TRPC3

transient receptor potential cation channel subfamily C member 3, the group of Transient receptor potential cation channels|Ankyrin repeat domain containing

Basic information

Region (hg38): 4:121874480-121952060

Links

ENSG00000138741 ∙ NCBI:7222 ∙ OMIM:602345 ∙ HGNC:12335 ∙ Uniprot:Q13507 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spinocerebellar ataxia type 41 (Supportive), mode of inheritance: AD
• spinocerebellar ataxia type 41 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia 41	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	25477146

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRPC3 gene.

• not provided (75 variants)
• Inborn genetic diseases (15 variants)
• Spinocerebellar ataxia type 41 (5 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRPC3 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				21	9	30
missense			42		2	44
nonsense			2			2
start loss						0
frameshift	1					1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding				10	4	14
Total	1	0	45	31	15

Variants in TRPC3

This is a list of pathogenic ClinVar variants found in the TRPC3 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-121879758-G-A			Uncertain significance (Dec 19, 2023)
4-121879767-T-G			Benign (Aug 16, 2023)
4-121879801-C-T		not specified	Uncertain significance (Jan 24, 2023)
4-121879811-T-A			Uncertain significance (Oct 13, 2022)
4-121879816-T-C			Benign (Jan 29, 2024)
4-121879818-T-C		not specified	Uncertain significance (Jun 09, 2022)
4-121879822-C-T		not specified	Uncertain significance (Aug 11, 2022)
4-121879832-T-C			Benign (Jan 22, 2024)
4-121879894-T-TA			Benign (Jan 15, 2024)
4-121882357-C-A			Uncertain significance (Jul 01, 2017)
4-121882400-A-G			Likely benign (Apr 01, 2022)
4-121899594-C-T			Likely benign (Sep 07, 2022)
4-121899595-G-A			Likely benign (May 23, 2023)
4-121899620-G-A			Uncertain significance (Feb 04, 2023)
4-121899678-C-T			Likely benign (Aug 17, 2022)
4-121899690-G-A		TRPC3-related disorder	Likely benign (May 29, 2023)
4-121899691-T-G			Uncertain significance (Jun 22, 2023)
4-121899709-C-T			Likely benign (Aug 10, 2023)
4-121902842-C-T			Likely benign (Jun 09, 2023)
4-121902843-G-A			Likely benign (Oct 17, 2023)
4-121902856-G-A			Uncertain significance (Apr 06, 2022)
4-121902868-C-T		not specified	Uncertain significance (Apr 11, 2023)
4-121902877-A-G			Uncertain significance (Apr 09, 2022)
4-121902885-A-G			Likely benign (Nov 27, 2023)
4-121902897-C-T			Benign (Jan 30, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRPC3	protein_coding	protein_coding	ENST00000379645	12	72728

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.08e-7	0.999	125691	0	57	125748	0.000227

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.84	267	512	0.522	0.0000303	6053
Missense in Polyphen		69	188.07	0.36689		2048
Synonymous	1.37	180	205	0.878	0.0000138	1758
Loss of Function	3.01	18	38.0	0.473	0.00000196	470

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000486	0.000483
Ashkenazi Jewish	0.000102	0.0000992
East Asian	0.00126	0.00125
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000150	0.000149
Middle Eastern	0.00126	0.00125
South Asian	0.0000981	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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. Activated by diacylglycerol (DAG) in a membrane-delimited fashion, independently of protein kinase C, and by inositol 1,4,5- triphosphate receptors (ITPR) with bound IP3. May also be activated by internal calcium store depletion. {ECO:0000269|PubMed:20095964, ECO:0000269|PubMed:8646775, ECO:0000269|PubMed:9417057, ECO:0000269|PubMed:9930701}.
• Pathway: Axon guidance - Homo sapiens (human);BDNF-TrkB Signaling;Signaling by GPCR;Signal Transduction;ion channels and their functional role in vascular endothelium;Stimuli-sensing channels;Ion channel transport;Transport of small molecules;Effects of PIP2 hydrolysis;Platelet activation, signaling and aggregation;Hemostasis;TRP channels;Elevation of cytosolic Ca2+ levels;Platelet calcium homeostasis;Platelet homeostasis;G alpha (q) signalling events;GPCR downstream signalling;Trk receptor signaling mediated by PI3K and PLC-gamma (Consensus)

Recessive Scores

• pRec: 0.246

Intolerance Scores

• loftool: 0.195
• rvis_EVS: -1.24
• rvis_percentile_EVS: 5.41

Haploinsufficiency Scores

• pHI: 0.349
• hipred: Y
• hipred_score: 0.737
• ghis: 0.589

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.762

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Trpc3
• Phenotype: growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; vision/eye phenotype; 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;single fertilization;phototransduction;positive regulation of calcium ion transport into cytosol;platelet activation;response to ATP;regulation of cytosolic calcium ion concentration;response to calcium ion;calcium ion transmembrane transport;positive regulation of cardiac muscle hypertrophy in response to stress
• Cellular component: plasma membrane;integral component of plasma membrane;cation channel complex
• Molecular function: calcium channel activity;protein binding;store-operated calcium channel activity;inositol 1,4,5 trisphosphate binding