INSR Gene (Protein Coding)

Insulin Receptor

GC19M007112
GIFtS:
54
This gene encodes a member of the receptor tyrosine kinase family of proteins. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that form a heterotetrameric receptor. Binding of insulin or other ligands to this receptor activates the insulin signaling pathway, which regulates glucose uptake and release, as well as the synthesis and stor... See more...

Aliases for INSR Gene

Aliases for INSR Gene

  • Insulin Receptor 2 3 4 5
  • EC 2.7.10.1 4 51
  • CD220 2 3
  • IR 3 4
  • CD220 Antigen 4
  • EC 2.7.10 51
  • HHF5 3
  • INSR 5

External Ids for INSR Gene

Previous GeneCards Identifiers for INSR Gene

  • GC19M007225
  • GC19M007056
  • GC19M007067
  • GC19M006847

Summaries for INSR Gene

Entrez Gene Summary for INSR Gene

  • This gene encodes a member of the receptor tyrosine kinase family of proteins. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that form a heterotetrameric receptor. Binding of insulin or other ligands to this receptor activates the insulin signaling pathway, which regulates glucose uptake and release, as well as the synthesis and storage of carbohydrates, lipids and protein. Mutations in this gene underlie the inherited severe insulin resistance syndromes including type A insulin resistance syndrome, Donohue syndrome and Rabson-Mendenhall syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

GeneCards Summary for INSR Gene

INSR (Insulin Receptor) is a Protein Coding gene. Diseases associated with INSR include Donohue Syndrome and Hyperinsulinemic Hypoglycemia, Familial, 5. Among its related pathways are RET signaling and Folate Metabolism. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is IGF1R.

UniProtKB/Swiss-Prot Summary for INSR Gene

  • Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosine residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin. In adipocytes, inhibits lipolysis (By similarity).

Tocris Summary for INSR Gene

  • Insulin receptors (IRs) and insulin-like growth factor receptors (IGFRs) are formed from two subunits, each of which is comprised of an extracellular alpha-subunit and a transmembrane beta-subunit with intracellular tyrosine kinase activity. IR homodimers are activated by insulin.

Gene Wiki entry for INSR Gene

Additional gene information for INSR Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for INSR Gene

Genomics for INSR Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for INSR 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
GH19J007292 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas 600.7 +0.7 713 4.2 SP1 HNRNPL GATAD2A ZNF629 TFE3 ZNF512 KDM1A CTCF ZNF692 RCOR2 INSR ZNF557 RF00017-2784
GH19J007394 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE CraniofacialAtlas 600.1 -101.2 -101187 3.2 SP1 TFE3 POLR2A RCOR2 ZNF7 BACH1 LARP7 GABPA ZNF143 ZIC2 ENSG00000267852 LOC107985284 ARHGEF18 INSR TEX45 PEX11G NDUFA7 ENSG00000268861 HSALNG0123637
GH19J007196 Promoter/Enhancer 2 FANTOM5 ENCODE CraniofacialAtlas dbSUPER 6.9 +95.7 95722 5 SP1 HNRNPL CREB1 GATAD2A TEAD4 PRDM10 ZNF629 REST TFE3 IKZF1 ZNF557 XAB2 MAP2K7 KHSRP ELAVL1 GTF2F1 ARHGEF18 PSPN GPR108 INSR
GH19J007205 Enhancer 1.3 Ensembl ENCODE dbSUPER 6.9 +83.3 83305 10.6 GATAD2A TFE3 NFKBIZ RCOR2 RELA ZIC2 RXRB IRF2 IKZF2 SP1 piR-50437-327 ARHGEF18 INSR SH2D3A ADGRE1 TRIP10 RF00017-2782 ZNF557
GH19J007223 Enhancer 1.1 Ensembl ENCODE dbSUPER 7.3 +68.5 68465 4.5 GATAD2A KDM1A IKZF2 CEBPA SOX13 RUNX3 ZBTB26 FOXA2 YY1 ZBTB33 INSR RF00017-2783 piR-50437-327 ZNF557
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around INSR on the GeneHancer Hub at the UCSC Golden Path

