INSR insulin receptor [Homo sapiens (human)] - Gene

Summary

Official Symbol: INSRprovided by HGNC
Official Full Name: insulin receptorprovided by HGNC
Primary source: HGNC:HGNC:6091
See related: Ensembl:ENSG00000171105 MIM:147670; AllianceGenome:HGNC:6091
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HHF5; CD220
Summary: 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]
Expression: Ubiquitous expression in kidney (RPKM 16.5), spleen (RPKM 15.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19p13.2

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (7112265..7294414, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (7103362..7286608, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (7112276..7294425, complement)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Activation of the insulin receptor by insulin-like growth factor 2.
Title: Activation of the insulin receptor by insulin-like growth factor 2.
The Insulin Receptor and Insulin like Growth Factor Receptor 5' UTRs Support Translation Initiation Independently of EIF4G1.
Title: The Insulin Receptor and Insulin like Growth Factor Receptor 5' UTRs Support Translation Initiation Independently of EIF4G1.
Insulin Signaling Through the Insulin Receptor Increases Linear Growth Through Effects on Bone and the GH-IGF-1 Axis.
Title: Insulin Signaling Through the Insulin Receptor Increases Linear Growth Through Effects on Bone and the GH-IGF-1 Axis.
Association between diabetes and stress-induced hyperglycemia with skeletal muscle gene expression of INSR in critically ill patients: A prospective cohort study.
Title: Association between diabetes and stress-induced hyperglycemia with skeletal muscle gene expression of INSR in critically ill patients: A prospective cohort study.
Can obesity exacerbate hyperinsulinaemia in the presence of the mutation of an insulin receptor gene?
Title: Can obesity exacerbate hyperinsulinaemia in the presence of the mutation of an insulin receptor gene?
Insulin receptor-inspired soluble insulin binder.
Title: Insulin receptor-inspired soluble insulin binder.
Repurposing antidiabetic drugs for rheumatoid arthritis: results from a two-sample Mendelian randomization study.
Title: Repurposing antidiabetic drugs for rheumatoid arthritis: results from a two-sample Mendelian randomization study.
The Activation Mechanism of the Insulin Receptor: A Structural Perspective.
Title: The Activation Mechanism of the Insulin Receptor: A Structural Perspective.
Associations between heredity, height, BMI, diabetes mellitus type 1 or 2 and gene variants in the insulin receptor (INSR) gene in patients with schizophrenia.
Title: Associations between heredity, height, BMI, diabetes mellitus type 1 or 2 and gene variants in the insulin receptor (INSR) gene in patients with schizophrenia.
Sphingosine kinase 2 regulates insulin receptor trafficking in hepatocytes.
Title: Sphingosine kinase 2 regulates insulin receptor trafficking in hepatocytes.

Submit: New GeneRIF Correction See all GeneRIFs (357)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Hyperinsulinism due to INSR deficiency MedGen: C1864952 OMIM: 609968 GeneReviews: Familial Hyperinsulinism	Compare labs
Insulin-resistant diabetes mellitus AND acanthosis nigricans MedGen: C0342278 OMIM: 610549 GeneReviews: Not available	Compare labs
Leprechaunism syndrome MedGen: C0265344 OMIM: 246200 GeneReviews: INSR-Related Severe Syndromic Insulin Resistance	Compare labs
Rabson-Mendenhall syndrome MedGen: C0271695 OMIM: 262190 GeneReviews: INSR-Related Severe Syndromic Insulin Resistance	Compare labs

EBI GWAS Catalog

Description
A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function. EBI GWAS Catalog EBI GWAS CatalogPubMed
Discovery and refinement of loci associated with lipid levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies eight new risk loci for polycystic ovary syndrome. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analysis for severe diabetic retinopathy. EBI GWAS Catalog EBI GWAS CatalogPubMed
Hundreds of variants clustered in genomic loci and biological pathways affect human height. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel associations for hypothyroidism include known autoimmune risk loci. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:182561 (e-PCR)
- UniSTS:155392

RH92589 (e-PCR)
- UniSTS:86297

G59704 (e-PCR)
- UniSTS:137003

INSR_4112 (e-PCR)
- UniSTS:462902

GDB:511361 (e-PCR)
- UniSTS:157501

GDB:511368 (e-PCR)
- UniSTS:157502

GDB:177803 (e-PCR)
- UniSTS:154964

RH80628 (e-PCR)
- UniSTS:92506

G10600 (e-PCR), detects polymorphism
- UniSTS:61539

STS-X02160 (e-PCR)
- UniSTS:32618

G07087 (e-PCR)
- UniSTS:59252

PMC152545P1 (e-PCR)
- UniSTS:271228

RH80156 (e-PCR)
- UniSTS:83587

RH66229 (e-PCR)
- UniSTS:78277

RH45939 (e-PCR)
- UniSTS:92371

GDB:177221 (e-PCR)
- UniSTS:154841

GDB:177257 (e-PCR)
- UniSTS:154848

Insr (e-PCR), detects polymorphism
- UniSTS:259557

INSR (e-PCR), detects polymorphism
- UniSTS:480234

SHGC-173117 (e-PCR)
- UniSTS:185327

RH93377 (e-PCR)
- UniSTS:90865

SHGC-32871 (e-PCR)
- UniSTS:45559

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IDA Inferred from Direct Assay more info	PubMed
enables GTP binding	IDA Inferred from Direct Assay more info	PubMed
enables PTB domain binding	IPI Inferred from Physical Interaction more info	PubMed
enables amyloid-beta binding	IPI Inferred from Physical Interaction more info	PubMed
enables cargo receptor activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables insulin binding	IDA Inferred from Direct Assay more info	PubMed
enables insulin binding	IPI Inferred from Physical Interaction more info	PubMed
enables insulin receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables insulin receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables insulin receptor activity	TAS Traceable Author Statement more info
enables insulin receptor substrate binding	IBA Inferred from Biological aspect of Ancestor more info
enables insulin receptor substrate binding	IPI Inferred from Physical Interaction more info	PubMed
enables insulin-like growth factor I binding	IPI Inferred from Physical Interaction more info	PubMed
enables insulin-like growth factor II binding	IPI Inferred from Physical Interaction more info	PubMed
enables insulin-like growth factor receptor binding	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidylinositol 3-kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein tyrosine kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein-containing complex binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in G protein-coupled receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in activation of protein kinase B activity	IDA Inferred from Direct Assay more info	PubMed
involved_in activation of protein kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in adrenal gland development	IEA Inferred from Electronic Annotation more info
involved_in amyloid-beta clearance	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in cell surface receptor protein tyrosine kinase signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to growth factor stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to insulin stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in dendritic spine maintenance	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in epidermis development	IEA Inferred from Electronic Annotation more info
involved_in exocrine pancreas development	IEA Inferred from Electronic Annotation more info
involved_in glucose homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in glucose homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in heart morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in insulin receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in insulin receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in insulin receptor signaling pathway	TAS Traceable Author Statement more info
involved_in learning	TAS Traceable Author Statement more info	PubMed
involved_in male gonad development	IEA Inferred from Electronic Annotation more info
involved_in male sex determination	IEA Inferred from Electronic Annotation more info
involved_in memory	TAS Traceable Author Statement more info	PubMed
involved_in multicellular organism development	IBA Inferred from Biological aspect of Ancestor more info
involved_in neuron projection maintenance	ISS Inferred from Sequence or Structural Similarity more info
involved_in peptidyl-tyrosine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
acts_upstream_of positive regulation of MAP kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of MAPK cascade	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of MAPK cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of MAPK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell population proliferation	IC Inferred by Curator more info	PubMed
involved_in positive regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of developmental growth	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of glucose import	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of glucose import	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of glycogen biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of glycolytic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of kinase activity	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of meiotic cell cycle	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of mitotic nuclear division	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of nitric oxide biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein-containing complex disassembly	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of receptor internalization	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of respiratory burst	IDA Inferred from Direct Assay more info	PubMed
involved_in protein autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein autophosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein phosphorylation	TAS Traceable Author Statement more info	PubMed
involved_in receptor internalization	IEA Inferred from Electronic Annotation more info
involved_in receptor-mediated endocytosis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of embryonic development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of female gonad development	IEA Inferred from Electronic Annotation more info
involved_in symbiont entry into host cell	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in transport across blood-brain barrier	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
is_active_in axon	IBA Inferred from Biological aspect of Ancestor more info
located_in caveola	IDA Inferred from Direct Assay more info	PubMed
located_in dendrite membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in endosome membrane	TAS Traceable Author Statement more info
located_in external side of plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in extracellular exosome	HDA more info	PubMed
part_of insulin receptor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of insulin receptor complex	IDA Inferred from Direct Assay more info	PubMed
part_of insulin receptor complex	IMP Inferred from Mutant Phenotype more info	PubMed
located_in late endosome	IEA Inferred from Electronic Annotation more info
located_in lysosome	IEA Inferred from Electronic Annotation more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in neuronal cell body membrane	ISS Inferred from Sequence or Structural Similarity more info
colocalizes_with nuclear envelope	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with nuclear lumen	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IC Inferred by Curator more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
part_of receptor complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: insulin receptor

Names: IR

NP_000199.2

EC 2.7.10.1

NP_001073285.1

EC 2.7.10.1

XP_011526290.2

EC 2.7.10.1

XP_011526291.2

EC 2.7.10.1

XP_054176873.1

EC 2.7.10.1

XP_054176874.1

EC 2.7.10.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008852.2 RefSeqGene

Range

4587..186736

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000208.4 → NP_000199.2 insulin receptor isoform Long preproprotein

See identical proteins and their annotated locations for NP_000199.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (Long).

Source sequence(s)

AC010606, AC125387, AK025527, BC117172, BU684722, HY015976, M10051, X02160

Consensus CDS

CCDS12176.1

UniProtKB/Swiss-Prot

P06213, Q17RW0, Q59H98, Q9UCB7, Q9UCB8, Q9UCB9

Related

ENSP00000303830.4, ENST00000302850.10

Conserved Domains (6) summary

cd05061
Location:1016 → 1303

PTKc_InsR; Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor

cd00063
Location:867 → 944

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cd00064
Location:234 → 281

FU; Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.

pfam00757
Location:179 → 337

Furin-like; Furin-like cysteine rich region

pfam01030
Location:359 → 472

Recep_L_domain; Receptor L domain

pfam07714
Location:1023 → 1290

Pkinase_Tyr; Protein tyrosine kinase
NM_001079817.3 → NP_001073285.1 insulin receptor isoform Short preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (Short) has the same N- and C-termini but is shorter compared to isoform Long.

Source sequence(s)

AC010606, AC125387, AK025527, BC117172, BU684722, HY015976, M10051, X02160

Consensus CDS

CCDS42487.1

UniProtKB/Swiss-Prot

P06213

Related

ENSP00000342838.4, ENST00000341500.9

Conserved Domains (6) summary

cd05061
Location:1004 → 1291

PTKc_InsR; Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor

cd00063
Location:855 → 932

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cd00064
Location:234 → 281

FU; Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.

pfam00757
Location:179 → 337

Furin-like; Furin-like cysteine rich region

pfam01030
Location:359 → 472

Recep_L_domain; Receptor L domain

pfam07714
Location:1011 → 1278

Pkinase_Tyr; Protein tyrosine kinase