IRS1 Gene (Protein Coding)

Insulin Receptor Substrate 1

GC02M226731
GIFtS:
47
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] See more...

Aliases for IRS1 Gene

Aliases for IRS1 Gene

  • Insulin Receptor Substrate 1 2 3 4 5
  • HIRS-1 2 3
  • IRS-1 3 4
  • IRS1 5

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 Rare Diabetes Mellitus Type 2. Among its related pathways are Common Cytokine Receptor Gamma-Chain Family Signaling Pathways and GDNF-Family Ligands and Receptor Interactions. 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 Summary 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 , Rfam classification and piRNA Summary for IRS1 Gene

Genomics for IRS1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for IRS1 Gene
GeneHancer (GH) Identifier GH Type GH
Score		 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 2.5 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 602.3 +4.3 4253 13.8 SP1 HNRNPL CREB1 GATAD2A CTCF TEAD4 PRDM10 REST TFE3 SOX13 RHBDD1 IRS1 ENSG00000261379 5MWI_A-095 ENSG00000272622 HSALNG0022707
GH02J226834 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 10.8 -37.6 -37611 6.7 CREB1 GATAD2A HNRNPL PRDM10 ZNF629 TFE3 LEF1 IKZF1 NFKBIZ KDM1A RHBDD1 lnc-COL4A3-4 lnc-IRS1-6 IRS1 piR-30521 COL4A4
GH02J227324 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 10.1 -526.1 -526084 3.3 SP1 HNRNPL CREB1 GATAD2A PRDM10 REST ZNF629 TFE3 SIX5 IKZF1 MFF MFF-DT IRS1 RHBDD1 STIP1P2 TM4SF20
GH02J226423 Enhancer 1.4 FANTOM5 ENCODE CraniofacialAtlas dbSUPER 15.7 +373.0 372998 7.3 GATAD2A SOX13 RXRB POLR2A SP1 TOE1 CEBPA EED CEBPB RAD21 IRS1 HSALNG0022696 lnc-IRS1-1
GH02J226771 Enhancer 1.5 Ensembl ENCODE CraniofacialAtlas dbSUPER 11.9 +27.1 27140 3.6 SP1 REST LEF1 IKZF1 RCOR2 BACH1 STAT3 GABPA RELA PKNOX1 IRS1 5MWI_A-095 HSALNG0022707
- 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 the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for IRS1

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

Genomic Locations for IRS1 Gene

Genomic Locations for IRS1 Gene
chr2:226,731,317-226,799,759
(GRCh38/hg38)
Size:
68,443 bases
Orientation:
Minus strand
chr2:227,596,033-227,664,475
(GRCh37/hg19)
Size:
68,443 bases
Orientation:
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 Structure • Gene Density

RefSeq DNA sequence for IRS1 Gene

Proteins for IRS1 Gene

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

    Protein Symbol:
    P35568-IRS1_HUMAN
    Recommended name:
    Insulin receptor substrate 1
    Protein Accession:
    P35568

    Protein attributes for IRS1 Gene

    Size:
    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 (PubMed:16127460). Interacts (via IRS-type PTB domain) with IGF1R and INSR (via the tyrosine-phosphorylated NPXY motif) (PubMed:7541045, PubMed:7559478, PubMed:7537849). Interacts with ALK (PubMed:15226403, PubMed:16878150). Interacts with EIF2AK2/PKR (By similarity). Interacts with GKAP1 (By similarity). Interacts with DGKZ in the absence of insulin; insulin stimulation decreases this interaction (By similarity). Found in a ternary complex with DGKZ and PIP5K1A in the absence of insulin stimulation (By similarity).

    Three dimensional structures from OCA and Proteopedia for IRS1 Gene

neXtProt entry for IRS1 Gene

Protein Expression for IRS1 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

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 (PubMed:18952604). Phosphorylated on tyrosine residues in response to insulin (PubMed:23401856). In skeletal muscles, dephosphorylated on Tyr-612 by TNS2 under anabolic conditions; dephosphorylation results in the proteasomal degradation of IRS1 (PubMed:23401856).
  • 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

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

Protein Domains for IRS1 Gene

InterPro:
Blocks:
  • Pleckstrin-like
  • Insulin receptor substrate-1 PTB domain signature
ProtoNet:

Suggested Antigen Peptide Sequences for IRS1 Gene

GenScript: Design optimal peptide antigens:
  • Insulin receptor substrate 1 (IRS1_HUMAN)
genes like me logo Genes that share domains with IRS1: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for IRS1 Gene

Function for IRS1 Gene

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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:0005068 transmembrane receptor protein tyrosine kinase adaptor activity TAS,ISS --
GO:0005070 SH3/SH2 adaptor activity IDA --
GO:0005080 protein kinase C binding ISS --
GO:0005158 insulin receptor binding IPI 7493946
genes like me logo Genes that share ontologies with IRS1: view
genes like me logo Genes that share phenotypes with IRS1: view

