AGER

advanced glycosylation end-product specific receptor, the group of C2-set domain containing|Scavenger receptors

Basic information

Region (hg38): 6:32180967-32184322

Links

ENSG00000204305 ∙ NCBI:177 ∙ OMIM:600214 ∙ HGNC:320 ∙ Uniprot:Q15109 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AGER gene.

• Inborn genetic diseases (20 variants)
• not provided (12 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AGER gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2		2
missense			18	4	4	26
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1	1	2
Total	0	0	18	7	5

Variants in AGER

This is a list of pathogenic ClinVar variants found in the AGER region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-32181181-C-T		not specified	Uncertain significance (May 05, 2023)
6-32181193-T-G		not specified	Uncertain significance (Jun 21, 2023)
6-32181234-G-A		not specified	Likely benign (Apr 07, 2022)
6-32181363-C-T			Benign (Jul 31, 2018)
6-32181442-G-A			Benign (Apr 24, 2018)
6-32181483-C-T		COPD, severe early onset	Uncertain significance (Aug 10, 2023)
6-32181622-C-T			Likely benign (May 10, 2018)
6-32182039-T-C		COPD, severe early onset	Likely risk allele (Aug 10, 2023)
6-32182270-C-T			Benign (Jun 06, 2018)
6-32182286-C-T			Likely benign (Jul 02, 2018)
6-32182291-C-A		not specified	Uncertain significance (Mar 06, 2023)
6-32182297-T-C		not specified	Uncertain significance (Jun 23, 2023)
6-32182309-C-G			Conflicting classifications of pathogenicity (Jul 21, 2018)
6-32182333-G-A		not specified	Uncertain significance (Dec 21, 2021)
6-32182339-A-G		not specified	Uncertain significance (Feb 28, 2024)
6-32182345-G-C		not specified	Uncertain significance (Nov 22, 2023)
6-32182369-G-A		not specified	Uncertain significance (May 18, 2023)
6-32182385-C-T		not specified	Likely benign (Sep 17, 2021)
6-32182519-C-A		COPD, severe early onset	Uncertain significance (Aug 10, 2023)
6-32182579-A-T			Conflicting classifications of pathogenicity (Jul 21, 2018)
6-32182608-A-T		not specified	Uncertain significance (Dec 14, 2021)
6-32182627-C-T		not specified	Uncertain significance (Jun 07, 2023)
6-32182636-C-T		not specified	Uncertain significance (Aug 09, 2021)
6-32182653-C-T		not specified	Uncertain significance (Dec 14, 2022)
6-32182707-T-G			Likely benign (Jul 20, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AGER	protein_coding	protein_coding	ENST00000375076	11	3357

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.35e-16	0.0148	125369	0	210	125579	0.000836

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0883	236	240	0.984	0.0000140	2538
Missense in Polyphen		74	76.194	0.9712		861
Synonymous	1.87	71	94.0	0.755	0.00000522	893
Loss of Function	0.198	24	25.1	0.957	0.00000153	240

