IRS1 insulin receptor substrate 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: IRS1provided by HGNC
Official Full Name: insulin receptor substrate 1provided by HGNC
Primary source: HGNC:HGNC:6125
See related: Ensembl:ENSG00000169047 MIM:147545; AllianceGenome:HGNC:6125
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: HIRS-1
Summary: This gene encodes a protein which is phosphorylated by insulin receptor tyrosine kinase. Mutations in this gene are associated with type II diabetes and susceptibility to insulin resistance. [provided by RefSeq, Nov 2009]
Expression: Broad expression in thyroid (RPKM 15.0), endometrium (RPKM 12.3) and 22 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q36.3

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (226731312..226799820, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (227214139..227282678, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (227596028..227664536, complement)

Chromosome 2 - NC_000002.12 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?

Association of IRS1 gene Pro512Ala polymorphism with nonalcoholic fatty liver disease.
Title: Association of IRS1 gene Pro512Ala polymorphism with nonalcoholic fatty liver disease.
Sex differences in adipose insulin resistance are linked to obesity, lipolysis and insulin receptor substrate 1.
Title: Sex differences in adipose insulin resistance are linked to obesity, lipolysis and insulin receptor substrate 1.
sh- Ambra1 inhibits IRS-1/PI3K/Akt signalling pathway to reduce autophagy in gestational diabetes.
Title: sh- Ambra1 inhibits IRS-1/PI3K/Akt signalling pathway to reduce autophagy in gestational diabetes.
IRS1 promotes thyroid cancer metastasis through EMT and PI3K/AKT pathways.
Title: IRS1 promotes thyroid cancer metastasis through EMT and PI3K/AKT pathways.
High risk genetic variants of human insulin receptor substrate 1(IRS1) infer structural instability and functional interference.
Title: High risk genetic variants of human insulin receptor substrate 1(IRS1) infer structural instability and functional interference.
Influence of polymorphisms in IRS1, IRS2, MC3R, and MC4R on metabolic and inflammatory status and food intake in Brazilian adults: An exploratory pilot study.
Title: Influence of polymorphisms in IRS1, IRS2, MC3R, and MC4R on metabolic and inflammatory status and food intake in Brazilian adults: An exploratory pilot study.
Gender Differences of Gly972Arg Polymorphism of the IRS-1 Gene Related to Cardiovascular Disease Risk Factors Among Indonesians.
Title: Gender Differences of Gly972Arg Polymorphism of the IRS-1 Gene Related to Cardiovascular Disease Risk Factors Among Indonesians.
Association of IRS-1 and IRS-2 polymorphisms with predisposition to type-2 diabetes (T2D): a meta-analysis and trial sequential analysis.
Title: Association of IRS-1 and IRS-2 polymorphisms with predisposition to type-2 diabetes (T2D): a meta-analysis and trial sequential analysis.
Long Non-coding RNA SPAG5-AS1 Attenuates Diabetic Retinal Vascular Dysfunction by Inhibiting Human Retinal Microvascular Endothelial Cell Proliferation, Migration, and Tube Formation by Regulating the MicroRNA-1224-5p/IRS-1 Axis.
Title: Long Non-coding RNA SPAG5-AS1 Attenuates Diabetic Retinal Vascular Dysfunction by Inhibiting Human Retinal Microvascular Endothelial Cell Proliferation, Migration, and Tube Formation by Regulating the MicroRNA-1224-5p/IRS-1 Axis.
Overexpression of Insulin Receptor Substrate 1 (IRS1) Relates to Poor Prognosis and Promotes Proliferation, Stemness, Migration, and Oxidative Stress Resistance in Cholangiocarcinoma.
Title: Overexpression of Insulin Receptor Substrate 1 (IRS1) Relates to Poor Prognosis and Promotes Proliferation, Stemness, Migration, and Oxidative Stress Resistance in Cholangiocarcinoma.

