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    IL12A interleukin 12A [ Homo sapiens (human) ]

    Gene ID: 3592, updated on 8-Jul-2021

    Summary

    Official Symbol
    IL12Aprovided by HGNC
    Official Full Name
    interleukin 12Aprovided by HGNC
    Primary source
    HGNC:HGNC:5969
    See related
    Ensembl:ENSG00000168811 MIM:161560
    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
    P35; CLMF; NFSK; NKSF1; IL-12A
    Summary
    This gene encodes a subunit of a cytokine that acts on T and natural killer cells, and has a broad array of biological activities. The cytokine is a disulfide-linked heterodimer composed of the 35-kD subunit encoded by this gene, and a 40-kD subunit that is a member of the cytokine receptor family. This cytokine is required for the T-cell-independent induction of interferon (IFN)-gamma, and is important for the differentiation of both Th1 and Th2 cells. The responses of lymphocytes to this cytokine are mediated by the activator of transcription protein STAT4. Nitric oxide synthase 2A (NOS2A/NOS2) is found to be required for the signaling process of this cytokine in innate immunity. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in esophagus (RPKM 2.2), lung (RPKM 1.4) and 19 other tissues See more
    Orthologs
    NEW
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    Genomic context

    See IL12A in Genome Data Viewer
    Location:
    3q25.33
    Exon count:
    7
    Annotation release Status Assembly Chr Location
    109.20210514 current GRCh38.p13 (GCF_000001405.39) 3 NC_000003.12 (159988835..159996019)
    105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (159706622..159713806)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene IQCJ-SCHIP1 readthrough Neighboring gene schwannomin interacting protein 1 Neighboring gene IQCJ-SCHIP1 readthrough antisense RNA 1 Neighboring gene uncharacterized LOC101928351 Neighboring gene RNA, U2 small nuclear 31, pseudogene Neighboring gene IL12A antisense RNA 1 Neighboring gene long intergenic non-protein coding RNA 1100 Neighboring gene bromodomain containing 7 pseudogene 2

    Genomic regions, transcripts, and products

    Expression

    • 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

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Common genetic variation and antidepressant efficacy in major depressive disorder: a meta-analysis of three genome-wide pharmacogenetic studies.
    GeneReviews: Not available
    Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.
    GeneReviews: Not available
    Genome-wide association analysis identifies new susceptibility loci for Behçet's disease and epistasis between HLA-B*51 and ERAP1.
    GeneReviews: Not available
    Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis.
    GeneReviews: Not available
    Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis.
    GeneReviews: Not available
    Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci.
    GeneReviews: Not available
    Multiple common variants for celiac disease influencing immune gene expression.
    GeneReviews: Not available
    Newly identified genetic risk variants for celiac disease related to the immune response.
    GeneReviews: Not available
    Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants.
    GeneReviews: Not available

