INSR Gene

HGNC Family	CD molecules (CD), Fibronectin type III domain containing, Receptor kinases
Name	insulin receptor
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The insulin receptor (INSR) is a pivotal regulator of metabolic homeostasis, exhibiting multifaceted roles that extend beyond classical glucose uptake. In bone, INSR signaling in osteoblasts modulates osteocalcin activity through a bone‐resorption–dependent mechanism that promotes whole‐body glucose metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In other tissues, transcriptional regulators such as HMGA1 have been shown to enhance INSR gene expression, thereby impacting insulin binding and downstream signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Vascular integrity is also maintained by endothelial INSR signaling; loss of insulin action in the endothelium has been linked to impaired vasodilation, upregulation of adhesion molecules, and accelerated atherosclerosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Post‐translational modifications further fine‐tune receptor activity, as phosphorylation of a critical threonine residue (Thr1160) by PKCε compromises INSR kinase function and contributes to hepatic insulin resistance observed in nonalcoholic fatty liver disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Structural investigations using cryo‐electron microscopy have elucidated the molecular basis of insulin binding, revealing discrete binding interfaces between insulin and the receptor that are essential for its activation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": " In the reproductive system, INSR is critical for Sertoli cell proliferation and testis development, ultimately determining sperm output."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Additionally, in the kidney, proper INSR signaling in podocytes is vital for maintaining glomerular homeostasis, with impairment contributing to the progression of diabetic nephropathy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In certain cancers, notably endocrine-resistant breast cancer, simultaneous targeting of INSR and the related IGF1 receptor enhances therapeutic efficacy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " In skeletal muscle, microRNAs such as miR-128a act in a cell-autonomous manner to modulate INSR abundance and insulin signaling, thereby regulating myoblast proliferation and myotube hypertrophy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Nutritional compounds may also influence INSR expression; for example, cinnamaldehyde, a bioactive component of cinnamon, upregulates insulin receptor gene expression in ghrelin-producing cells, contributing to improved metabolic parameters and reduced adiposity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Finally, in aggressive prostate cancer, IGF2-driven activation of INSR (along with IGF1R) has been implicated in promoting tumorigenicity, suggesting that targeting this pathway could enhance chemosensitivity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mathieu Ferron, Jianwen Wei, Tatsuya Yoshizawa, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Lack of the architectural factor HMGA1 causes insulin resistance and diabetes in humans and mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm1254"}], "href": "https://doi.org/10.1038/nm1254"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15924147"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15924147"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Christian Rask-Madsen, Qian Li, Bryn Freund, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of insulin signaling in vascular endothelial cells accelerates atherosclerosis in apolipoprotein E null mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Metab (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cmet.2010.03.013"}], "href": "https://doi.org/10.1016/j.cmet.2010.03.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20444418"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20444418"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Max C Petersen, Anila K Madiraju, Brandon M Gassaway, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "An essential role for insulin and IGF1 receptors in regulating sertoli cell proliferation, testis size, and FSH action in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/me.2012-1258"}], "href": "https://doi.org/10.1210/me.2012-1258"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23518924"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23518924"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Thati Madhusudhan, Hongjie Wang, Wei Dong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Defective podocyte insulin signalling through p85-XBP1 promotes ATF6-dependent maladaptive ER-stress response in diabetic nephropathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms7496"}], "href": "https://doi.org/10.1038/ncomms7496"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25754093"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25754093"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Emily M Fox, Todd W Miller, Justin M Balko, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Regulation of IRS1/Akt insulin signaling by microRNA-128a during myogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.119966"}], "href": "https://doi.org/10.1242/jcs.119966"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23606743"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23606743"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Susana Camacho, Stephanie Michlig, Carole de Senarclens-Bezençon, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "A targetable GATA2-IGF2 axis confers aggressiveness in lethal prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccell.2014.11.013"}], "href": "https://doi.org/10.1016/j.ccell.2014.11.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25670080"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25670080"}]}]}]}
Synonyms	CD220, HHF5
Proteins	INSR_HUMAN
NCBI Gene ID	3643
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

INSR has 16,168 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 150 datasets.

Click the + buttons to view associations for INSR from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

INSR Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by INSR gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of INSR gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of INSR gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of INSR gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of INSR gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of INSR gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of INSR gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving INSR protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of INSR gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of INSR gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of INSR gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of INSR gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of INSR gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of INSR gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with INSR gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with INSR protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with INSR gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of INSR gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of INSR gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of INSR gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with INSR gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with INSR gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing INSR protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of INSR gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing INSR protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing INSR protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing INSR protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with INSR protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with INSR protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing INSR protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of INSR gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with INSR gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with INSR gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with INSR gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with INSR gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of INSR protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by INSR gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DEPOD Substrates of Phosphatases	phosphatases that dephosphorylate INSR protein from the curated DEPOD Substrates of Phosphatases dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving INSR gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving INSR gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.