Submit: New GeneRIF Correction See all GeneRIFs (368)

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
Type 2 diabetes mellitus MedGen: C0011860 OMIM: 125853 GeneReviews: WFS1 Spectrum Disorder	Compare labs

EBI GWAS Catalog

Description
A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. EBI GWAS Catalog EBI GWAS CatalogPubMed
Biological, clinical and population relevance of 95 loci for blood lipids. EBI GWAS Catalog EBI GWAS CatalogPubMed
Discovery and refinement of loci associated with lipid levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals. EBI GWAS Catalog EBI GWAS CatalogPubMed
Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits. EBI GWAS Catalog EBI GWAS CatalogPubMed
Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. 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

WI-18042 (e-PCR)
- UniSTS:11534

RH48158 (e-PCR)
- UniSTS:70162

SHGC-52849 (e-PCR)
- UniSTS:10265

GDB:456117 (e-PCR)
- UniSTS:157470

GDB:456125 (e-PCR)
- UniSTS:157472

RH17903 (e-PCR)
- UniSTS:46669

D2S2647 (e-PCR)
- UniSTS:57707

PMC86565P4 (e-PCR)
- UniSTS:273537

D2S2389 (e-PCR), detects polymorphism
- UniSTS:49035

IRS1_760 (e-PCR)
- UniSTS:277390

IRS1_V113 (e-PCR)
- UniSTS:277390

RH68643 (e-PCR)
- UniSTS:34203

SHGC-82871 (e-PCR)
- UniSTS:103348

RH69408 (e-PCR)
- UniSTS:68843

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables SH2 domain binding	ISS Inferred from Sequence or Structural Similarity more info
enables insulin receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables insulin receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables insulin-like growth factor receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables phosphatidylinositol 3-kinase binding	IBA Inferred from Biological aspect of Ancestor more info
enables phosphatidylinositol 3-kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables phosphatidylinositol 3-kinase binding	ISS Inferred from Sequence or Structural Similarity more info
enables phosphotyrosine residue binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase C binding	ISS Inferred from Sequence or Structural Similarity more info
enables signaling adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables signaling receptor complex adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables transmembrane receptor protein tyrosine kinase adaptor activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in cellular response to fatty acid	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to insulin stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cytokine-mediated signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in glucose homeostasis	TAS Traceable Author Statement more info	PubMed
involved_in insulin receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in insulin receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in insulin receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in insulin receptor signaling pathway	IPI Inferred from Physical Interaction more info	PubMed
involved_in insulin-like growth factor receptor signaling pathway	IPI Inferred from Physical Interaction more info	PubMed
involved_in negative regulation of insulin receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of insulin secretion	IDA Inferred from Direct Assay more info	PubMed
involved_in phosphatidylinositol 3-kinase/protein kinase B signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of D-glucose import	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of D-glucose import	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell population proliferation	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of fatty acid beta-oxidation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of glucose metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of glycogen biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of glycogen biosynthetic process	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of insulin receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of insulin receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to insulin	IDA Inferred from Direct Assay more info	PubMed
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in caveola	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
part_of insulin receptor complex	ISS Inferred from Sequence or Structural Similarity more info
located_in intracellular membrane-bounded organelle	ISS Inferred from Sequence or Structural Similarity more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleus	ISS Inferred from Sequence or Structural Similarity more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: insulin receptor substrate 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_015830.1 RefSeqGene

Range

3971..72479

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_005544.3 → NP_005535.1 insulin receptor substrate 1

See identical proteins and their annotated locations for NP_005535.1

Status: REVIEWED

Source sequence(s)

AC010735, BC053895

Consensus CDS

CCDS2463.1

UniProtKB/Swiss-Prot

P35568

Related

ENSP00000304895.4, ENST00000305123.6

Conserved Domains (2) summary

cd01204
Location:160 → 263

PTB_IRS; Insulin receptor substrate phosphotyrosine-binding domain (PTBi)

cd01257
Location:11 → 118

PH_IRS; Insulin receptor substrate (IRS) pleckstrin homology (PH) domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

226731312..226799820 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047444224.1 → XP_047300180.1 insulin receptor substrate 1 isoform X1

UniProtKB/Swiss-Prot

P35568
XM_047444223.1 → XP_047300179.1 insulin receptor substrate 1 isoform X1

UniProtKB/Swiss-Prot

P35568