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    ITPR2 inositol 1,4,5-trisphosphate receptor type 2 [ Homo sapiens (human) ]

    Gene ID: 3709, updated on 5-May-2024

    Summary

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    Official Symbol
    ITPR2provided by HGNC
    Official Full Name
    inositol 1,4,5-trisphosphate receptor type 2provided by HGNC
    Primary source
    HGNC:HGNC:6181
    See related
    Ensembl:ENSG00000123104 MIM:600144; AllianceGenome:HGNC:6181
    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
    ANHD; IP3R2; CFAP48; INSP3R2
    Summary
    The protein encoded by this gene belongs to the inositol 1,4,5-triphosphate receptor family, whose members are second messenger intracellular calcium release channels. These proteins mediate a rise in cytoplasmic calcium in response to receptor activated production of inositol triphosphate. Inositol triphosphate receptor-mediated signaling is involved in many processes including cell migration, cell division, smooth muscle contraction, and neuronal signaling. This protein is a type 2 receptor that consists of a cytoplasmic amino-terminus that binds inositol triphosphate, six membrane-spanning helices that contribute to the ion pore, and a short cytoplasmic carboxy-terminus. A mutation in this gene has been associated with anhidrosis, suggesting that intracellular calcium release mediated by this protein is required for eccrine sweat production. [provided by RefSeq, Apr 2015]
    Expression
    Ubiquitous expression in liver (RPKM 15.0), kidney (RPKM 7.5) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    12p11.23
    Exon count:
    62
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (26335352..26833194, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (26207897..26705197, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (26488285..26986127, complement)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105369705 Neighboring gene uncharacterized LOC105369704 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6121 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6120 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6122 Neighboring gene uncharacterized LOC107984482 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6123 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr12:26512284-26513483 Neighboring gene RNA, 5S ribosomal pseudogene 354 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr12:26662897-26663668 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_26952 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_26967 Neighboring gene NANOG hESC enhancer GRCh37_chr12:26726101-26726602 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:26796645-26797336 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr12:26800684-26801883 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6124 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6125 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:26881161-26881390 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4302 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:26896687-26897188 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6127 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6126 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:26937397-26938110 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr12:26939539-26940250 Neighboring gene uncharacterized LOC124902903 Neighboring gene uncharacterized LOC124902902 Neighboring gene enoyl-CoA hydratase domain containing 2 pseudogene Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_27003 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6128 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4303 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4305 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4304 Neighboring gene Sharpr-MPRA regulatory region 14818 Neighboring gene MPRA-validated peak1624 silencer Neighboring gene ReSE screen-validated silencer GRCh37_chr12:27037949-27038123 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:27091219-27091728 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:27091729-27092237 Neighboring gene integrator complex subunit 13 Neighboring gene FGFR1 oncogene partner 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
    • 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. Genetic variants in the ITPR2 gene are associated with Kashin-Beck Disease in Tibetan. He X, et al. Mol Genet Genomic Med, 2019 Jul. PMID 31066235, Free PMC Article
    2. Experimental and theoretical study of IBC domain from human IP3R2; molecular cloning, bacterial expression and protein purification. Amroudie MN, et al. Int J Biol Macromol, 2019 Mar 1. PMID 30244130
    3. Nonalcoholic fatty liver disease impairs expression of the type II inositol 1,4,5-trisphosphate receptor. Khamphaya T, et al. Hepatology, 2018 Feb. PMID 29023819, Free PMC Article
    4. High expression of inositol 1,4,5-trisphosphate receptor, type 2 (ITPR2) as a novel biomarker for worse prognosis in cytogenetically normal acute myeloid leukemia. Shi JL, et al. Oncotarget, 2015 Mar 10. PMID 25779662, Free PMC Article
    5. Genome-wide association study identifies ITPR2 as a susceptibility gene for Kashin-Beck disease in Han Chinese. Zhang F, et al. Arthritis Rheumatol, 2015 Jan. PMID 25303641

    See all (109) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Candidate Gene of NOS3, MMP3, AGT, and AGT1R and Pathway Analyses for Platelet Reactivity and Clinical Outcomes of Repeat Revascularization After First PCI in Chinese Patients.
      Title: Candidate Gene of NOS3, MMP3, AGT, and AGT1R and Pathway Analyses for Platelet Reactivity and Clinical Outcomes of Repeat Revascularization After First PCI in Chinese Patients.
    2. Inositol 1,4,5-trisphosphate receptor gene variants are related to the risk of breast cancer in a Chinese population.
      Title: Inositol 1,4,5-trisphosphate receptor gene variants are related to the risk of breast cancer in a Chinese population.
    3. Calcium channel ITPR2 and mitochondria-ER contacts promote cellular senescence and aging.
      Title: Calcium channel ITPR2 and mitochondria-ER contacts promote cellular senescence and aging.
    4. Type 3 Inositol 1,4,5-Trisphosphate Receptor is a Crucial Regulator of Calcium Dynamics Mediated by Endoplasmic Reticulum in HEK Cells.
      Title: Type 3 Inositol 1,4,5-Trisphosphate Receptor is a Crucial Regulator of Calcium Dynamics Mediated by Endoplasmic Reticulum in HEK Cells.
    5. The SNP rs11048526 were significantly association with Kashin-Beck Disease which increased the Kashin-Beck Disease risk.
      Title: Genetic variants in the ITPR2 gene are associated with Kashin-Beck Disease in Tibetan.
    6. Fatty liver induces a c-Jun-mediated decrease in ITPR2 in hepatocytes.
      Title: Nonalcoholic fatty liver disease impairs expression of the type II inositol 1,4,5-trisphosphate receptor.
    7. Molecular cloning, bacterial expression and protein purification of the IBC domain from human IP3R2 have been described.
      Title: Experimental and theoretical study of IBC domain from human IP3R2; molecular cloning, bacterial expression and protein purification.
    8. we systematically evaluating RCC risk-associated SNPs indentified from previous GWAS in a Chinese population, finding that one SNP located in PDZD2 and two SNPs located in ITPR2 were ccRCC-risk associated in Chinese population.
      Title: Germline genetic variations in PDZD2 and ITPR2 genes are associated with clear cell renal cell carcinoma in Chinese population.
    9. Studies indicate that the ryanodine receptors (RyRs: RyR1, RyR2, RyR3) and inositol 1,4,5-trisphosphate receptors (IP3Rs: IP3R1, IP3R2, IP3R3) are the major Ca(2+) release channels (CRCs) on the endo/sarcoplasmic reticulum (ER/SR).
      Title: Essential Roles of Intracellular Calcium Release Channels in Muscle, Brain, Metabolism, and Aging.
    10. Data suggest miR-1290 as the new oncomiR involved in laryngeal squamous cell carcinoma pathogenesis probably through downregulation of its target genes MAF and ITPR2.
      Title: Global miRNA Expression Profiling Identifies miR-1290 as Novel Potential oncomiR in Laryngeal Carcinoma.
    Submit: New GeneRIF Correction See all GeneRIFs (37)

    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
    Isolated anhidrosis with normal sweat glands
    MedGen: C5568836 OMIM: 106190 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    A genome-wide association study identifies a novel susceptibility locus for renal cell carcinoma on 12p11.23.
    EBI GWAS Catalog
    Genome-wide association study identifies ITPR2 as a susceptibility gene for Kashin-Beck disease in Han Chinese.
    EBI GWAS Catalog
    Genome-wide association study of primary dentition pit-and-fissure and smooth surface caries.
    EBI GWAS Catalog
    Genome-wide association study of smoking behaviours among Bangladeshi adults.
    EBI GWAS Catalog
    ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study.
    EBI GWAS Catalog
    Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution.
    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
    Pr55(Gag) gag IP3R differentially associates with HIV-1 wild-type Gag and P7L-Gag, indicating that Gag and IP3R are in proximity at the plasma membrane PubMed
    gag Inositol (1,4,5)-triphosphate receptor (IP3R) is required for efficient release of HIV-1 Gag PubMed
    gag SPRY-mediated inhibition of HIV-1 Gag release is repressed by IP3R PubMed
    Tat tat HIV-1 Tat induces release of calcium from inositol 1,4,5-triphosphate receptor-regulated stores in neurons and astrocytes, an effect that plays an important role in Tat-induced TNF-alpha production 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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables calcium ion binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables calcium ion transmembrane transporter activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables inositol 1,4,5 trisphosphate binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables inositol 1,4,5-trisphosphate-gated calcium channel activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables inositol 1,4,5-trisphosphate-gated calcium channel activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables inositol 1,4,5-trisphosphate-gated calcium channel activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables phosphatidylinositol binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables scaffold protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables transmembrane transporter binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in calcium-mediated signaling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cellular response to cAMP IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cellular response to ethanol IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in release of sequestered calcium ion into cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in release of sequestered calcium ion into cytosol ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in response to hypoxia IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cell cortex IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in endoplasmic reticulum membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in membrane HDA PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in platelet dense tubular network membrane TAS
    Traceable Author Statement
    more info
    		  
    part_of receptor complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in sarcoplasmic reticulum IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in sarcoplasmic reticulum membrane IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    is_active_in secretory granule membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    inositol 1,4,5-trisphosphate receptor type 2
    Names
    IP3 receptor
    IP3R 2
    cilia and flagella associated protein 48
    type 2 InsP3 receptor

    NCBI Reference Sequences (RefSeq)

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    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_042142.1 RefSeqGene

      Range
      5005..502847
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001414174.1 → NP_001401103.1  inositol 1,4,5-trisphosphate receptor type 2 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC023051, AC023425, AC024093, AC024145, AC055720

    2. NM_001414175.1 → NP_001401104.1  inositol 1,4,5-trisphosphate receptor type 2 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AC023051, AC023425, AC024093, AC024145, AC055720

    3. NM_002223.4 → NP_002214.2  inositol 1,4,5-trisphosphate receptor type 2 isoform 1

      See identical proteins and their annotated locations for NP_002214.2

      Status: REVIEWED

      Source sequence(s)
      AC024093, AC055720, AI339141, AL711179, BE439696, BP314401, BP364657, BU173910, BX495410, CA419735, D26350, DB144849
      Consensus CDS
      CCDS41764.1
      UniProtKB/Swiss-Prot
      O94773, Q14571
      Related
      ENSP00000370744.3, ENST00000381340.8
      Conserved Domains (7) summary
      smart00472
      Location:294 → 342
      MIR; Domain in ryanodine and inositol trisphosphate receptors and protein O-mannosyltransferases
      pfam00520
      Location:2306 → 2552
      Ion_trans; Ion transport protein
      pfam01365
      Location:475 → 665
      RYDR_ITPR; RIH domain
      pfam02815
      Location:232 → 432
      MIR; MIR domain
      pfam08454
      Location:1917 → 2022
      RIH_assoc; RyR and IP3R Homology associated
      pfam08709
      Location:4 → 225
      Ins145_P3_rec; Inositol 1,4,5-trisphosphate/ryanodine receptor
      cl07918
      Location:2257 → 2417
      Virul_fac_BrkB; Virulence factor BrkB

    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_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      26335352..26833194 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017019266.2 → XP_016874755.1  inositol 1,4,5-trisphosphate receptor type 2 isoform X1

    2. XM_047428801.1 → XP_047284757.1  inositol 1,4,5-trisphosphate receptor type 2 isoform X2

    3. XM_017019269.3 → XP_016874758.1  inositol 1,4,5-trisphosphate receptor type 2 isoform X3

    RNA

    1. XR_001748686.3 RNA Sequence

    2. XR_001748687.2 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      26207897..26705197 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054371970.1 → XP_054227945.1  inositol 1,4,5-trisphosphate receptor type 2 isoform X1

    2. XM_054371971.1 → XP_054227946.1  inositol 1,4,5-trisphosphate receptor type 2 isoform X2

    3. XM_054371972.1 → XP_054227947.1  inositol 1,4,5-trisphosphate receptor type 2 isoform X3

    RNA

    1. XR_008488578.1 RNA Sequence

    2. XR_008488579.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q14571.2 GenPept UniProtKB/Swiss-Prot:Q14571

    Gene LinkOut

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

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