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

Top Transcription factor binding sites by QIAGEN in the INSR gene promoter:
  • AREB6
  • E47
  • NF-kappaB
  • NF-kappaB1
  • p53
  • S8
  • STAT1
  • STAT1alpha
  • STAT1beta
  • STAT3

Genomic Locations for INSR Gene

Genomic Locations for INSR Gene
chr19:7,112,255-7,294,414
(GRCh38/hg38)
Size:
182,160 bases
Orientation:
Minus strand
chr19:7,112,266-7,294,045
(GRCh37/hg19)
Size:
181,780 bases
Orientation:
Minus strand

Genomic View for INSR Gene

Genes around INSR on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for INSR Gene

Proteins for INSR Gene

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

    Protein Symbol:
    P06213-INSR_HUMAN
    Recommended name:
    Insulin receptor
    Protein Accession:
    P06213
    Secondary Accessions:
    • Q17RW0
    • Q59H98
    • Q9UCB7
    • Q9UCB8
    • Q9UCB9

    Protein attributes for INSR Gene

    Size:
    1382 amino acids
    Molecular mass:
    156333 Da
    Quaternary structure:
    • Tetramer of 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains carry the insulin-binding regions, while the beta chains carry the kinase domain. Forms a hybrid receptor with IGF1R, the hybrid is a tetramer consisting of 1 alpha chain and 1 beta chain of INSR and 1 alpha chain and 1 beta chain of IGF1R. Interacts with SORBS1 but dissociates from it following insulin stimulation. Binds SH2B2. Activated form of INSR interacts (via Tyr-999) with the PTB/PID domains of IRS1 and SHC1. The sequences surrounding the phosphorylated NPXY motif contribute differentially to either IRS1 or SHC1 recognition. Interacts (via tyrosines in the C-terminus) with IRS2 (via PTB domain and 591-786 AA); the 591-786 would be the primary anchor of IRS2 to INSR while the PTB domain would have a stabilizing action on the interaction with INSR. Interacts with the SH2 domains of the 85 kDa regulatory subunit of PI3K (PIK3R1) in vitro, when autophosphorylated on tyrosine residues. Interacts with SOCS7. Interacts (via the phosphorylated Tyr-999), with SOCS3. Interacts (via the phosphorylated Tyr-1185, Tyr-1189, Tyr-1190) with SOCS1. Interacts with CAV2 (tyrosine-phosphorylated form); the interaction is increased with 'Tyr-27'phosphorylation of CAV2 (By similarity). Interacts with ARRB2 (By similarity). Interacts with GRB10; this interaction blocks the association between IRS1/IRS2 and INSR, significantly reduces insulin-stimulated tyrosine phosphorylation of IRS1 and IRS2 and thus decreases insulin signaling. Interacts with GRB7. Interacts with PDPK1. Interacts (via Tyr-1190) with GRB14 (via BPS domain); this interaction protects the tyrosines in the activation loop from dephosphorylation, but promotes dephosphorylation of Tyr-999, this results in decreased interaction with, and phosphorylation of, IRS1. Interacts (via subunit alpha) with ENPP1 (via 485-599 AA); this interaction blocks autophosphorylation. Interacts with PTPRE; this interaction is dependent of Tyr-1185, Tyr-1189 and Tyr-1190 of the INSR. Interacts with STAT5B (via SH2 domain). Interacts with PTPRF. Interacts with ATIC; ATIC together with PRKAA2/AMPK2 and HACD3/PTPLAD1 is proposed to be part of a signaling netwok regulating INSR autophosphorylation and endocytosis (By similarity). Interacts with the cone snail venom insulin Con-Ins G1 (PubMed:27617429). Interacts with the insulin receptor SORL1; this interaction strongly increases its surface exposure, hence strengthens insulin signal reception (PubMed:27322061). Interacts (tyrosine phosphorylated) with CCDC88A/GIV (via SH2-like region); binding requires autophosphorylation of the INSR C-terminal region (PubMed:25187647). Interacts with GNAI3; the interaction is probably mediated by CCDC88A/GIV (PubMed:25187647).

