ABCC8
Chr 11ADARATP binding cassette subfamily C member 8
The ABCC8 protein is a regulatory subunit of pancreatic ATP-sensitive potassium channels that controls insulin release by forming KATP channels with KCNJ11. Mutations cause a spectrum of glucose homeostasis disorders including neonatal hyperinsulinemic hypoglycemia, transient and permanent neonatal diabetes, and maturity-onset diabetes of the young type 12. Inheritance can be either autosomal dominant or autosomal recessive depending on the specific condition and mutation.
Definitive — sufficient evidence for diagnostic panels
4 total gene-disease associations curated
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
ABCC8 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
A Study of Endocrine, Metabolic, and Genetic Risk Factors of Pediatric Persistent Hypoglycemia at Sohag University Hospital
NOT YET RECRUITINGExercise to Fight Obesity
RECRUITINGExternal Resources
Links to major genomics databases and tools