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INSR gene

Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

INSR gene

The INSR gene provides instructions for the insulin receptor, which is essential for regulating blood glucose levels and cellular energy use.

Normal Function

The INSR gene provides instructions for making the insulin receptor. These receptors are embedded in the cell membrane and bind to the hormone insulin circulating in the bloodstream. This binding regulates blood glucose levels by controlling the movement of sugar (glucose) from the blood into cells for energy.

The receptor is processed into two alpha subunits (which bind to insulin) and two beta subunits (which trigger internal cell signaling pathways). This process is vital for the receptor to function correctly.

Health Conditions Related to Genetic Changes

Donohue syndrome

This is the most severe of the severe insulin resistance syndromes. Mutations in both copies of the INSR gene prevent the formation of functional receptors or disrupt insulin binding. Consequently, cells cannot respond to insulin, leading to severe blood glucose regulation issues and impaired development. Affected children typically do not survive beyond age 2.

Rabson-Mendenhall syndrome

This syndrome is intermediate in severity. Mutations in both copies of the gene reduce the number of receptors reaching the cell membrane or impair their function. While less severe than Donohue syndrome, it causes severe insulin resistance and diabetes mellitus, with affected individuals often surviving into their teens or twenties.

Type A insulin resistance syndrome

This is the mildest form, often caused by "dominant-negative" mutations in one copy of the gene, where the faulty receptor interferes with the normal one. Symptoms, which often appear at puberty, include diabetes mellitus, acanthosis nigricans, and in females, menstrual abnormalities, hirsutism, and ovarian cysts.

Polycystic ovary syndrome

The INSR gene is also associated with polycystic ovary syndrome.

Other Names for This Gene

  • CD220
  • HHF5
  • insulin receptor isoform Long preproprotein
  • insulin receptor isoform Short preproprotein
  • IR

Frequently Asked Questions

Donohue syndrome and Rabson-Mendenhall syndrome are autosomal recessive conditions, meaning a child must inherit two mutated copies of the INSR gene, one from each parent, to develop the condition. In contrast, Type A insulin resistance syndrome is typically caused by a dominant-negative mutation in only one copy of the gene. This means that a single faulty copy can interfere with the function of the normal copy, leading to symptoms that often emerge at puberty rather than in infancy.
Type A insulin resistance often presents in females at puberty with a combination of severe insulin resistance and hyperandrogenism. Key distinguishing signs include acanthosis nigricans (dark, velvety patches of skin), hirsutism (excessive hair growth), menstrual irregularities, and polycystic ovaries. Unlike typical Type 2 diabetes, which is strongly associated with obesity, Type A insulin resistance can occur in individuals with a normal body weight, and the insulin levels are markedly elevated despite the presence of high blood glucose.
Yes, this is possible depending on the type of mutation. For autosomal recessive conditions like Donohue syndrome, parents are usually asymptomatic carriers who each have one mutated copy but do not show symptoms because their single normal copy is sufficient for function. However, for Type A insulin resistance, which is often dominant, a parent with the mutation may show mild or late-onset symptoms. In some cases, the severity of the condition can vary significantly between family members due to genetic modifiers or environmental factors, meaning a parent might have subtle signs while a child presents with more severe clinical features.
While the primary role of the insulin receptor is to facilitate glucose entry into cells, it also plays a critical role in regulating lipid and protein synthesis. When insulin binds to the receptor, it triggers signaling pathways that promote the storage of fat and the synthesis of proteins, while inhibiting the breakdown of these stores. In conditions like Donohue syndrome, the complete lack of functional receptors means cells cannot utilize glucose for energy, leading to severe metabolic derangement, impaired growth, and an inability to store energy effectively, which contributes to the rapid deterioration seen in affected infants.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.