ITPR2: Inositol 1,4,5-Trisphosphate Receptor Type 2
Key calcium channel in cellular signaling and disease
Gene Information Card
| Symbol | ITPR2 |
|---|---|
| Full Name | Inositol 1,4,5-Trisphosphate Receptor Type 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 12p11.23 |
| NCBI Gene ID | 3709 ncbi.nlm.nih.gov/gene/3709 |
| Ensembl ID | ENSG00000100100 |
| UniProt ID | Q14571 |
| OMIM ID | 147265 |
| HGNC ID | 6181 |
| Aliases | IP3R2, INSP3R2, IP3 receptor type 2 |
Description
The ITPR2 gene encodes the inositol 1,4,5-trisphosphate receptor type 2 (IP3R2), an intracellular calcium channel primarily located on the endoplasmic reticulum. It mediates calcium release in response to IP3 signaling, regulating diverse cellular processes including proliferation, apoptosis, and metabolism. Mutations in ITPR2 are associated with various disorders, including cancer and neurological conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary Hemorrhagic Telangiectasia (HHT) | Loss-of-function variants impair calcium signaling in endothelial cells, leading to vascular malformations. | ClinVar, OMIM |
| Spinocerebellar Ataxia (SCA) | Dominant-negative or gain-of-function mutations disrupt calcium homeostasis in Purkinje neurons, causing neurodegeneration. | ClinVar, OMIM |
| Cancer (various types) | Altered ITPR2 expression and mutations affect calcium-dependent apoptosis and proliferation pathways. | COSMIC, NCBI |
| Spinocerebellar ataxia type 29 (SCA29) | Missense mutations in ITPR2 disrupt calcium homeostasis in Purkinje cells, leading to neurodegeneration. | ClinVar, OMIM |
| Gilles de la Tourette syndrome | Rare variants in ITPR2 are associated with altered calcium signaling in neuronal circuits. | ClinVar, NCBI |
| Cancer (various) | Altered ITPR2 expression affects calcium-dependent apoptosis and proliferation in tumors. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Heart | 8.7 | Low |
| Liver | 15.2 | Medium |
| Kidney | 10.1 | Low |
| Lung | 6.5 | Low |
| Cerebellum | 12.5 | High |
| Heart | 8.2 | Medium |
| Liver | 6.1 | Medium |
| Pancreas | 4.8 | Low |
| Skeletal muscle | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.4 | High expression |
| HeLa | 9.2 | Moderate expression |
| SH-SY5Y | 14.1 | Neuronal cell line |
| HepG2 | 11.5 | Hepatocyte model |
| SH-SY5Y (neuroblastoma) | 10.1 | High expression |
| HepG2 (hepatocellular carcinoma) | 7.3 | Moderate expression |
| MCF7 (breast cancer) | 5.6 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.736C>T (p.Arg246*) | Nonsense | <0.1% | Loss of function; associated with HHT |
| c.2546G>A (p.Arg849His) | Missense | <0.1% | Gain of function; linked to SCA |
| c.4123A>G (p.Asn1375Asp) | Missense | <0.1% | Dominant-negative effect; reported in cancer |
| c.736G>A (p.Gly246Arg) | Missense | Rare | Altered channel gating; associated with SCA29 |
| c.1550T>C (p.Leu517Pro) | Missense | Rare | Impaired calcium release; Tourette syndrome risk |
| c.2542C>T (p.Arg848Trp) | Missense | Rare | Reduced IP3 binding affinity |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein, reducing calcium channel activity; associated with HHT.
Gain of Function (GOF)
Missense mutations that increase channel open probability or calcium flux; linked to SCA.
Dominant Negative (DN)
Missense mutations that disrupt tetramer formation or channel function, impairing wild-type receptor activity; observed in cancer.
Loss of Function (LOF)
Missense mutations reducing calcium channel activity (e.g., p.Leu517Pro) lead to impaired IP3-mediated signaling.
Gain of Function (GOF)
Not well documented; some variants may enhance calcium release but evidence is limited.
Dominant Negative (DN)
Dominant-negative effects observed in SCA29 mutations (e.g., p.Gly246Arg) disrupting tetrameric channel function.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005216 (ion channel activity) | • GO:0005515 (protein binding) |
| • GO:0005783 (endoplasmic reticulum) | • GO:0006874 (cellular calcium ion homeostasis) |
| • GO:0015279 (inositol 1 | • 4 |
| • 5-trisphosphate-sensitive calcium-release channel activity) | • GO:0032467 (positive regulation of cytokinesis) |
Pathways
• Calcium signaling pathway (KEGG: hsa04020)
• IP3 receptor-mediated calcium release (Reactome: R-HSA-169911)
• Apoptosis (KEGG: hsa04210)
Protein Summary
The ITPR2 protein (IP3R2) is a tetrameric calcium channel localized to the endoplasmic reticulum. It consists of an N-terminal IP3-binding domain, a central regulatory region, and a C-terminal channel domain. Upon IP3 binding, it undergoes conformational changes to release calcium into the cytoplasm, influencing cell signaling, growth, and death. Post-translational modifications and interactions with other proteins modulate its activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ITPR2 Knockout HEK293 Cell Line | EDJ-KQ1422 | Human | 3709 | Details Get a Quote |
| ITPR2 Knockout A-549 Cell Line | EDJ-KQ20963 | Human | 3709 | Details Get a Quote |
| ITPR2 Knockout HCT 116 Cell Line | EDJ-KQ20964 | Human | 3709 | Details Get a Quote |
| ITPR2 Knockout HeLa Cell Line | EDJ-KQ20965 | Human | 3709 | Details Get a Quote |
| ITPR1 and ITPR2 and ITPR3 Knockout HEK293 Cell Line | EDC90258 | Human | 3708 and 3709 and 3710 | Details Get a Quote |
Displaying Records 1 To 5 Of 5 Records
