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Aliases for IRS1 Gene

Aliases for IRS1 Gene

  • Insulin Receptor Substrate 1 2 3 3 5
  • IRS-1 3 4
  • HIRS-1 3

External Ids for IRS1 Gene

Previous GeneCards Identifiers for IRS1 Gene

  • GC02M225622
  • GC02M226321
  • GC02M227563
  • GC02M227802
  • GC02M227425
  • GC02M227308
  • GC02M219439

Summaries for IRS1 Gene

Entrez Gene Summary for IRS1 Gene

  • This gene encodes a protein which is phosphorylated by insulin receptor tyrosine kinase. Mutations in this gene are associated with type II diabetes and susceptibility to insulin resistance. [provided by RefSeq, Nov 2009]

GeneCards Summary for IRS1 Gene

IRS1 (Insulin Receptor Substrate 1) is a Protein Coding gene. Diseases associated with IRS1 include Diabetes Mellitus, Noninsulin-Dependent and Diabetes Mellitus. Among its related pathways are ERK Signaling and Akt Signaling. Gene Ontology (GO) annotations related to this gene include protein kinase binding and protein kinase C binding. An important paralog of this gene is IRS2.

UniProtKB/Swiss-Prot for IRS1 Gene

  • May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit (By similarity).

Gene Wiki entry for IRS1 Gene

Additional gene information for IRS1 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for IRS1 Gene

Genomics for IRS1 Gene

GeneHancer (GH) Regulatory Elements for IRS1 Gene

Promoters and enhancers for IRS1 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J226788 Promoter/Enhancer 2.8 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 652.4 +4.4 4351 13.6 HDGF PKNOX1 CLOCK FOXA2 MLX ARID4B SIN3A DMAP1 ZNF2 YY1 RHBDD1 IRS1 ENSG00000261379 ENSG00000272622 GC02P226775
GH02J226834 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 10.8 -37.8 -37774 6.4 HDGF PKNOX1 FOXA2 SMAD1 ARNT ARID4B SIN3A DMAP1 ZNF2 IRF4 RHBDD1 IRS1 PIR31520 GC02P226865
GH02J226423 Enhancer 1.5 FANTOM5 Ensembl ENCODE dbSUPER 15.8 +373.0 372998 7.3 FOXA2 RAD21 RARA YY1 FOS ETV6 CREM RUNX3 MIXL1 RXRA IRS1 LOC105373915 GC02M226320
GH02J227324 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 10.2 -526.2 -526182 3.1 MLX ZFP64 ARID4B SIN3A DMAP1 ZNF2 ZBTB7B IRF4 YY1 SLC30A9 MFF LOC654841 IRS1 RHBDD1 STIP1P2
GH02J226771 Enhancer 1.4 Ensembl ENCODE dbSUPER 11.9 +27.0 27017 3.4 PKNOX1 SMAD1 ATF1 FOXA2 ARNT FEZF1 IRF4 NCOA2 TCF12 ATF7 RHBDD1 IRS1 GC02P226775 MIR5702
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around IRS1 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the IRS1 gene promoter:
  • STAT3
  • AP-1
  • CREB
  • deltaCREB
  • ATF-2
  • c-Jun
  • c-Fos
  • c-Ets-1

Genomic Locations for IRS1 Gene

Genomic Locations for IRS1 Gene
68,443 bases
Minus strand
68,443 bases
Minus strand

Genomic View for IRS1 Gene

Genes around IRS1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
IRS1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for IRS1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for IRS1 Gene

Proteins for IRS1 Gene

  • Protein details for IRS1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Insulin receptor substrate 1
    Protein Accession:

    Protein attributes for IRS1 Gene

    1242 amino acids
    Molecular mass:
    131591 Da
    Quaternary structure:
    • Interacts with UBTF and PIK3CA (By similarity). Interacts (via phosphorylated YXXM motifs) with PIK3R1 (By similarity). Interacts with ROCK1 and FER (By similarity). Interacts (via PH domain) with PHIP (By similarity). Interacts with GRB2 (By similarity). Interacts with SOCS7. Interacts (via IRS-type PTB domain) with IGF1R and INSR (via the tyrosine-phosphorylated NPXY motif). Interacts with ALK. Interacts with EIF2AK2/PKR (By similarity).

