GNAI1

Chr 7AD

G protein subunit alpha i1

Also known as: Gi, HG1B, NEDHISB

NCBI Gene: 2770 ENSG00000127955 UniProt: P63096 OMIM: 139310

The protein is the alpha subunit of an inhibitory G protein complex that responds to beta-adrenergic signals by inhibiting adenylate cyclase. Heterozygous mutations cause a neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities through an autosomal dominant inheritance pattern. The high pLI score (0.91) and low LOEUF score (0.38) indicate the gene is highly intolerant to loss-of-function variants, suggesting haploinsufficiency as the likely pathogenic mechanism.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Guanine nucleotide binding proteins are heterotrimeric signal-transducing molecules consisting of alpha, beta, and gamma subunits. The alpha subunit binds guanine nucleotide, can hydrolyze GTP, and can interact with other proteins. The protein encoded by this gene represents the alpha subunit of an inhibitory complex. The encoded protein is part of a complex that responds to beta-adrenergic signals by inhibiting adenylate cyclase. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalitiesMIM #619854

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder · ADDefinitivesufficient evidence for diagnostic panels

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

0.38

LOEUF

Multiple*

Mechanism· predicted

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GeneReview available — GNAI1