INSR Gene: Insulin Receptor
Key regulator of glucose homeostasis and growth signaling
Gene Information Card
| Symbol | INSR |
|---|---|
| Full Name | Insulin Receptor |
| Gene Type | protein-coding |
| Chromosomal Location | 19p13.2 |
| NCBI Gene ID | 3643 ncbi.nlm.nih.gov/gene/3643 |
| Ensembl ID | ENSG00000171105 |
| UniProt ID | P06213 |
| OMIM ID | 147670 |
| HGNC ID | 6091 |
| Aliases | CD220, HHF5 |
Description
The INSR gene encodes the insulin receptor, a transmembrane tyrosine kinase receptor that binds insulin and mediates its metabolic and mitogenic effects. Upon insulin binding, the receptor undergoes autophosphorylation and activates downstream signaling pathways, including PI3K/AKT and MAPK, regulating glucose uptake, lipid metabolism, and cell growth. Mutations in INSR cause severe insulin resistance syndromes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Donohue syndrome (Leprechaunism) | Biallelic loss-of-function mutations in INSR lead to complete or near-complete insulin receptor deficiency, causing severe insulin resistance, growth retardation, and early death. | OMIM #246200 |
| Rabson-Mendenhall syndrome | Compound heterozygous or homozygous mutations in INSR result in partial insulin receptor dysfunction, presenting with severe insulin resistance, acanthosis nigricans, and pineal hyperplasia. | OMIM #262190 |
| Type A insulin resistance syndrome | Heterozygous dominant-negative mutations in INSR cause mild to moderate insulin resistance, often with acanthosis nigricans and hyperandrogenism. | OMIM #610549 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 15.2 | Medium |
| Liver | 12.8 | Medium |
| Skeletal muscle | 18.5 | Medium |
| Pancreas | 6.3 | Low |
| Kidney | 10.1 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.5 | Hepatocellular carcinoma cell line |
| MCF7 | 8.2 | Breast cancer cell line |
| A549 | 6.7 | Lung carcinoma cell line |
| HEK293 | 11.3 | Embryonic kidney cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.3572G>A (p.Arg1191Gln) | Missense | Rare | Impaired receptor autophosphorylation and kinase activity |
| c.3610C>T (p.Arg1204Trp) | Missense | Rare | Dominant-negative effect; reduced insulin binding |
| c.2053C>T (p.Arg685*) | Nonsense | Very rare | Truncated receptor; loss of function |
| c.1A>G (p.Met1?) | Start loss | Very rare | No protein production; complete loss of function |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations cause Donohue syndrome; complete absence of functional insulin receptor leads to severe insulin resistance and early lethality.
Gain of Function (GOF)
Not commonly described; some somatic mutations in cancer may lead to constitutive activation, but evidence is limited.
Dominant Negative (DN)
Heterozygous missense mutations in the tyrosine kinase domain (e.g., Arg1204Trp) exert dominant-negative effects, causing Type A insulin resistance syndrome.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • insulin binding |
| • insulin receptor signaling pathway | • protein tyrosine kinase activity |
| • transmembrane receptor protein tyrosine kinase signaling pathway | • glucose homeostasis |
| • positive regulation of cell proliferation |
Pathways
• Insulin signaling pathway (KEGG: hsa04910)
• PI3K-Akt signaling pathway (KEGG: hsa04151)
• MAPK signaling pathway (KEGG: hsa04010)
• Regulation of lipolysis in adipocytes (KEGG: hsa04923)
Protein Summary
The insulin receptor is a heterotetrameric glycoprotein composed of two extracellular alpha subunits and two transmembrane beta subunits. The alpha subunits contain the insulin-binding domain, while the beta subunits possess intrinsic tyrosine kinase activity. Insulin binding induces conformational changes leading to autophosphorylation of specific tyrosine residues, which then recruit and phosphorylate adaptor proteins such as IRS-1 and IRS-2, initiating downstream signaling cascades. The receptor is widely expressed, with highest levels in insulin-sensitive tissues including adipose, liver, and skeletal muscle.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| INSR Knockout HEK293 Cell Line | EDJ-KQ679 | Human | 3643 | Details Get a Quote |
| INSRR Knockout HEK293 Cell Line | EDJ-KQ5003 | Human | 3645 | Details Get a Quote |
| INSR Knockout A-549 Cell Line | EDJ-KQ19214 | Human | 3643 | Details Get a Quote |
| INSR Knockout HCT 116 Cell Line | EDJ-KQ19215 | Human | 3643 | Details Get a Quote |
| INSR Knockout HeLa Cell Line | EDJ-KQ19216 | Human | 3643 | Details Get a Quote |
| INSRR Knockout HeLa Cell Line | EDJ-KQ53669 | Human | 3645 | Details Get a Quote |
| INSRR Knockout A-549 Cell Line | EDJ-KQ62143 | Human | 3645 | Details Get a Quote |
| INSRR Knockout HCT 116 Cell Line | EDJ-KQ70634 | Human | 3645 | Details Get a Quote |
| INSR Knockout HAP1 Cell Line | EDC08159 | Human | 3643 | Details Get a Quote |
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