U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination
    • Showing Current items.

    IRS4 insulin receptor substrate 4 [ Homo sapiens (human) ]

    Gene ID: 8471, updated on 27-Nov-2024

    Summary

    Go to the top of the page Help
    Official Symbol
    IRS4provided by HGNC
    Official Full Name
    insulin receptor substrate 4provided by HGNC
    Primary source
    HGNC:HGNC:6128
    See related
    Ensembl:ENSG00000133124 MIM:300904; AllianceGenome:HGNC:6128
    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
    CHNG9; IRS-4; PY160
    Summary
    IRS4 encodes the insulin receptor substrate 4, a cytoplasmic protein that contains many potential tyrosine and serine/threonine phosphorylation sites. Tyrosine-phosphorylated IRS4 protein has been shown to associate with cytoplasmic signalling molecules that contain SH2 domains. The IRS4 protein is phosphorylated by the insulin receptor tyrosine kinase upon receptor stimulation.. [provided by RefSeq, Jul 2008]
    Expression
    Biased expression in ovary (RPKM 3.0), thyroid (RPKM 1.0) and 3 other tissues See more
    Orthologs
    mouse all
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    Go to the top of the page Help
    See IRS4 in Genome Data Viewer
    Location:
    Xq22.3
    Exon count:
    3
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (108719946..108736563, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (107157529..107174147, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (107963176..107979793, complement)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124905205 Neighboring gene collagen type IV alpha 6 chain Neighboring gene BRD4-independent group 4 enhancer GRCh37_chrX:107513459-107514658 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chrX:107596629-107597181 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chrX:107609798-107610337 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:107634248-107634889 Neighboring gene collagen type IV alpha 5 chain Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:107843610-107844540 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chrX:107884720-107885919 Neighboring gene IRS4 antisense RNA 1 Neighboring gene RNA, U6 small nuclear 309, pseudogene Neighboring gene NANOG hESC enhancer GRCh37_chrX:108268814-108269381 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:108356812-108357387 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chrX:108387340-108387890 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chrX:108426594-108427161 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chrX:108427729-108428296 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:108483829-108484360 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29840 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29841 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29842 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chrX:108542338-108542938 Neighboring gene GAPDH pseudogene 77

    Genomic regions, transcripts, and products

    Go to the top of the page Help

    Go to nucleotide: Graphics FASTA GenBank

    Expression

    Go to the top of the page Help
    • 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

    Go to the top of the pageHelp

    Related articles in PubMed

    1. A novel 160-kDa phosphotyrosine protein in insulin-treated embryonic kidney cells is a new member of the insulin receptor substrate family. Lavan BE, et al. J Biol Chem, 1997 Aug 22. PMID 9261155
    2. Chronic venous disease patients show increased IRS-4 expression in the great saphenous vein wall. Ortega MA, et al. J Int Med Res, 2021 Sep. PMID 34590920, Free PMC Article
    3. Screening for Mutations in Isolated Central Hypothyroidism Reveals a Novel Mutation in Insulin Receptor Substrate 4. Patyra K, et al. Front Endocrinol (Lausanne), 2021. PMID 34093435, Free PMC Article
    4. Role of insulin receptor substrate-4 in IGF-I-stimulated HEPG2 proliferation. Cuevas EP, et al. J Hepatol, 2007 Jun. PMID 17408801
    5. Insulin receptor substrate-4 is expressed in muscle tissue without acting as a substrate for the insulin receptor. Schreyer S, et al. Endocrinology, 2003 Apr. PMID 12639902

    See all (212) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Further Delineation of Central Congenital Hypothyroidism due to Variants in TBL1X and IRS4.
      Title: Further Delineation of Central Congenital Hypothyroidism due to Variants in TBL1X and IRS4.
    2. Patients with Invasive Lobular Carcinoma Show a Significant Increase in IRS-4 Expression Compared to Infiltrative Ductal Carcinoma-A Histopathological Study.
      Title: Patients with Invasive Lobular Carcinoma Show a Significant Increase in IRS-4 Expression Compared to Infiltrative Ductal Carcinoma-A Histopathological Study.
    3. FER-mediated phosphorylation and PIK3R2 recruitment on IRS4 promotes AKT activation and tumorigenesis in ovarian cancer cells.
      Title: FER-mediated phosphorylation and PIK3R2 recruitment on IRS4 promotes AKT activation and tumorigenesis in ovarian cancer cells.
    4. Screening for Mutations in Isolated Central Hypothyroidism Reveals a Novel Mutation in Insulin Receptor Substrate 4.
      Title: Screening for Mutations in Isolated Central Hypothyroidism Reveals a Novel Mutation in Insulin Receptor Substrate 4.
    5. Chronic venous disease patients show increased IRS-4 expression in the great saphenous vein wall.
      Title: Chronic venous disease patients show increased IRS-4 expression in the great saphenous vein wall.
    6. IRS4 promotes the progression of non-small cell lung cancer and confers resistance to EGFR-TKI through the activation of PI3K/Akt and Ras-MAPK pathways.
      Title: IRS4 promotes the progression of non-small cell lung cancer and confers resistance to EGFR-TKI through the activation of PI3K/Akt and Ras-MAPK pathways.
    7. Mutations in IRS4 are associated with isolated congenital central hypothyroidism (CeH) in male carriers. As IRS4 is involved in leptin signalling, the phenotype may be related to disrupted leptin signalling.
      Title: Mutations in IRS4 are associated with central hypothyroidism.
    8. IRS4, as a new substrate of CHIP, is negatively regulated by CK1gamma2 at the posttranslational level.
      Title: Phosphorylation of IRS4 by CK1γ2 promotes its degradation by CHIP through the ubiquitin/lysosome pathway.
    9. increase of IRS-4 expression may be involved to some extent in colorectal cancer.
      Title: Overexpression of insulin receptor substrate-4 is correlated with clinical staging in colorectal cancer patients.
    10. IRS4 overexpression is associated with cancer.
      Title: Pan-cancer analysis of somatic copy-number alterations implicates IRS4 and IGF2 in enhancer hijacking.
    Submit: New GeneRIF Correction See all GeneRIFs (33)

