Gene: INSR
Alternate names for this Gene: CD220|HHF5
Gene 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.
Gene is located in Chromosome: 19
Location in Chromosome : 19p13.2
Description of this Gene: insulin receptor
Type of Gene: protein-coding
rs12978472 in
INSR gene and
Alcohol consumption
PMID 29912962 2018 Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.
PMID 30698716 2019 Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions.
rs1035942 in
INSR gene and
Arthritis, Gouty
PMID 23263486 2013 Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.
rs8106042 in
INSR gene and
Birth Weight
PMID 31043758 2019 Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors.
rs8106700 in
INSR gene and
Blood urea nitrogen measurement
PMID 31152163 2019 A catalog of genetic loci associated with kidney function from analyses of a million individuals.
rs10421414 in
INSR gene and
Body Height
PMID 31562340 2019 Characterizing rare and low-frequency height-associated variants in the Japanese population.
PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.
PMID 20881960 2010 Hundreds of variants clustered in genomic loci and biological pathways affect human height.
PMID 25282103 2014 Defining the role of common variation in the genomic and biological architecture of adult human height.
rs12978472 in
INSR gene and
Cardiovascular Diseases
PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.
rs121913135 in
INSR gene and
Diabetes Mellitus, Insulin-Resistant, with Acanthosis Nigricans
PMID 12107746 2002 An arginine to cysteine(252) mutation in insulin receptors from a patient with severe insulin resistance inhibits receptor internalisation but preserves signalling events.
PMID 11260230 2001 Identification of novel C253Y missense and Y864X nonsense mutations in the insulin receptor gene in type A insulin-resistant patients.
PMID 8243830 1993 Ala1048-->Asp mutation in the kinase domain of insulin receptor causes defective kinase activity and insulin resistance.
PMID 10733238 2000 Identification of three novel mutations in the insulin receptor gene in type A insulin resistant patients.
PMID 2002058 1991 Insulin resistance and diabetes due to different mutations in the tyrosine kinase domain of both insulin receptor gene alleles.
PMID 9175790 1997 Identification of two novel insulin receptor mutations, Asp59Gly and Leu62Pro, in type A syndrome of extreme insulin resistance.
PMID 1963473 1990 Functional properties of a naturally occurring Trp1200----Ser1200 mutation of the insulin receptor.
PMID 1563582 1992 Detection of mutations in the insulin receptor gene in patients with insulin resistance by analysis of single-stranded conformational polymorphisms.
PMID 2365819 1990 Five mutant alleles of the insulin receptor gene in patients with genetic forms of insulin resistance.
PMID 2544998 1989 Human diabetes associated with a mutation in the tyrosine kinase domain of the insulin receptor.
PMID 3283938 1988 Insulin-resistant diabetes due to a point mutation that prevents insulin proreceptor processing.
PMID 2168397 1990 A naturally occurring mutation of insulin receptor alanine 1134 impairs tyrosine kinase function and is associated with dominantly inherited insulin resistance.
PMID 12970295 2003 Identification and functional assessment of novel and known insulin receptor mutations in five patients with syndromes of severe insulin resistance.
PMID 28765322 2017 Structural Basis and Genotype-Phenotype Correlations of INSR Mutations Causing Severe Insulin Resistance.
PMID 8314008 1994 Molecular scanning of the insulin receptor gene in syndromes of insulin resistance.
PMID 8388389 1993 Antibodies to the extracellular receptor domain restore the hormone-insensitive kinase and conformation of the mutant insulin receptor valine 382.
PMID 8288049 1994 Prevalence of mutations in the insulin receptor gene in subjects with features of the type A syndrome of insulin resistance.
rs121913150 in
INSR gene and
Diabetes Mellitus, Non-Insulin-Dependent
PMID 22962670 2012 Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline.
PMID 23492873 2013 Recommendations from the EGAPP Working Group: does genomic profiling to assess type 2 diabetes risk improve health outcomes?
