TRPC4
protein-codingtransient receptor potential cation channel subfamily C member 4, the group of Ankyrin repeat domain containing|Transient receptor potential cation channels
Gene summary
This gene encodes a member of the canonical subfamily of transient receptor potential cation channels. The encoded protein forms a non-selective calcium-permeable cation channel that is activated by Gq-coupled receptors and tyrosine kinases, and plays a role in multiple processes including endothelial permeability, vasodilation, neurotransmitter release and cell proliferation. Single nucleotide polymorphisms in this gene may be associated with generalized epilepsy with photosensitivity. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~237.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TRPC4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016179.4. 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 | 2 | 1 | 2 | 5 | ||
| missense | 87 | 1 | 88 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | 2 | |||
| Total | 1 | 0 | 92 | 2 | 2 | 97 |
Highest pathogenic variant AF is 0.0000044672306
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057263.1 | 10 | MANE Select | |
| Ensembl | ENSP00000369027.4 | 10 | MANE Select | |
| RefSeq | NP_001129427.1 | 11 | Standard | |
| RefSeq | NP_001129428.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Axon guidance - Homo sapiens (human)
- ion channels and their functional role in vascular endothelium
- Stimuli-sensing channels
- Ion channel transport
- Transport of small molecules
Biological Process
- calcium ion transport
- manganese ion transport
- gamma-aminobutyric acid secretion
- oligodendrocyte differentiation
- regulation of cytosolic calcium ion concentration
Molecular Function
- calcium channel activity
- protein binding
- beta-catenin binding
- store-operated calcium channel activity
- cadherin binding
Cellular Component
- plasma membrane
- integral component of plasma membrane
- caveola
- cell-cell junction
- cell surface
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000379681
- Coding exons
- 10
- Length
- 233790
- Individuals with no LoFs
- 125722
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 26
- Defined
- 125748
- p
- 0.000103
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.61 | 353 | 521 | 0.678 | 0.0000273 | 6439 |
| Missense (PolyPhen) | 92 | 212.69 | 0.43255 | 2715 | ||
| Synonymous | -0.829 | 216 | 201 | 1.07 | 0.0000112 | 1890 |
| Loss of Function | 4.87 | 10 | 45.5 | 0.220 | 0.00000261 | 527 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000062 | 0.000062 | rare |
| South Asian | 0.00033 | 0.00033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Form a receptor-activated non-selective calcium permeant cation channel. Acts as a cell-cell contact-dependent endothelial calcium entry channel. Probably operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Mediates cation entry, with an enhanced permeability to barium over calcium. May also be activated by intracellular calcium store depletion. {ECO:0000269|PubMed:16144838, ECO:0000269|PubMed:19996314}.;
Intolerance Scores
- LoFtool
- 0.541
- RVIS EVS
- -1.18
- RVIS percentile EVS
- 5.97
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.866
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |