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rs37369

From SNPedia

Elevated urinary beta-aminoisobutyrate acid excretion
Orientationplus
Stabilizedplus
Geno Mag Summary
(C;C) 0
Make rs37369(C;T)
Make rs37369(T;T)
ReferenceGRCh38 38.1/141
Chromosome5
Position35037010
GeneAGXT2
is asnp
is mentioned by
dbSNPrs37369
ebirs37369
HLIrs37369
Exacrs37369
Varsomers37369
Maprs37369
PheGenIrs37369
hapmaprs37369
1000 genomesrs37369
hgdprs37369
ensemblrs37369
gopubmedrs37369
geneviewrs37369
scholarrs37369
googlers37369
pharmgkbrs37369
gwascentralrs37369
openSNPrs37369
23andMers37369
23andMe allrs37369
SNP Nexus

SNPshotrs37369
SNPdbers37369
MSV3drs37369
GWAS Ctlgrs37369
GMAF0.3659
Max Magnitude0
? (C;C) (C;T) (T;T) 28

rs37369 is a SNP located in the coding region of the alanine-glyoxylate aminotransferase-2 (AGXT2) gene within chromosome 5 at position 35,072,872. This polymorphism constitues a nonsynonymous valine-to-isoleucine (V140I) substitution in the AGXT2 protein. rs37369 has been proposed by one study to be the causative SNP of hyper-beta-aminoisobutyric aciduria.

Beta-aminoisobutyric acid (BAIB) is the end product of pyrimidine metabolism. Hyper-BAIB is an autosomal recessive phenotype that is distinguished by high urinary excretion levels of beta-aminoisobutyric acid [PMID 10819024]. Elevated levels of BAIB have been suggested to contribute to neurological and developmental problems, as BAIB is a structural analog of gamma-aminobutyric acid and glycine--two major inhibitory neurotransmitters in the central nervous system [PMID 15385443]. The Online Mendelian Inheritance in Man (OMIM) database states that hyper-beta-aminoisobutyric aciduria is likely the most common Mendelian metabolic variant in man [1].

In a 2011 study, rs37369 was found to have a strong association with hyper-beta-aminoisobutyric aciduria [PMID 21572414]. In this study, 59 urine metabolite concentrations and 1,661 ratios between metabolite concentrations were tested for associations in 645,249 autosomal SNPs in 862 male German individuals. After correcting for multiple testing, rs37369 was found to have a significant association (p-value = 3.17 x 10^-75). The study further confirmed this result by replicating it twice more with 992 German samples of both sexes, and 870 German female samples. Resulting in p-values of 3.3 x 10^-52 and 1.3 x 10^-56, respectively. In all, these three independent replicates had a joint p-value of 2.1 x 10^-182.

The AGXT2 gene, where the coding rs37369 SNP resides, encodes a mitochondrial aminotransferase expressed primarily in the kidney that catalyzes the reactions of BAIB with pyruvate to form 2-methyl-3-oxopropanoate ([2]) and alanine. High excretion of BAIB is thought to result from an impairment in BAIB catabolism due to a deficiency in the activity of the AGXT2 enzyme. The association of rs37369 with BAIB matches the enzymatic function of AGXT2. Given the strength of the association (2.1 x 10^-182), and the fact that rs37369 codes for a nonsynonymous substitution (V140I), it has been posed as the causal SNP of hyper-beta-aminoisobutyric aciduria, although this hypothesis has not yet been experimentally verified [PMID 21572414].

GWAS snp
PMID [PMID 21931564OA-icon.png]
Trait
Title A genome-wide metabolic QTL analysis in Europeans implicates two loci shaped by recent positive selection.
Risk Allele T
P-val 0.000001
Odds Ratio 1.2500 None


GET Evidence
AGXT2-V140I
aa_change Val140Ile
aa_change_short V140I
impact not reviewed
qualified_impact Insufficiently evaluated not reviewed
overall_frequency 0.24103
summary



[PMID 24159190] Genome-wide association study on dimethylarginines reveals novel AGXT2 variants associated with heart rate variability but not with overall mortality


[PMID 23023372] Alanine-glyoxylate aminotransferase-2 metabolizes endogenous methylarginines, regulates NO, and controls blood pressure.

GWAS snp
PMID [PMID 24586186OA-icon.png]
Trait Urinary metabolites (H-NMR features)
Title Genome-wide association study of metabolic traits reveals novel gene-metabolite-disease links.
Risk Allele C
P-val 8E-15
Odds Ratio .41 [NR] unit increase


[PMID 25620171] Missense variants of the alanine: glyoxylate aminotransferase 2 gene correlated with carotid atherosclerosis in the Japanese population