PMID 1470163 1992 [Insulin receptor Arg1131-->Gln: a novel mutation in the catalytic loop of insulin receptor observed in insulin resistant diabetes].
PMID 1607076 1992 NIDDM associated with mutation in tyrosine kinase domain of insulin receptor gene.
PMID 7657032 1995 Frequency of mutations of insulin receptor gene in Japanese patients with NIDDM.
rs10427021 in
INSR gene and
Diastolic blood pressure
PMID 27841878 2017 Genome-wide association analyses using electronic health records identify new loci influencing blood pressure variation.
PMID 29912962 2018 Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.
PMID 28739976 2017 Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.
PMID 29455858 2018 A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure.
PMID 27618452 2016 The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals.
rs121913136 in
INSR gene and
Donohue Syndrome
PMID 9703342 1998 Multiple molecular mechanisms of insulin receptor dysfunction in a patient with Donohue syndrome.
PMID 8326490 1993 A syndrome of insulin resistance resembling leprechaunism in five sibs of consanguineous parents.
PMID 8188715 1994 A mutation in the insulin receptor that impairs proreceptor processing but not insulin binding.
PMID 9249867 1997 Molecular analysis of the insulin receptor gene for prenatal diagnosis of leprechaunism in two families.
PMID 22768670 2012 A novel mutation of the insulin receptor gene in a preterm infant with Donohue syndrome and heart failure.
PMID 8636294 1996 Deletion of Asn281 in the alpha-subunit of the human insulin receptor causes constitutive activation of the receptor and insulin desensitization.
PMID 8419945 1993 Activation of glucose transport by a natural mutation in the human insulin receptor.
PMID 9299395 1997 Four mutant alleles of the insulin receptor gene associated with genetic syndromes of extreme insulin resistance.
PMID 2365819 1990 Five mutant alleles of the insulin receptor gene in patients with genetic forms of insulin resistance.
PMID 2834824 1988 Two mutant alleles of the insulin receptor gene in a patient with extreme insulin resistance.
PMID 28765322 2017 Structural Basis and Genotype-Phenotype Correlations of INSR Mutations Causing Severe Insulin Resistance.
PMID 2479553 1989 A leucine-to-proline mutation in the insulin receptor in a family with insulin resistance.
PMID 7538143 1995 Two mutations in the insulin receptor gene of a patient with leprechaunism: application to prenatal diagnosis.
PMID 12538626 2003 Deletion of V335 from the L2 domain of the insulin receptor results in a conformationally abnormal receptor that is unable to bind insulin and causes Donohue's syndrome in a human subject.
PMID 12970295 2003 Identification and functional assessment of novel and known insulin receptor mutations in five patients with syndromes of severe insulin resistance.
PMID 1607067 1992 Detection of mutations in insulin receptor gene by denaturing gradient gel electrophoresis.
PMID 24498630 2014 Two novel mutations identified in familial cases with Donohue syndrome.
PMID 1730625 1992 An Arg for Gly substitution at position 31 in the insulin receptor, linked to insulin resistance, inhibits receptor processing and transport.
PMID 7815442 1994 Homozygosity for a new mutation (Ile119-->Met) in the insulin receptor gene in five sibs with familial insulin resistance.
PMID 12023989 2002 Genotype-phenotype correlation in inherited severe insulin resistance.
PMID 2365819 1990 The patient with leprechaunism (leprechaun/Winnipeg) came from a consanguineous pedigree and was homozygous for a missense mutation substituting arginine for His209 in the alpha-subunit of the insulin receptor.
PMID 8188715 1994 Here we report the identification of a new mutation in the alpha-chain of the insulin receptor, changing Trp412 into Ser using DNA from consanguineous parents who gave birth to a child with leprechaunism.
PMID 12970295 2003 A patient with leprechaunism is compound heterozygous for the previously described Arg1092Trp mutation and a nonsense mutation in codon 897.
