AGER

protein-coding

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

Gene 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, development, and inflammation, and certain diseases, such as diabetes and Alzheimer's disease. Many alternatively spliced transcript variants encoding different isoforms, as well as non-protein-coding variants, have been described for this gene (PMID:18089847). [provided by RefSeq, May 2011]

MANE transcript

NM_001136.5

Inheritance

—

ClinVar variants

U:75B:18

Top phenotype

COPD, severe early onset

gnomAD constraint

pLI —, LoF o/e 0.96

Max pathogenic AF

—

Genomic locus

chr6:32,180,968-32,184,322

External References & Databases

Ensembl (ENSG00000204305)

Transcript & Mutation Effects

hg38 • Region Span ~3.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AGER variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 71

not providedTotal: 11

COPD, severe early onsetTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001136.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	7 clinvar	1 clinvar	10
missense			63 clinvar	7 clinvar	3 clinvar	73
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	0	0	75	14	4	93

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 94 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001136.5	RefSeq	NP_001127.1	11	MANE Select
ENST00000375076.9	Ensembl	ENSP00000364217.4	11	MANE Select
NM_001206929.2	RefSeq	NP_001193858.1	11	Standard
NM_001206932.2	RefSeq	NP_001193861.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human)
AGE-RAGE pathway
Nuclear Receptors Meta-Pathway
NRF2 pathway
RAGE

Biological Process

response to hypoxia
regulation of T cell mediated cytotoxicity
positive regulation of protein phosphorylation
receptor-mediated endocytosis
inflammatory response

Molecular Function

amyloid-beta binding
transmembrane signaling receptor activity
scavenger receptor activity
protein binding
signaling receptor activity

Cellular Component

fibrillar center
extracellular region
plasma membrane
integral component of plasma membrane
cell surface

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000375076
Coding exons: 11
Length: 3357
Individuals with no LoFs: 125369
Homozygous LoFs: 0
Heterozygous LoFs: 210
Defined: 125579
p: 0.000836

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0883	236	240	0.984	0.0000140	2538
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0048	0.0045	notable
Latino/Admixed American	0.00064	0.00064	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00055	0.00054	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00076	0.00074	rare
South Asian	0.00039	0.00039	rare
Other	0.00082	0.00082	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.0829

Intolerance Scores

LoFtool: 0.604
RVIS EVS: 0.6
RVIS percentile EVS: 82.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0192

Gene Damage Prediction

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