Leucine-induced hypoglycemia: genes and variants
Leucine-induced hypoglycemia is linked to 1 analyzed protein (ABCC8). 5 DNA variants are known to cause it; 112 more are uncertain, and 1 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Leucine-induced hypoglycemia
ABCC8: ATP-binding cassette sub-family C member 8
It senses cellular nucleotide levels as the regulatory component of pancreatic beta-cell ATP-sensitive potassium channels and thereby couples glucose metabolism to insulin secretion. Loss-of-function variants cause congenital hyperinsulinism, whereas activating variants can cause neonatal diabetes.
5 disease-causing and 112 uncertain variants in ABCC8 are linked to Leucine-induced hypoglycemia.
Where Leucine-induced hypoglycemia variants cluster
- ABCC8 ABC transporter 2 (positions 1344–1578): 3 of 5 disease-causing changes, 4.0× more than its size predicts.
Known disease-causing variants in Leucine-induced hypoglycemia
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| ABCC8 Q444H | 444 | ABC transmembrane type-1 1 | Disease-causing (★★) |
| ABCC8 R1393C | 1393 | ABC transporter 2 | Disease-causing (★★) |
| ABCC8 P1413L | 1413 | ABC transporter 2 | Disease-causing (★★) |
| ABCC8 G1554V | 1554 | ABC transporter 2 | Disease-causing (★★) |
| ABCC8 V607M | 607 | Cytoplasmic | Disease-causing (★★) |
Uncertain variants in Leucine-induced hypoglycemia that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| ABCC8 R1393H | 1393 | ABC transporter 2 | Conflicting reports (★) | +6: in a 3D region that tolerates change poorly (1R); R1393C at the same position is pathogenic; REVEL 0.877 |
Same protein, different disease
- Hyperinsulinemic hypoglycemia, familial, 1 is also caused by ABCC8 variants; they fall mostly in different places as the Leucine-induced hypoglycemia variants (31 disease-causing).
- Type 2 diabetes mellitus is also caused by ABCC8 variants; they fall mostly in different places as the Leucine-induced hypoglycemia variants (27 disease-causing).
- Hereditary hyperinsulinism is also caused by ABCC8 variants; they fall mostly in different places as the Leucine-induced hypoglycemia variants (22 disease-causing).
- Familial hyperinsulinism is also caused by ABCC8 variants; they fall mostly in different places as the Leucine-induced hypoglycemia variants (20 disease-causing).
- Diabetes mellitus, transient neonatal, 2 is also caused by ABCC8 variants; they fall mostly in different places as the Leucine-induced hypoglycemia variants (19 disease-causing).
Diseases related to Leucine-induced hypoglycemia
- Monogenic diabetes, also linked to ABCC8
- Maturity-onset diabetes of the young, also linked to ABCC8
- Type 2 diabetes mellitus, also linked to ABCC8
- Hyperinsulinemic hypoglycemia, familial, 1, also linked to ABCC8
- Atrial septal defect, also linked to ABCC8
- Diabetes mellitus, permanent neonatal 3, also linked to ABCC8
- Pulmonary arterial hypertension, also linked to ABCC8
- Neonatal diabetes mellitus, also linked to ABCC8
- Familial hyperinsulinism, also linked to ABCC8
- Diabetes mellitus, transient neonatal, 2, also linked to ABCC8
- Hereditary hyperinsulinism, also linked to ABCC8
- Permanent neonatal diabetes mellitus, also linked to ABCC8
Frequently asked questions
Which genes are linked to Leucine-induced hypoglycemia?
In CATVariant, Leucine-induced hypoglycemia is linked to 1 analyzed protein: ABCC8 (ATP-binding cassette sub-family C member 8).
How many genetic variants are linked to Leucine-induced hypoglycemia?
118 variants: 5 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 112 are of uncertain significance or have conflicting reports.
Which uncertain variants in Leucine-induced hypoglycemia look disease-causing?
1 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example ABCC8 R1393H. These are leads for expert review, not diagnoses.
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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