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

Gene ID: 8471, updated on 7-Apr-2024

Summary

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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
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Genomic context

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See IRS4 in Genome Data Viewer
Location:
Xq22.3
Exon count:
3
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (108719946..108736563, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (107157529..107174147, complement)
105.20220307 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

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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. Patients with Invasive Lobular Carcinoma Show a Significant Increase in IRS-4 Expression Compared to Infiltrative Ductal Carcinoma-A Histopathological Study. Ortega MA, et al. Medicina (Kaunas), 2022 May 28. PMID 35743985, Free PMC Article
  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. Mutations in IRS4 are associated with central hypothyroidism. Heinen CA, et al. J Med Genet, 2018 Oct. PMID 30061370, Free PMC Article
  5. Effect of IRS4 levels on PI 3-kinase signalling. Hoxhaj G, et al. PLoS One, 2013. PMID 24039912, Free PMC Article

See all (186) 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

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

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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 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

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Preferred Names
insulin receptor substrate 4
Names
160 kDa phosphotyrosine protein
phosphoprotein of 160 kDa
pp160

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.

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_2023_10

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

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