protein
Guanine nucleotide-binding protein G(i) subunit alpha-1
Gene
GNAI1
Organism
Homo sapiens(9606)
Length
354 aa
Mass
40,361 Da
GNAI1 (guanine nucleotide-binding protein G(i) subunit alpha-1) is a heterotrimeric G protein alpha subunit that functions as a molecular transducer downstream of G protein-coupled receptors (UniProt: P63096). The protein cycles between an active GTP-bound state and an inactive GDP-bound state, with its intrinsic GTPase activity terminating signaling by hydrolyzing GTP to GDP. GNAI1 primarily inhibits adenylate cyclase activity, reducing intracellular cAMP levels, and also regulates cytoskeletal dynamics including dynein-dynactin complex recruitment during cell division.
GNAI1 is broadly expressed and participates in multiple cellular processes spanning signal transduction, cytokinesis, and cortical organization. Mutations in GNAI1 are associated with neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities (NEDHISB), an autosomal dominant condition characterized by global developmental delay, intellectual disability, speech impairment, hypotonia, behavioral abnormalities, and epilepsy, often with dysmorphic features and brain imaging abnormalities (UniProt: P63096).
GNAI1 is classified as SFARI Category 2 (likely ASD risk gene) (SFARI Cat 2), reflecting evidence linking this G protein subunit to autism spectrum disorder and related neurodevelopmental conditions.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
Strong candidate — functional studies support ASD association
Source: SFARI Gene database · gene.sfari.org
Related Publications
Browse all →Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades (PubMed:18434541, PubMed:33762731, PubMed:34239069, PubMed:35610220, PubMed:37935376, PubMed:37935377, PubMed:37963465, PubMed:38552625, PubMed:8774883, PubMed:38918398, PubMed:40080544). The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state (PubMed:18434541, PubMed:8774883). Signaling by an activated GPCR promotes GDP release and GTP binding (PubMed:18434541, PubMed:8774883). The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal (PubMed:18434541, PubMed:8774883). Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (PubMed:18434541, PubMed:8774883). Signaling is mediated via effector proteins, such as adenylate cyclase: inhibits adenylate cyclase activity of ADCY1, ADCY5 and ADCY6, leading to decreased intracellular cAMP levels (PubMed:8119955). The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. Required for normal cytokinesis during mitosis (PubMed:17635935). Required for cortical dynein-dynactin complex recruitment during metaphase (PubMed:22327364)
Disease associations
Neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalitiesNEDHISB
An autosomal dominant disorder characterized by global developmental delay, impaired intellectual development, delayed or absent speech, hypotonia, behavioral abnormalities, and epilepsy that ranges from self-limiting to intractable. More variable features include non-specific dysmorphic facial features, distal skeletal anomalies, and brain imaging abnormalities.
Sources
Last updated 5/6/2026, 5:24:04 AM