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

    Gene ID: 2773, updated on 2-Nov-2024

    Summary

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    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
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    Genomic context

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    See GNAI3 in Genome Data Viewer
    Location:
    1p13.3
    Exon count:
    9
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (109548615..109600195)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (109581338..109632911)
    RS_2024_09 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

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues 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

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    Related articles in PubMed

    1. Identification of cDNA encoding an additional alpha subunit of a human GTP-binding protein: expression of three alpha i subtypes in human tissues and cell lines. Kim SY, et al. Proc Natl Acad Sci U S A, 1988 Jun. PMID 3132707, Free PMC Article
    2. Leukotriene D4-induced activation and translocation of the G-protein alpha i3-subunit in human epithelial cells. Adolfsson JL, et al. Biochem Biophys Res Commun, 1996 Sep 13. PMID 8806649
    3. Novel variants in GNAI3 associated with auriculocondylar syndrome strengthen a common dominant negative effect. Romanelli Tavares VL, et al. Eur J Hum Genet, 2015 Apr. PMID 25026904, Free PMC Article
    4. Changes in expression of adenyl cyclase activity in human endometrium during hormone replacement therapy and ovarian stimulation. Bernardini L, et al. Mol Hum Reprod, 1999 Oct. PMID 10508224
    5. 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

    See all (213) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. GNAI3 mediated by Lin28A regulates lipopolysaccharide-induced inflammation and osteogenic differentiation in periodontal stem cells by mediating the NF-kappaB/NLRP3 inflammasome pathway.
      Title: GNAI3 mediated by Lin28A regulates lipopolysaccharide-induced inflammation and osteogenic differentiation in periodontal stem cells by mediating the NF-κB/NLRP3 inflammasome pathway.
    2. 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.
    3. Galphai1/3 mediate Netrin-1-CD146-activated signaling and angiogenesis.
      Title: Gαi1/3 mediate Netrin-1-CD146-activated signaling and angiogenesis.
    4. 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.
    5. A highly conserved delta-opioid receptor region determines RGS4 interaction.
      Title: A highly conserved δ-opioid receptor region determines RGS4 interaction.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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.
    Submit: New GeneRIF Correction See all GeneRIFs (36)

    Phenotypes

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    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

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    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

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    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 G protein-coupled dopamine receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    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 division 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

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    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)

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    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_2024_08

    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.

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