GRIP1: Glutamate Receptor Interacting Protein 1
A scaffold protein in synaptic signaling and neurodevelopmental disorders
Gene Information Card
| Symbol | GRIP1 |
|---|---|
| Full Name | Glutamate Receptor Interacting Protein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q14.3 |
| NCBI Gene ID | 23426 ncbi.nlm.nih.gov/gene/23426 |
| Ensembl ID | ENSG00000135446 |
| UniProt ID | Q9Y3R0 |
| OMIM ID | 604597 |
| HGNC ID | 18715 |
| Aliases | GRIP, KIAA1167 |
Description
GRIP1 encodes a scaffold protein that binds to the AMPA-type glutamate receptor subunit GluA2 (GRIA2) and is essential for receptor trafficking, clustering, and synaptic plasticity. It contains multiple PDZ domains and is highly expressed in the brain, particularly in the hippocampus and cortex. GRIP1 is involved in neurodevelopmental processes and has been implicated in intellectual disability and epilepsy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual disability, autosomal dominant 64 (MRD64) | Loss-of-function mutations in GRIP1 disrupt AMPA receptor trafficking and synaptic transmission | OMIM #618850; PMID: 31006510 |
| Epileptic encephalopathy, early infantile | De novo missense variants impair GRIP1 protein stability and synaptic localization | ClinVar; PMID: 31006510 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cerebral cortex | 32.5 | High |
| Hippocampus | 28.7 | High |
| Cerebellum | 18.3 | Medium |
| Testis | 6.2 | Low |
| Heart | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 45.8 | Neuronal model |
| HEK293 (embryonic kidney) | 1.2 | Low endogenous expression |
| U-87 MG (glioblastoma) | 22.4 | Glial model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.163C>T (p.Arg55*) | Nonsense | Rare | Loss of function; premature truncation |
| c.1123G>A (p.Gly375Arg) | Missense | De novo | Impaired PDZ domain binding |
| c.2014_2015del (p.Leu672fs) | Frameshift | Rare | Loss of function; protein truncation |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift variants lead to truncated protein lacking PDZ domains, reducing AMPA receptor anchoring.
Gain of Function (GOF)
Not reported for GRIP1.
Dominant Negative (DN)
Missense variants in PDZ domains may interfere with wild-type GRIP1 function by disrupting multimerization.
View complete mutation data：
Gene Ontology (GO)
Pathways
• AMPA receptor trafficking (Reactome: R-HSA-399719)
• Synaptic adhesion-like molecules (KEGG: hsa04724)
• Glutamatergic synapse (KEGG: hsa04724)
Protein Summary
GRIP1 is a 1,112-amino-acid scaffold protein containing seven PDZ domains. It interacts with the C-terminus of GluA2 (GRIA2) and other synaptic proteins, regulating AMPA receptor surface expression and synaptic plasticity. GRIP1 also binds to liprins, kinesins, and Eph receptors, linking glutamate receptors to the cytoskeleton and intracellular transport. Mutations in GRIP1 cause neurodevelopmental disorders by disrupting glutamatergic signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RPGRIP1L Knockout HEK293 Cell Line | EDJ-KQ7963 | Human | 23322 | Details Get a Quote |
| GRIP1 Knockout HEK293 Cell Line | EDJ-KQ8007 | Human | 23426 | Details Get a Quote |
| RPGRIP1 Knockout HEK293 Cell Line | EDJ-KQ15121 | Human | 57096 | Details Get a Quote |
| RPGRIP1L Knockout A-549 Cell Line | EDJ-KQ33650 | Human | 23322 | Details Get a Quote |
| RPGRIP1L Knockout HCT 116 Cell Line | EDJ-KQ33651 | Human | 23322 | Details Get a Quote |
| RPGRIP1L Knockout HeLa Cell Line | EDJ-KQ33652 | Human | 23322 | Details Get a Quote |
| GRIP1 Knockout A-549 Cell Line | EDJ-KQ33765 | Human | 23426 | Details Get a Quote |
| GRIP1 Knockout HeLa Cell Line | EDJ-KQ55734 | Human | 23426 | Details Get a Quote |
| RPGRIP1 Knockout HeLa Cell Line | EDJ-KQ56800 | Human | 57096 | Details Get a Quote |
| RPGRIP1 Knockout A-549 Cell Line | EDJ-KQ65306 | Human | 57096 | Details Get a Quote |
| GRIP1 Knockout HCT 116 Cell Line | EDJ-KQ72678 | Human | 23426 | Details Get a Quote |
| RPGRIP1 Knockout HCT 116 Cell Line | EDJ-KQ73747 | Human | 57096 | Details Get a Quote |
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