    Three dimensional structures from OCA and Proteopedia for INSR Gene

    Alternative splice isoforms for INSR Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for INSR Gene

Protein Expression for INSR Gene

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

Selected DME Specific Peptides for INSR Gene

P06213:
  • DGQDACG
  • LMRMCWQ
  • PESLKDG
  • RDLAARN
  • YALVIFEM
  • KCIPECPSGYT
  • YVPDEWEV
  • FPNLTVI
  • GLLPVRWM
  • GVVLWEI
  • RERIEFLNEASVMK
  • FGMVYEG
  • HCQKVCP
  • KTIDSVTSAQ
  • LFFNYALV
  • KFVHRDLAARNCMV
  • HVVRLLGV
  • NITRGSVRIEKN
  • EGHLQILLMF
  • PNGNITHY
  • TDYLLLFRVYGLESL
  • LKPWTQYA
  • HFTGYRIE
  • SQIILKWKPPS
  • DGMAYLNA
  • EIADGMAYL
  • RTYGAKS
  • FVHRDLA
  • QPYQGLSNE
  • GPCPKVC
  • KGLKLPSRTW
  • PNGLIVLYEV

Post-translational modifications for INSR Gene

  • After being transported from the endoplasmic reticulum to the Golgi apparatus, the single glycosylated precursor is further glycosylated and then cleaved, followed by its transport to the plasma membrane.
  • Autophosphorylated on tyrosine residues in response to insulin. Phosphorylation of Tyr-999 is required for binding to IRS1, SHC1 and STAT5B. Dephosphorylated by PTPRE at Tyr-999, Tyr-1185, Tyr-1189 and Tyr-1190. Dephosphorylated by PTPRF and PTPN1. Dephosphorylated by PTPN2; down-regulates insulin-induced signaling.
  • Glycosylation at Asn43, Asn52, Asn105, Asn138, Asn242, Asn282, Asn322, Asn364, Asn424, Asn445, Asn541, Asn633, Asn651, Asn698, Asn769, Asn782, Asn920, and Asn933
  • Ubiquitination at Lys1057
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect

Other Protein References for INSR Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

Domains & Families for INSR Gene

Gene Families for INSR Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • CD markers
  • Disease related genes
  • Enzymes
  • FDA approved drug targets
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for INSR Gene

InterPro:
Blocks:
  • Tyrosine protein kinase, active site
  • Fibronectin type III repeat signature
  • Epidermal growth-factor receptor (EGFR), L domain
  • Furin-like cysteine rich region
  • Furin-like repeat
  • Receptor tyrosine kinase, class II
ProtoNet:

Suggested Antigen Peptide Sequences for INSR Gene

GenScript: Design optimal peptide antigens:
  • Insulin receptor (INSR_HUMAN)
  • INSR protein (Q86WY9_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P06213

UniProtKB/Swiss-Prot:

INSR_HUMAN :
  • The tetrameric insulin receptor binds insulin via non-identical regions from two alpha chains, primarily via the C-terminal region of the first INSR alpha chain. Residues from the leucine-rich N-terminus of the other INSR alpha chain also contribute to this insulin binding site. A secondary insulin-binding site is formed by residues at the junction of fibronectin type-III domain 1 and 2.
  • Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.
Domain:
  • The tetrameric insulin receptor binds insulin via non-identical regions from two alpha chains, primarily via the C-terminal region of the first INSR alpha chain. Residues from the leucine-rich N-terminus of the other INSR alpha chain also contribute to this insulin binding site. A secondary insulin-binding site is formed by residues at the junction of fibronectin type-III domain 1 and 2.
Family:
  • Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.
genes like me logo Genes that share domains with INSR: view

Function for INSR Gene

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Molecular function for INSR Gene

UniProtKB/Swiss-Prot Function:
Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosine residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin. In adipocytes, inhibits lipolysis (By similarity).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028, ECO:0000269|PubMed:11124964, ECO:0000269|PubMed:11598120, ECO:0000269|PubMed:12707268, ECO:0000269|PubMed:18278056, ECO:0000269|PubMed:19056263, ECO:0000269|PubMed:19071018, ECO:0000269|PubMed:19394223, ECO:0000269|PubMed:9312016};.
UniProtKB/Swiss-Prot EnzymeRegulation:
Activated in response to insulin. Autophosphorylation activates the kinase activity. PTPN1, PTPRE and PTPRF dephosphorylate important tyrosine residues, thereby reducing INSR activity. Inhibited by ENPP1. GRB10 and GRB14 inhibit the catalytic activity of the INSR, they block access of substrates to the activated receptor. SOCS1 and SOCS3 act as negative regulators of INSR activity, they bind to the activated INRS and interfere with the phosphorylation of INSR substrates.
GENATLAS Biochemistry:
insulin receptor precursor of two subunits alpha and beta

