Table 2.
Monogenic Causes of Type 2 Diabetes
| Gene Name | Common/Other Name | Cellular Function | Chromosome Location | OMIM Number | Diabetes Phenotype |
|---|---|---|---|---|---|
| Monogenic Causes of β Cell Dysfunction | |||||
| MODY Diabetes | |||||
| HNF4A | HNF4alpha | Transcription factor | 20q12 | 600281 | MODY1; β-cell dysfunction |
| GCK | Glucokinase | Glucose phosphorylation | 7p15 | 138079 | MODY2; mild life-long fasting hyperglycemia |
| TCF1 | HNF1alpha | Transcription factor | 12q24 | 142410 | MODY3; progressive β-cell dysfunction |
| PDX1 | Insulin promoter factor 1 (IPF1) | Homeodomain transcription factor | 13q12 | 600733 | MODY4: Heterozygote: similar to HNF1A (rare); homozygote: pancreatic agenesis and neonatal diabetes |
| TCF2 | HNF1beta | Transcription factor | 17q21 | 189907 | MODY5; Renal cysts and diabetes, pancreatic atrophy, neonatal diabetes |
| NEUROD1 | Beta2 | bHLH Transcription factor | 2q32 | 601724 | MODY6; Similar to HNF1A (rare) |
| KLF11 | Kruppel-like factor 11 | TGF-beta inducible Transcription Factor | 2p25 | 610508 | MODY7; impairs activation of insulin promoter |
| CEL | Carboxyl-ester lipase | Lipid metabolism | 9q34.3 | 114840 | MODY8; Exocrine and β-cell dysfunction (rare) |
| Neonatal Diabetes | |||||
| KCNJ11 | Kir6.2 | Potassium channel | 11p15.1 | 600937 | Permanent and transient neonatal diabetes |
| ABCC8 | Sur1 | Sulfonylurea receptor | 11p15.1 | 600509 | Permanent and transient neonatal diabetes |
| EIF2AK3 | PERK | Pancreatic eIF2-alpha kinase | 2p12 | 604032 | Wolcott-Rallison Syndrome |
| PLAGL1 | Pleomorhpic adenoma | Plagl1 – Nuclear zinc finger | 6p24 | 606546 | Imprinted region, exact gene |
| HYMA1 | gene 1; hydatidiform mole transcript | protein | 603044 | unclear; transient neonatal diabetes type 1 | |
| PTF1A | Pancreas transcription factor 1 | Alpha subunit of PTF1 | 10p12 | 607194 | Permanent neonatal diabetes with cerebellar agenesis |
| INS | Insulin | Hormone | 11p15.5 | 176730 | Mutation in insulin, proinsulin, and proinsulin processing |
| Mitochondrial Diabetes | |||||
| Mitochondrial genome | MIDD | tRNA for leucine | Mutation at 3243 mtDNA | 590050 | Maternally inherited diabetes and deafness; other mitochondrial mutation also observed |
| Mitochondrial genome | Mitochondrial myopathy, lipid type | tRNA for glutamic acid | Mutation at 14709 mtDNA | 500002 | Mitochondrial myopathy with diabetes |
| Other | |||||
| WFS1 | Wolframin | 10 transmembrane domain protein, function unknown | 4p16.1 | 2223000 | Diabetes insipidus and mellitus with optic atrophy and deafness; DIDMOAD; Wolfram Syndrome |
| ZCD2 | ERIS | Zinc finger protein ZCD2 | 4q22–q24 | 604928 | Wolfram Syndrome 2 |
| Monogenic Causes of Insulin Resistance | |||||
| Severe Insulin Resistance | |||||
| INSR | Insulin receptor | Receptor tyrosine kinase | 19p13 | 147670 | Insulin-resistant diabetes with various phenotypes: leprechaunism, Rabson-Mendenhall or type A syndrome |
| AKT2 | PKB-beta | Serine-threonine kinase | 19q1 | 164731 | Severe insulin resistance |
| Lipoatrophic Forms of Diabetes | |||||
| LMNA | Lamin A/C | Inner nuclear membrane protein | 1q21 | 150330 | Face-sparing partial lipodystrophy with peripheral fat loss; mutations also associated with cardiomyopathy; muscular dystrophy; and Hutchinson-Gilford Progeria |
| LMNB2 | Lamin B2 | Inner nuclear membrane protein | 19p13 | 150341 | Partial lipodystrophy sparing legs (Barraquer-Simon Syndrome) |
| AGPAT2 | 1-acylglycerol-3-phosphophate O-acyltransferase 2 | Enzyme of phospholipid metabolism | 9q34 | 603100 | Congenital generalized lipodystrophy with skeletal lytic lesions (Bernardinelli-Seip Syndrome) |
| BSCL2 | Seipin | 398 amino acid protein of unknown function | 11q13 | 606158 | Congenital generalized lipodystrophy, learning disabilities |
| PPARG | Peroxisome proliferator activated receptor γ | Nuclear receptor for prostaglands and thiazolidine-diones | 3p25 | 601487 | Rare variants in ligand binding domain associated with insulin resistance, hypertension, buttock lipodystrophy |