ITPR1 Gene: Inositol 1,4,5-Trisphosphate Receptor Type 1
Comprehensive guide to ITPR1: function, associated diseases, expression, mutations, and more.
Gene Information Card
| Symbol | ITPR1 |
|---|---|
| Full Name | inositol 1,4,5-trisphosphate receptor type 1 |
| Gene Type | gene with protein product |
| Chromosomal Location | 3p26.1 |
| NCBI Gene ID | 3708 ncbi.nlm.nih.gov/gene/3708 |
| Ensembl ID | ENSG00000150995 |
| UniProt ID | Q14643 |
| OMIM ID | 147265 |
| HGNC ID | HGNC:6180 |
| Aliases | Insp3r1, IP3R1, ACV, PPP1R94, SCA15, SCA16, SCA29 |
Description
The ITPR1 gene encodes the inositol 1,4,5-trisphosphate receptor type 1, a ligand-gated calcium channel located primarily in the endoplasmic reticulum. It plays a crucial role in intracellular calcium signaling by releasing calcium from internal stores upon binding to inositol 1,4,5-trisphosphate (IP3). ITPR1 is highly expressed in the central nervous system, particularly in cerebellar Purkinje cells, and is essential for neuronal function and plasticity. Mutations in ITPR1 are associated with spinocerebellar ataxia types 15, 16, and 29, as well as other neurological disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spinocerebellar ataxia type 15 (SCA15) | Haploinsufficiency due to heterozygous deletion or loss-of-function mutations | OMIM, ClinVar |
| Spinocerebellar ataxia type 16 (SCA16) | Missense mutations leading to altered channel function | OMIM, ClinVar |
| Spinocerebellar ataxia type 29 (SCA29) | Missense mutations with dominant-negative or gain-of-function effects | OMIM, ClinVar |
| Gilles de la Tourette syndrome | Association with ITPR1 variants, mechanism unclear | ClinVar, literature |
| Huntington disease (modifier) | ITPR1 expression may influence disease progression | Literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cerebellum | 100.0 | High |
| Cerebral cortex | 50.0 | Medium |
| Hippocampus | 40.0 | Medium |
| Basal ganglia | 30.0 | Medium |
| Testis | 20.0 | Low |
| Heart | 10.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 80.0 | High expression |
| U-87 MG (glioblastoma) | 60.0 | Moderate expression |
| HeLa (cervical cancer) | 30.0 | Low expression |
| HepG2 (hepatocellular carcinoma) | 20.0 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.806G>A (p.Arg269His) | Missense | Rare | Altered IP3 binding affinity |
| c.413C>T (p.Pro138Leu) | Missense | Rare | Impaired channel function |
| c.2386C>T (p.Arg796*) | Nonsense | Rare | Loss of function due to truncation |
| Whole gene deletion | Copy number variant | Rare | Haploinsufficiency |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations, including deletions and nonsense variants, lead to haploinsufficiency, reducing ITPR1 protein levels and impairing calcium signaling.
Gain of Function (GOF)
Some missense mutations may result in increased channel activity, leading to excessive calcium release and neuronal toxicity.
Dominant Negative (DN)
Certain missense mutations may exert a dominant-negative effect by forming non-functional tetramers with wild-type subunits, reducing overall channel function.
View complete mutation data：
Gene Ontology (GO)
| • inositol 1 | • 4 |
| • 5-trisphosphate-sensitive calcium-release channel activity | • calcium ion binding |
| • calcium channel activity | • endoplasmic reticulum membrane |
| • integral component of membrane | • calcium ion transport |
| • response to calcium ion |
Pathways
• Calcium signaling pathway
• IP3 and DAG signaling
• Neurotrophin signaling pathway
• Long-term depression
Protein Summary
The ITPR1 protein is a large tetrameric channel (~313 kDa per subunit) that mediates the release of calcium from the endoplasmic reticulum into the cytoplasm upon binding of IP3. It is composed of an N-terminal ligand-binding domain, a central coupling domain, and a C-terminal channel domain. ITPR1 is critical for various cellular processes including synaptic plasticity, muscle contraction, and cell proliferation. Its activity is regulated by calcium, ATP, and phosphorylation. Dysregulation of ITPR1 is implicated in several neurological disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ITPR1 Knockout HEK293 Cell Line | EDJ-KQ1421 | Human | 3708 | Details Get a Quote |
| ITPR1 Knockout A-549 Cell Line | EDJ-KQ20960 | Human | 3708 | Details Get a Quote |
| ITPR1 Knockout HCT 116 Cell Line | EDJ-KQ20961 | Human | 3708 | Details Get a Quote |
| ITPR1 Knockout HeLa Cell Line | EDJ-KQ20962 | Human | 3708 | Details Get a Quote |
| ITPR1 and ITPR2 and ITPR3 Knockout HEK293 Cell Line | EDC90258 | Human | 3708 and 3709 and 3710 | Details Get a Quote |
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