Human Phenotype Ontology for IRS1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

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) , Transcription Factor Targets and HOMER Transcription for IRS1 Gene

Localization for IRS1 Gene

Subcellular locations from

COMPARTMENTS
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 3
mitochondrion 3
endoplasmic reticulum 3
cytoskeleton 2
peroxisome 2
endosome 2
lysosome 2
golgi apparatus 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 ISS --
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm TAS,ISS --
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane TAS --
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

PathCards logo

SuperPathways for IRS1 Gene

SuperPathway Contained pathways
1 RET signaling
Frs2-mediated activation
.95
GRB2 events in EGFR signaling
.95
MAPK1/MAPK3 signaling
.95
Prolonged ERK activation events
.95
RAF/MAP kinase cascade
.95
SHC1 events in EGFR signaling
.95
Signaling by Leptin
.95
SOS-mediated signalling
.95
VEGFR2 mediated cell proliferation
.95
ARMS-mediated activation
.95
Signalling to ERKs
.95
Signalling to p38 via RIT and RIN
.95
Signalling to RAS
.95
Interleukin receptor SHC signaling
.95
Interleukin-3, 5 and GM-CSF signaling
.94
Interleukin-2 signaling
.94
Downstream signal transduction
.94
Signaling by PDGF
.94
DAP12 signaling
.92
RET signaling
.92
Insulin receptor signalling cascade
.92
Signaling by Insulin receptor
.92
IRS-mediated signalling
.91
Signaling by EGFR
.90
FCERI mediated MAPK activation
.90
IGF1R signaling cascade
.90
IRS-related events triggered by IGF1R
.90
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
.90
DAP12 interactions
.89
NCAM signaling for neurite out-growth
.89
NGF signalling via TRKA from the plasma membrane
.87
MAPK family signaling cascades
.87
Signaling by SCF-KIT
.85
Signalling by NGF
.81
Fc epsilon receptor (FCERI) signaling
.79
VEGFA-VEGFR2 Pathway
.78
Signaling by VEGF
.76
Gastrin-CREB signalling pathway via PKC and MAPK
.55
2 Regulation of lipid metabolism Insulin signaling-generic cascades
Regulation of lipid metabolism Insulin signaling-generic cascades
.59
Translation Insulin regulation of translation
.59
Transcription Receptor-mediated HIF regulation
.51
Translation Regulation of EIF2 activity
.47
Translation Regulation of EIF4F activity
.44
Development Growth hormone signaling via PI3K/AKT and MAPK cascades
.34
Insulin signaling pathway
.32
IRS activation
.01
Signal attenuation
.01
3 Common Cytokine Receptor Gamma-Chain Family Signaling Pathways
IL-21 Signaling Pathways
.90
IL-7 Signaling Pathways
.90
IL-9 Signaling Pathways
.90
Common Cytokine Receptor Gamma-Chain Family Signaling Pathways
.90
IL-15 Signaling Pathways
.88
IL-2 Signaling Pathways
.88
IL-4 Signaling Pathways
.84
Immune response IL-9 signaling pathway
.42
Adipocytokines and Insulin Signaling
.34
4 GAB1 signalosome
Negative regulation of the PI3K/AKT network
.93
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
.93
PIP3 activates AKT signaling
.91
Role of LAT2/NTAL/LAB on calcium mobilization
.91
GAB1 signalosome
.89
PI3K/AKT activation
.89
Constitutive Signaling by Aberrant PI3K in Cancer
.75
PI3K/AKT Signaling in Cancer
.72
5 IL-2 Pathway
Prolactin Signaling
.54
Growth Hormone Signaling
.49
PI3K Signaling in B-Lymphocyte
.35
IL-4 Pathway
.34
genes like me logo Genes that share pathways with IRS1: view

Pathways by source for IRS1 Gene

2 Sino Biological pathways for IRS1 Gene
22 GeneGo (Thomson Reuters) pathways for IRS1 Gene
  • Apoptosis and survival BAD phosphorylation
  • Apoptosis and survival Caspase cascade
  • Development EGFR signaling via PIP3
  • Development GDNF family signaling
  • Development Growth hormone signaling via PI3K/AKT and MAPK cascades
19 Qiagen pathways for IRS1 Gene
  • Akt Signaling
  • AMPK Enzyme Complex Pathway
  • BAD Phosphorylation
  • GDNF-Family Ligands and Receptor Interactions
  • Growth Hormone Signaling
2 Cell Signaling Technology pathways for IRS1 Gene
1 GeneTex pathway for IRS1 Gene

SIGNOR curated interactions for IRS1 Gene

Activates:
Is activated by:
Is inactivated by:
Other effect:

