Hereditary hyperinsulinism: genes and variants
Hereditary hyperinsulinism is linked to 1 analyzed protein (ABCC8). 22 DNA variants are known to cause it; 38 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 Hereditary hyperinsulinism
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.
22 disease-causing and 38 uncertain variants in ABCC8 are linked to Hereditary hyperinsulinism.
Where Hereditary hyperinsulinism variants cluster
- ABCC8 ABC transporter 2 (positions 1344–1578): 11 of 22 disease-causing changes, 3.4× more than its size predicts.
Known disease-causing variants in Hereditary hyperinsulinism
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| ABCC8 G1378S | 1378 | ABC transporter 2 | Disease-causing (★★) |
| ABCC8 R1418C | 1418 | ABC transporter 2 | Disease-causing (★★) |
| ABCC8 R1418H | 1418 | ABC transporter 2 | Disease-causing (★★) |
| ABCC8 R74W | 74 | Transmembrane | Disease-causing (★★) |
| ABCC8 G1378R | 1378 | ABC transporter 2 | Disease-causing (★★) |
| ABCC8 R74Q | 74 | Transmembrane | Disease-causing (★★) |
| ABCC8 Q444H | 444 | ABC transmembrane type-1 1 | Disease-causing (★★) |
| ABCC8 L1459R | 1459 | ABC transporter 2 | Disease-causing (★★) |
| ABCC8 R1493Q | 1493 | ABC transporter 2 | Disease-causing (★★) |
| ABCC8 R168C | 168 | Extracellular | Disease-causing (★★) |
| ABCC8 R1214W | 1214 | ABC transmembrane type-1 2 | Disease-causing (★★) |
| ABCC8 R1393L | 1393 | ABC transporter 2 | Disease-causing (★★) |
| ABCC8 G1400R | 1400 | ABC transporter 2 | Disease-causing (★★) |
| ABCC8 R1436Q | 1436 | ABC transporter 2 | Disease-causing (★★) |
| ABCC8 G1554D | 1554 | ABC transporter 2 | Disease-causing (★★) |
| ABCC8 D310N | 310 | ABC transmembrane type-1 1 | Disease-causing (★★) |
| ABCC8 V607M | 607 | Cytoplasmic | Disease-causing (★★) |
| ABCC8 G1255S | 1255 | ABC transmembrane type-1 2 | Disease-causing (★★) |
| ABCC8 R526C | 526 | ABC transmembrane type-1 1 | Disease-causing (★★) |
| ABCC8 S1382R | 1382 | ABC transporter 2 | Disease-causing (★) |
| ABCC8 G70E | 70 | Cytoplasmic | Disease-causing (★) |
| ABCC8 A390E | 390 | ABC transmembrane type-1 1 | Disease-causing (★) |
Uncertain variants in Hereditary hyperinsulinism 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); R1393L 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 Hereditary hyperinsulinism variants (31 disease-causing).
- Type 2 diabetes mellitus is also caused by ABCC8 variants; they fall mostly in different places as the Hereditary hyperinsulinism variants (27 disease-causing).
- Familial hyperinsulinism is also caused by ABCC8 variants; they fall mostly in different places as the Hereditary hyperinsulinism variants (20 disease-causing).
- Diabetes mellitus, transient neonatal, 2 is also caused by ABCC8 variants; they fall mostly in different places as the Hereditary hyperinsulinism variants (19 disease-causing).
- Diabetes mellitus, permanent neonatal 3 is also caused by ABCC8 variants; they fall mostly in different places as the Hereditary hyperinsulinism variants (17 disease-causing).
Diseases related to Hereditary hyperinsulinism
- 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
- Permanent neonatal diabetes mellitus, also linked to ABCC8
- Diabetes mellitus, also linked to ABCC8
Frequently asked questions
Which genes are linked to Hereditary hyperinsulinism?
In CATVariant, Hereditary hyperinsulinism is linked to 1 analyzed protein: ABCC8 (ATP-binding cassette sub-family C member 8).
How many genetic variants are linked to Hereditary hyperinsulinism?
60 variants: 22 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 38 are of uncertain significance or have conflicting reports.
Which uncertain variants in Hereditary hyperinsulinism 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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