    Three dimensional structures from OCA and Proteopedia for IRS1 Gene

neXtProt entry for IRS1 Gene

Post-translational modifications for IRS1 Gene

  • Serine phosphorylation of IRS1 is a mechanism for insulin resistance. Ser-312 phosphorylation inhibits insulin action through disruption of IRS1 interaction with the insulin receptor (By similarity). Phosphorylation of Tyr-896 is required for GRB2-binding (By similarity). Phosphorylated by ALK. Phosphorylated at Ser-270, Ser-307, Ser-636 and Ser-1101 by RPS6KB1; phosphorylation induces accelerated degradation of IRS1.
  • Ubiquitinated by the Cul7-RING(FBXW8) complex in a mTOR-dependent manner, leading to its degradation: the Cul7-RING(FBXW8) complex recognizes and binds IRS1 previously phosphorylated by S6 kinase (RPS6KB1 or RPS6KB2).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for IRS1 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Abcam antibodies for IRS1

No data available for DME Specific Peptides for IRS1 Gene

Domains & Families for IRS1 Gene

Gene Families for IRS1 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins

Suggested Antigen Peptide Sequences for IRS1 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

genes like me logo Genes that share domains with IRS1: view

No data available for UniProtKB/Swiss-Prot for IRS1 Gene

Function for IRS1 Gene

Molecular function for IRS1 Gene

UniProtKB/Swiss-Prot Function:
May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit (By similarity).
GENATLAS Biochemistry:
insulin receptor,substrate 1,overexpressed in skeletal muscle,and adipocytes (polymorphism associated to susceptibility to NIDDM),located in the low density microsome fraction,tyrosine phosphorylated in response to insulin stimulation,interacting with several proteins containing SH2 domains,such as PIKRs,GRB2

Phenotypes From GWAS Catalog for IRS1 Gene

Gene Ontology (GO) - Molecular Function for IRS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001784 phosphotyrosine residue binding IPI 20624904
GO:0004871 obsolete signal transducer activity TAS --
GO:0005068 transmembrane receptor protein tyrosine kinase adaptor activity TAS,ISS --
GO:0005080 protein kinase C binding ISS --
GO:0005088 Ras guanyl-nucleotide exchange factor activity TAS --
genes like me logo Genes that share ontologies with IRS1: view
genes like me logo Genes that share phenotypes with IRS1: view

Animal Models for IRS1 Gene

MGI Knock Outs for IRS1:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for IRS1

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for IRS1 Gene

Localization for IRS1 Gene

Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for IRS1 gene
Compartment Confidence
plasma membrane 5
nucleus 5
cytosol 5
extracellular 2
cytoskeleton 2
mitochondrion 2
peroxisome 2
endoplasmic reticulum 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nucleoplasm (3)
  • Plasma membrane (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for IRS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA,ISS --
GO:0005737 cytoplasm ISS,TAS --
GO:0005829 cytosol IBA,TAS --
GO:0005886 plasma membrane TAS --
GO:0005899 insulin receptor complex ISS --
genes like me logo Genes that share ontologies with IRS1: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for IRS1 Gene

Pathways & Interactions for IRS1 Gene

SuperPathway Contained pathways
1 RET signaling
2 Regulation of lipid metabolism Insulin signaling-generic cascades
3 Common Cytokine Receptor Gamma-Chain Family Signaling Pathways
4 PI3K/AKT activation
5 IL-2 Pathway
genes like me logo Genes that share pathways with IRS1: view

