TRPC4

transient receptor potential cation channel subfamily C member 4, the group of Ankyrin repeat domain containing|Transient receptor potential cation channels

Basic information

Region (hg38): 13:37632062-37869802

Links

ENSG00000133107 ∙ NCBI:7223 ∙ OMIM:603651 ∙ HGNC:12336 ∙ Uniprot:Q9UBN4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRPC4 gene.

• Inborn genetic diseases (21 variants)
• not provided (2 variants)
• Autism, susceptiblity to (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRPC4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					2	2
missense			21			21
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)	1					1
splice region						0
non coding						0
Total	1	0	21	0	2

Highest pathogenic variant AF is 0.00000682

Variants in TRPC4

This is a list of pathogenic ClinVar variants found in the TRPC4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
13-37636909-T-C			Benign (Dec 31, 2019)
13-37636971-T-C		not specified	Uncertain significance (Jun 06, 2023)
13-37637100-C-T		not specified	Uncertain significance (Oct 06, 2022)
13-37637117-A-T		not specified	Uncertain significance (Oct 13, 2021)
13-37637169-C-T		not specified	Uncertain significance (Feb 05, 2024)
13-37637201-G-T		not specified	Uncertain significance (Jun 07, 2023)
13-37637211-C-G		not specified	Uncertain significance (Jul 13, 2022)
13-37637219-C-T		not specified	Uncertain significance (Aug 13, 2021)
13-37637264-T-C		not specified	Uncertain significance (Nov 18, 2022)
13-37637342-T-C		not specified	Uncertain significance (Feb 28, 2024)
13-37637415-C-T		not specified	Uncertain significance (Oct 12, 2021)
13-37637534-G-A		not specified	Uncertain significance (Nov 18, 2023)
13-37637558-G-A		not specified	Uncertain significance (Jan 22, 2024)
13-37639074-T-C		not specified	Uncertain significance (Jun 21, 2022)
13-37639099-C-T		not specified	Uncertain significance (Nov 17, 2022)
13-37639290-C-T		not specified	Uncertain significance (Apr 28, 2022)
13-37651293-C-A		not specified	Uncertain significance (May 23, 2023)
13-37651446-A-G		not specified	Uncertain significance (Feb 16, 2023)
13-37663461-G-A		not specified	Uncertain significance (Mar 11, 2024)
13-37692047-C-T		not specified	Uncertain significance (Feb 21, 2024)
13-37692234-A-G			Benign (Feb 25, 2018)
13-37692295-C-T		not specified	Uncertain significance (Nov 03, 2022)
13-37692308-G-C		not specified	Uncertain significance (Apr 07, 2023)
13-37745957-T-C		not specified	Uncertain significance (Jan 22, 2024)
13-37746004-A-G		not specified	Uncertain significance (Jul 12, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRPC4	protein_coding	protein_coding	ENST00000379681	10	233790

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.482	0.518	125722	0	26	125748	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.61	353	521	0.678	0.0000273	6439
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.0000544	0.0000544
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.0000621	0.0000615
Middle Eastern	0.0000544	0.0000544
South Asian	0.000328	0.000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: Axon guidance - Homo sapiens (human);ion channels and their functional role in vascular endothelium;Stimuli-sensing channels;Ion channel transport;Transport of small molecules;TRP channels (Consensus)

Intolerance Scores

• loftool: 0.541
• rvis_EVS: -1.18
• rvis_percentile_EVS: 5.97

Haploinsufficiency Scores

• pHI: 0.478
• hipred: Y
• hipred_score: 0.725
• ghis: 0.559

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.866

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Trpc4
• Phenotype: muscle phenotype; normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: calcium ion transport;manganese ion transport;gamma-aminobutyric acid secretion;oligodendrocyte differentiation;regulation of cytosolic calcium ion concentration;calcium ion import;calcium ion transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;caveola;cell-cell junction;cell surface;basolateral plasma membrane;cortical cytoskeleton;cation channel complex;calcium channel complex
• Molecular function: calcium channel activity;protein binding;beta-catenin binding;store-operated calcium channel activity;cadherin binding;inositol 1,4,5 trisphosphate binding