AGER (advanced glycosylation end-product specific receptor)

Gene

• Entrez ID: 177
• Gene name: Advanced glycosylation end-product specific receptor
• Gene symbol: AGER
• Synonyms: RAGE, SCARJ1, sRAGE
• Chromosome: 6
• Chromosome location: 6p21.32
• Summary: The advanced glycosylation end product (AGE) receptor encoded by this gene is a member of the immunoglobulin superfamily of cell surface receptors. It is a multiligand receptor, and besides AGE, interacts with other molecules implicated in homeostasis, de

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs138178120	C>G,T	Conflicting-interpretations-of-pathogenicity	Missense variant, non coding transcript variant, intron variant, coding sequence variant
rs140930365	A>T	Conflicting-interpretations-of-pathogenicity	Missense variant, non coding transcript variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT051103	hsa-miR-16-5p	CLASH	23622248
MIRT047532	hsa-miR-10a-5p	CLASH	23622248
MIRT044860	hsa-miR-195-5p	CLASH	23622248

Transcription factors

Transcription factor	Regulation	Reference
NFKB1	Activation	18622638;19616578
PPARG	Repression	18855759
RELA	Activation	18622638;19616578

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001540	Function	Amyloid-beta binding	IDA	29518356
GO:0001540	Function	Amyloid-beta binding	IPI	22406537, 23973487
GO:0001540	Function	Amyloid-beta binding	NAS	18367618
GO:0001540	Function	Amyloid-beta binding	TAS	15457210, 26871627
GO:0001650	Component	Fibrillar center	IDA
GO:0001666	Process	Response to hypoxia	IEA
GO:0001774	Process	Microglial cell activation	IGI	15457210
GO:0001774	Process	Microglial cell activation	ISS	22406537
GO:0001914	Process	Regulation of T cell mediated cytotoxicity	IDA	22473704
GO:0001934	Process	Positive regulation of protein phosphorylation	IGI	15457210
GO:0004888	Function	Transmembrane signaling receptor activity	TAS	1378843
GO:0005044	Function	Scavenger receptor activity	TAS	11240025
GO:0005515	Function	Protein binding	IPI	16061848, 16716307, 16954185, 17474147, 17660747, 17726019, 18922799, 19386136, 19944695, 21706016, 21829704, 24474694, 25910212, 26758977, 32296183, 32814053
GO:0005576	Component	Extracellular region	IEA
GO:0005886	Component	Plasma membrane	IDA
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	NAS	15457210
GO:0006897	Process	Endocytosis	IEA
GO:0006954	Process	Inflammatory response	IEA
GO:0007166	Process	Cell surface receptor signaling pathway	TAS	10835680
GO:0007611	Process	Learning or memory	IGI	15457210
GO:0009611	Process	Response to wounding	TAS	10399917
GO:0009986	Component	Cell surface	NAS	15457210
GO:0010255	Process	Glucose mediated signaling pathway	IDA	25689357
GO:0016324	Component	Apical plasma membrane	IDA	26005850
GO:0030054	Component	Cell junction	IDA
GO:0031175	Process	Neuron projection development	IGI	10391939
GO:0032693	Process	Negative regulation of interleukin-10 production	IDA	22473704
GO:0032722	Process	Positive regulation of chemokine production	ISS	22406537
GO:0032731	Process	Positive regulation of interleukin-1 beta production	ISS	22406537
GO:0032735	Process	Positive regulation of interleukin-12 production	IMP	15944249
GO:0032755	Process	Positive regulation of interleukin-6 production	ISS	22406537
GO:0032760	Process	Positive regulation of tumor necrosis factor production	ISS	22406537
GO:0034116	Process	Positive regulation of heterotypic cell-cell adhesion	IGI	11078691
GO:0038023	Function	Signaling receptor activity	IMP	15457210
GO:0042104	Process	Positive regulation of activated T cell proliferation	IMP	15944249
GO:0042802	Function	Identical protein binding	IPI	24119142
GO:0043507	Process	Positive regulation of JUN kinase activity	IEA
GO:0044548	Function	S100 protein binding	IPI	15033494
GO:0044877	Function	Protein-containing complex binding	IPI	29518356
GO:0045056	Process	Transcytosis	ISS	12808450, 22406537
GO:0045087	Process	Innate immune response	TAS
GO:0046330	Process	Positive regulation of JNK cascade	IGI	20739563
GO:0048143	Process	Astrocyte activation	IGI	15457210
GO:0048167	Process	Regulation of synaptic plasticity	TAS	18367618, 19221410, 20739563
GO:0050727	Process	Regulation of inflammatory response	IEA
GO:0050785	Function	Advanced glycation end-product receptor activity	NAS	15457210
GO:0050930	Process	Induction of positive chemotaxis	IEA
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	IDA	10391939
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	IGI	15457210
GO:0051101	Process	Regulation of DNA binding	IEA
GO:0070374	Process	Positive regulation of ERK1 and ERK2 cascade	IGI	15457210
GO:0071639	Process	Positive regulation of monocyte chemotactic protein-1 production	IEA
GO:0072657	Process	Protein localization to membrane	IEA
GO:0090647	Process	Modulation of age-related behavioral decline	IGI	15457210
GO:0098794	Component	Postsynapse	TAS	26224839
GO:0150003	Process	Regulation of spontaneous synaptic transmission	IGI	15457210
GO:0150104	Process	Transport across blood-brain barrier	IDA	23973487
GO:0150104	Process	Transport across blood-brain barrier	NAS	26590417, 30280653
GO:1900271	Process	Regulation of long-term synaptic potentiation	ISS
GO:1900272	Process	Negative regulation of long-term synaptic potentiation	IGI	15457210
GO:1900272	Process	Negative regulation of long-term synaptic potentiation	ISS
GO:1900453	Process	Negative regulation of long-term synaptic depression	IGI	20739563
GO:1900744	Process	Regulation of p38MAPK cascade	ISS
GO:1900745	Process	Positive regulation of p38MAPK cascade	IGI	20739563
GO:1901222	Process	Regulation of NIK/NF-kappaB signaling	NAS	15457210
GO:1901224	Process	Positive regulation of NIK/NF-kappaB signaling	IGI	15457210
GO:1902961	Process	Positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process	IGI	22406537
GO:1903523	Process	Negative regulation of blood circulation	ISS	12808450
GO:1904472	Process	Positive regulation of endothelin production	ISS	12808450
GO:1904597	Process	Negative regulation of connective tissue replacement involved in inflammatory response wound healing	IEA
GO:1904645	Process	Response to amyloid-beta	ISS
GO:1904645	Process	Response to amyloid-beta	TAS	18367618, 20739563
GO:1904646	Process	Cellular response to amyloid-beta	ISS
GO:2000439	Process	Positive regulation of monocyte extravasation	IMP	11078691
GO:2000514	Process	Regulation of CD4-positive, alpha-beta T cell activation	IDA	22473704
GO:2001200	Process	Positive regulation of dendritic cell differentiation	IMP	15944249

