ITPR3

Chr 6

inositol 1,4,5-trisphosphate receptor type 3

Also known as: CMT1J, IMD132, IMD133, IP3R, IP3R-3, IP3R3

NCBI Gene: 3710 ENSG00000096433 UniProt: Q14573

The protein functions as an inositol 1,4,5-trisphosphate-gated calcium channel that releases calcium from the endoplasmic reticulum to the cytoplasm, participating in cellular calcium homeostasis. Mutations cause Charcot-Marie-Tooth disease type 1J (demyelinating peripheral neuropathy) and immunodeficiency with ectodermal dysplasia that may include peripheral neuropathy, affecting the immune system, skin/hair/teeth development, and peripheral nervous system. The gene follows autosomal dominant inheritance and is moderately constrained against loss-of-function variants (LOEUF 0.569).

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium. The receptor contains a calcium channel at the C-terminus and the ligand-binding site at the N-terminus. Knockout studies in mice suggest that type 2 and type 3 inositol 1,4,5-trisphosphate receptors play a key role in exocrine secretion underlying energy metabolism and growth. [provided by RefSeq, Aug 2010]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCharcot-Marie-Tooth disease, demyelinating, type 1J

UniProtImmunodeficiency 133 with ectodermal dysplasia with or without peripheral neuropathy

Clinical highlights

Gene-disease validity (ClinGen)

Charcot-Marie-Tooth disease, demyelinating, type 1J · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

A dominant-negative effect is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.57

LOEUF

Mechanism· G2P

Some data sources returned errors (1)

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