AGE-RAGE signaling pathway in diabetic complications Gene Set

Dataset KEGG Pathways 2026
Category structural or functional annotations
Type pathway
Description Advanced glycation end products (AGEs) are a complex group of compounds produced through the non-enzymatic glycation and oxidation of proteins, lipids and nucleic acids, primarily due to aging and under certain pathologic condition such as huperglycemia. Some of the best chemically characterized AGEs include N-epsilon-carboxy-methyl-lysine (CML), N-epsilon-carboxy-ethyl-lysine (CEL), and Imidazolone. The major receptor for AGEs, known as receptor for advanced glycation end products (RAGE or AGER), belongs to the immunoglobulin superfamily and has been described as a pattern recognition receptor. AGE/RAGE signaling elicits activation of multiple intracellular signal pathways involving NADPH oxidase, protein kinase C, and MAPKs, then resulting in NF-kappaB activity. NF-kappa B promotes the expression of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-alpha and a variety of atherosclerosis-related genes, including VCAM-1, tissue factor, VEGF, and RAGE. In addition, JAK-STAT-mediated and PI3K-Akt-dependent pathways are induced via RAGE, which in turn participate in cell proliferation and apoptosis respectively. Hypoxia-mediated induction of Egr-1 was also shown to require the AGE-RAGE interaction. The results of these signal transductions have been reported to be the possible mechanism that initates diabetic complications. (Kyoto Encyclopedia of Genes and Genomes, hsa04933)
External Link https://www.kegg.jp/entry/hsa04933
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100 proteins participating in the AGE-RAGE signaling pathway in diabetic complications pathway from the KEGG Pathways 2026 dataset.

Symbol Name
AGER advanced glycosylation end product-specific receptor
AGTR1 angiotensin II receptor, type 1
AGXT alanine-glyoxylate aminotransferase
AKT1 v-akt murine thymoma viral oncogene homolog 1
AKT2 v-akt murine thymoma viral oncogene homolog 2
AKT3 v-akt murine thymoma viral oncogene homolog 3
BAX BCL2-associated X protein
BCL2 B-cell CLL/lymphoma 2
CASP3 caspase 3, apoptosis-related cysteine peptidase
CCL2 chemokine (C-C motif) ligand 2
CCND1 cyclin D1
CDC42 cell division cycle 42
CDK4 cyclin-dependent kinase 4
CDKN1B cyclin-dependent kinase inhibitor 1B (p27, Kip1)
CLSTN1 calsyntenin 1
COL1A1 collagen, type I, alpha 1
COL1A2 collagen, type I, alpha 2
COL3A1 collagen, type III, alpha 1
COL4A1 collagen, type IV, alpha 1
COL4A2 collagen, type IV, alpha 2
COL4A3 collagen, type IV, alpha 3 (Goodpasture antigen)
COL4A4 collagen, type IV, alpha 4
COL4A5 collagen, type IV, alpha 5
COL4A6 collagen, type IV, alpha 6
CXCL8 chemokine (C-X-C motif) ligand 8
CYBB cytochrome b-245, beta polypeptide
DIAPH1 diaphanous-related formin 1
EDN1 endothelin 1
EGR1 early growth response 1
F3 coagulation factor III (thromboplastin, tissue factor)
FN1 fibronectin 1
FOXO1 forkhead box O1
HRAS Harvey rat sarcoma viral oncogene homolog
ICAM1 intercellular adhesion molecule 1
IL1A interleukin 1, alpha
IL1B interleukin 1, beta
IL6 interleukin 6
JAK2 Janus kinase 2
JUN jun proto-oncogene
LNCEGFL7OS lncRNA EGFL7 opposite strand
LONP1 lon peptidase 1, mitochondrial
MAPK1 mitogen-activated protein kinase 1
MAPK10 mitogen-activated protein kinase 10
MAPK11 mitogen-activated protein kinase 11
MAPK12 mitogen-activated protein kinase 12
MAPK13 mitogen-activated protein kinase 13
MAPK14 mitogen-activated protein kinase 14
MAPK3 mitogen-activated protein kinase 3
MAPK8 mitogen-activated protein kinase 8
MAPK9 mitogen-activated protein kinase 9
MMP2 matrix metallopeptidase 2
NANOS3 nanos homolog 3 (Drosophila)
NFATC1 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
NFKB1 nuclear factor of kappa light polypeptide gene enhancer in B-cells 1
NOX1 NADPH oxidase 1
NOX4 NADPH oxidase 4
NRAS neuroblastoma RAS viral (v-ras) oncogene homolog
PIK3CA phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha
PIK3CB phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta
PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha)
PIK3R2 phosphoinositide-3-kinase, regulatory subunit 2 (beta)
PIK3R3 phosphoinositide-3-kinase, regulatory subunit 3 (gamma)
PLCB1 phospholipase C, beta 1 (phosphoinositide-specific)
PLCB2 phospholipase C, beta 2
PLCB3 phospholipase C, beta 3 (phosphatidylinositol-specific)
PLCB4 phospholipase C, beta 4
PLCD1 phospholipase C, delta 1
PLCD3 phospholipase C, delta 3
PLCD4 phospholipase C, delta 4
PLCE1 phospholipase C, epsilon 1
PLCG1 phospholipase C, gamma 1
PLCG2 phospholipase C, gamma 2 (phosphatidylinositol-specific)
PRKCA protein kinase C, alpha
PRKCB protein kinase C, beta
PRKCD protein kinase C, delta
PRKCE protein kinase C, epsilon
PRKCZ protein kinase C, zeta
RELA v-rel avian reticuloendotheliosis viral oncogene homolog A
RNASE1 ribonuclease, RNase A family, 1 (pancreatic)
SELE selectin E
SERPINE1 serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1
SMAD2 SMAD family member 2
SMAD3 SMAD family member 3
SMAD4 SMAD family member 4
STAT1 signal transducer and activator of transcription 1, 91kDa
STAT3 signal transducer and activator of transcription 3 (acute-phase response factor)
STAT5A signal transducer and activator of transcription 5A
STAT5B signal transducer and activator of transcription 5B
TGFB1 transforming growth factor, beta 1
TGFB2 transforming growth factor, beta 2
TGFB3 transforming growth factor, beta 3
TGFBR1 transforming growth factor, beta receptor 1
TGFBR2 transforming growth factor, beta receptor II (70/80kDa)
THBD thrombomodulin
TNF tumor necrosis factor
VCAM1 vascular cell adhesion molecule 1
VEGFA vascular endothelial growth factor A
VEGFB vascular endothelial growth factor B
VEGFC vascular endothelial growth factor C
VEGFD vascular endothelial growth factor D