TMC6 (Transmembrane Channel Like 6)
Epidermodysplasia Verruciformis Associated Gene
Gene Information Card
| Symbol | TMC6 |
|---|---|
| Full Name | Transmembrane Channel Like 6 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q25.3 |
| NCBI Gene ID | 11322 ncbi.nlm.nih.gov/gene/11322 |
| Ensembl ID | ENSG00000141574 |
| UniProt ID | Q8NFQ8 |
| OMIM ID | 605828 |
| HGNC ID | 18021 |
| Aliases | EVER1, EV1, FLJ11747, dJ366L4.1 |
Description
TMC6 (Transmembrane Channel Like 6) encodes a transmembrane protein that localizes to the endoplasmic reticulum and is involved in zinc homeostasis. It forms a complex with TMC8 (EVER2) to regulate intracellular zinc distribution, which is critical for keratinocyte differentiation and antiviral immunity. Loss-of-function mutations in TMC6 cause epidermodysplasia verruciformis (EV), a rare autosomal recessive skin disorder characterized by susceptibility to specific human papillomavirus (HPV) types and increased risk of skin cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epidermodysplasia Verruciformis (EV) | Loss-of-function mutations impair zinc homeostasis, leading to defective keratinocyte differentiation and permissiveness to beta-HPV infection. | OMIM #226400; multiple case reports and functional studies |
| Squamous Cell Carcinoma (SCC) of Skin | EV-associated HPV infection promotes malignant transformation in sun-exposed skin. | ClinVar; COSMIC; literature review |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.5 | Medium |
| Esophagus | 8.3 | Low |
| Lung | 6.1 | Low |
| Testis | 4.7 | Low |
| Thyroid | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocyte) | 15.2 | High expression; relevant for EV studies |
| A431 (epidermoid carcinoma) | 10.8 | Moderate expression |
| HEK293 (embryonic kidney) | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.744C>A (p.Cys248Ter) | Nonsense | Rare | Loss of function; truncation of protein |
| c.280G>A (p.Gly94Arg) | Missense | Rare | Loss of function; disrupts zinc binding |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; no translation initiation |
Mutation functional classification
Loss of Function (LOF)
Most TMC6 mutations are loss-of-function, leading to impaired zinc homeostasis and susceptibility to beta-HPV.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported; EV is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Zinc homeostasis (Reactome: R-HSA-435354)
• Keratinocyte differentiation (KEGG: hsa04510)
Protein Summary
TMC6 is a 805-amino acid transmembrane protein with multiple membrane-spanning domains. It localizes to the endoplasmic reticulum and forms a complex with TMC8 to regulate zinc transport. The protein is essential for maintaining intracellular zinc levels in keratinocytes, which in turn controls the activity of transcription factors involved in differentiation and antiviral responses. Mutations in TMC6 disrupt zinc homeostasis, leading to permissiveness for beta-HPV replication and the development of epidermodysplasia verruciformis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TMC6 Knockout HEK293 Cell Line | EDJ-KQ7370 | Human | 11322 | Details Get a Quote |
| TMC6 Knockout HCT 116 Cell Line | EDJ-KQ31119 | Human | 11322 | Details Get a Quote |
| TMC6 Knockout A-549 Cell Line | EDJ-KQ32487 | Human | 11322 | Details Get a Quote |
| TMC6 Knockout HeLa Cell Line | EDJ-KQ32489 | Human | 11322 | Details Get a Quote |
