Table 1.
Genes implicated in monogenic diabetes; MODY and neonatal diabetes
| Gene | Protein | Function | Inheritance |
|---|---|---|---|
| Maturity onset diabetes of the young | |||
| Common causes of MODY with well-established evidence-base | |||
| HNF1A | Hepatocyte nuclear factor 1α | Beta-cell transcription factor | Autosomal dominant |
| HNF4A | Hepatocyte nuclear factor 4α | Beta-cell transcription factor | Autosomal dominant |
| GCK | Glucokinase | Glucose-sensor, first rate-limiting enzyme in glycolysis | Autosomal dominant |
| HNF1B | Hepatocyte nuclear factor 1β | Beta-cell transcription factor | Autosomal dominant |
| ABCC8 | Sulphonylurea receptor subunit of β-cell K-ATP channel | Closure of the ATP-sensitive potassium channel leads to beta-cell membrane depolarisation, calcium influx and fusion of insulin secretory granules with beta-cell membrane | Autosomal dominant |
| KCNJ11 | Potassium channel subunit of β-cell K-ATP channel | Autosomal dominant | |
| INS | Insulin | Production of insulin or insulin action | Autosomal dominant |
| Rare causes of MODY with reasonable evidence supporting | |||
| NEUROD1 | Neurogenic differentiation factor 1 | Beta-cell transcription factor | Autosomal dominant |
| IPF1 | Insulin promotor factor 1 | Beta-cell transcription factor | Recessive |
| CEL | Carboxyl ester lipase | Exocrine pancreas function | Deletion of variable number tandem repeat |
| WSF1 | Wolframin | Function of the endoplasmic reticulum | Recessive |
| RFX6 | Regulatory factor X 6 | Beta-cell transcription factor | Dominant protein truncating variant |
| APPL1 | Adaptor protein, phosphotyrosine interaction, PH domain, and leucine zipper containing 1 | Protein that bind to AKT in the insulin-signalling pathway | Autosomal dominant |
| Neonatal diabetes | |||
| Causes of neonatal diabetes, accounting for > 2.5% of cases | |||
| ABCC8 | Sulphonylurea receptor subunit of β-cell K-ATP channel | Closure of the ATP-sensitive potassium channel leads to beta-cell membrane depolarisation, calcium influx and fusion of insulin secretory granules with beta-cell membrane | Dominant, often de novo or recessive |
| KCNJ11 | Potassium channel subunit of β-cell K-ATP channel | Dominant, often de novo | |
| GCK | Glucokinase | Glucose-sensor, first rate-limiting enzyme in glycolysis | Autosomal recessive |
| GATA6 | GATA binding factor 6 | Transcription factor | Dominant, often de novo |
| INS | Insulin | Production of insulin or insulin action | Dominant, often de novo or recessive |
| PTF1A | Pancreatic associate transcription factor 1 A | Transcription factor involved in pancreatic development | Recessive |
| EIF2AK3 | Eukaryotic translation initiation factor 2 alpha kinase 3 | Kinase enzyme in endoplasmic reticulum | Recessive |
| RFX6 | Regulatory factor X 6 | Beta-cell transcription factor | Recessive |
Some of the information in Table 1 came from https://www.diabetesgenes.org/tests-for-diabetes-subtypes/targeted-next-generation-sequencing-analysis-of-45-monogenic-diabetes-genes/” [5]