PMID 26874853 2016 First molecular diagnosis of Donohue syndrome in Africa: novel unusual insertion/deletion mutation in the INSR gene.
rs1035942 in
INSR gene and
Gout
PMID 23263486 2013 Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.
rs8108622 in
INSR gene and
Height
PMID 21194676 2011 Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height.
PMID 20881960 2010 Hundreds of variants clustered in genomic loci and biological pathways affect human height.
rs4804411 in
INSR gene and
High density lipoprotein measurement
PMID 30698716 2019 Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions.
PMID 30275531 2018 Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.
rs4804416 in
INSR gene and
Hormone measurement
PMID 23408906 2013 A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function.
rs4804433 in
INSR gene and
Hypothyroidism
PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.
PMID 27182965 2016 Detection and interpretation of shared genetic influences on 42 human traits.
rs12978472 in
INSR gene and
Mean blood pressure
PMID 29912962 2018 Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.
rs2059807 in
INSR gene and
Polycystic Ovary Syndrome
PMID 22885925 2012 Genome-wide association study identifies eight new risk loci for polycystic ovary syndrome.
rs76729345 in
INSR gene and
RDW - Red blood cell distribution width result
PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.
rs121913143 in
INSR gene and
Rabson-Mendenhall Syndrome
PMID 12023989 2002 Genotype-phenotype correlation in inherited severe insulin resistance.
PMID 17201797 2007 Functional characterization of a novel insulin receptor mutation contributing to Rabson-Mendenhall syndrome.
PMID 28765322 2017 Structural Basis and Genotype-Phenotype Correlations of INSR Mutations Causing Severe Insulin Resistance.
PMID 2365819 1990 In the patient with the Rabson-Mendenhall syndrome (patient RM-1), the missense mutation substituted lysine for Asn15 in the alpha-subunit.
PMID 2121734 1990 Substitution of lysine for asparagine at position 15 in the alpha-subunit of the human insulin receptor. A mutation that impairs transport of receptors to the cell surface and decreases the affinity of insulin binding.
PMID 10443650 1999 Progressive decline in insulin levels in Rabson-Mendenhall syndrome.
PMID 8314008 1994 Molecular scanning of the insulin receptor gene in syndromes of insulin resistance.
PMID 2365819 1990 Five mutant alleles of the insulin receptor gene in patients with genetic forms of insulin resistance.
PMID 26691667 2016 A novel homozygous missense mutation in the insulin receptor gene results in an atypical presentation of Rabson-Mendenhall syndrome.
rs76729345 in
INSR gene and
Red cell distribution width determination
PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.
rs4804368 in
INSR gene and
Renal Cell Carcinoma
PMID 28598434 2017 Genome-wide association study identifies multiple risk loci for renal cell carcinoma.
rs10427021 in
INSR gene and
Systolic Pressure
PMID 27841878 2017 Genome-wide association analyses using electronic health records identify new loci influencing blood pressure variation.
PMID 28135244 2017 Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk.
PMID 29912962 2018 Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.
PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.
PMID 28739976 2017 Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.
PMID 27618452 2016 The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals.
PMID 29455858 2018 A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure.
PMID 27618448 2016 Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci.
PMID 30578418 2019 Trans-ethnic association study of blood pressure determinants in over 750,000 individuals.
rs4804416 in
INSR gene and
Thyroid stimulating hormone measurement
PMID 23408906 2013 A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function.
rs2303672 in
INSR gene and
Triglycerides measurement
PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.
PMID 30698716 2019 Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions.
PMID 29507422 2018 A large electronic-health-record-based genome-wide study of serum lipids.
PMID 30275531 2018 Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.
PMID 28334899 2017 Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels.
PMID 24097068 2013 Discovery and refinement of loci associated with lipid levels.
rs1035941 in
INSR gene and
Uric acid measurement (procedure)
PMID 30993211 2019 Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals.
PMID 23263486 2013 Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.
PMID 31578528 2019 Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.
rs1035940 in
INSR gene and
Waist-Hip Ratio
PMID 30239722 2019 Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry.
PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.