ITPR2 Gene

ITPR2 Gene

Introduction

Itpr2 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene"> [@supsup2022]
<table> [@supsup2021a]
<tr><th>Gene Symbol</th><td>ITPR2</td></tr> [@supsup2023]
<tr><th>Full Name</th><td>Inositol 1,4,5-Trisphosphate Receptor Type 2</td></tr> [@supsup2022a]
<tr><th>Chromosomal Location</th><td>12p11.23</td></tr>
<tr><th>NCBI Gene ID</th><td>3709</td></tr>
<tr><th>OMIM</th><td>600144</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000123104</td></tr>
<tr><th>UniProt ID</th><td>Q14571</td></tr>
<tr><th>Associated Diseases</th><td>Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Spinocerebellar Ataxia</td></tr>
</table>
</div>

Overview

ITPR2 Gene

Introduction

Itpr2 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene"> [@supsup2022]
<table> [@supsup2021a]
<tr><th>Gene Symbol</th><td>ITPR2</td></tr> [@supsup2023]
<tr><th>Full Name</th><td>Inositol 1,4,5-Trisphosphate Receptor Type 2</td></tr> [@supsup2022a]
<tr><th>Chromosomal Location</th><td>12p11.23</td></tr>
<tr><th>NCBI Gene ID</th><td>3709</td></tr>
<tr><th>OMIM</th><td>600144</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000123104</td></tr>
<tr><th>UniProt ID</th><td>Q14571</td></tr>
<tr><th>Associated Diseases</th><td>Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Spinocerebellar Ataxia</td></tr>
</table>
</div>

Overview

ITPR2 encodes the type 2 inositol 1,4,5-trisphosphate receptor (IP3R2), a ligand-gated calcium release channel on the endoplasmic reticulum. IP3R2 mediates calcium release in response to IP3 signaling and plays crucial roles in cellular calcium homeostasis.

Function

IP3R2 is one of three mammalian IP3 receptor isoforms:

• Calcium Release Channel: Opens in response to IP3 binding, releasing Ca²⁺ from ER stores
• Calcium Signaling: Generates cytosolic Ca²⁺ waves for various cellular processes
• Tissue Distribution: Predominantly expressed in [neurons](/entities/neurons) and endocrine cells
• Channel Properties: Forms tetrameric channels (~1.4 MDa)

Key Functions

• Neuronal Calcium Signaling: Regulates Ca²⁺ dynamics in neurons
• Synaptic Plasticity: Ca²⁺ release affects [LTP](/mechanisms/long-term-potentiation), LTD, and neurotransmitter release
• Gene Expression: Ca²⁺ influx activates transcription factors (CREB, NFAT)
• Metabolism: Links G-protein signaling to metabolic responses
• [Apoptosis](/entities/apoptosis): Calcium release can trigger programmed cell death

Disease Associations

Alzheimer's Disease

• IP3R2 expression altered in AD brain
• [Aβ](/proteins/amyloid-beta) affects IP3-mediated calcium signaling
• Dysregulated calcium contributes to [tau](/proteins/tau) pathology
• Synaptic calcium dysregulation affects memory

Parkinson's Disease

• Dopaminergic neurons vulnerable to calcium dysregulation
• [α-Synuclein](/proteins/alpha-synuclein) affects ER calcium stores
• IP3 signaling pathways implicated in PD
• Mitochondrial and ER stress intersect

Huntington's Disease

• Mutant [huntingtin](/proteins/huntingtin-protein) affects IP3 receptor function
• Calcium signaling dysregulation contributes to neuronal dysfunction
• Altered ER-mitochondria contacts
• Therapeutic targeting of calcium pathways ongoing

Spinocerebellar Ataxia (SCA15)

• ITPR2 mutations cause SCA15 and SCA16
• Purkinje cell dysfunction due to calcium signaling defects
• Progressive ataxia from cerebellar degeneration

Expression Pattern

ITPR2 is expressed in:

• Brain (cerebellum > [cortex](/brain-regions/cortex) > hippocampus)
• Endocrine tissues (pancreas, pituitary)
• Heart and smooth muscle
• Liver

• Cerebellar Purkinje cells (highest)
• Hippocampal pyramidal neurons
• Cortical pyramidal neurons
• Substantia nigra dopaminergic neurons

Therapeutic Implications

• IP3 Receptor Modulators: Targeting channel function
• Calcium Stabilizers: Preventing excitotoxicity
• Store-Operated Calcium Entry (SOCE) Modulators
• ER Stress Reducers: Improving calcium homeostasis

Research Directions

• Developing IP3R-targeted therapeutics
• Understanding isoform-specific functions
• Calcium dysregulation as biomarker

Animal Models

• ITPR2 knockout mice show viability but with deficits
• Conditional knockout in neurons
• Transgenic models with mutant IP3R2 show ataxia

Background

The study of Itpr2 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

See Also

• [Calcium Signaling](/mechanisms/calcium-signaling)
• [Excitotoxicity](/mechanisms/excitotoxicity-neurodegeneration)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Huntington's Disease](/diseases/huntingtons-disease)
• [Spinocerebellar Ataxia](/diseases/spinocerebellar-ataxia)

Pathway Diagram

The following diagram shows the key molecular relationships involving ITPR2 Gene discovered through SciDEX knowledge graph analysis: