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    IRAG1 inositol 1,4,5-triphosphate receptor associated 1 [ Homo sapiens (human) ]

    Gene ID: 10335, updated on 28-Oct-2024

    Summary

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    Official Symbol
    IRAG1provided by HGNC
    Official Full Name
    inositol 1,4,5-triphosphate receptor associated 1provided by HGNC
    Primary source
    HGNC:HGNC:7237
    See related
    Ensembl:ENSG00000072952 MIM:604673; AllianceGenome:HGNC:7237
    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
    IRAG; JAW1L; MRVI1
    Summary
    This gene is similar to a putative mouse tumor suppressor gene (Mrvi1) that is frequently disrupted by mouse AIDS-related virus (MRV). The encoded protein, which is found in the membrane of the endoplasmic reticulum, is similar to Jaw1, a lymphoid-restricted protein whose expression is down-regulated during lymphoid differentiation. This protein is a substrate of cGMP-dependent kinase-1 (PKG1) that can function as a regulator of IP3-induced calcium release. Studies in mouse suggest that MRV integration at Mrvi1 induces myeloid leukemia by altering the expression of a gene important for myeloid cell growth and/or differentiation, and thus this gene may function as a myeloid leukemia tumor suppressor gene. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene, and alternative translation start sites, including a non-AUG (CUG) start site, are used. [provided by RefSeq, May 2011]
    Expression
    Broad expression in endometrium (RPKM 35.8), gall bladder (RPKM 20.9) and 19 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See IRAG1 in Genome Data Viewer
    Location:
    11p15.4
    Exon count:
    22
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (10573095..10693755, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (10657620..10778670, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (10594642..10715302, complement)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr11:10532526-10533436 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4437 Neighboring gene ring finger protein 141 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4438 Neighboring gene IRAG1 antisense RNA 1 Neighboring gene lymphatic vessel endothelial hyaluronan receptor 1 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr11:10615146-10616345 Neighboring gene Sharpr-MPRA regulatory regions 8950 and 14430 Neighboring gene MPRA-validated peak1195 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4439 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4440 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4441 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr11:10678394-10679593 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr11:10680716-10681915 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:10696121-10696708 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:10697483-10697984 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4443 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4444 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:10772162-10772662 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4447 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr11:10785333-10786532 Neighboring gene CTR9 homolog, Paf1/RNA polymerase II complex component Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:10813405-10813954 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:10813955-10814504 Neighboring gene eukaryotic translation initiation factor 4 gamma 2 Neighboring gene small nucleolar RNA, C/D box 97

    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. Homozygous mutation in murine retrovirus integration site 1 gene associated with a non-syndromic form of isolated familial achalasia. Koehler K, et al. Neurogastroenterol Motil, 2020 Dec. PMID 32573102
    2. Substrates of cGMP kinase in vascular smooth muscle and their role in the relaxation process. Baltensperger K, et al. Biochemistry, 1990 Oct 16. PMID 2271613
    3. Whole exome sequencing identifies MRVI1 as a susceptibility gene for moyamoya syndrome in neurofibromatosis type 1. Santoro C, et al. PLoS One, 2018. PMID 30001348, Free PMC Article
    4. InsP3R-associated cGMP kinase substrate (IRAG) is essential for nitric oxide-induced inhibition of calcium signaling in human colonic smooth muscle. Fritsch RM, et al. J Biol Chem, 2004 Mar 26. PMID 14729908
    5. Truncated IRAG variants modulate cGMP-mediated inhibition of human colonic smooth muscle cell contraction. Werder Av, et al. Am J Physiol Cell Physiol, 2011 Dec. PMID 21865585

    See all (30) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Homozygous mutation in murine retrovirus integration site 1 gene associated with a non-syndromic form of isolated familial achalasia.
      Title: Homozygous mutation in murine retrovirus integration site 1 gene associated with a non-syndromic form of isolated familial achalasia.
    2. P53-induced MRVI1 mediates carcinogenesis of colorectal cancer.
      Title: P53-induced MRVI1 mediates carcinogenesis of colorectal cancer.
    3. forced expression of MRVI1 in miR-940 mimic transfected cells abolished the facilitation of miR-940 on cell proliferation, migration, and invasion of RL95-2 and KLE cells. In conclusion, our study demonstrates that miR-940 might function as a reliable diagnostic and prognostic signature in endometrial carcinoma.
      Title: miR-940 potentially promotes proliferation and metastasis of endometrial carcinoma through regulation of MRVI1.
    4. p.P186S substitution (rs35857561) in MRVI1 that segregated with moyamoya syndrome in both the Italian and German family. rs35857561 polymorphism in MRVI1 may be a genetic susceptibility factor for moyamoya in European patients with neurofibromatosis type 1. MRVI1 is a functional partner of ITPR1, PRKG1 and GUCY1A3, which are involved in response to nitric oxide.
      Title: Whole exome sequencing identifies MRVI1 as a susceptibility gene for moyamoya syndrome in neurofibromatosis type 1.
    5. In the present study we analyzed the structure and function of the human IRAG/MRVI1 gene
      Title: Truncated IRAG variants modulate cGMP-mediated inhibition of human colonic smooth muscle cell contraction.
    6. IRAG is required for PKG1beta-regulated cyclic calcium release during motility of osteoclasts
      Title: Functional osteoclast attachment requires inositol-1,4,5-trisphosphate receptor-associated cGMP-dependent kinase substrate.
    7. Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
      Title: Genome-wide meta-analyses identifies seven loci associated with platelet aggregation in response to agonists.
    8. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    9. Observational study of gene-disease association. (HuGE Navigator)
      Title: Inherited genetic variant predisposes to aggressive but not indolent prostate cancer.
    10. These findings reveal that interaction between IRAG and InsP3RI has a central role in NO/cGMP-dependent inhibition of platelet aggregation and in vivo thrombosis.
      Title: IRAG mediates NO/cGMP-dependent inhibition of platelet aggregation and thrombus formation.
    Submit: New GeneRIF Correction See all GeneRIFs (13)

