GRIA1

Chr 5

glutamate ionotropic receptor AMPA type subunit 1

Also known as: GLUH1, GLUR1, GLURA, GluA1, HBGR1, MRD67, MRT76

NCBI Gene: 2890 ENSG00000155511 UniProt: P42261

This gene encodes a subunit of AMPA glutamate receptors, which form ligand-gated ion channels that mediate excitatory neurotransmission in the brain. Mutations cause intellectual developmental disorder through both autosomal dominant and autosomal recessive inheritance patterns. The high pLI score (0.999) and low LOEUF score (0.259) indicate the protein is highly intolerant to loss-of-function mutations, suggesting haploinsufficiency as a likely mechanism for the dominant form.

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 with multiple subunits, each possessing transmembrane regions, and all arranged to form a ligand-gated ion channel. The classification of glutamate receptors is based on their activation by different pharmacologic agonists. This gene belongs to a family of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder, autosomal dominant 67

UniProtIntellectual developmental disorder, autosomal recessive 76

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder · ADModerateconsider for supplementary testing2 gene-disease associations curated in total

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.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

0.26

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

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