GNAI2

Chr 3p21.31

G protein subunit alpha i2

Aliases:: GIP
MANE:: ENST00000313601.11

OMIM: 139360 ↗NCBI: 2771 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

GNAI2 · P04899

v62025-08-01

Predicted Aligned Error matrix for GNAI2 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

94.1/ 100

Very high

355 residues

Confidence breakdown

Very high(≥ 90)88%
Confident(70–90)9%
Low(50–70)3%
Very low(< 50)1%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Fetal anomalies
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Disease associations (Open Targets)

ovarian granulosa cell tumor
0.42
ovarian granulosa tumour
0.42
adrenal cortex carcinoma
0.42
syndromic intellectual disability
0.37
non-Hodgkin lymphoma
0.35
hypopituitarism
0.27
Decreased circulating total IgM
0.27
Recurrent infections
0.27
Retractile testis
0.27
Short stature
0.27

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Guanine nucleotide-binding protein G(i) subunit alpha-2

Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades (PubMed:38505600, PubMed:29925945, PubMed:35637350, PubMed:35365641). The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state (PubMed:12359238). Signaling by an activated GPCR promotes GDP release and GTP binding (PubMed:29925945). Examples of interacting GPCRs include the adenosine A1 receptor/ADORA1, CNR1, and FPR2 (PubMed:29925945, PubMed:35637350, PubMed:35365641). The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (PubMed:12359238). 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. Plays an important role in the activation of the transcription factor NFAT in endothelial cells to promote angiogenesis (PubMed:38505600). The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. Plays an essential role for neutrophil recruitment in the context of acute inflammation suggesting a linked function of both GNAI2 in neutrophils and endothelial cells for polymorphonuclear neutrophils transmigration (By similarity)