    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

    EBI GWAS Catalog

    Description
    Genome-wide meta-analyses identifies seven loci associated with platelet aggregation in response to agonists.
    EBI GWAS Catalog
    Genome-wide meta-analysis identifies new susceptibility loci for migraine.
    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

    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 protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cGMP-mediated signaling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in perinuclear region of cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in platelet dense tubular network membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in sarcoplasmic reticulum IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    inositol 1,4,5-triphosphate receptor associated 1
    Names
    IP3R-associated cGMP kinase substrate
    JAW1-related protein MRVI1
    inositol 1,4,5-triphosphate receptor-associated cGMP kinase substrate
    inositol 1,4,5-trisphosphate receptor-associated cGMP kinase substrate
    murine retrovirus integration site 1 homolog

    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_001098579.3 → NP_001092049.2  inositol 1,4,5-triphosphate receptor associated 1 isoform a

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes isoform a, also known as MRVI1A.
      Source sequence(s)
      AC009532
      Consensus CDS
      CCDS44538.2
      UniProtKB/Swiss-Prot
      B7Z3T4, B7Z6I2, B7Z9A3, E9PQY6, F5H6A1, J3KQZ7, Q17S00, Q9UNY1, Q9Y6F6
      Related
      ENSP00000432436.1, ENST00000531107.5
      Conserved Domains (2) summary
      PRK08691
      Location:180 → 380
      PRK08691; DNA polymerase III subunits gamma and tau; Validated
      pfam05781
      Location:318 → 904
      MRVI1; MRVI1 protein

    2. NM_001100163.3 → NP_001093633.1  inositol 1,4,5-triphosphate receptor associated 1 isoform b

      Status: REVIEWED

      Source sequence(s)
      AC009532
      Consensus CDS
      CCDS44539.1
      Conserved Domains (1) summary
      pfam05781
      Location:235 → 821
      MRVI1; MRVI1 protein

    3. NM_001100167.3 → NP_001093637.1  inositol 1,4,5-triphosphate receptor associated 1 isoform c

      See identical proteins and their annotated locations for NP_001093637.1

      Status: REVIEWED

      Source sequence(s)
      AC009532
      Consensus CDS
      CCDS44540.1
      UniProtKB/Swiss-Prot
      Q9Y6F6
      Related
      ENSP00000453013.1, ENST00000558540.5
      Conserved Domains (1) summary
      pfam05781
      Location:11 → 597
      MRVI1; MRVI1 protein

    4. NM_001206880.2 → NP_001193809.1  inositol 1,4,5-triphosphate receptor associated 1 isoform e

      Status: REVIEWED

      Source sequence(s)
      AC009532
      Consensus CDS
      CCDS55745.1
      UniProtKB/Swiss-Prot
      Q9Y6F6
      Related
      ENSP00000437784.1, ENST00000541483.5
      Conserved Domains (1) summary
      pfam05781
      Location:176 → 706
      MRVI1; MRVI1 protein

    5. NM_001206881.2 → NP_001193810.1  inositol 1,4,5-triphosphate receptor associated 1 isoform c

      See identical proteins and their annotated locations for NP_001193810.1

      Status: REVIEWED

      Source sequence(s)
      AC009532
      Consensus CDS
      CCDS44540.1
      UniProtKB/Swiss-Prot
      Q9Y6F6
      Related
      ENSP00000448278.2, ENST00000547195.5
      Conserved Domains (1) summary
      pfam05781
      Location:11 → 597
      MRVI1; MRVI1 protein

    6. NM_130385.4 → NP_569056.4  inositol 1,4,5-triphosphate receptor associated 1 isoform d

      Status: REVIEWED

      Source sequence(s)
      AC009532
      Consensus CDS
      CCDS55746.1
      Related
      ENSP00000412130.2, ENST00000423302.7
      Conserved Domains (1) summary
      pfam05781
      Location:326 → 912
      MRVI1; MRVI1 protein

    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_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      10573095..10693755 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      10657620..10778670 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9Y6F6.4 GenPept UniProtKB/Swiss-Prot:Q9Y6F6

    Gene LinkOut

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

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