ITPR2
Chr 12ARinositol 1,4,5-trisphosphate receptor type 2
Also known as: ANHD, CFAP48, INSP3R2, IP3R2
This gene encodes an inositol 1,4,5-trisphosphate receptor that functions as a calcium channel, transporting calcium from the endoplasmic reticulum to the cytoplasm in response to inositol trisphosphate binding. Autosomal recessive mutations cause isolated anhidrosis with normal sweat glands, indicating that this calcium signaling pathway is essential for eccrine sweat production. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.615).
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
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.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
405 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 | 1 | 36 | 0 | 37 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 1 | 256 | 5 | 0 | 262 |
Likely Benign | 0 | 10 | 5 | 17 | 32 |
Benign | 0 | 1 | 6 | 13 | 20 |
Conflicting | — | 2 | |||
| Total | 1 | 268 | 53 | 30 | 354 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ITPR2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools