TRPC3

Chr 4AD

transient receptor potential cation channel subfamily C member 3

Also known as: SCA41, TRP3

NCBI Gene: 7222ENSG00000138741UniProt: Q13507

The protein encoded by this gene is a membrane protein that can form a non-selective channel permeable to calcium and other cations. The encoded protein appears to be induced to form channels by a receptor tyrosine kinase-activated phosphatidylinositol second messenger system and also by depletion of intracellular calcium stores. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

Primary Disease Associations & Inheritance

?Spinocerebellar ataxia 41MIM #616410
AD
249
ClinVar variants
23
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— TRPC3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 138 VUS of 249 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.70LOEUF
pLI 0.000
Z-score 3.01
OE 0.47 (0.33–0.70)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.84Z-score
OE missense 0.52 (0.47–0.58)
267 obs / 511.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.47 (0.33–0.70)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.52 (0.47–0.58)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.88
0≤1.21.6
LoF obs/exp: 18 / 38.0Missense obs/exp: 267 / 511.6Syn Z: 1.37

ClinVar Variant Classifications

249 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic1
VUS138
Likely Benign73
Benign15
22
Pathogenic
1
Likely Pathogenic
138
VUS
73
Likely Benign
15
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
21
0
22
Likely Pathogenic
0
0
1
0
1
VUS
0
125
13
0
138
Likely Benign
0
1
20
52
73
Benign
0
2
4
9
15
Total11285961249

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TRPC3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Spinocerebellar ataxia 41

MIM #616410

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Structural mechanism of human TRPC3 and TRPC6 channel regulation by their intracellular calcium-binding sites.
Guo W et al.·Neuron
2022Functional
TRP channels in cardiac and intestinal fibrosis.
Inoue R et al.·Semin Cell Dev Biol
2019Review
Discovery of a potent and selective TRPC3 antagonist with neuroprotective effects.
Wang J et al.·Bioorg Med Chem
2025
Epigenetic Study of Cohort of Monozygotic Twins With Hypertrophic Cardiomyopathy Due to MYBPC3 (Cardiac Myosin-Binding Protein C).
Peñarroya A et al.·J Am Heart Assoc
2024Cohort
Pathophysiological significance and modulation of the transient receptor potential canonical 3 ion channel.
Boda VK et al.·Med Res Rev
2024Review
Emerging pathways driving early synaptic pathology in Alzheimer's disease.
Briggs CA et al.·Biochem Biophys Res Commun
2017Review
Calcium signalling in salivary gland physiology and dysfunction.
Ambudkar IS·J Physiol
2016Review
The contribution of GTF2I haploinsufficiency to Williams syndrome.
Chailangkarn T et al.·Mol Cell Probes
2018Review
Ablation of TRPC3 disrupts Ca(2+) signaling in salivary ductal cells and promotes sialolithiasis.
Choi BE et al.·Sci Rep
2023
The Role of TRP Channels in Colitis and Inflammatory Bowel Disease: A Systematic Review.
Dvornikova KA et al.·Int J Mol Sci
2025Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Transplantation InfectionKidney Diseases

Molecular Biological and Moleculargenetic Monitoring of Therapy After Kidney Transplantation

RECRUITING
NCT01515605Odense University HospitalStarted 2011-01-01

External Resources

Links to major genomics databases and tools