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Gene Review

AGXT  -  alanine-glyoxylate aminotransferase

Homo sapiens

Synonyms: AGT, AGT1, AGXT1, Alanine--glyoxylate aminotransferase, PH1, ...
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Disease relevance of AGXT


Psychiatry related information on AGXT

  • There was no significant association between alcohol consumption and the development of SPT positivity or specific IgE positivity [6].
  • The new observations presented in this paper are compatible with our previous demonstration of a relationship between AGT1 subcellular distribution and either present or putative ancestral dietary habit, and our previous suggestion that the molecular evolution of the AGT gene has been markedly influenced by dietary selection pressure [7].
  • The data indicated that the SPT indirectly assesses short-term memory, is resistant to practice effects, and is drug-sensitive [8].
  • Improved recall has consistently been demonstrated following motor activation at encoding (SPT), compared to traditional verbal learning (VT) [9].

High impact information on AGXT

  • Fifty-eight percent of hepatocellular carcinomas (HCCs) from Qidong, China, contain an AGG to AGT mutation at codon 249 of the p53 tumor suppressor gene, a mutation that is rarely seen in HCCs from Western countries [10].
  • Bone marrow showed BG-resistant O6-alkylguanine-DNA-alkyltransferase (AGT) activity, and CFUs were stained intensely for AGT protein, indicating high transgene expression [11].
  • The T235 allele of the angiotensinogen gene (AGT) has been associated with hypertension [12].
  • The nucleotide sequence of the codon in 53% of ductal hyperplastic foci was TGT or AGT, both of which were not found in 30 cases of adenocarcinoma [13].
  • RESULTS: Of 20 biliary tract tumors showing a mutation band, G to A single base substitutions were confirmed in 15 cases as the most frequent changes, which were divided into changes for aspartic acid (GAT) and (14) serine (AGT) (1) [14].

Chemical compound and disease context of AGXT

  • Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder that is caused by a deficiency of alanine: glyoxylate aminotransferase (AGT), which is encoded by a single copy gene (AGXT) [15].
  • Primary hyperoxaluria type 1 is an autosomal recessive disorder of glyoxylate metabolism, caused by a deficiency of alanine:glyoxylate aminotransferase, which is encoded by a single copy gene (AGXT [16].
  • We have previously shown that in some patients with primary hyperoxaluria type 1 (PH1), disease is associated with mistargeting of the normally peroxisomal enzyme alanine/glyoxylate aminotransferase (AGT) to mitochondria (Danpure, C.J., P.J. Cooper, P.J. Wise, and P.R. Jennings. J. Cell Biol. 108:1345-1352) [17].
  • The autosomal recessive disorder primary hyperoxaluria type 1 (PH1) is caused by a deficiency of the liver-specific pyridoxal-phosphate-dependent enzyme alanine:glyoxylate aminotransferase (AGT) [18].
  • Primary hyperoxaluria type 1 (PH 1), an inborn error of glyoxylate metabolism characterized by excessive synthesis of oxalate and glycolate, is caused by a defect in serine:pyruvate/alanine:glyoxylate aminotransferase (SPT/AGT) [19].

Biological context of AGXT


Anatomical context of AGXT

  • Like its rat homologue, the larger mRNA species transcribed encodes a conserved amino terminal end characteristic of AGXT forms known to be targeted to the mitochondria [22].
  • Unlike normal individuals in whom the AGT is confined to the peroxisomal matrix, the immunoreactive AGT in these three patients was distributed approximately equally between the peroxisomes and mitochondria [23].
  • Such apparent import inefficiency is very marked in guinea pig (Cavia porcellus) hepatocytes in which the cytosolic levels of two peroxisomal proteins, catalase and alanine:glyoxylate aminotransferase (AGT), are much higher than those found in human (Homo sapiens) hepatocytes, for example [24].
  • The results of genomic Southern blotting indicate that human AGT is probably encoded by a single copy gene, and a combination of in situ hybridization and PCR analysis of rodent/human somatic cell hybrids suggests that this gene is located on chromosome 2q36-q37 [25].
  • In some mammals, AGT is peroxisomal in others it is mainly mitochondrial while in yet others it is more-or-less equally divided between both organelles [26].