Pathways by source for IRS1 Gene

SIGNOR curated interactions for IRS1 Gene

Gene Ontology (GO) - Biological Process for IRS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade TAS --
GO:0007165 signal transduction TAS 1311924
GO:0008284 positive regulation of cell proliferation NAS 17925406
GO:0008286 insulin receptor signaling pathway IMP,IPI 7537849
GO:0010907 positive regulation of glucose metabolic process IMP 16814735
genes like me logo Genes that share ontologies with IRS1: view

Drugs & Compounds for IRS1 Gene

(59) Drugs for IRS1 Gene - From: DrugBank, PharmGKB, DGIdb, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Clopidogrel Approved Pharma P2Y12 receptor antagonist 814
Cyclophosphamide Approved, Investigational Pharma Nitrogen mustard alkylating agent and prodrug. 3113
Epirubicin Approved Pharma 426
Fluorouracil Approved Pharma RNA processing inhibitor and thymidylate synthase inhibitor 1970

(35) Additional Compounds for IRS1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with IRS1: view

Transcripts for IRS1 Gene

mRNA/cDNA for IRS1 Gene

(1) REFSEQ mRNAs :
(2) Additional mRNA sequences :
(115) Selected AceView cDNA sequences:
(2) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for IRS1 Gene

Insulin receptor substrate 1:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for IRS1

Alternative Splicing Database (ASD) splice patterns (SP) for IRS1 Gene

No ASD Table

Relevant External Links for IRS1 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for IRS1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for IRS1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for IRS1 Gene

This gene is overexpressed in Brain (66.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for IRS1 Gene

NURSA nuclear receptor signaling pathways regulating expression of IRS1 Gene:


SOURCE GeneReport for Unigene cluster for IRS1 Gene:


Evidence on tissue expression from TISSUES for IRS1 Gene

  • Liver(4.7)
  • Muscle(4.7)
  • Eye(4.3)
  • Nervous system(3.5)
  • Pancreas(2.6)
  • Blood(2.5)
  • Heart(2.3)
  • Kidney(2)
genes like me logo Genes that share expression patterns with IRS1: view

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for IRS1 Gene

Orthologs for IRS1 Gene

This gene was present in the common ancestor of animals.

Orthologs for IRS1 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia IRS1 34 33
  • 99.19 (n)
(Canis familiaris)
Mammalia IRS1 34 33
  • 88.97 (n)
(Bos Taurus)
Mammalia IRS1 34 33
  • 88.74 (n)
(Mus musculus)
Mammalia Irs1 16 34 33
  • 85.37 (n)
(Rattus norvegicus)
Mammalia Irs1 33
  • 84.97 (n)
(Monodelphis domestica)
Mammalia IRS1 34
  • 74 (a)
(Gallus gallus)
Aves IRS1 34 33
  • 74.2 (n)
(Anolis carolinensis)
Reptilia IRS1 34
  • 63 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100495320 33
  • 62.74 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.957 33
(Danio rerio)
Actinopterygii irs1 34 33
  • 61.99 (n)
fruit fly
(Drosophila melanogaster)
Insecta chico 34
  • 21 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 38 (a)
Species where no ortholog for IRS1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for IRS1 Gene

Gene Tree for IRS1 (if available)
Gene Tree for IRS1 (if available)
Evolutionary constrained regions (ECRs) for IRS1: view image

Paralogs for IRS1 Gene

Paralogs for IRS1 Gene

(1) SIMAP similar genes for IRS1 Gene using alignment to 4 proteins:

  • W0KR29_HUMAN
genes like me logo Genes that share paralogs with IRS1: view

Variants for IRS1 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for IRS1 Gene

