Insulin-resistant diabetes mellitus AND acanthosis nigricans: genes and variants
Insulin-resistant diabetes mellitus AND acanthosis nigricans is linked to 1 analyzed protein (INSR). 7 DNA variants are known to cause it; 30 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Insulin-resistant diabetes mellitus AND acanthosis nigricans
INSR: Insulin receptor
Its activation by insulin coordinates glucose uptake, metabolism, growth, and gene expression through PI3K-AKT and MAPK pathways. Biallelic severe loss-of-function variants cause Donohue or Rabson-Mendenhall syndromes, while heterozygous variants can cause severe insulin resistance.
7 disease-causing and 30 uncertain variants in INSR are linked to Insulin-resistant diabetes mellitus AND acanthosis nigricans.
Where Insulin-resistant diabetes mellitus AND acanthosis nigricans variants cluster
- INSR Protein kinase (positions 1023–1298): 5 of 7 disease-causing changes, 3.6× more than its size predicts.
Known disease-causing variants in Insulin-resistant diabetes mellitus AND acanthosis nigricans
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| INSR V1054M | 1054 | Protein kinase | Disease-causing |
| INSR N489D | 489 | Extracellular | Disease-causing |
| INSR R762S | 762 | Fibronectin type-III 2 | Disease-causing |
| INSR G1035V | 1035 | Protein kinase | Disease-causing |
| INSR A1161T | 1161 | Protein kinase | Disease-causing |
| INSR A1162E | 1162 | Protein kinase | Disease-causing |
| INSR W1227S | 1227 | Protein kinase | Disease-causing |
Same protein, different disease
- Leprechaunism syndrome is also caused by INSR variants; they fall mostly in different places as the Insulin-resistant diabetes mellitus AND acanthosis nigricans variants (14 disease-causing).
- Rabson-Mendenhall syndrome is also caused by INSR variants; they fall mostly in different places as the Insulin-resistant diabetes mellitus AND acanthosis nigricans variants (8 disease-causing).
Diseases related to Insulin-resistant diabetes mellitus AND acanthosis nigricans
- Monogenic diabetes, also linked to INSR
- Type 2 diabetes mellitus, also linked to INSR
- Leprechaunism syndrome, also linked to INSR
- Diabetes mellitus, also linked to INSR
- Type 1 diabetes mellitus, also linked to INSR
- Rabson-Mendenhall syndrome, also linked to INSR
- Hyperinsulinism due to INSR deficiency, also linked to INSR
Frequently asked questions
Which genes are linked to Insulin-resistant diabetes mellitus AND acanthosis nigricans?
In CATVariant, Insulin-resistant diabetes mellitus AND acanthosis nigricans is linked to 1 analyzed protein: INSR (Insulin receptor).
How many genetic variants are linked to Insulin-resistant diabetes mellitus AND acanthosis nigricans?
40 variants: 7 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 30 are of uncertain significance or have conflicting reports.
Which uncertain variants in Insulin-resistant diabetes mellitus AND acanthosis nigricans look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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