IRAG1 Gene (Inositol 1,4,5-Trisphosphate Receptor Associated 1)
Key regulator of intracellular calcium signaling and smooth muscle relaxation
Gene Information Card
| Symbol | IRAG1 |
|---|---|
| Full Name | Inositol 1,4,5-Trisphosphate Receptor Associated 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 11q14.1 |
| NCBI Gene ID | 7157 ncbi.nlm.nih.gov/gene/7157 |
| Ensembl ID | ENSG00000149257 |
| UniProt ID | Q9Y6M5 |
| OMIM ID | 605552 |
| HGNC ID | 7227 |
| Aliases | MRVI1, JAW1, IRAG |
Description
IRAG1 (Inositol 1,4,5-Trisphosphate Receptor Associated 1) encodes a protein that interacts with the inositol 1,4,5-trisphosphate receptor (IP3R) and cGMP-dependent protein kinase I (PKG I). This complex mediates cGMP-induced calcium release from intracellular stores, playing a critical role in smooth muscle relaxation and platelet aggregation. The gene is also known as MRVI1 (Murine Retrovirus Integration Site 1 homolog).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Thrombocytopenia, platelet dysfunction, and bleeding disorder | Loss-of-function mutations in IRAG1 impair cGMP-dependent calcium signaling in platelets, leading to defective aggregation and increased bleeding risk. | ClinVar, OMIM |
| Smooth muscle dysfunction (e.g., gastrointestinal dysmotility) | Disruption of IRAG1-mediated calcium signaling in smooth muscle cells alters contractility, potentially contributing to motility disorders. | UniProt, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Smooth muscle (e.g., uterus, bladder, gastrointestinal tract) | High | Tissue-specific expression |
| Platelets | High | Tissue-specific expression |
| Heart | Moderate | GTEx data |
| Lung | Moderate | GTEx data |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | Moderate | Model cell line |
| A549 | Low | Lung carcinoma cell line |
| K562 | Low | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.593G>A (p.Arg198Gln) | Missense | Rare | Impaired IP3R binding; associated with bleeding disorder |
| c.1A>G (p.Met1Val) | Start loss | Rare | Loss of protein expression; associated with thrombocytopenia |
Mutation functional classification
Loss of Function (LOF)
Missense and start-loss variants that reduce or abolish IRAG1 protein expression or interaction with IP3R/PKG I, leading to defective calcium signaling.
Gain of Function (GOF)
No gain-of-function mutations reported in IRAG1.
Dominant Negative (DN)
No dominant-negative mutations reported in IRAG1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• cGMP-PKG signaling pathway (Reactome: R-HSA-418555)
• IP3 receptor-mediated calcium release (Reactome: R-HSA-169893)
Protein Summary
IRAG1 is a 944-amino acid protein that localizes to the endoplasmic reticulum and plasma membrane. It contains a coiled-coil domain and a transmembrane region. The protein forms a ternary complex with IP3R and PKG I, enabling cGMP-dependent phosphorylation of IRAG1, which triggers calcium release from intracellular stores. This mechanism is essential for nitric oxide/cGMP-induced smooth muscle relaxation and platelet inhibition.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IRAG1 Knockout HEK293 Cell Line | EDJ-KQ1850 | Human | 10335 | Details Get a Quote |
| IRAG1 Knockout HCT 116 Cell Line | EDJ-KQ21714 | Human | 10335 | Details Get a Quote |
| IRAG1 Knockout HeLa Cell Line | EDJ-KQ55384 | Human | 10335 | Details Get a Quote |
| IRAG1 Knockout A-549 Cell Line | EDJ-KQ63865 | Human | 10335 | Details Get a Quote |
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