GRIA2

Chr 4

glutamate ionotropic receptor AMPA type subunit 2

Also known as: GLUR2, GLURB, GluA2, GluR-K2, HBGR2, NEDLIB, gluR-2, gluR-B

NCBI Gene: 2891 ENSG00000120251 UniProt: P42262

The protein functions as the GRIA2 subunit of AMPA glutamate receptors, which are ligand-activated cation channels that mediate excitatory neurotransmission in the brain and undergo RNA editing to become impermeable to calcium. Mutations cause autosomal dominant neurodevelopmental disorder with language impairment and behavioral abnormalities. The pathogenic mechanism likely involves disrupted excitatory neurotransmission due to altered AMPA receptor function.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. This gene product belongs to a family of glutamate receptors that are sensitive to alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), and function as ligand-activated cation channels. These channels are assembled from 4 related subunits, GRIA1-4. The subunit encoded by this gene (GRIA2) is subject to RNA editing (CAG->CGG; Q->R) within the second transmembrane domain, which is thought to render the channel impermeable to Ca(2+). Human and animal studies suggest that pre-mRNA editing is essential for brain function, and defective GRIA2 RNA editing at the Q/R site may be relevant to amyotrophic lateral sclerosis (ALS) etiology. Alternative splicing, resulting in transcript variants encoding different isoforms, (including the flip and flop isoforms that vary in their signal transduction properties), has been noted for this gene. [provided by RefSeq, Jul 2008]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder with language impairment and behavioral abnormalities

Clinical highlights

Gene-disease validity (ClinGen)

neurodevelopmental disorder with language impairment and behavioral abnormalities · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.25

LOEUF· LoF intol.

LOF

Mechanism· G2P

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GeneReview available — GRIA2