GRIN2A
GRIN2A (Glutamate receptor ionotropic, NMDA 2A) is a gene that drives cell growth when it is altered. The public catalogues list it as a drug target, an oncogene driver and a fusion partner, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Colorectal cancer, Lung cancer, Skin cancer and 5 more.
Overview
Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+). NMDARs participate in synaptic plasticity for learning and memory formation by contributing to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning. Channel activation requires binding of the neurotransmitter L-glutamate to the GluN2 subunit, glycine or D-serine binding to the GluN1 subunit, plus membrane depolarisation to eliminate channel inhibition by Mg(2+).
Open Targets scores its association with cancer at 0.75 (direct and indirect evidence; datatypes clinical 0.59, literature 0.41, genetic association 0.49, somatic mutation 0.87, animal model 0.32). IntOGen calls it a driver in 6 cohorts (4 activating, 0 loss-of-function), covering Bladder Urothelial Carcinoma, Cholangiocarcinoma, Colorectal Adenocarcinoma, Malignant Tumour, Pancreas.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · GRIN2A (Glutamate receptor ionotropic, NMDA 2A) is a gene that drives cell growth when it is altered. The public catalogues list it as a drug target, an oncogene driver and a fusion partner, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Colorectal cancer, Lung cancer, Skin cancer and 5 more.
- 1 · What it is
GRIN2A (Glutamate receptor ionotropic, NMDA 2A) is a gene that drives cell growth when it is altered. The public catalogues list it as a drug target, an oncogene driver and a fusion partner, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Colorectal cancer, Lung cancer, Skin cancer and 5 more.
- 2 · What goes wrong in cancer
Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+).
- 3 · How drugs use it
No product in this corpus aims at GRIN2A yet. Drugs fit a pocket that exists only in one shape of the mutant protein and hold it there, off.
External identifiers
Sources: HGNC HGNC:4585 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q12879 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000183454 (association with cancer (MONDO_0004992) 0.75; per-cancer scores at or above 0.5: prostate cancer 0.51, melanoma 0.59, skin cancer 0.57, breast cancer 0.57, lung cancer 0.58, biliary tract cancer 0.50 (GraphQL API, CC0)); IntOGen GRIN2A (driver in 6 cohorts (Act 4, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+). NMDARs participate in synaptic plasticity for learning and memory formation by contributing to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning. Channel activation requires binding of the neurotransmitter L-glutamate to the GluN2 subunit, glycine or D-serine binding to the GluN1 subunit, plus membrane depolarisation to eliminate channel inhibition by Mg(2+). NMDARs mediate simultaneously the potassium efflux and the influx of calcium and sodium. Each GluN2 subunit confers differential attributes to channel properties, including activation, deactivation and desensitisation kinetics, pH sensitivity, Ca2(+) permeability, and binding to allosteric modulators. Participates in the synaptic plasticity regulation through activation by the L-glutamate releaseed by BEST1, into the synaptic cleft, upon F2R/PAR-1 activation in astrocyte. Location: Cell projection, dendritic spine; Cell membrane; Synapse; Postsynaptic cell membrane (UniProt). Locus 16p13.2 (HGNC).
- Colorectal cancer: IntOGen driver in 2 cohorts (COADREAD)
- Lung cancer: Open Targets association 0.58 with lung cancer (MONDO_0008903)
- Skin cancer: Open Targets association 0.57 with skin cancer (MONDO_0002898)
- Bladder & urothelial cancer: IntOGen driver in 1 cohort (BLCA)
- Pancreatic ductal adenocarcinoma: IntOGen driver in 1 cohort (PANCREAS)
- Breast cancer: Open Targets association 0.57 with breast cancer (MONDO_0007254)
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: Open Targets known-drug datatype score 0.59; IntOGen calls it an activating (Act) driver in 4 cohorts; UniProt disease notes describe a translocation or gene fusion involving the gene. Evidence tier "clinical-evidence" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"GRIN2A" OR ABSTRACT:"GRIN2A" OR TITLE:"glutamate ionotropic receptor NMDA type subunit 2A" OR ABSTRACT:"glutamate ionotropic receptor NMDA type subunit 2A" OR TITLE:"Glutamate receptor ionotropic, NMDA 2A" OR ABSTRACT:"Glutamate receptor ionotropic, NMDA 2A" OR TITLE:"GluN2A" OR ABSTRACT:"GluN2A" OR TITLE:"NR2A" OR ABSTRACT:"NR2A" OR TITLE:"NMDAR2A" OR ABSTRACT:"NMDAR2A") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about GRIN2A, not a curated reading list.
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