TRPM3
Chr 9ADtransient receptor potential cation channel subfamily M member 3
Also known as: CTRCT50, GON-2, LTRPC3, MLSN2, NEDFSS
This gene encodes a constitutively active calcium channel that mediates calcium entry into cells and functions in heat sensing, pain sensitivity, and insulin secretion. Mutations cause autosomal dominant neurodevelopmental disorder with hypotonia, dysmorphic features, and skeletal anomalies with or without seizures, as well as cataract with or without glaucoma. The gene is highly constrained against loss-of-function variants (LOEUF 0.453), indicating that such mutations are likely pathogenic.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Highly missense-constrained (top ~0.1%)
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
316 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 14 | 0 | 14 |
Likely Pathogenic | 1 | 2 | 2 | 0 | 5 |
VUS | 9 | 202 | 8 | 1 | 220 |
Likely Benign | 0 | 13 | 4 | 18 | 35 |
Benign | 0 | 4 | 3 | 8 | 15 |
Conflicting | — | 5 | |||
| Total | 10 | 221 | 31 | 27 | 294 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TRPM3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools