U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

GNAI3 G protein subunit alpha i3 [ Homo sapiens (human) ]

Gene ID: 2773, updated on 7-Apr-2024

Summary

Go to the top of the page Help
Official Symbol
GNAI3provided by HGNC
Official Full Name
G protein subunit alpha i3provided by HGNC
Primary source
HGNC:HGNC:4387
See related
Ensembl:ENSG00000065135 MIM:139370; AllianceGenome:HGNC:4387
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
87U6; HG1A; ARCND1; ARCODS
Summary
Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling pathways. G proteins are composed of 3 units: alpha, beta and gamma. This gene encodes an alpha subunit and belongs to the G-alpha family. Mutation in this gene, resulting in a gly40-to-arg substitution, is associated with auriculocondylar syndrome, and shown to affect downstream targets in the G protein-coupled endothelin receptor pathway. [provided by RefSeq, Jun 2012]
Expression
Ubiquitous expression in esophagus (RPKM 27.0), bone marrow (RPKM 22.0) and 25 other tissues See more
Orthologs
mouse all
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help
Location:
1p13.3
Exon count:
9
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (109548615..109600195)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (109581338..109632911)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (110091237..110142817)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105378893 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1442 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1443 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:110073289-110073457 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:110082007-110082508 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:110082509-110083008 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:110086313-110086851 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:110089013-110089249 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1444 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1445 Neighboring gene G protein-coupled receptor 61 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr1:110106789-110107398 Neighboring gene RNA, U6 small nuclear variant sequence with SNRPE pseudogene sequence Neighboring gene MPRA-validated peak357 silencer Neighboring gene microRNA 197 Neighboring gene G protein subunit alpha transducin 2 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:110161626-110162156 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:110162157-110162685 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:110163216-110163744 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1448 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:110164805-110165334 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:110166705-110167518 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr1:110170748-110171947 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:110171947-110172506 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:110173069-110173628 Neighboring gene adenosine monophosphate deaminase 2

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help
  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the pageHelp

Related articles in PubMed

  1. A novel missense variant of the GNAI3 gene and recognisable morphological characteristics of the mandibula in ARCND1. Yanagi K, et al. J Hum Genet, 2021 Oct. PMID 33723370, Free PMC Article
  2. Novel CpG-SNPs in the gastric acid secretion pathway GNAI3 and susceptibility to gastric cancer. Liu M, et al. Gene, 2020 Apr 30. PMID 32032744
  3. Gαi3 nuclear translocation causes irradiation resistance in human glioma cells. Cai S, et al. Oncotarget, 2017 May 23. PMID 28456783, Free PMC Article
  4. Dynamic regulation of GDP binding to G proteins revealed by magnetic field-dependent NMR relaxation analyses. Toyama Y, et al. Nat Commun, 2017 Feb 22. PMID 28223697, Free PMC Article
  5. GNAI3: Another Candidate Gene to Screen in Persons with Ocular Albinism. Young A, et al. PLoS One, 2016. PMID 27607449, Free PMC Article

See all (196) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Integrins regulate hERG1 dynamics by girdin-dependent Galphai3: signaling and modeling in cancer cells.
    Title: Integrins regulate hERG1 dynamics by girdin-dependent Gαi3: signaling and modeling in cancer cells.
  2. Galphai1/3 mediate Netrin-1-CD146-activated signaling and angiogenesis.
    Title: Gαi1/3 mediate Netrin-1-CD146-activated signaling and angiogenesis.
  3. A novel missense variant of the GNAI3 gene and recognisable morphological characteristics of the mandibula in ARCND1.
    Title: A novel missense variant of the GNAI3 gene and recognisable morphological characteristics of the mandibula in ARCND1.
  4. A highly conserved delta-opioid receptor region determines RGS4 interaction.
    Title: A highly conserved δ-opioid receptor region determines RGS4 interaction.
  5. The CpG-SNP rs11810577 in GNAI3 in the gastric acid secretion pathway was significantly associated with susceptibility to gastric cancer.
    Title: Novel CpG-SNPs in the gastric acid secretion pathway GNAI3 and susceptibility to gastric cancer.
  6. We found that the inhibitory Galphai3 protein selectively bound to the G-protein-binding domain on the C-terminus of PC1. The dissociation of Galphai3 upon cleavage of PC1 increased TRPC4 activity.
    Title: Gα(i)-mediated TRPC4 activation by polycystin-1 contributes to endothelial function via STAT1 activation.
  7. These results provide mechanistic insights into the critical role played by Galphai1/3 proteins in VEGF-induced VEGFR2 endocytosis, signaling and angiogenesis.
    Title: Gαi1 and Gαi3mediate VEGF-induced VEGFR2 endocytosis, signaling and angiogenesis.
  8. direct binding of GATA4 to the GNAI3 promoter, both in vitro and in vivo, is reported.
    Title: Role of GATA binding protein 4 (GATA4) in the regulation of tooth development via GNAI3.
  9. magnetic field-dependent nuclear magnetic resonance relaxation analyses were used to investigate the structural and dynamic properties of GDP bound Galpha on a microsecond timescale.
    Title: Dynamic regulation of GDP binding to G proteins revealed by magnetic field-dependent NMR relaxation analyses.
  10. Results show that Galphai3 nuclear translocation causes irradiation resistance in human glioma cells through its complexation with DNA-PKcs leading to DNA repair.
    Title: Gαi3 nuclear translocation causes irradiation resistance in human glioma cells.
Submit: New GeneRIF Correction See all GeneRIFs (35)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Auriculocondylar syndrome 1
MedGen: C4551996 OMIM: 602483 GeneReviews: Not available
Compare labs

Copy number response

Description
Copy number response
Haploinsufficency

No evidence available (Last evaluated 2013-07-18)

ClinGen Genome Curation Page
Triplosensitivity

No evidence available (Last evaluated 2013-07-18)

ClinGen Genome Curation Page

EBI GWAS Catalog

Description
Genome-wide association study of recurrent early-onset major depressive disorder.
EBI GWAS Catalog

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

Go to the top of the page Help

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120-mediated phosphorylation of WAVE2 requires both G(alpha)i-dependent and -independent pathways, and is conserved both in X4 and R5 viral infection of resting CD4 T cells and primary macrophages PubMed
env HIV-1 gp120 induces IL-1beta release from macrophages in a time- and concentration-dependent manner through binding to the chemokine receptor CCR5 and coupling to G(i)alpha protein PubMed
env CXCR4-tropic and CXCR4/CCR5 dual-tropic HIV-1 gp120 induce the cleavage of CD62 ligand by a mechanism dependent on matrix metalloproteinases 1 and 3, CD4, CXCR4, Galpha(i), and p38 MAPK, whereas CCR5-tropic gp120 does not PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Go to the top of the page

Interactions

Go to the top of the page Help
Products Interactant Other Gene Complex Source Pubs Description

General gene information

Go to the top of the page Help

Markers

Homology

Clone Names

  • FLJ26559

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables G protein-coupled receptor binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables G-protein beta/gamma-subunit complex binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables GDP binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables GTP binding IEA
Inferred from Electronic Annotation
more info
  
enables GTPase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables GTPase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in GTP metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in adenylate cyclase-modulating G protein-coupled receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in cell cycle IEA
Inferred from Electronic Annotation
more info
  
involved_in cell division IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in dopamine receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in dopamine receptor signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of adenylate cyclase activity TAS
Traceable Author Statement
more info
 PubMed 
involved_in positive regulation of macroautophagy IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
colocalizes_with Golgi membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in centrosome IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
colocalizes_with endoplasmic reticulum membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in extracellular exosome HDA PubMed 
part_of heterotrimeric G-protein complex IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in lysosomal membrane HDA PubMed 
located_in membrane HDA PubMed 
located_in midbody IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleolus IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  

General protein information

Go to the top of the page Help
Preferred Names
guanine nucleotide-binding protein G(i) subunit alpha-3
Names
g(i) alpha-3
guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 3
guanine nucleotide-binding protein G(i) subunit alpha
guanine nucleotide-binding protein G(k) subunit alpha
heterotrimeric guanine nucleotide-binding protein 1A

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_032795.1 RefSeqGene

    Range
    5001..52280
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_006496.4 → NP_006487.1  guanine nucleotide-binding protein G(i) subunit alpha-3

    See identical proteins and their annotated locations for NP_006487.1

    Status: REVIEWED

    Source sequence(s)
    AL355310
    Consensus CDS
    CCDS802.1
    UniProtKB/Swiss-Prot
    P08754, P17539, Q5TZX1
    Related
    ENSP00000358867.4, ENST00000369851.7
    Conserved Domains (1) summary
    cd00066
    Location:34 → 348
    G-alpha; Alpha subunit of G proteins (guanine nucleotide binding)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    109548615..109600195
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    109581338..109632911
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P08754.3 GenPept UniProtKB/Swiss-Prot:P08754

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Chemical Information
Medical
Molecular Biology Databases
Research Materials
Tools
Miscellaneous