Enzyme Numbers (IUBMB) for INSR Gene

Phenotypes From GWAS Catalog for INSR Gene

Gene Ontology (GO) - Molecular Function for INSR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0001540 amyloid-beta binding IPI 19406747
GO:0004672 protein kinase activity IEA --
GO:0004713 protein tyrosine kinase activity IDA,IMP 7537849
GO:0004714 transmembrane receptor protein tyrosine kinase activity IBA 21873635
genes like me logo Genes that share ontologies with INSR: view
genes like me logo Genes that share phenotypes with INSR: view

Human Phenotype Ontology for INSR Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for INSR Gene

MGI Knock Outs for INSR:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

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

No data available for Transcription Factor Targets and HOMER Transcription for INSR Gene

Localization for INSR Gene

Subcellular locations from UniProtKB/Swiss-Prot for INSR Gene

Cell membrane. Single-pass type I membrane protein. Late endosome. Lysosome. Note=Binding of insulin to INSR induces internalization and lysosomal degradation of the receptor, a means for downregulating this signaling pathway after stimulation. In the presence of SORL1, internalized INSR molecules are redirected back to the cell surface, thereby preventing their lysosomal catabolism and strengthening insulin signal reception. {ECO:0000250 UniProtKB:P15208}.

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 INSR gene
Compartment Confidence
plasma membrane 5
extracellular 4
endosome 4
lysosome 4
cytoskeleton 2
mitochondrion 2
nucleus 2
endoplasmic reticulum 2
cytosol 2
peroxisome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (3)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for INSR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005635 colocalizes_with nuclear envelope IDA 19406747
GO:0005764 lysosome IEA --
GO:0005768 endosome IEA --
GO:0005770 late endosome IEA --
GO:0005886 plasma membrane IC,TAS --
genes like me logo Genes that share ontologies with INSR: view

Pathways & Interactions for INSR Gene

PathCards logo

SuperPathways for INSR Gene

SuperPathway Contained pathways
1 RET signaling
Downstream signal transduction
.94
Signaling by PDGF
.94
DAP12 signaling
.92
Insulin receptor signalling cascade
.92
Signaling by Insulin receptor
.92
Signaling by EGFR
.90
DAP12 interactions
.89
NGF signalling via TRKA from the plasma membrane
.87
Signaling by SCF-KIT
.85
Signalling by NGF
.81
Fc epsilon receptor (FCERI) signaling
.79
2 GPCR Pathway
Paxillin Interactions
.73
Ras Pathway
.73
GPCR Pathway
.62
Pancreatic Adenocarcinoma
.59
Breast Cancer Regulation by Stathmin1
.58
NFAT in Immune Response
.58
Estrogen Pathway
.55
P2Y Receptor Signaling
.38
3 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
Insulin signaling pathway
.32
IRS activation
.01
Signal attenuation
.01
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
5 ERK Signaling
ERK Signaling
.61
Rho Family GTPases
.61
MAPK Signaling
.58
Molecular Mechanisms of Cancer
.51
ILK Signaling
.49
genes like me logo Genes that share pathways with INSR: view

Pathways by source for INSR Gene

2 Sino Biological pathways for INSR Gene
6 GeneGo (Thomson Reuters) pathways for INSR Gene
  • Regulation of lipid metabolism Insulin signaling-generic cascades
  • Transcription PPAR Pathway
  • Transcription Receptor-mediated HIF regulation
  • Transcription_Transcription factor Tubby signaling pathways
  • Translation Regulation of EIF2 activity
41 Qiagen pathways for INSR Gene
  • 14-3-3 Induced Intracellular Signaling
  • Actin Nucleation and Branching
  • Actin Nucleation by ARP-WASP Complex
  • Activation of cAMP-Dependent PKA
  • Activation of PKA through GPCR
2 Cell Signaling Technology pathways for INSR Gene
1 GeneTex pathway for INSR Gene

SIGNOR curated interactions for INSR Gene

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

Gene Ontology (GO) - Biological Process for INSR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000187 activation of MAPK activity IMP 17001305
GO:0001934 positive regulation of protein phosphorylation IDA 7556070
GO:0002092 positive regulation of receptor internalization IDA 25401701
GO:0003007 heart morphogenesis IMP 7693131
GO:0005975 carbohydrate metabolic process IEA --
genes like me logo Genes that share ontologies with INSR: view

Drugs & Compounds for INSR Gene

Products:

  1. Drug

(101) Drugs for INSR Gene - From: DrugBank, PharmGKB, ApexBio, DGIdb, IUPHAR, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Insulin aspart Approved Pharma Target, agonist 544
Insulin detemir Approved Pharma Target, agonist 221
Insulin glargine Approved Pharma Target, agonist 622
Insulin glulisine Approved Pharma Target, agonist 112
Cyclophosphamide Approved, Investigational Pharma Nitrogen mustard alkylating agent and prodrug. 3670

(51) Additional Compounds for INSR Gene - From: HMDB, Novoseek, and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
 Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist 58-64-0
GSK 1838705
1116235-97-2
Insulin (human) recombinant
11061-68-0
Picropodophyllotoxin
477-47-4

(5) Tocris Compounds for INSR Gene

Compound Action Cas Number
Demethylasterriquinone B1 Selective insulin RTK activator 78860-34-1
GSK 1838705 Potent IR and IGF1R inhibitor; also inhibits anaplastic lymphoma kinase (ALK) 1116235-97-2
Insulin (human) recombinant Endogenous peptide agonist 11061-68-0
Picropodophyllotoxin Selective IGF1R inhibitor 477-47-4
PQ 401 IGF1R inhibitor 196868-63-0

(7) ApexBio Compounds for INSR Gene

Compound Action Cas Number
BMS-536924 IR/IGF-1R inhibitor 468740-43-4
BMS-754807 IGF-1R/InsR inhibitor,potent and selective 1001350-96-4
Demethylasterriquinone B1 78860-34-1
GSK1838705A IGF-IR/IR/ALK inhibitor, ATP-competitive 1116235-97-2
GSK1904529A Selective IGF-1R/IR inhibitor 1089283-49-7
HNGF6A 1093111-54-6
Linsitinib IGF1R/IR inhibitor,potent and novel 867160-71-2
genes like me logo Genes that share compounds with INSR: view

Transcripts for INSR Gene

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

mRNA/cDNA for INSR Gene

2 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
7 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 INSR

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

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10a · 10b ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22
SP1: -
SP2: - -
SP3:

Relevant External Links for INSR Gene

GeneLoc Exon Structure for
INSR

Expression for INSR Gene

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  1. Primer
  2. Gene Expression Assay

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

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

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for INSR Gene

This gene is overexpressed in Pancreas (x4.2).

Protein differential expression in normal tissues from HIPED for INSR Gene

This gene is overexpressed in Plasma (10.2), Pancreas (9.9), and Placenta (8.1).

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



Protein tissue co-expression partners for INSR Gene

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

SOURCE GeneReport for Unigene cluster for INSR Gene:

Hs.465744

mRNA Expression by UniProt/SwissProt for INSR Gene:

P06213-INSR_HUMAN
Tissue specificity: Isoform Long and isoform Short are predominantly expressed in tissue targets of insulin metabolic effects: liver, adipose tissue and skeletal muscle but are also expressed in the peripheral nerve, kidney, pulmonary alveoli, pancreatic acini, placenta vascular endothelium, fibroblasts, monocytes, granulocytes, erythrocytes and skin. Isoform Short is preferentially expressed in fetal cells such as fetal fibroblasts, muscle, liver and kidney. Found as a hybrid receptor with IGF1R in muscle, heart, kidney, adipose tissue, skeletal muscle, hepatoma, fibroblasts, spleen and placenta (at protein level). Overexpressed in several tumors, including breast, colon, lung, ovary, and thyroid carcinomas.

Evidence on tissue expression from TISSUES for INSR Gene

  • Liver(4.7)
  • Nervous system(4.6)
  • Skin(4.5)
  • Muscle(3.2)
  • Pancreas(3.1)
  • Spleen(2.9)
  • Kidney(2.9)
  • Heart(2.9)
  • Blood(2.7)
  • Lung(2.7)
  • Adrenal gland(2.7)
  • Intestine(2.6)
  • Thyroid gland(2.3)
  • Stomach(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for INSR Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • immune
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • chin
  • ear
  • eye
  • eyelid
  • face
  • forehead
  • head
  • jaw
  • lip
  • mandible
  • maxilla
  • mouth
  • neck
  • nose
  • outer ear
  • pituitary gland
  • skull
  • thyroid
  • tooth
Thorax:
  • breast
  • chest wall
  • clavicle
  • heart
  • rib
  • rib cage
  • scapula
  • sternum
Abdomen:
  • abdominal wall
  • adrenal gland
  • biliary tract
  • gallbladder
  • intestine
  • kidney
  • liver
  • pancreas
Pelvis:
  • fallopian tube
  • ovary
  • pelvis
  • penis
  • prostate
  • testicle
  • uterus
  • vagina
  • vas deferens
  • vulva
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • nail
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • blood
  • blood vessel
  • coagulation system
  • hair
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal column
  • sweat gland
  • vertebrae
  • white blood cell
genes like me logo Genes that share expression patterns with INSR: view

Orthologs for INSR Gene

This gene was present in the common ancestor of animals.

Orthologs for INSR Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia INSR 30 31
  • 99.21 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia IR-A 31
  • 95 (a)
 OneToOne
INSR 30
  • 89.7 (n)
Dog
(Canis familiaris)
 Mammalia INSR 30 31
  • 88.91 (n)
 OneToOne
Mouse
(Mus musculus)
 Mammalia Insr 30 17 31
  • 87.34 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Insr 30
  • 87.23 (n)
Oppossum
(Monodelphis domestica)
 Mammalia INSR 31
  • 83 (a)
 OneToOne
Platypus
(Ornithorhynchus anatinus)
 Mammalia INSR 31
  • 70 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves CTK-1 31
  • 82 (a)
 OneToOne
INSR 30
  • 77 (n)
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia LOC100492718 30
  • 67.83 (n)
African clawed frog
(Xenopus laevis)
 Amphibia LOC398006 30
Zebrafish
(Danio rerio)
 Actinopterygii insra 30 31
  • 69.41 (n)
 OneToMany
insrb 31
  • 67 (a)
 OneToMany
Rainbow Trout
(Oncorhynchus mykiss)
 Actinopterygii Omy.8035 30
Fruit Fly
(Drosophila melanogaster)
 Insecta InR 32
  • 36 (a)
CG3837 31 32
  • 28 (a)
 OneToMany
CG10702 32
  • 26 (a)
Worm
(Caenorhabditis elegans)
 Secernentea W02A2.4 32
  • 37 (a)
K09B11.5 32
  • 36 (a)
T21G5.1 32
  • 33 (a)
T25B9.5 32
  • 30 (a)
Y69E1A.3 32
  • 30 (a)
daf-2 31
  • 24 (a)
 OneToMany
Sea Squirt
(Ciona savignyi)
 Ascidiacea -- 31
  • 40 (a)
 OneToMany
Species where no ortholog for INSR 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)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • 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)

Evolution for INSR Gene

ENSEMBL:
Gene Tree for INSR (if available)
TreeFam:
Gene Tree for INSR (if available)
Aminode:
Evolutionary constrained regions (ECRs) for INSR: view image

Paralogs for INSR Gene

Paralogs for INSR Gene

(23) SIMAP similar genes for INSR Gene using alignment to 3 proteins:

  • INSR_HUMAN
  • M0R3E6_HUMAN
  • Q86WY9_HUMAN
genes like me logo Genes that share paralogs with INSR: view

Variants for INSR Gene

Products:

  1. SNP Genotyping and Copy Number Assay

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for INSR Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
430587 Pathogenic: Pineal hyperplasia AND diabetes mellitus syndrome 7,150,495(-) ACCTAGGGTCCTCGGC SPLICE_ACCEPTOR_VARIANT,SPLICE_DONOR_VARIANT
691357 Uncertain Significance: Pyloric stenosis; Esophageal atresia 7,122,884(-) C/T MISSENSE_VARIANT
714005 Likely Benign: not provided 7,166,344(-) C/T SYNONYMOUS_VARIANT
715542 Benign: not provided 7,184,402(-) C/T SYNONYMOUS_VARIANT
720063 Likely Benign: not provided 7,150,514(-) A/G SYNONYMOUS_VARIANT,INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for INSR Gene

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

Variant ID Type Subtype PubMed ID
dgv1017e212 CNV loss 25503493
dgv1018e212 CNV loss 25503493
dgv1019e212 CNV loss 25503493
dgv136e55 CNV gain 17911159
dgv3421n100 CNV gain 25217958
dgv3423n100 CNV gain 25217958
dgv3424n100 CNV gain 25217958
dgv393n27 CNV gain 19166990
dgv395n27 CNV gain 19166990
dgv6237n54 CNV gain 21841781
dgv6245n54 CNV gain 21841781
dgv6246n54 CNV gain 21841781
esv1005113 CNV deletion 20482838
esv1122975 CNV insertion 17803354
esv1602115 CNV deletion 17803354
esv1934161 CNV deletion 18987734
esv2568778 CNV insertion 19546169
esv2600509 CNV insertion 19546169
esv26586 CNV loss 19812545
esv2659640 CNV deletion 23128226
esv2667178 CNV deletion 23128226
esv2671138 CNV deletion 23128226
esv2673294 CNV deletion 23128226
esv2675376 CNV deletion 23128226
esv2718083 CNV deletion 23290073
esv2718085 CNV deletion 23290073
esv2718086 CNV deletion 23290073
esv2718087 CNV deletion 23290073
esv2718088 CNV deletion 23290073
esv2751809 CNV gain 17911159
esv3302632 CNV tandem duplication 20981092
esv3302902 CNV tandem duplication 20981092
esv3383975 CNV duplication 20981092
esv3555964 CNV deletion 23714750
esv3583229 CNV loss 25503493
esv3643579 CNV loss 21293372
esv3643580 CNV loss 21293372
esv3643581 CNV loss 21293372
esv3893162 CNV loss 25118596
esv9300 CNV loss 19470904
nsv1056752 CNV gain 25217958
nsv1057262 CNV gain 25217958
nsv1058745 CNV loss 25217958
nsv1060476 CNV gain 25217958
nsv1060887 CNV gain 25217958
nsv1113966 CNV deletion 24896259
nsv1125376 OTHER inversion 24896259
nsv1131392 CNV deletion 24896259
nsv1133253 CNV tandem duplication 24896259
nsv1138663 CNV deletion 24896259
nsv1141947 OTHER inversion 24896259
nsv458347 CNV gain 19166990
nsv473021 CNV novel sequence insertion 20440878
nsv473511 CNV novel sequence insertion 20440878
nsv474542 CNV novel sequence insertion 20440878
nsv475210 CNV novel sequence insertion 20440878
nsv476950 CNV novel sequence insertion 20440878
nsv478625 CNV novel sequence insertion 20440878
nsv479065 CNV novel sequence insertion 20440878
nsv480227 CNV novel sequence insertion 20440878
nsv513513 CNV insertion 21212237
nsv521213 CNV gain 19592680
nsv521868 CNV loss 19592680
nsv524177 CNV loss 19592680
nsv578500 CNV gain 21841781
nsv578502 CNV gain 21841781

Variation tolerance for INSR Gene

Residual Variation Intolerance Score: 3.75% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.60; 44.99% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for INSR Gene

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

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for INSR Gene

Disorders for INSR Gene

MalaCards: The human disease database

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

Disorder Aliases PubMed IDs
donohue syndrome
  • leprechaunism
hyperinsulinemic hypoglycemia, familial, 5
  • persistent hyperinsulinemic hypoglycemia of infancy
pineal hyperplasia, insulin-resistant diabetes mellitus, and somatic abnormalities
  • rabson-mendenhall syndrome
diabetes mellitus, insulin-resistant, with acanthosis nigricans
  • insulin receptor, defect in, with insulin-resistant diabetes mellitus and acanthosis nigricans
diabetes mellitus, noninsulin-dependent
  • niddm
- elite association - COSMIC cancer census association via MalaCards
Search INSR in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