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00543	0.00510
Ashkenazi Jewish	0.00	0.00
East Asian	0.000548	0.000544
Finnish	0.000231	0.000231
European (Non-Finnish)	0.000760	0.000740
Middle Eastern	0.000548	0.000544
South Asian	0.000395	0.000392
Other	0.000825	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mediates interactions of advanced glycosylation end products (AGE). These are nonenzymatically glycosylated proteins which accumulate in vascular tissue in aging and at an accelerated rate in diabetes. Acts as a mediator of both acute and chronic vascular inflammation in conditions such as atherosclerosis and in particular as a complication of diabetes. AGE/RAGE signaling plays an important role in regulating the production/expression of TNF- alpha, oxidative stress, and endothelial dysfunction in type 2 diabetes. Interaction with S100A12 on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key proinflammatory mediators. Interaction with S100B after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling (By similarity). Receptor for amyloid beta peptide. Contributes to the translocation of amyloid-beta peptide (ABPP) across the cell membrane from the extracellular to the intracellular space in cortical neurons. ABPP-initiated RAGE signaling, especially stimulation of p38 mitogen-activated protein kinase (MAPK), has the capacity to drive a transport system delivering ABPP as a complex with RAGE to the intraneuronal space. Can also bind oligonucleotides. {ECO:0000250, ECO:0000269|PubMed:19906677, ECO:0000269|PubMed:20943659, ECO:0000269|PubMed:21559403, ECO:0000269|PubMed:21565706}.
• Pathway: AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);AGE-RAGE pathway;Nuclear Receptors Meta-Pathway;NRF2 pathway;RAGE;Toll Like Receptor 7/8 (TLR7/8) Cascade;Signaling by Interleukins;Cytokine Signaling in Immune system;Toll Like Receptor 9 (TLR9) Cascade;MyD88 cascade initiated on plasma membrane;Toll Like Receptor 10 (TLR10) Cascade;Toll Like Receptor 3 (TLR3) Cascade;Toll Like Receptor 5 (TLR5) Cascade;ZBP1(DAI) mediated induction of type I IFNs;Toll-Like Receptors Cascades;TRAF6 mediated NF-kB activation;DDX58/IFIH1-mediated induction of interferon-alpha/beta;DEx/H-box helicases activate type I IFN and inflammatory cytokines production ;Interleukin-1 signaling;Innate Immune System;Immune System;RIP-mediated NFkB activation via ZBP1;TAK1 activates NFkB by phosphorylation and activation of IKKs complex;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;MyD88 dependent cascade initiated on endosome;Advanced glycosylation endproduct receptor signaling;Cytosolic sensors of pathogen-associated DNA ;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;MyD88:Mal cascade initiated on plasma membrane;Toll Like Receptor TLR1:TLR2 Cascade;Toll Like Receptor TLR6:TLR2 Cascade;Toll Like Receptor 2 (TLR2) Cascade;amb2 Integrin signaling;Interleukin-1 family signaling (Consensus)

Recessive Scores

• pRec: 0.0829

Intolerance Scores

• loftool: 0.604
• rvis_EVS: 0.6
• rvis_percentile_EVS: 82.74

Haploinsufficiency Scores

• pHI: 0.412
• hipred: N
• hipred_score: 0.171
• ghis: 0.412

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0192

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ager
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype; skeleton phenotype; immune system phenotype; muscle phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: response to hypoxia;regulation of T cell mediated cytotoxicity;positive regulation of protein phosphorylation;receptor-mediated endocytosis;inflammatory response;cell surface receptor signaling pathway;learning or memory;response to wounding;glucose mediated signaling pathway;astrocyte development;neuron projection development;negative regulation of interleukin-10 production;positive regulation of interleukin-12 production;positive regulation of activated T cell proliferation;positive regulation of JUN kinase activity;innate immune response;positive regulation of JNK cascade;regulation of synaptic plasticity;induction of positive chemotaxis;positive regulation of NF-kappaB transcription factor activity;regulation of DNA binding;positive regulation of astrocyte activation;positive regulation of ERK1 and ERK2 cascade;positive regulation of monocyte chemotactic protein-1 production;protein localization to membrane;modulation of age-related behavioral decline;amyloid-beta clearance;regulation of spontaneous synaptic transmission;regulation of long-term synaptic potentiation;negative regulation of long-term synaptic potentiation;negative regulation of long-term synaptic depression;regulation of p38MAPK cascade;positive regulation of p38MAPK cascade;regulation of NIK/NF-kappaB signaling;positive regulation of NIK/NF-kappaB signaling;positive regulation of microglial cell activation;negative regulation of connective tissue replacement involved in inflammatory response wound healing;response to amyloid-beta;cellular response to amyloid-beta;regulation of CD4-positive, alpha-beta T cell activation;positive regulation of dendritic cell differentiation
• Cellular component: fibrillar center;extracellular region;plasma membrane;integral component of plasma membrane;cell surface;apical plasma membrane;cell junction;postsynapse
• Molecular function: amyloid-beta binding;transmembrane signaling receptor activity;scavenger receptor activity;protein binding;signaling receptor activity;identical protein binding;S100 protein binding;advanced glycation end-product receptor activity