GRIA3

Chr XXLR

glutamate ionotropic receptor AMPA type subunit 3

Also known as: GLUR-C, GLUR-K3, GLUR3, GLURC, GluA3, MRX94, MRXSW, iGluR3

NCBI Gene: 2892 ENSG00000125675 UniProt: P42263 OMIM: 305915

The protein functions as an AMPA-sensitive glutamate receptor subunit that forms ligand-gated ion channels mediating excitatory neurotransmission in the brain. Mutations cause X-linked syndromic intellectual developmental disorder (Wu type) through an X-linked recessive inheritance pattern. The high constraint scores (pLI 0.999, LOEUF 0.193) indicate that pathogenic variants likely cause disease through loss of function of this essential glutamate receptor subunit.

OMIM 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. These receptors are heteromeric protein complexes composed of multiple subunits, arranged to form ligand-gated ion channels. The classification of glutamate receptors is based on their activation by different pharmacologic agonists. The subunit encoded by this gene belongs to a family of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate)-sensitive glutamate receptors, and is subject to RNA editing (AGA->GGA; R->G). Alternative splicing at this locus results in different isoforms, which may vary in their signal transduction properties. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, X-linked syndromic, Wu typeMIM #300699

XLR

Clinical highlights

Gene-disease validity (ClinGen)

X-linked complex neurodevelopmental disorder · XLDefinitivesufficient 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

—

P/LP missense

0.19

LOEUF· LoF intol.

LOF

Mechanism· G2P