TMC8: Transmembrane Channel-Like 8 Gene in Epidermodysplasia Verruciformis
TMC8 (TMC8) is a transmembrane channel-like protein gene implicated in susceptibility to epidermodysplasia verruciformis and cutaneous squamous cell carcinoma.
Gene Information Card
| Symbol | TMC8 |
|---|---|
| Full Name | Transmembrane Channel-Like 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 17p13.1 |
| NCBI Gene ID | 147138 ncbi.nlm.nih.gov/gene/147138 |
| Ensembl ID | ENSG00000141510 |
| UniProt ID | Q8IU68 |
| OMIM ID | 605829 |
| HGNC ID | HGNC:20466 |
| Aliases | EVER2, EV2, FLJ11730 |
Description
TMC8 (Transmembrane Channel-Like 8), also known as EVER2, is a protein-coding gene located on chromosome 17p13.1. It encodes a transmembrane protein that localizes to the endoplasmic reticulum and is involved in zinc homeostasis, keratinocyte differentiation, and antiviral immunity. Loss-of-function mutations in TMC8 are associated with epidermodysplasia verruciformis (EV), a rare autosomal recessive skin disorder characterized by susceptibility to specific beta-human papillomavirus (HPV) types and increased risk of cutaneous squamous cell carcinoma.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epidermodysplasia verruciformis (EV) | Loss-of-function mutations in TMC8 disrupt zinc transport, impairing keratinocyte antiviral response and allowing beta-HPV replication. | OMIM #226400; ClinVar pathogenic variants |
| Cutaneous squamous cell carcinoma (cSCC) | EV patients with TMC8 mutations have high risk of HPV-driven cSCC; TMC8 loss may promote oncogenic transformation. | COSMIC; literature review |
| HPV susceptibility (beta-HPV types) | TMC8 deficiency reduces zinc-mediated inhibition of HPV E5/E6, facilitating viral persistence. | NCBI Gene; UniProt |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.3 | Medium |
| Lung | 8.1 | Low |
| Spleen | 6.5 | Low |
| Testis | 5.2 | Low |
| Esophagus | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocyte) | 15.2 | High expression; relevant for EV studies |
| A431 (epidermoid carcinoma) | 10.5 | Moderate expression |
| HEK293 (embryonic kidney) | 3.1 | Low expression |
| HeLa (cervical carcinoma) | 2.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.744C>A (p.Cys248*) | Nonsense | Rare (EV families) | Loss of function; truncated protein |
| c.1A>G (p.Met1?) | Start loss | Rare (EV families) | Loss of function; no translation |
| c.917T>C (p.Leu306Pro) | Missense | Rare (EV families) | Loss of function; impaired zinc transport |
| c.1240C>T (p.Arg414*) | Nonsense | Rare (EV families) | Loss of function; premature stop |
Mutation functional classification
Loss of Function (LOF)
Most TMC8 mutations in EV are loss-of-function (nonsense, frameshift, start loss, missense) that disrupt zinc homeostasis and antiviral defense.
Gain of Function (GOF)
No gain-of-function mutations reported for TMC8.
Dominant Negative (DN)
No dominant-negative mutations reported; EV is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005515 (protein binding) | • GO:0005783 (endoplasmic reticulum) |
| • GO:0006810 (transport) | • GO:0008270 (zinc ion binding) |
| • GO:0016021 (integral component of membrane) | • GO:0045087 (innate immune response) |
| • GO:0055085 (transmembrane transport) |
Pathways
• Zinc homeostasis in keratinocytes
• Beta-HPV infection and evasion of immune response
• Keratinocyte differentiation and antiviral signaling
Protein Summary
The TMC8 protein (EVER2) is a 731-amino-acid transmembrane channel-like protein predominantly localized to the endoplasmic reticulum. It forms a complex with TMC6 (EVER1) and the zinc transporter ZnT-1 to regulate intracellular zinc levels in keratinocytes. By controlling zinc availability, TMC8 inhibits the activity of beta-HPV E5 and E6 proteins, thereby restricting viral replication. Loss of TMC8 function leads to elevated free zinc, enhanced HPV gene expression, and susceptibility to epidermodysplasia verruciformis and associated skin cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TMC8 Knockout HEK293 Cell Line | EDJ-KQ9846 | Human | 147138 | Details Get a Quote |
| TMC8 Knockout HCT 116 Cell Line | EDJ-KQ38005 | Human | 147138 | Details Get a Quote |
| TMC8 Knockout HeLa Cell Line | EDJ-KQ58567 | Human | 147138 | Details Get a Quote |
| TMC8 Knockout A-549 Cell Line | EDJ-KQ67057 | Human | 147138 | Details Get a Quote |
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