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Levels of IL-12 in LPS-treated myeloid dendritic cells are modulated in the presence of HIV-1 gp120 PubMed
    env HIV-1 gp120 inhibits early and late production of interleukin (IL)-12 by peripheral blood mononuclear cells (PBMC) PubMed
    env Secretion of IL-12 is found in macrophages primed with gamma interferon (IFN-gamma) and subsequently treated with gp120 PubMed
    env Apoptosis of CD4+ lymphocytes induced by HIV-1 gp120 cross-linking to CD4 is inhibited by IL-12 PubMed
    env HIV-gp120 induces a significant IL-10 synthesis, which in turn inhibits IL-12 subunits mRNA accumulation and protein secretion after Staphylococcus aureus strain cowan I (SAC)-activation PubMed
    Envelope surface glycoprotein gp160, precursor env IL-7 and IL-12 significantly augment proliferative responses to HIV-1 gp160 PubMed
    env Chimeric HIV-1 gp140 - CD40L trimers can target and activate dendritic cells to release IL-6, IL-10 and IL-12 PubMed
    Nef nef IL-12 and GM-CSF increase the magnitude of the specific immune response with higher breadth by targeting HIV-1 Nef peptides (amino acids 9-23, 11-26, 140-155, 179-193, and 181-195) PubMed
    nef IL-1beta, IL-12, and IL-15 are factors involved in the upregulation of IFN-gamma expression in coculture between Nef-pulsed iDCs and NK cells PubMed
    nef HIV-1 Nef upregulates IL-12 release in immature human and macaque dendritic cells PubMed
    Tat tat HIV-1 Tat upregulates IL-12 expression in Jurkat T-cells, Raji B-cells, monocyte-derived dendritic cells, and primary human Muller glia PubMed
    tat Wild-type Tat but not Cys-22 and oxidized Tat induces CD1A-expressing monocyte-derived dendritic cells (MDDC) maturation and increases the production of cytokines TNF-alpha, IL-12, MIP-1alpha, and MIP-1beta PubMed
    tat HIV-1 Tat downregulates IL-12 production by human dendritic cells by blocking extracellular calcium influx PubMed
    tat HIV-1 Tat downregulates IL-12 production by human peripheral blood mononuclear cells (PBMCs) PubMed
    Vpr vpr HIV-1 Vpr impairs NK cell function through cytokine dysregulation, including diminshed expression of CD107a, reduced production of IFN-gamma, differential regulation of IL-12 and TGF-beta, and activation of the Smad3 signalling pathway PubMed
    vpr The C-terminal domain or the R90 residue of HIV-1 Vpr are important for Vpr-mediated IL-12 degradation via ubiquitin-dependent pathway PubMed
    vpr HIV-1 Vpr downregulates the production of interleukin 12 (IL-12) in dendritic cells PubMed
    vpr HIV-1 Vpr suppresses expression and secretion of IL-12 subunit p35 and IL-12 holo-protein, but not IL-12 subunit p40 PubMed
    matrix gag HIV-1 Matrix upregulates levels of IL-2, IL-12 and IL-15 in natural killer cells and induces natural killer cell proliferation PubMed
    reverse transcriptase gag-pol The addition of anti-IFN-gamma antibodies block the IL-12-induced downregulation of HIV-1 RT activity in HIV-1-infected macrophages PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    contributes_to cytokine activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    contributes_to cytokine activity TAS
    Traceable Author Statement
    more info
    PubMed 
    contributes_to growth factor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    contributes_to growth factor activity NAS
    Non-traceable Author Statement
    more info
    PubMed 
    enables interleukin-12 beta subunit binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables interleukin-12 receptor binding NAS
    Non-traceable Author Statement
    more info
    PubMed 
    enables interleukin-27 binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein heterodimerization activity IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    involved_in cell migration IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in cellular response to virus IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in defense response to Gram-positive bacterium IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in extrinsic apoptotic signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in immune response TAS
    Traceable Author Statement
    more info
    PubMed 
    acts_upstream_of negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    involved_in negative regulation of interleukin-17 production IDA
    Inferred from Direct Assay
    more info
    PubMed 
    acts_upstream_of_or_within negative regulation of protein secretion IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    involved_in negative regulation of smooth muscle cell proliferation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    acts_upstream_of negative regulation of vascular endothelial growth factor signaling pathway IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    involved_in positive regulation of NK T cell activation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of T cell mediated cytotoxicity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of cell adhesion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of dendritic cell chemotaxis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of interferon-gamma production IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of lymphocyte proliferation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of mononuclear cell proliferation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of natural killer cell activation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of natural killer cell mediated cytotoxicity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of smooth muscle cell apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of tyrosine phosphorylation of STAT protein IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of cell cycle IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in response to UV-B IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in response to lipopolysaccharide IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in response to virus IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    Component Evidence Code Pubs
    located_in endoplasmic reticulum lumen TAS
    Traceable Author Statement
    more info
     
    located_in extracellular region TAS
    Traceable Author Statement
    more info
     
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of interleukin-12 complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of interleukin-12 complex NAS
    Non-traceable Author Statement
    more info
    PubMed 
    located_in late endosome lumen TAS
    Traceable Author Statement
    more info
     

    General protein information

    Preferred Names
    interleukin-12 subunit alpha
    Names
    CLMF p35
    IL-12, subunit p35
    IL35 subunit
    NF cell stimulatory factor chain 1
    NK cell stimulatory factor chain 1
    cytotoxic lymphocyte maturation factor 1, p35
    cytotoxic lymphocyte maturation factor 35 kDa subunit
    interleukin 12, p35
    interleukin 12A (natural killer cell stimulatory factor 1, cytotoxic lymphocyte maturation factor 1, p35)
    interleukin-12 alpha chain

    NCBI Reference Sequences (RefSeq)

    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_033022.1 RefSeqGene

      Range
      5000..12184
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000882.4NP_000873.2  interleukin-12 subunit alpha isoform 1 precursor

      See identical proteins and their annotated locations for NP_000873.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AC010370, AW472810, BC104982, M65291
      Consensus CDS
      CCDS3187.1
      UniProtKB/Swiss-Prot
      P29459
      UniProtKB/TrEMBL
      O60595
      Related
      ENSP00000303231.2, ENST00000305579.7
      Conserved Domains (1) summary
      pfam03039
      Location:51253
      IL12; Interleukin-12 alpha subunit
    2. NM_001354582.2NP_001341511.1  interleukin-12 subunit alpha isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.
      Source sequence(s)
      AC010370
      Consensus CDS
      CCDS87161.1
      Related
      ENSP00000419046.1, ENST00000466512.1
      Conserved Domains (1) summary
      pfam03039
      Location:51239
      IL12; Interleukin-12 alpha subunit
    3. NM_001354583.2NP_001341512.1  interleukin-12 subunit alpha isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (3) has the same N- and C-termini but is shorter compared to isoform 1.
      Source sequence(s)
      AC010370
      Consensus CDS
      CCDS87162.1
      Related
      ENSP00000420184.1, ENST00000480787.5
      Conserved Domains (1) summary
      pfam03039
      Location:51215
      IL12; Interleukin-12 alpha subunit

    RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

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

    Reference GRCh38.p13 Primary Assembly

    Genomic

    1. NC_000003.12 Reference GRCh38.p13 Primary Assembly

      Range
      159988835..159996019
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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