The Arg-971 polymorphism impairs the ability of insulin to stimulate glucose transport, glucose transporter translocation, and glycogen synthesis by affecting the PI3K/AKT1/GSK3 signaling pathway. The polymorphism at Arg-971 may contribute to the in vivo insulin resistance observed in carriers of this variant. Arg-971 could contribute to the risk for atherosclerotic cardiovascular diseases associated with non-insulin-dependent diabetes mellitus (NIDDM) by producing a cluster of insulin resistance-related metabolic abnormalities. In insulin-stimulated human endothelial cells from carriers of the Arg-971 polymorphism, genetic impairment of the IRS1/PI3K/PDPK1/AKT1 insulin signaling cascade results in impaired insulin-stimulated nitric oxide (NO) release and suggested that this may be a mechanism through which the Arg-971 polymorphism contributes to the genetic predisposition to develop endothelial dysfunction and cardiovascular disease. The Arg-971 polymorphism not only reduces phosphorylation of the substrate but allows IRS1 to act as an inhibitor of PI3K, producing global insulin resistance.

Sequence variations from dbSNP and Humsavar for IRS1 Gene

SNP ID Clin Chr 02 pos Variation AA Info Type
rs104893642 pathogenic, Diabetes mellitus type 2 226,796,916(-) G/A/C coding_sequence_variant, missense_variant
rs148962208 uncertain-significance, Diabetes mellitus type 2 226,795,504(-) G/A coding_sequence_variant, missense_variant
rs1801278 risk-factor, Insulin resistance, susceptibility to, Coronary artery disease, susceptibility to 226,795,828(-) C/G/T coding_sequence_variant, missense_variant
VAR_005302 Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853] p.Ser1043Tyr
VAR_005303 Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853] p.Cys1095Tyr

Structural Variations from Database of Genomic Variants (DGV) for IRS1 Gene

Variant ID Type Subtype PubMed ID
dgv4178n100 CNV gain 25217958
nsv3190 CNV deletion 18451855
nsv584594 CNV gain 21841781
nsv821910 CNV gain 20364138

Variation tolerance for IRS1 Gene

Residual Variation Intolerance Score: 61.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.46; 71.54% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for IRS1 Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

SNP Genotyping and Copy Number Assay Products

Disorders for IRS1 Gene

MalaCards: The human disease database

(19) MalaCards diseases for IRS1 Gene - From: HGMD, OMIM, ClinVar, GTR, Swiss-Prot, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search IRS1 in MalaCards View complete list of genes associated with diseases


  • Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the bodys own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269 PubMed:10206679, ECO:0000269 PubMed:12843189, ECO:0000269 PubMed:8723689}. Note=The gene represented in this entry may be involved in disease pathogenesis.

Additional Disease Information for IRS1

Genetic Association Database
Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with IRS1: view

No data available for Genatlas for IRS1 Gene

Publications for IRS1 Gene

  1. A novel T608R missense mutation in insulin receptor substrate-1 identified in a subject with type 2 diabetes impairs metabolic insulin signaling. (PMID: 12679424) Esposito DL … Cama A (The Journal of clinical endocrinology and metabolism 2003) 3 4 22 44 58
  2. Aminoacid polymorphisms of insulin receptor substrate-1 in non-insulin-dependent diabetes mellitus. (PMID: 8104271) Almind K … Pedersen O (Lancet (London, England) 1993) 3 4 22 44 58
  3. [Effect of the Gly972Arg, SNP43 and Prol2Ala polymorphisms of the genes IRS1, CAPN10 and PPARG2 on secondary failure to sulphonylurea and metformin in patients with type 2 diabetes in Yucatán, México]. (PMID: 19418728) García-Escalante MG … Laviada-Molina H (Investigacion clinica 2009) 3 22 44 58
  4. Leptin and leptin receptor genotypes and colon cancer: gene-gene and gene-lifestyle interactions. (PMID: 18059035) Slattery ML … Potter JD (International journal of cancer 2008) 3 22 44 58
  5. S6K directly phosphorylates IRS-1 on Ser-270 to promote insulin resistance in response to TNF-(alpha) signaling through IKK2. (PMID: 18952604) Zhang J … Ye J (The Journal of biological chemistry 2008) 3 4 22 58

Products for IRS1 Gene

  • Addgene plasmids for IRS1