Associations of AGXT with chemical compounds

  • While genetic analysis of PH2 is still at a relatively early stage, the AGXT gene defective in the Type 1 disorder is well characterized, and a number of mutations have been identified [27].
  • Many of the mutations in the gene encoding AGT are associated with specific enzymatic phenotypes such as accelerated proteolysis (Ser205Pro), intra-peroxisomal aggregation (Gly41Arg), inhibition of pyridoxal phosphate binding and loss of catalytic activity (Gly82Glu), and peroxisome-to-mitochondrion mistargeting (Gly170Arg) [28].
  • They also suggest that the non-consensus PTS1 of human AGT might interact with HsPex5p very differently compared with the consensus PTS1, Ser-Lys-Leu [24].
  • O(6)-benzylguanine (O(6)-BG), an inhibitor for AGT, reduced resistance to TMZ [29].
  • This revealed the presence of a single point mutation (G----A at cDNA nucleotide 367), which is predicted to cause a glycine-to-glutamate substitution at residue 82 of the AGT protein [30].

Physical interactions of AGXT

  • Using the two-hybrid system, we show that human AGT interacts with human Pex5p in mammalian cells, but not yeast cells [31].

Other interactions of AGXT

  • METHODS: Polymerase chain reaction (PCR) was used to detect three common mutations in the AGXT gene (c.33_34insC, c.508G>A, and c.731T>C) and one, c.103delG, in the GRHPR gene in DNA samples from 365 unrelated individuals referred for diagnosis of PH1 and/or PH2 by liver enzyme analysis [32].
  • ORF analysis revealed that intron 1b retention in isoform B1 stabilizes the initiation of translation to the AGT at position 297 of the ClC-5 cDNA coding region [33].
  • Although human alanine:glyoxylate aminotransferase (AGT) is imported into peroxisomes by a Pex5p-dependent pathway, the properties of its C-terminal tripeptide (KKL) are unlike those of any other type 1 peroxisomal targeting sequence (PTS1) [31].
  • Furthermore, the reaction of copper(II)/ascorbate with the peptide gave two products (AGT-1 and AGT-2) selectively [34].
  • Both, fastest changing serine pyruvate aminotransferase and most slowly changing glutamate decarboxylase are members of the alpha family [35].

Analytical, diagnostic and therapeutic context of AGXT

  • Presentation and role of transplantation in adult patients with type 1 primary hyperoxaluria and the I244T AGXT mutation: Single-center experience [36].
  • We have assessed the clinical value of two polymorphisms located in introns 1 and 4 of the AGXT gene as linkage markers for the prenatal diagnosis of PH1 in 12 families [37].
  • The aim of this research was to standardize denaturing high-performance liquid chromatography, a new, sensitive, relatively inexpensive, and automated technique, for the detection of AGXT mutation [16].
  • We planned to identify new mutations of the AGXT gene by heteroduplex analysis followed by direct sequencing [38].
  • PH can be diagnosed using percutaneous hepatic needle biopsy and assay of AGT, whose activity may be useful in determining the prognosis and likely severity of the disease [39].