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

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(58) 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 934
Cyclophosphamide Approved, Investigational Pharma Nitrogen mustard alkylating agent and prodrug. 3670
Epirubicin Approved Pharma 483
Fluorouracil Approved Pharma RNA processing inhibitor and thymidylate synthase inhibitor 2338
[4-({5-(AMINOCARBONYL)-4-[(3-METHYLPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)PHENYL]ACETIC ACID Experimental Pharma Target 0

(36) 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

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  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for IRS1 Gene

1 REFSEQ mRNAs :
3 NCBI additional mRNA sequence :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

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
IRS1

Expression for IRS1 Gene

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  1. Primer
  2. Gene Expression Assay

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

mRNA expression in normal human tissues for IRS1 Gene
mRNA expression by BioGPS for IRS1 GenemRNA expression by GTEx 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



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for IRS1

SOURCE GeneReport for Unigene cluster for IRS1 Gene:

Hs.471508

Evidence on tissue expression from TISSUES for IRS1 Gene

  • Liver(4.8)
  • Muscle(4.8)
  • Eye(4.4)
  • Nervous system(3.9)
  • Pancreas(3.3)
  • Blood(3.2)
  • Heart(3.1)
  • Kidney(2.9)
  • Intestine(2.8)
  • Thyroid gland(2.7)
  • Adrenal gland(2.7)
  • Skin(2.7)
  • Bone marrow(2.6)
  • Stomach(2.3)
  • Lung(2.2)
  • Spleen(2.2)
  • Bone(2.1)
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
Chimpanzee
(Pan troglodytes)
 Mammalia IRS1 30 31
  • 99.19 (n)
 OneToOne
Dog
(Canis familiaris)
 Mammalia IRS1 30 31
  • 88.97 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia IRS1 30 31
  • 88.74 (n)
 OneToOne
Mouse
(Mus musculus)
 Mammalia Irs1 30 17 31
  • 85.37 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Irs1 30
  • 84.97 (n)
Oppossum
(Monodelphis domestica)
 Mammalia IRS1 31
  • 74 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves IRS1 30 31
  • 74.2 (n)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia IRS1 31
  • 63 (a)
 OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia LOC100495320 30
  • 62.74 (n)
African clawed frog
(Xenopus laevis)
 Amphibia Xl.957 30
Zebrafish
(Danio rerio)
 Actinopterygii irs1 30 31
  • 61.99 (n)
 OneToOne
Fruit Fly
(Drosophila melanogaster)
 Insecta chico 31
  • 21 (a)
 OneToMany
Sea Squirt
(Ciona savignyi)
 Ascidiacea -- 31
  • 38 (a)
 OneToMany
Species where no ortholog for IRS1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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 Vase (Ciona intestinalis)
  • 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

ENSEMBL:
Gene Tree for IRS1 (if available)
TreeFam:
Gene Tree for IRS1 (if available)
Aminode:
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:

  • IRS1_HUMAN
  • W0KMC7_HUMAN
  • W0KR29_HUMAN
  • W0KRH6_HUMAN
genes like me logo Genes that share paralogs with IRS1: view

Variants for IRS1 Gene

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Polymorphic Variants from UniProtKB/Swiss-Prot for IRS1 Gene

IRS1_HUMAN-P35568
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, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for IRS1 Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
708764 Likely Benign: not provided 226,797,596(-) G/A SYNONYMOUS_VARIANT
715476 Benign: not provided 226,796,399(-) C/T SYNONYMOUS_VARIANT
722785 Benign: not provided 226,795,250(-) T/G SYNONYMOUS_VARIANT
725911 Benign: not provided 226,796,065(-) T/C MISSENSE_VARIANT
725974 Likely Benign: not provided 226,797,719(-) G/A SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for IRS1 Gene

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)
IRS1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
IRS1

SNP Genotyping and Copy Number Assay Products

Disorders for IRS1 Gene

MalaCards: The human disease database

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

Disorder Aliases PubMed IDs
diabetes mellitus, noninsulin-dependent
  • niddm
rare diabetes mellitus type 2
  • rare insulin-independent diabetes mellitus
lipoprotein quantitative trait locus
  • coronary heart disease
diabetes mellitus
  • diabetes
gestational diabetes
  • gdm
- elite association - COSMIC cancer census association via MalaCards
Search IRS1 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

IRS1_HUMAN
  • Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's 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
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
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 23 41
  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 23 41
  3. No association of the G972S polymorphism of the insulin receptor substrate-1 gene with polycystic ovary syndrome in lean PCOS women with biochemical hyperandrogenemia. (PMID: 20012307) Marioli DJ … Georgopoulos NA (Archives of gynecology and obstetrics 2010) 3 23 41
  4. [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 23 41
  5. Genetic variation in insulin-like growth factor signaling genes and breast cancer risk among BRCA1 and BRCA2 carriers. (PMID: 19843326) Neuhausen SL … Gillen DL (Breast cancer research : BCR 2009) 3 23 41

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