Other IDs

• MIM: 600214
• HGNC: 320
• e!Ensembl: ENSG00000204305

Protein

• UniProt ID: Q15109
• Protein name: Advanced glycosylation end product-specific receptor (Receptor for advanced glycosylation end products)
• Protein function: Cell surface pattern recognition receptor that senses endogenous stress signals with a broad ligand repertoire including advanced glycation end products, S100 proteins, high-mobility group box 1 protein/HMGB1, amyloid beta/APP oligomers, nucleic
• PDB: 2E5E, 2ENS, 2L7U, 2LE9, 2LMB, 2M1K, 2MJW, 2MOV, 3CJJ, 3O3U, 4LP4, 4LP5, 4OF5, 4OFV, 4OI7, 4OI8, 4P2Y, 4XYN, 4YBH, 5D7F, 6VXG, 6XQ1, 6XQ3, 6XQ5, 6XQ6, 6XQ7, 6XQ8, 6XQ9, 7LML, 7LMW, 8I9M
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00047	ig	21 → 112	Immunoglobulin domain	Domain
  PF08205	C2-set_2	124 → 219	CD80-like C2-set immunoglobulin domain	Domain
  PF13895	Ig_2	237 → 320	Immunoglobulin domain	Domain

• Sequence:

  MAAGTAVGAWVLVLSLWGAVVGAQNITARIGEPLVLKCKGAPKKPPQRLEWKLNTGRTEA
  WKVLSPQGGGPWDSVARVLPNGSLFLPAVGIQDEGIFRCQAMNRNGKETKSNYRVRVYQI
  PGKPEIVDSASELTAGVPNKVGTCVSEGSYPAGTLSWHLDGKPLVPNEKGVSVKEQTRRH
  PETGLFTLQSELMVTPARGGDPRPTFSCSFSPGLPRHRALRTAPIQPRVWEPVPLEEVQL
  VVEPEGGAVAPGGTVTLTCEVPAQPSPQIHWMKDGVPLPLPPSPVLILPEIGPQDQGTYS
  CVATHSSHGPQESRAVSISIIEPGEEGPTAGSVGGSGLGTLALALGILGGLGTAALLIGV
  ILWQRRQRRGEERKAPENQEEEEERAELNQSEEPEAGESSTGGP

• Sequence length: 404

Pathways

KEGG:

Efferocytosis
Neutrophil extracellular trap formation
AGE-RAGE signaling pathway in diabetic complications
Alzheimer disease
Pathways of neurodegeneration - multiple diseases
Diabetic cardiomyopathy
Lipid and atherosclerosis

Reactome:

TAK1 activates NFkB by phosphorylation and activation of IKKs complex
Advanced glycosylation endproduct receptor signaling
TRAF6 mediated NF-kB activation

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Arthritis	Degenerative polyarthritis	rs1594890601, rs1594882933, rs184370809, rs776489319, rs1594883470	16948116
Chronic obstructive pulmonary disease	Chronic Obstructive Airway Disease	rs2227956, rs1008438, rs1043618, rs562047, rs1061581, rs2763979, rs6457452, rs13147758, rs1828591, rs13118928	28166215, 30804561
Diabetes mellitus	Diabetes Mellitus, Insulin-Dependent	rs587776515, rs61730328, rs606231121, rs606231122, rs79020217, rs77625743, rs78378398, rs606231123, rs4402960, rs1362648752, rs3745368, rs3792267, rs3842570, rs5030952, rs2975760, rs119489103, rs7903146, rs12255372, rs11196205, rs104893649, rs80356624, rs80356616, rs80356625, rs80356611, rs104894237, rs80356613, rs137852740, rs137852786, rs387906407, rs151344623, rs28938469, rs28936371, rs137852672, rs80356637, rs80356642, rs80356653, rs137852673, rs137852674, rs80356634, rs80356651, rs193929360, rs137853334, rs137853335, rs137853336, rs1600731198, rs137853338, rs121964882, rs121964883, rs387906511, rs121964884, rs121964885, rs2147483647, rs387906512, rs121964887, rs121964888, rs121964889, rs121964890, rs121964891, rs28934878, rs74315383, rs121964893, rs886037620, rs886037621, rs80356663, rs121434593, rs121913150, rs587776825, rs137853236, rs2135842335, rs137853237, rs137853238, rs2135818776, rs1566092470, rs1463923467, rs137853243, rs137853244, rs2135839114, rs137853245, rs2135847417, rs121918407, rs104894005, rs104894006, rs80356655, rs104894008, rs104894009, rs104894010, rs104894011, rs80356654, rs104894016, rs193929376, rs193929374, rs193929375, rs193929373, rs80356666, rs80356669, rs80356664, rs193929366, rs1048095, rs193929355, rs193929356, rs1259467443, rs104893642, rs387906777, rs387906779, rs141804752, rs182349376, rs184917682, rs193922396, rs193922400, rs193922401, rs137852676, rs193922407, rs193922638, rs193922257, rs193922258, rs193922259, rs193922260, rs193922261, rs193922262, rs193922263, rs193922264, rs193922265, rs193922268, rs193921338, rs193922269, rs193922272, rs193922273, rs193922275, rs193922278, rs193922279, rs193922280, rs193922281, rs193922282, rs193922283, rs193922284, rs193922286, rs193922287, rs193922289, rs193922291, rs193922295, rs193922297, rs193922300, rs193922302, rs193922303, rs193922308, rs193922313, rs193922314, rs144723656, rs193922315, rs193922316, rs193922317, rs148311934, rs193922319, rs193922320, rs193922326, rs193922329, rs193922330, rs193922331, rs193922335, rs193922336, rs193922338, rs193922340, rs193922341, rs193922471, rs193922475, rs193922476, rs193922479, rs193922355, rs193922356, rs193922576, rs193922578, rs193922582, rs193922588, rs193922592, rs193922594, rs193922596, rs386134267, rs193922598, rs193922599, rs193922600, rs193922604, rs193922605, rs397514580, rs397515519, rs267601516, rs587780343, rs587780345, rs587780346, rs587780347, rs587780357, rs148954387, rs61736969, rs587783673, rs587783672, rs587783669, rs786204676, rs794727236, rs151344624, rs794727775, rs794727839, rs199946797, rs869320673, rs796065047, rs759072800, rs797045595, rs797045209, rs797045207, rs797045213, rs797045623, rs863225280, rs149703259, rs864321656, rs139964066, rs777870079, rs878853246, rs769268803, rs886039380, rs886041392, rs886041391, rs886042610, rs143064649, rs1057516192, rs746480424, rs1057516281, rs576684889, rs754728827, rs1057520291, rs1057520779, rs893256143, rs1057520504, rs1057524790, rs1057524902, rs1057524904, rs1057524905, rs764232985, rs1064793998, rs1064794268, rs769086289, rs369429452, rs1085307913, rs1131691416, rs765432081, rs1131692182, rs748749585, rs1554335441, rs762263694, rs1312678560, rs767565869, rs1375656631, rs1554335391, rs1360415315, rs1554335616, rs1554335752, rs1554909277, rs769518471, rs757171524, rs768951263, rs762703502, rs1555212248, rs1555212359, rs1555813319, rs1555816654, rs1553638903, rs1553638909, rs948820149, rs371977235, rs1553784995, rs76474829, rs200998587, rs1415041911, rs1554334894, rs1260178539, rs1554335421, rs1555211904, rs779184183, rs1554335564, rs200670692, rs1400535021, rs1554334872, rs1555212749, rs1553876668, rs1553878211, rs954727530, rs1554924035, rs372307320, rs925231098, rs1554913069, rs1554933565, rs766431403, rs746714109, rs751279984, rs770664202, rs1008906426, rs758844607, rs1554924540, rs1566092307, rs753998395, rs1565885935, rs1167124132, rs1376796469, rs556436603, rs1562715657, rs1486280029, rs1564869850, rs755259997, rs769569410, rs1172328722, rs1286294151, rs1375557127, rs1568731279, rs1562715426, rs556581174, rs1564865302, rs1565886545, rs776793516, rs1568724014, rs1392795567, rs781260712, rs1562719705, rs1382448285, rs1564977373, rs750586210, rs1598842892, rs1583592247, rs780612692, rs1593060859, rs1476637197, rs751279776, rs1593060890, rs1191912908, rs1167675604, rs1583601110, rs1593058932, rs778611627, rs753296261	17632545
Rheumatoid arthritis	Rheumatoid Arthritis	rs3766379, rs3792876, rs2071592, rs3087456, rs587776843, rs1566328963, rs2240340, rs1557787212	16385501, 17804836, 21156761
Schizophrenia	Schizophrenia	rs74315508, rs74315509, rs13447324, rs1558507406, rs387906932, rs387906933, rs863223354, rs863223355, rs776061422, rs863223349, rs748809996, rs759748655, rs863223353, rs863223350, rs863223356, rs781821239, rs863223348, rs863223346, rs863223347, rs863223351, rs863223352, rs61734270, rs797045205, rs869312829, rs869312830, rs770913157, rs869312832, rs869312831, rs781720548, rs1262969313	22146151

Unknown
Disease name	Disease term	dbSNP ID	References
Atherosclerosis	Atherosclerosis	rs699947, rs59439148	20372816, 19939336
Diabetic cardiomyopathy	Diabetic Angiopathies, Microangiopathy, Diabetic		20372816
Emphysema	Focal Emphysema		30659203
Hyperglycemia	Hyperglycemia		24036142
Lewy body disease	Lewy Body Disease		16141792
Osteoarthrosis deformans	Osteoarthrosis Deformans		16948116
Ovarian epithelial carcinoma	Carcinoma, Ovarian Epithelial		28811376
Panacinar emphysema	Panacinar Emphysema		30659203
Pancreatic diseases	Pancreatic Diseases		24036142
Pulmonary emphysema	Pulmonary Emphysema, Centriacinar Emphysema		30659203
Scleroderma	Systemic Scleroderma		20383147