TRPC5
protein-codingtransient receptor potential cation channel subfamily C member 5, the group of Transient receptor potential cation channels|Protein phosphatase 1 regulatory subunits|Ankyrin repeat domain containing
Gene summary
This gene belongs to the transient receptor family. It encodes one of the seven mammalian TRPC (transient receptor potential channel) proteins. The encoded protein is a multi-pass membrane protein and is thought to form a receptor-activated non-selective calcium permeant cation channel. The protein is active alone or as a heteromultimeric assembly with TRPC1, TRPC3, and TRPC4. It also interacts with multiple proteins including calmodulin, CABP1, enkurin, Na(+)-H+ exchange regulatory factor (NHERF ), interferon-induced GTP-binding protein (MX1), ring finger protein 24 (RNF24), and SEC14 domain and spectrin repeat-containing protein 1 (SESTD1). [provided by RefSeq, May 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~314.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: XL
Disease ID:MONDO:0700092
Submitter: PanelApp Australia
Inheritance Pattern: XL
Disease ID:MONDO:0700092
Submitter: G2P
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TRPC5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012471.3. 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 | 15 | 111 | 5 | 131 | ||
| missense | 197 | 6 | 203 | |||
| nonsense | 21 | 21 | ||||
| start loss | 0 | |||||
| frameshift | 4 | 4 | ||||
| splice donor/acceptor (+/-2bp) | 21 | 21 | ||||
| Total | 0 | 0 | 258 | 117 | 5 | 380 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036603.1 | 10 | MANE Select | |
| Ensembl | ENSP00000262839.2 | 10 | MANE Select | |
| RefSeq | XP_016885263.1 | 10 | Standard | |
| RefSeq | XP_047298369.1 | 9 | 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
- positive regulation of cytosolic calcium ion concentration
- nervous system development
- positive regulation of cell population proliferation
Molecular Function
- actin binding
- calcium channel activity
- protein binding
- store-operated calcium channel activity
- clathrin binding
Cellular Component
- cytoplasm
- plasma membrane
- integral component of plasma membrane
- dendrite
- growth cone
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000262839
- Coding exons
- 10
- Length
- 308462
- Individuals with no LoFs
- 125411
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 2
- Defined
- 125414
- p
- 0.0000120
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.27 | 197 | 375 | 0.525 | 0.0000288 | 6435 |
| Missense (PolyPhen) | 65 | 175.8 | 0.36975 | 2948 | ||
| Synonymous | -0.413 | 146 | 140 | 1.04 | 0.0000104 | 1869 |
| Loss of Function | 4.72 | 1 | 27.9 | 0.0358 | 0.00000213 | 484 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000076 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000013 | 0.0000088 | rare |
| South Asian | 0.000055 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Thought to form a receptor-activated non-selective calcium permeant cation channel. Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Has also been shown to be calcium-selective (By similarity). May also be activated by intracellular calcium store depletion. {ECO:0000250, ECO:0000269|PubMed:16284075}.;
Recessive Scores
- pRec
- 0.174
Intolerance Scores
- LoFtool
- 0.0223
- RVIS EVS
- -0.47
- RVIS percentile EVS
- 23.51
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0289
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |