TMC8

Chr 17q25.3

transmembrane channel like 8

Aliases:: EVIN2
MANE:: ENST00000318430.10

OMIM: 605829 ↗NCBI: 147138 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

TMC8 · Q8IU68

v62025-08-01

Predicted Aligned Error matrix for TMC8 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

75.9/ 100

Confident

726 residues

Confidence breakdown

Very high(≥ 90)27%
Confident(70–90)48%
Low(50–70)10%
Very low(< 50)15%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

COVID-19 research
BIALLELIC, autosomal or pseudoautosomal
Epidermodysplasia verruciformis
BIALLELIC, autosomal or pseudoautosomal
Pigmentary skin disorders
BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease
BIALLELIC, autosomal or pseudoautosomal
Multiple monogenic benign skin tumours
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

epidermodysplasia verruciformis
0.74
hemolysis
0.34
type 2 diabetes mellitus
0.29
diabetes mellitus
0.29
male reproductive system disorder
0.24
hereditary disease
0.19
neoplasm
0.04
hemoglobin D disease
0.04
infection
0.04
Abnormality of the skeletal system
0.03

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Transmembrane channel-like protein 8

Acts as a regulatory protein involved in the regulation of numerous cellular processes (PubMed:18158319, PubMed:23429285, PubMed:30068544, PubMed:32917726). Together with its homolog TMC6/EVER1, forms a complex with calcium-binding protein CIB1 in lymphocytes and keratynocytes where TMC6 and TMC8 stabilize CIB1 levels and reciprocally (PubMed:30068544, PubMed:32917726). Together with TMC6, also forms a complex with and activates zinc transporter ZNT1 at the ER membrane of keratynocytes, thereby facilitating zinc uptake into the ER (PubMed:18158319). Also inhibits receptor-mediated calcium release from ER stores and calcium activated and volume regulated chloride channels (PubMed:25220380). Down-regulates the activity of transcription factors induced by zinc and cytokines (PubMed:18158319). Also sequesters TRADD which impairs the recruitment of TRAF2 and RIPK1 in the pro-survival complex I and promotes proapoptotic complex II formation, and may therefore be involved in TNF-induced cell death/survival decisions (PubMed:23429285)