Table 1.
Diabetes Gene | Proposed Diabetes Target Cell Type / Tissue1 | Monogenic Diabetes4 | Type 2 Diabetes5 | Proposed Function(s) for Gene Product2 | Drug(s) Affecting the Same Pathway as the Diabetes Gene3 |
---|---|---|---|---|---|
ABCC8 | Pancreas β-Cell | X | - B-cell ion homeostasis and insulin secretion; ATP-binding cassette transporter that modulates ATP-sensitive potassium channels and insulin release | Sulfonylurea derivatives | |
ADAMTS9 | Unknown | X | - Cleavage of proteoglycans | Unknown | |
CDC123 | Pancreas β-Cell | X | - Cell cycle regulation | Unknown | |
CDKAL1 | Pancreas β-Cell | X | - Growth and development - Proinsulin to insulin conversion |
Unknown | |
CDKN2A | Pancreas β-Cell | X | - Cell cycle regulation | Unknown | |
CEL | Unknown | X | - Glycoprotein that is important in regulation of cholesterol metabolism | Unknown | |
FTO | Hypothalamus | X | - Associated to obesity | Unknown | |
GCK | Unknown | X | - Catalyzes reaction from glucose to glucose-6-phosphate | Unknown | |
HHEX | Pancreas β-Cell | X | - Growth and development; transcription factor | Unknown | |
HNF4α | Pancreas β-Cell | X | - Growth and development; transcription factor | Unknown | |
IDE | Pancreas β-Cell | X | - Termination of the response to insulin | Unknown | |
IGF2BP2 | Pancreas β-Cell | X | - Growth and development | Unknown | |
JAZF1 | Pancreas β-Cell | X | - Cell cycle regulation; transcriptional repressor | Unknown | |
KCNJ11 | Pancreas β-Cell | X | X | - B-cell ion homeostasis and insulin secretion | Sulfonylurea derivatives |
KCNQ1 | Pancreas β-Cell | X | - B-cell ion homeostasis and insulin secretion | Sulfonylurea derivatives | |
KLF11 | Unknown | X | - Unknown | Unknown | |
NEUROD1 | Pancreas β-Cell | X | - Growth and development; transcription factor that activates several genes including insulin and is important for early β-cell development | Unknown | |
NOTCH2 | Pancreas β-Cell | X | - Growth and development; transcription factor; receptor for membrane bound ligands | Unknown | |
PDX1 | Pancreas β-Cell | X | - Growth and development; nuclear protein that acts as a transcriptional activator of several genes including insulin and is important for early β-cell development | Unknown | |
PPARG | Adipocyte | X | - Nuclear receptor (transcription factor) that regulates adipocyte differentiation | Thiazolidinediones | |
SLC30A8 | Pancreas β-Cell | X | - B-cell ion homeostasis and insulin secretion; cellular efflux of Zn2+ ions - Proinsulin to insulin conversion |
Sulfonylurea derivatives | |
TCF1 | Pancreas β-Cell | X | - Growth and development; Transcription factor that forms a complex with the product of TCF2 important for Wnt signaling | Unknown | |
TCF2 | Pancreas β-Cell | X | X | - Growth and development; transcription factor that forms a complex with the product of TCF1 important for Wnt signaling - Cell cycle regulation |
Unknown |
TCF7L2 | Pancreas β-Cell | X | - Wnt signaling - Proinsulin to insulin conversion |
Unknown | |
THADA | Pancreas β-Cell | X | - Apoptosis | Unknown | |
TSPAN8 | Unknown | X | - Glycoprotein involved in the mediation of signal transduction | Unknown | |
WFS1 | Pancreas β-Cell | X | X | - Apoptosis; Endoplasmic Reticulum stress pathway activation | Unknown |
Genes included in the list are involved in type 2 diabetes, Maturity Onset Diabetes of the Young (MODY), or Permanent Neonatal Diabetes Mellitus (PNDM). The cut-off p-value for the inclusion of type 2 diabetes genes identified by GWAS is 1 x 10-8 [12, 21-23]. The third and fourth columns of the table show whether a gene is involved in monogenic4 or complexly inherited type 2 diabetes5.