INSR_HUMAN
  • Rabson-Mendenhall syndrome (RMS) [MIM:262190]: Severe insulin resistance syndrome characterized by insulin-resistant diabetes mellitus with pineal hyperplasia and somatic abnormalities. Typical features include coarse, senile-appearing facies, dental and skin abnormalities, abdominal distension, and phallic enlargement. Inheritance is autosomal recessive. {ECO:0000269 PubMed:10443650, ECO:0000269 PubMed:12023989, ECO:0000269 PubMed:17201797, ECO:0000269 PubMed:2121734, ECO:0000269 PubMed:2365819, ECO:0000269 PubMed:28765322, ECO:0000269 PubMed:8314008}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Leprechaunism (LEPRCH) [MIM:246200]: Represents the most severe form of insulin resistance syndrome, characterized by intrauterine and postnatal growth retardation and death in early infancy. Inheritance is autosomal recessive. {ECO:0000269 PubMed:12023989, ECO:0000269 PubMed:12538626, ECO:0000269 PubMed:12970295, ECO:0000269 PubMed:1607067, ECO:0000269 PubMed:1730625, ECO:0000269 PubMed:22768670, ECO:0000269 PubMed:2365819, ECO:0000269 PubMed:24498630, ECO:0000269 PubMed:2479553, ECO:0000269 PubMed:2834824, ECO:0000269 PubMed:28765322, ECO:0000269 PubMed:7538143, ECO:0000269 PubMed:7815442, ECO:0000269 PubMed:8188715, ECO:0000269 PubMed:8326490, ECO:0000269 PubMed:8419945, ECO:0000269 PubMed:8636294, ECO:0000269 PubMed:9249867, ECO:0000269 PubMed:9299395, ECO:0000269 PubMed:9703342}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • 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:1470163, ECO:0000269 PubMed:1607076, ECO:0000269 PubMed:7657032}. Note=The gene represented in this entry may be involved in disease pathogenesis.
  • Familial hyperinsulinemic hypoglycemia 5 (HHF5) [MIM:609968]: Familial hyperinsulinemic hypoglycemia [MIM:256450], also referred to as congenital hyperinsulinism, nesidioblastosis, or persistent hyperinsulinemic hypoglycemia of infancy (PPHI), is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels. {ECO:0000269 PubMed:15161766}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Insulin-resistant diabetes mellitus with acanthosis nigricans type A (IRAN type A) [MIM:610549]: Characterized by the association of severe insulin resistance (manifested by marked hyperinsulinemia and a failure to respond to exogenous insulin) with the skin lesion acanthosis nigricans and ovarian hyperandrogenism in adolescent female subjects. Women frequently present with hirsutism, acne, amenorrhea or oligomenorrhea, and virilization. This syndrome is different from the type B that has been demonstrated to be secondary to the presence of circulating autoantibodies against the insulin receptor. {ECO:0000269 PubMed:10733238, ECO:0000269 PubMed:11260230, ECO:0000269 PubMed:12107746, ECO:0000269 PubMed:12970295, ECO:0000269 PubMed:1563582, ECO:0000269 PubMed:1963473, ECO:0000269 PubMed:2002058, ECO:0000269 PubMed:2168397, ECO:0000269 PubMed:2365819, ECO:0000269 PubMed:2544998, ECO:0000269 PubMed:28765322, ECO:0000269 PubMed:3283938, ECO:0000269 PubMed:8243830, ECO:0000269 PubMed:8288049, ECO:0000269 PubMed:8314008, ECO:0000269 PubMed:8388389, ECO:0000269 PubMed:9175790}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Genatlas disease for INSR Gene

insulin resistance,type A (hyperinsulinemia,decreased insulin binding,acanthocytosis)

Additional Disease Information for INSR

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
Tumor Gene Database
(TGDB)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with INSR: view

Publications for INSR Gene