ITPR1: Inositol 1,4,5-Trisphosphate Receptor Type 1
Key calcium channel in neuronal signaling and cerebellar function
Gene Information Card
| Symbol | ITPR1 |
|---|---|
| Full Name | Inositol 1,4,5-Trisphosphate Receptor Type 1 |
| Gene Type | Protein coding |
| 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 | 6180 |
| Aliases | IP3R1, IP3R, INSP3R1, SCA15, SCA29 |
Description
ITPR1 encodes the inositol 1,4,5-trisphosphate receptor type 1 (IP3R1), a ligand-gated calcium channel predominantly expressed in the cerebellum. It mediates calcium release from the endoplasmic reticulum in response to IP3, playing a critical role in neuronal signaling, synaptic plasticity, and muscle contraction. Mutations in ITPR1 are associated with spinocerebellar ataxia types 15 and 29, as well as Gillespie syndrome.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spinocerebellar ataxia type 15 (SCA15) | Heterozygous deletions or missense mutations cause haploinsufficiency, reducing IP3R1-mediated calcium signaling in Purkinje cells, leading to progressive ataxia. | ClinVar, OMIM |
| Spinocerebellar ataxia type 29 (SCA29) | Heterozygous missense mutations (e.g., p.Gly2506Arg) result in altered channel gating, causing congenital non-progressive ataxia. | ClinVar, OMIM |
| Gillespie syndrome | Biallelic loss-of-function mutations (e.g., nonsense, frameshift) lead to complete loss of IP3R1 function, causing cerebellar hypoplasia, ataxia, and aniridia. | ClinVar, OMIM |
| Spinocerebellar ataxia type 15 (SCA15) | Partial loss of function due to heterozygous deletions or missense mutations reducing IP3R1 channel activity, leading to Purkinje cell dysfunction. | ClinVar, OMIM |
| Spinocerebellar ataxia type 29 (SCA29) | Dominant-negative or gain-of-function missense mutations altering calcium flux, causing early-onset ataxia. | ClinVar, OMIM |
| Gillespie syndrome | Biallelic loss-of-function mutations (including nonsense and frameshift) leading to complete loss of IP3R1, resulting in cerebellar hypoplasia, ataxia, and aniridia. | ClinVar, OMIM |
| Congenital nonprogressive cerebellar ataxia | Homozygous or compound heterozygous ITPR1 mutations impair calcium signaling in developing cerebellum. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cerebellum | 33.2 | High |
| Cerebral cortex | 12.5 | Medium |
| Hippocampus | 10.8 | Medium |
| Heart | 3.1 | Low |
| Skeletal muscle | 2.5 | Low |
| Cerebellum | 89.5 | High |
| Cerebral cortex | 12.3 | Medium |
| Hippocampus | 10.1 | Medium |
| Testis | 8.7 | Medium |
| Heart | 2.1 | Low |
| Liver | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.4 | High expression |
| HeLa (cervical carcinoma) | 8.2 | Medium expression |
| HEK293 (embryonic kidney) | 6.1 | Medium expression |
| HepG2 (hepatocellular carcinoma) | 2.3 | Low expression |
| SH-SY5Y (neuroblastoma) | 15.2 | Neuronal model |
| U-87 MG (glioblastoma) | 8.9 | Astrocytic expression |
| HEK293 (embryonic kidney) | 3.4 | Low endogenous expression |
| HepG2 (hepatocellular carcinoma) | 0.8 | Minimal expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.7516G>A (p.Gly2506Arg) | Missense | Rare | Gain-of-function; altered calcium flux; associated with SCA29 |
| c.805C>T (p.Arg269*) | Nonsense | Rare | Loss-of-function; premature truncation; associated with Gillespie syndrome |
| Whole gene deletion | Deletion | Rare | Haploinsufficiency; associated with SCA15 |
| c.805C>T (p.Arg269Trp) | Missense | Rare | Gain-of-function; associated with SCA29 |
| c.413G>A (p.Arg138His) | Missense | Rare | Dominant-negative; reduced channel activity |
| Whole gene deletion | Deletion | Rare | Loss-of-function; causes SCA15 |
| c.2260C>T (p.Arg754*) | Nonsense | Rare | Loss-of-function; associated with Gillespie syndrome |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and whole gene deletions reduce IP3R1 protein levels or function, leading to haploinsufficiency (SCA15) or complete loss (Gillespie syndrome).
Gain of Function (GOF)
Missense mutations such as p.Gly2506Arg enhance channel activity, causing abnormal calcium release and SCA29.
Dominant Negative (DN)
Some missense mutations may produce a dominant-negative effect by forming non-functional tetramers with wild-type subunits, though this is less characterized.
Loss of Function (LOF)
Heterozygous deletions or nonsense mutations reduce IP3R1 protein levels or channel activity, leading to SCA15 or Gillespie syndrome (biallelic).
Gain of Function (GOF)
Missense mutations (e.g., p.Arg269Trp) increase calcium release, causing SCA29 with early-onset ataxia.
Dominant Negative (DN)
Certain missense mutations (e.g., p.Arg138His) impair channel function and interfere with wild-type subunits, reducing overall calcium flux.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005216 - ion channel activity | • GO:0005262 - calcium channel activity |
| • GO:0005515 - protein binding | • GO:0005783 - endoplasmic reticulum |
| • GO:0006816 - calcium ion transport | • GO:0006874 - cellular calcium ion homeostasis |
| • GO:0015278 - inositol 1 | • 4 |
| • 5-trisphosphate-sensitive calcium-release channel activity | • GO:0032469 - endoplasmic reticulum calcium ion homeostasis |
Pathways
• Calcium signaling pathway (KEGG: hsa04020)
• Phosphatidylinositol signaling system (KEGG: hsa04070)
• Alzheimer disease (KEGG: hsa05010)
• Long-term depression (KEGG: hsa04730)
Protein Summary
ITPR1 encodes the inositol 1,4,5-trisphosphate receptor type 1 (IP3R1), a tetrameric calcium channel localized to the endoplasmic reticulum. It consists of an N-terminal ligand-binding domain, a central modulatory domain, and a C-terminal channel domain. IP3R1 is highly expressed in cerebellar Purkinje cells and is essential for calcium signaling underlying motor coordination and synaptic plasticity. Dysregulation of IP3R1 function is linked to neurodegenerative ataxias and developmental 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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