    Phenotypes

    Go to the top of the page Help

    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
    Hypothyroidism, congenital, nongoitrous, 9
    MedGen: C5231396 OMIM: 301035 GeneReviews: Not available
    		Compare labs

    Variation

    Go to the top of the page Help

    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

    Go to the top of the page Help

    Protein interactions

    Protein Gene Interaction Pubs
    Pr55(Gag) gag Cellular biotinylated insulin receptor substrate 4 (IRS4) is incorporated into HIV-1 Gag virus-like particles PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Go to the top of the page

    Interactions

    Go to the top of the page Help
    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Go to the top of the page Help

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables insulin receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables phosphatidylinositol 3-kinase binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in insulin receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

    Go to the top of the page Help
    Preferred Names
    insulin receptor substrate 4
    Names
    160 kDa phosphotyrosine protein
    phosphoprotein of 160 kDa
    pp160

    NCBI Reference Sequences (RefSeq)

    Go to the top of the page Help

    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_013239.2 RefSeqGene

      Range
      5000..21617
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001379150.1 → NP_001366079.1  insulin receptor substrate 4 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AL035425
      Consensus CDS
      CCDS94648.1
      UniProtKB/TrEMBL
      A0A804CF45
      Related
      ENSP00000361202.3, ENST00000372129.4
      Conserved Domains (2) summary
      cd01204
      Location:231 → 334
      PTB_IRS; Insulin receptor substrate phosphotyrosine-binding domain (PTBi)
      cd01257
      Location:79 → 202
      PH_IRS; Insulin receptor substrate (IRS) pleckstrin homology (PH) domain

    2. NM_003604.2 → NP_003595.1  insulin receptor substrate 4 isoform 1

      See identical proteins and their annotated locations for NP_003595.1

      Status: REVIEWED

      Source sequence(s)
      AF007567
      Consensus CDS
      CCDS14544.1
      UniProtKB/Swiss-Prot
      O14654
      Related
      ENSP00000505547.1, ENST00000564206.2
      Conserved Domains (2) summary
      cd01204
      Location:231 → 334
      PTB_IRS; Insulin receptor substrate phosphotyrosine-binding domain (PTBi)
      cd01257
      Location:79 → 202
      PH_IRS; Insulin receptor substrate (IRS) pleckstrin homology (PH) domain

    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_000023.11 Reference GRCh38.p14 Primary Assembly

      Range
      108719946..108736563 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011531061.2 → XP_011529363.1  insulin receptor substrate 4 isoform X1

      Conserved Domains (2) summary
      cd01204
      Location:231 → 334
      PTB_IRS; Insulin receptor substrate phosphotyrosine-binding domain (PTBi)
      cd01257
      Location:79 → 202
      PH_IRS; Insulin receptor substrate (IRS) pleckstrin homology (PH) domain

    2. XM_006724713.4 → XP_006724776.1  insulin receptor substrate 4 isoform X2

      Conserved Domains (2) summary
      cd01204
      Location:231 → 334
      PTB_IRS; Insulin receptor substrate phosphotyrosine-binding domain (PTBi)
      cd01257
      Location:79 → 202
      PH_IRS; Insulin receptor substrate (IRS) pleckstrin homology (PH) domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060947.1 Alternate T2T-CHM13v2.0

      Range
      107157529..107174147 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054328000.1 → XP_054183975.1  insulin receptor substrate 4 isoform X1

    2. XM_054328001.1 → XP_054183976.1  insulin receptor substrate 4 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O14654.1 GenPept UniProtKB/Swiss-Prot:O14654

    Gene LinkOut

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

    Chemical Information
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous