Table 1.
Genetic mutations and clinical significance in MODY subtypes.
| Subtype | Gene Name | Gene Symbol | Locus | Mutation | Clinical Significance | Ref. | |
|---|---|---|---|---|---|---|---|
| DNA | Amino Acid | ||||||
| MODY 1 | Hepatocyte nuclear factor 4α | HNF4A | 20q13.12 | 763C>T 826G>C |
Gln255Ter Glu276Gln |
Mild hyperglycemia | [3,31] |
| MODY 2 | Glucokinase | GCK | 7p13 | 89T>C 203G>T 748C>T 905T>A 1363G>C |
Leu30Pro Gly68Val Arg250Cys Val302Glu Ala455Leu |
Mild hyperglycemia | [5,32,33,34,35,36] |
| MODY 3 | Hepatocyte nuclear factor 1α | HNF1A | 12q24.31 | 511C>G 733G>C 788G>A 1460G>A |
Arg171Gly Gly245Arg Arg263His Ser487Asn |
Neonatal hypoglycemia | [19,20,37,38] |
| MODY 4 | Insulin promoter factor 1 |
PDX1 | 13q12.2 | 176A>T 188del 533A>G 590G>A 947G>A |
Gln59Leu Pro63fs* Glu178Gly Arg197His Gly316Asp |
Neonatal hypoglycemia | [10,21,39,40,41] |
| MODY 5 | Hepatocyte nuclear factor 1β | HNF1B | 17q12 | 335G>C 406C>G 490A>C 494G>A 884G>A |
Arg112Pro Gln136Glu Lys164Gln Arg165His Arg295His |
Renal disease Diabetic ketosis Glomerulocystic kidney disease |
[22,42,43,44,45,46,47,48] |
| MODY 6 | Neuronal differentiation 1 | NEUROD1 | 2q31.3 | 34G>C 590C>A |
Gly12Arg Pro197His |
Adult onset (mid-20s) | [49,50] |
| MODY 7 | KLF transcription factor 11 | KLF11 | 2p25.1 | 86G>A 185A>G 659C>T 1039G>T |
Arg29Gln Gln62Arg Thr220Met Ala347Ser |
Pancreatic malignancy | [51,52,53,54] |
| MODY 8 | Carboxyl ester lipase | CEL | 9q34.13 | 1402G>A 1454T>C |
Ala468Thr Ile485Thr |
Adult onset (36 years) Hypoglycemia |
[18,55,56] |
| MODY 9 | Paired box 4 | PAX4 | 7q32.1 | 385C>T 514C>T 539G>A |
Arg129Trp Arg172Trp Ser180Asn |
Nephrological diseases | [57,58] |
| MODY 10 | Insulin | INS | 11p15.5 | 25C>T 130G>A 137G>A 155C>A 290C>G |
Pro9Ser Gly44Arg Arg46Gln Pro52His Thr97Ser |
Neonatal hypoglycemia | [59,60,61] |
| MODY 11 | BLK proto-oncogene, Src family tyrosine kinase | BLK | 8p23.1 | 41C>T 116C>T 164A>G 177C>G 187G>A 311G>T 391C>T 713G>A |
Pro14Leu Pro39Leu His55Arg Asp59Glu Val63Met Arg104Ile Arg131Trp Arg238Gln |
Neonatal hypoglycemia obesity |
[62,63,64] |
| MODY 12 | ATP binding cassette subfamily C member | ABCC8 | 11p15.1 | 502C>T 2477G>A 3158G>A 3202T>A 4148G>C 4500C4A |
Arg168Cys Gly826Asp Ser1053Asn Phe1068Ile Gly1383Ala Ser1500Arg |
Renal diabetes | [65,66,67,68] |
| MODY 13 | Potassium inwardly rectifying channel subfamily J member 11 | KCNJ11 | 11p15.1 | 67A>G 679G>A 808C>G 902G>A 964G>A 973C>A 1034C>T 1040G>A |
Lys23Glu Glu227 Lys Leu270Val Arg301His Glu322Lys Arg325Ser Thr345Met Arg347His |
Renal diabetes Hyperinsulinemic hypoglycemia Neonatal diabetes |
[69,70,71,72,73] |
| MODY 14 | Leucine zipper containing 1 |
APPL1 | 3p14.3 | 280G>A 1655T>A 1926A>G |
Asp94Asn Leu552Ter Ile642Met |
Wolfram or DIDMOAD syndrome |
[74,75,76,77] |
*Fs, frameshift.