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    IL22RA2 interleukin 22 receptor subunit alpha 2 [ Homo sapiens (human) ]

    Gene ID: 116379, updated on 14-Nov-2024

    Summary

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    Official Symbol
    IL22RA2provided by HGNC
    Official Full Name
    interleukin 22 receptor subunit alpha 2provided by HGNC
    Primary source
    HGNC:HGNC:14901
    See related
    Ensembl:ENSG00000164485 MIM:606648; AllianceGenome:HGNC:14901
    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
    CRF2X; CRF2-10; CRF2-S1; IL-22BP; IL-22RA2; ZCYTOR16; IL-22R-alpha-2
    Summary
    This gene encodes a member of the class II cytokine receptor family. The encoded soluble protein specifically binds to and inhibits interleukin 22 activity by blocking the interaction of interleukin 22 with its cell surface receptor. The encoded protein may be important in the regulation of inflammatory response, and has been implicated in the regulation of tumorigenesis in the colon. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2013]
    Expression
    Low expression observed in reference dataset See more
    Orthologs
    mouse all
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    Genomic context

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    See IL22RA2 in Genome Data Viewer
    Location:
    6q23.3
    Exon count:
    7
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (137143820..137173644, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (138332180..138362006, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (137464957..137494781, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:137311375-137312331 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:137322965-137323508 Neighboring gene neuroblastoma highly expressed DDX5 stabilizing lncRNA 1 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_90349 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_90351 Neighboring gene interleukin 20 receptor subunit alpha Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17577 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17578 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17579 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:137382319-137382457 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25128 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:137410449-137410629 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25129 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25130 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25131 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_90355 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_90356 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25132 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25133 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_90359 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_90362 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr6:137492881-137493639 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_90370 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr6:137500946-137502145 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_90375 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25135 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17580 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:137540162-137540892 Neighboring gene interferon gamma receptor 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25137 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25138 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25139 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr6:137618853-137619479 Neighboring gene uncharacterized LOC105378017

    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. IL-22BP production is heterogeneously distributed in Crohn's disease. Fantou A, et al. Front Immunol, 2022. PMID 36311796, Free PMC Article
    2. Crystallization and preliminary X-ray diffraction analysis of human IL-22 bound to its soluble decoy receptor IL-22BP. Watanabe L, et al. Acta Crystallogr Sect F Struct Biol Cryst Commun, 2009 Feb 1. PMID 19193995, Free PMC Article
    3. The Rare IL22RA2 Signal Peptide Coding Variant rs28385692 Decreases Secretion of IL-22BP Isoform-1, -2 and -3 and Is Associated with Risk for Multiple Sclerosis. Gómez-Fernández P, et al. Cells, 2020 Jan 10. PMID 31936765, Free PMC Article
    4. A novel, soluble homologue of the human IL-10 receptor with preferential expression in placenta. Gruenberg BH, et al. Genes Immun, 2001 Oct. PMID 11607789
    5. Low Interleukin-22 Binding Protein Is Associated With High Mortality in Alcoholic Hepatitis and Modulates Interleukin-22 Receptor Expression. Støy S, et al. Clin Transl Gastroenterol, 2020 Aug. PMID 32955203, Free PMC Article

    See all (39) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Circulating apelin, IL22RA2 and VEGF in pre-capillary pulmonary hypertension.
      Title: Circulating apelin, IL22RA2 and VEGF in pre-capillary pulmonary hypertension.
    2. IL-22BP production is heterogeneously distributed in Crohn's disease.
      Title: IL-22BP production is heterogeneously distributed in Crohn's disease.
    3. Down-regulating Interleukin-22/Interleukin-22 binding protein axis promotes inflammation and aggravates diet-induced metabolic disorders.
      Title: Down-regulating Interleukin-22/Interleukin-22 binding protein axis promotes inflammation and aggravates diet-induced metabolic disorders.
    4. Liver expression of IL-22, IL-22R1 and IL-22BP in patients with chronic hepatitis C with different fibrosis stages.
      Title: Liver expression of IL-22, IL-22R1 and IL-22BP in patients with chronic hepatitis C with different fibrosis stages.
    5. The good and the bad about separation anxiety: roles of IL-22 and IL-22BP in liver pathologies.
      Title: The good and the bad about separation anxiety: roles of IL-22 and IL-22BP in liver pathologies.
    6. Elevated IL-22 in psoriasis plays an anti-apoptotic role in keratinocytes through mediating Bcl-xL/Bax.
      Title: Elevated IL-22 in psoriasis plays an anti-apoptotic role in keratinocytes through mediating Bcl-xL/Bax.
    7. Low Interleukin-22 Binding Protein Is Associated With High Mortality in Alcoholic Hepatitis and Modulates Interleukin-22 Receptor Expression.
      Title: Low Interleukin-22 Binding Protein Is Associated With High Mortality in Alcoholic Hepatitis and Modulates Interleukin-22 Receptor Expression.
    8. The Rare IL22RA2 Signal Peptide Coding Variant rs28385692 Decreases Secretion of IL-22BP Isoform-1, -2 and -3 and Is Associated with Risk for Multiple Sclerosis.
      Title: The Rare IL22RA2 Signal Peptide Coding Variant rs28385692 Decreases Secretion of IL-22BP Isoform-1, -2 and -3 and Is Associated with Risk for Multiple Sclerosis.
    9. Our results demonstrate a pathogenic role of IL-22BP in three species with a potential mechanism of action involving T cell polarization
      Title: IL-22 Binding Protein Promotes the Disease Process in Multiple Sclerosis.
    10. Upon silencing of interleukin 22 receptor subunit alpha 2 (IL22RA2) expression in immature dendritic cells (moDC), molecular chaperone GRP78 (GRP78) levels were significantly reduced, suggesting that native IL22RA2 expression naturally contributes to upregulating GRP78 levels in these cells.
      Title: Long Interleukin-22 Binding Protein Isoform-1 Is an Intracellular Activator of the Unfolded Protein Response.
    Submit: New GeneRIF Correction See all GeneRIFs (22)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.
    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)

    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

    • MGC150509, MGC150510

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cytokine receptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables interleukin-22 binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables interleukin-22 receptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cytokine-mediated signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in interleukin-22-mediated signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of inflammatory response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of tyrosine phosphorylation of STAT protein ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    located_in cytosol IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular space NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    interleukin-22 receptor subunit alpha-2
    Names
    cytokine receptor class-II member 10
    cytokine receptor family type 2, soluble 1
    interleukin 22 receptor, alpha 2
    interleukin 22-binding protein

    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.

    mRNA and Protein(s)

    1. NM_052962.3 → NP_443194.1  interleukin-22 receptor subunit alpha-2 isoform 1 precursor

      See identical proteins and their annotated locations for NP_443194.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AI824338, AJ313162, AY040566
      Consensus CDS
      CCDS5182.1
      UniProtKB/Swiss-Prot
      Q08AH7, Q6UWM1, Q969J5, Q96A41, Q96QR0
      Related
      ENSP00000296980.2, ENST00000296980.7
      Conserved Domains (2) summary
      pfam01108
      Location:24 → 146
      Tissue_fac; Tissue factor
      pfam09294
      Location:158 → 263
      Interfer-bind; Interferon-alpha/beta receptor, fibronectin type III

    2. NM_181309.2 → NP_851826.1  interleukin-22 receptor subunit alpha-2 isoform 2 precursor

      See identical proteins and their annotated locations for NP_851826.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an in-frame exon in the central coding region, compared to variant 1. The resulting isoform (2) is shorter, compared to isoform 1.
      Source sequence(s)
      AI824338, AJ313161, AY040566
      Consensus CDS
      CCDS5183.1
      UniProtKB/Swiss-Prot
      Q969J5
      Related
      ENSP00000296979.4, ENST00000349184.9
      Conserved Domains (2) summary
      pfam01108
      Location:23 → 114
      Tissue_fac; Tissue factor
      pfam09294
      Location:126 → 231
      Interfer-bind; Interferon-alpha/beta receptor, fibronectin type III

    3. NM_181310.2 → NP_851827.1  interleukin-22 receptor subunit alpha-2 isoform 3 precursor

      See identical proteins and their annotated locations for NP_851827.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks two alternate exons in the coding region, which leads to a translation frameshift, compared to variant 1. The resulting isoform (3) is shorter and has a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AI824338, AJ313161, AY040568
      Consensus CDS
      CCDS5184.1
      UniProtKB/Swiss-Prot
      Q969J5
      Related
      ENSP00000340920.3, ENST00000339602.3
      Conserved Domains (1) summary
      pfam01108
      Location:24 → 114
      Tissue_fac; Tissue factor

    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_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      137143820..137173644 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      138332180..138362006 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q969J5.1 GenPept UniProtKB/Swiss-Prot:Q969J5

    Gene LinkOut

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

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