  1. Primary hyperoxaluria type 1 in the Canary Islands: a conformational disease due to I244T mutation in the P11L-containing alanine:glyoxylate aminotransferase. Santana, A., Salido, E., Torres, A., Shapiro, L.J. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  2. The molecular basis of kidney stones. Langman, C.B. Curr. Opin. Pediatr. (2004) [Pubmed]
  3. Novel mutations of the AGXT gene causing primary hyperoxaluria type 1. Yuen, Y.P., Lai, C.K., Tong, G.M., Wong, P.N., Wong, F.K., Mak, S.K., Lo, K.Y., Wong, A.K., Tong, S.F., Chan, Y.W., Lam, C.W. J. Nephrol. (2004) [Pubmed]
  4. Alanine-glyoxylate aminotransferase-deficient mice, a model for primary hyperoxaluria that responds to adenoviral gene transfer. Salido, E.C., Li, X.M., Lu, Y., Wang, X., Santana, A., Roy-Chowdhury, N., Torres, A., Shapiro, L.J., Roy-Chowdhury, J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  5. Overexpression of human alanine:glyoxylate aminotransferase in Escherichia coli: renaturation from guanidine-HCl and affinity for pyridoxal phosphate co-factor. Coulter-Mackie, M.B., Lian, Q., Wong, S.G. Protein Expr. Purif. (2005) [Pubmed]
  6. The relationship of alcohol consumption to total immunoglobulin E and the development of immunoglobulin E sensitization: the Copenhagen Allergy Study. Linneberg, A., Petersen, J., Nielsen, N.H., Madsen, F., Frølund, L., Dirksen, A., Jørgensen, T. Clin. Exp. Allergy (2003) [Pubmed]
  7. Evolution of alanine:glyoxylate aminotransferase 1 peroxisomal and mitochondrial targeting. A survey of its subcellular distribution in the livers of various representatives of the classes Mammalia, Aves and Amphibia. Danpure, C.J., Fryer, P., Jennings, P.R., Allsop, J., Griffiths, S., Cunningham, A. Eur. J. Cell Biol. (1994) [Pubmed]
  8. A memory assessment technique for use in geriatric psychopharmacology: drug efficacy trial with naftidrofuryl. Branconnier, R.J., Cole, J.O. Journal of the American Geriatrics Society. (1977) [Pubmed]
  9. Enactment enhances integration between verb and noun, but not relational processing, in episodic memory. von Essen, J.D. Scandinavian journal of psychology. (2005) [Pubmed]
  10. Geographic variation of p53 mutational profile in nonmalignant human liver. Aguilar, F., Harris, C.C., Sun, T., Hollstein, M., Cerutti, P. Science (1994) [Pubmed]
  11. In vivo selection of MGMT(P140K) lentivirus-transduced human NOD/SCID repopulating cells without pretransplant irradiation conditioning. Zielske, S.P., Reese, J.S., Lingas, K.T., Donze, J.R., Gerson, S.L. J. Clin. Invest. (2003) [Pubmed]
  12. The serum angiotensinogen concentration and variants of the angiotensinogen gene in white and black children. Bloem, L.J., Manatunga, A.K., Tewksbury, D.A., Pratt, J.H. J. Clin. Invest. (1995) [Pubmed]
  13. Analysis of K-ras gene mutation in hyperplastic duct cells of the pancreas without pancreatic disease. Tada, M., Ohashi, M., Shiratori, Y., Okudaira, T., Komatsu, Y., Kawabe, T., Yoshida, H., Machinami, R., Kishi, K., Omata, M. Gastroenterology (1996) [Pubmed]
  14. Point mutation of K-ras gene codon 12 in biliary tract tumors. Watanabe, M., Asaka, M., Tanaka, J., Kurosawa, M., Kasai, M., Miyazaki, T. Gastroenterology (1994) [Pubmed]
  15. AGXT gene mutations and their influence on clinical heterogeneity of type 1 primary hyperoxaluria. Amoroso, A., Pirulli, D., Florian, F., Puzzer, D., Boniotto, M., Crovella, S., Zezlina, S., Spanò, A., Mazzola, G., Savoldi, S., Ferrettini, C., Berutti, S., Petrarulo, M., Marangella, M. J. Am. Soc. Nephrol. (2001) [Pubmed]
  16. Detection of AGXT bgene mutations by denaturing high-performance liquid chromatography for diagnosis of hyperoxaluria type 1. Pirulli, D., Giordano, M., Lessi, M., Spanò, A., Puzzer, D., Zezlina, S., Boniotto, M., Crovella, S., Florian, F., Marangella, M., Momigliano-Richiardi, P., Savoldi, S., Amoroso, A. Clin. Exp. Med. (2001) [Pubmed]
  17. Identification of mutations associated with peroxisome-to-mitochondrion mistargeting of alanine/glyoxylate aminotransferase in primary hyperoxaluria type 1. Purdue, P.E., Takada, Y., Danpure, C.J. J. Cell Biol. (1990) [Pubmed]
  18. Functional synergism between the most common polymorphism in human alanine:glyoxylate aminotransferase and four of the most common disease-causing mutations. Lumb, M.J., Danpure, C.J. J. Biol. Chem. (2000) [Pubmed]
  19. ATP-dependent degradation of a mutant serine: pyruvate/alanine:glyoxylate aminotransferase in a primary hyperoxaluria type 1 case. Nishiyama, K., Funai, T., Yokota, S., Ichiyama, A. J. Cell Biol. (1993) [Pubmed]
  20. Primary hyperoxaluria type 1: a cluster of new mutations in exon 7 of the AGXT gene. von Schnakenburg, C., Rumsby, G. J. Med. Genet. (1997) [Pubmed]
  21. Molecular analysis of hyperoxaluria type 1 in Italian patients reveals eight new mutations in the alanine: glyoxylate aminotransferase gene. Pirulli, D., Puzzer, D., Ferri, L., Crovella, S., Amoroso, A., Ferrettini, C., Marangella, M., Mazzola, G., Florian, F. Hum. Genet. (1999) [Pubmed]
  22. The mouse alanine:glyoxylate aminotransferase gene (Agxt1): cloning, expression, and mapping to chromosome 1. Li, X.M., Salido, E.C., