQ7
    • Q9HAG5

    Protein attributes for TMC6 Gene

    Size:
    805 amino acids
    Molecular mass:
    90045 Da
    Quaternary structure:
    • Interacts with CIB1.
    SequenceCaution:
    • Sequence=AAH35648.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAA24179.2; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAB84891.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Alternative splice isoforms for TMC6 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TMC6 Gene

Post-translational modifications for TMC6 Gene

  • Glycosylation at Asn312 and Asn103
  • Ubiquitination at Lys409 and Lys151
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for TMC6 Gene

Domains & Families for TMC6 Gene

Gene Families for TMC6 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Potential drug targets
  • Predicted intracellular proteins
  • Predicted membrane proteins
  • Transporters

Protein Domains for TMC6 Gene

Blocks:
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for TMC6 Gene

GenScript: Design optimal peptide antigens:
  • TMC6 protein (Q7L2M4_HUMAN)
  • TMC6 protein (Q96I77_HUMAN)
  • Protein LAK-4 (TMC6_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q7Z403

UniProtKB/Swiss-Prot:

TMC6_HUMAN :
  • Belongs to the TMC family.
Family:
  • Belongs to the TMC family.
genes like me logo Genes that share domains with TMC6: view

Function for TMC6 Gene

Molecular function for TMC6 Gene

UniProtKB/Swiss-Prot Function:
Probable ion channel.

Phenotypes From GWAS Catalog for TMC6 Gene

Gene Ontology (GO) - Molecular Function for TMC6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005216 ion channel activity IBA 21873635
GO:0005515 protein binding IPI 18158319
GO:0008381 mechanosensitive ion channel activity IBA 21873635
genes like me logo Genes that share ontologies with TMC6: view
genes like me logo Genes that share phenotypes with TMC6: view

Human Phenotype Ontology for TMC6 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for TMC6 Gene

MGI Knock Outs for TMC6:
  • Tmc6 Tmc6<tm1a(EUCOMM)Wtsi>

Animal Model Products

CRISPR Products

miRNA for TMC6 Gene

miRTarBase miRNAs that target TMC6

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TMC6

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for TMC6 Gene

Localization for TMC6 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TMC6 Gene

Endoplasmic reticulum membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TMC6 gene
Compartment Confidence
plasma membrane 5
nucleus 5
endoplasmic reticulum 5
golgi apparatus 5
endosome 1

Gene Ontology (GO) - Cellular Components for TMC6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA 12426567
GO:0005783 endoplasmic reticulum IEA,IDA 12426567
GO:0005789 endoplasmic reticulum membrane IEA --
GO:0005794 Golgi apparatus IDA 18158319
GO:0005886 plasma membrane TAS --
genes like me logo Genes that share ontologies with TMC6: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for TMC6 Gene

Pathways & Interactions for TMC6 Gene

PathCards logo

SuperPathways for TMC6 Gene

genes like me logo Genes that share pathways with TMC6: view

Pathways by source for TMC6 Gene

3 Reactome pathways for TMC6 Gene

Gene Ontology (GO) - Biological Process for TMC6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006811 ion transport IEA --
GO:0008150 biological_process ND --
GO:0034220 ion transmembrane transport IEA --
GO:0043312 neutrophil degranulation TAS --
GO:0055085 transmembrane transport IEA --
genes like me logo Genes that share ontologies with TMC6: view

No data available for SIGNOR curated interactions for TMC6 Gene

Drugs & Compounds for TMC6 Gene

No Compound Related Data Available

Transcripts for TMC6 Gene

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TMC6

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for TMC6 Gene

ExUns: 1 ^ 2 ^ 3a · 3b · 3c · 3d · 3e · 3f · 3g ^ 4a · 4b · 4c · 4d ^ 5 ^ 6a · 6b · 6c · 6d · 6e ^ 7 ^ 8a · 8b · 8c ^ 9 ^ 10a · 10b ^
SP1: - - - - - - - - - - - - - - -
SP2: - - - - - - -
SP3: - - - - -
SP4: - - - - -
SP5:
SP6: - - - - - - - -
SP7:
SP8: - - - - - - - - - - - - -
SP9: - - - - - - - -
SP10: - - - -
SP11: - - - - - -
SP12:
SP13: - - -
SP14: - -
SP15:
SP16: - - - - -
SP17: - - - -
SP18:
SP19:

ExUns: 11a · 11b · 11c ^ 12a · 12b ^ 13 ^ 14 ^ 15 ^ 16a · 16b ^ 17 ^ 18a · 18b ^ 19 ^ 20a · 20b ^ 21
SP1: - - - -
SP2: - - - -
SP3: - - - -
SP4: - - - - - - - - - - - - -
SP5: - - - -
SP6:
SP7: - - -
SP8:
SP9:
SP10:
SP11:
SP12:
SP13:
SP14:
SP15:
SP16:
SP17:
SP18:
SP19:

Relevant External Links for TMC6 Gene

GeneLoc Exon Structure for
TMC6
ECgene alternative splicing isoforms for
TMC6

Expression for TMC6 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for TMC6 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for TMC6 Gene

This gene is overexpressed in Whole Blood (x6.2) and Spleen (x5.0).

Protein differential expression in normal tissues from HIPED for TMC6 Gene

This gene is overexpressed in Monocytes (22.6), Plasma (12.6), Peripheral blood mononuclear cells (10.5), NK cells (6.9), and CD8 Tcells (6.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for TMC6 Gene



Protein tissue co-expression partners for TMC6 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of TMC6 Gene:

TMC6

SOURCE GeneReport for Unigene cluster for TMC6 Gene:

Hs.632227

mRNA Expression by UniProt/SwissProt for TMC6 Gene:

Q7Z403-TMC6_HUMAN
Tissue specificity: Expressed in placenta, prostate, testis, activated T-lymphocytes and lymphokine-activated killer (LAK) lymphocytes.

Evidence on tissue expression from TISSUES for TMC6 Gene

  • Spleen(4.4)
  • Nervous system(4.4)
  • Blood(3)
  • Skin(2.4)

Phenotype-based relationships between genes and organs from Gene ORGANizer for TMC6 Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • cardiovascular
  • immune
  • integumentary
Regions:
Limb:
  • digit
  • foot
  • lower limb
  • toe
General:
  • blood
  • blood vessel
  • hair
  • skin
  • sweat gland
  • white blood cell
genes like me logo Genes that share expression patterns with TMC6: view

Orthologs for TMC6 Gene

This gene was present in the common ancestor of animals.

Orthologs for TMC6 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia TMC6 33 32
  • 99.55 (n)
OneToOne
cow
(Bos Taurus)
Mammalia TMC6 33 32
  • 84.17 (n)
OneToOne
dog
(Canis familiaris)
Mammalia TMC6 33 32
  • 83.93 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Tmc6 17 33 32
  • 78.95 (n)
oppossum
(Monodelphis domestica)
Mammalia TMC6 33
  • 66 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia TMC6 33
  • 42 (a)
OneToOne
chicken
(Gallus gallus)
Aves LOC100859142 32
  • 66.31 (n)
TMC6 33
  • 56 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia TMC6 33
  • 60 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia tmc6 32
  • 56.19 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.6120 32
zebrafish
(Danio rerio)
Actinopterygii tmc6b 32
  • 59.22 (n)
TMC6 (1 of 2) 33
  • 44 (a)
OneToMany
tmc6a 33
  • 42 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta CG3280 33
  • 8 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea tmc-2 33
  • 12 (a)
ManyToMany
tmc-1 33
  • 11 (a)
ManyToMany
Species where no ortholog for TMC6 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rat (Rattus norvegicus)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for TMC6 Gene

ENSEMBL:
Gene Tree for TMC6 (if available)
TreeFam:
Gene Tree for TMC6 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TMC6: view image

Paralogs for TMC6 Gene

Paralogs for TMC6 Gene

(1) SIMAP similar genes for TMC6 Gene using alignment to 7 proteins:

  • TMC6_HUMAN
  • K7ELP1_HUMAN
  • K7ENC4_HUMAN
  • K7ENM6_HUMAN
  • K7ERH0_HUMAN
  • Q7L2M4_HUMAN
  • Q96I77_HUMAN

Pseudogenes.org Pseudogenes for TMC6 Gene

genes like me logo Genes that share paralogs with TMC6: view

Variants for TMC6 Gene

Sequence variations from dbSNP and Humsavar for TMC6 Gene

SNP ID Clin Chr 17 pos Variation AA Info Type
rs114853749 benign, EPIDERMODYSPLASIA VERRUCIFORMIS 78,121,077(-) G/A coding_sequence_variant, intron_variant, missense_variant, non_coding_transcript_variant
rs117156381 benign, EPIDERMODYSPLASIA VERRUCIFORMIS 78,133,538(-) C/T upstream_transcript_variant
rs117553598 benign, EPIDERMODYSPLASIA VERRUCIFORMIS 78,120,836(-) C/T intron_variant
rs121908327 risk-factor, EPIDERMODYSPLASIA VERRUCIFORMIS 78,125,876(-) G/A 5_prime_UTR_variant, coding_sequence_variant, genic_upstream_transcript_variant, non_coding_transcript_variant, stop_gained, upstream_transcript_variant
rs121908328 risk-factor, EPIDERMODYSPLASIA VERRUCIFORMIS 78,119,382(-) C/A/T coding_sequence_variant, intron_variant, missense_variant, non_coding_transcript_variant, stop_gained

Structural Variations from Database of Genomic Variants (DGV) for TMC6 Gene

Variant ID Type Subtype PubMed ID
esv2716301 CNV deletion 23290073
esv2716302 CNV deletion 23290073
esv2716303 CNV deletion 23290073
esv2716304 CNV deletion 23290073
nsv1113890 CNV deletion 24896259
nsv470607 CNV loss 18288195
nsv515500 CNV loss 19592680
nsv833554 CNV gain+loss 17160897

Variation tolerance for TMC6 Gene

Residual Variation Intolerance Score: 89.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 12.76; 94.70% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TMC6 Gene

Human Gene Mutation Database (HGMD)
TMC6
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TMC6

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TMC6 Gene

Disorders for TMC6 Gene

MalaCards: The human disease database

(4) MalaCards diseases for TMC6 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
epidermodysplasia verruciformis 1
  • epidermodysplasia verruciformis, susceptibility to, 1
skin carcinoma
  • carcinoma of skin
pityriasis versicolor
  • infection by pityrosporum furfur
superficial mycosis
  • piedra
- elite association - COSMIC cancer census association via MalaCards
Search TMC6 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

TMC6_HUMAN
  • Epidermodysplasia verruciformis 1 (EV1) [MIM:226400]: A form of epidermodysplasia verruciformis, a rare genodermatosis associated with a high risk of skin carcinoma that results from an abnormal susceptibility to infection by specific human papillomaviruses, including the oncogenic HPV5. Infection leads to the early development of disseminated flat wart-like and pityriasis versicolor-like skin lesions. Cutaneous Bowen's carcinomas in situ and invasive squamous cell carcinomas develop in about half of the patients, mainly on sun-exposed skin areas. EV1 inheritance is autosomal recessive. {ECO:0000269 PubMed:12426567, ECO:0000269 PubMed:15042430}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for TMC6

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with TMC6: view

No data available for Genatlas for TMC6 Gene

Publications for TMC6 Gene

  1. Mutations in two adjacent novel genes are associated with epidermodysplasia verruciformis. (PMID: 12426567) Ramoz N … Favre M (Nature genetics 2002) 2 3 4 23 56
  2. Novel mutations of EVER1/TMC6 gene in a Japanese patient with epidermodysplasia verruciformis. (PMID: 15042430) Tate G … Mitsuya T (Journal of human genetics 2004) 3 4 23 56
  3. Characterization of the transmembrane channel-like (TMC) gene family: functional clues from hearing loss and epidermodysplasia verruciformis. (PMID: 12906855) Kurima K … Griffith AJ (Genomics 2003) 3 4 23 56
  4. The human CIB1-EVER1-EVER2 complex governs keratinocyte-intrinsic immunity to β-papillomaviruses. (PMID: 30068544) de Jong SJ … Casanova JL (The Journal of experimental medicine 2018) 3 4 56
  5. Autosomal dominant epidermodysplasia verruciformis lacking a known EVER1 or EVER2 mutation. (PMID: 19706093) McDermott DF … Hwang ST (Pediatric dermatology 2009) 3 23 56

Products for TMC6 Gene

Sources for TMC6 Gene