TMC8
protein-codingtransmembrane channel like 8, the group of Transmembrane channel like family
Gene 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 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 8 predicted transmembrane domains and 3 leucine zipper motifs. [provided by RefSeq, Jul 2008]
- EVER2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~12.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0032614
Submitter: Genomics England PanelApp
Inheritance Pattern: AR
Disease ID:MONDO:0032614
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0032614
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0009176
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0032614
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious; Dermatologic; Oncologic
Intervention: Oncologic
Rationale: Individuals are at high-risk of developing skin cancers, and surveillance may be beneficial to allow early detection and treatment
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TMC8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_152468.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 166 | 4 | 174 | ||
| missense | 287 | 22 | 1 | 310 | ||
| nonsense | 6 | 1 | 2 | 9 | ||
| start loss | 1 | 1 | 2 | |||
| frameshift | 22 | 3 | 4 | 29 | ||
| splice donor/acceptor (+/-2bp) | 10 | 6 | 16 | |||
| Total | 28 | 15 | 304 | 188 | 5 | 540 |
Highest pathogenic variant AF is 0.00024659475
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_689681.2 | 15 | MANE Select | |
| Ensembl | ENSP00000325561.4 | 15 | MANE Select | |
| Ensembl | ENSP00000467482.1 | 10 | Standard | |
| Ensembl | ENSP00000467482.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- regulation of cell growth
- negative regulation of protein binding
- negative regulation of protein oligomerization
- ion transmembrane transport
- zinc ion homeostasis
Molecular Function
- signaling receptor binding
- ion channel activity
- protein binding
- mechanosensitive ion channel activity
Cellular Component
- extracellular space
- cytoplasm
- endoplasmic reticulum
- endoplasmic reticulum membrane
- Golgi apparatus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000318430
- Coding exons
- 15
- Length
- 12199
- Individuals with no LoFs
- 125535
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 209
- Defined
- 125744
- p
- 0.000831
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.566 | 380 | 412 | 0.922 | 0.0000257 | 4537 |
| Missense (PolyPhen) | 107 | 113.23 | 0.94501 | 1422 | ||
| Synonymous | 0.257 | 191 | 196 | 0.977 | 0.0000127 | 1603 |
| Loss of Function | 1.01 | 25 | 31.1 | 0.805 | 0.00000147 | 344 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.00043 | 0.00043 | rare |
| Ashkenazi Jewish | 0.00050 | 0.00050 | rare |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0.0060 | 0.0060 | notable |
| European (Non-Finnish) | 0.00029 | 0.00029 | rare |
| South Asian | 0.00049 | 0.00049 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Probable ion channel. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.102
Intolerance Scores
- LoFtool
- 0.899
- RVIS EVS
- 0.21
- RVIS percentile EVS
- 67.5
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.136
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |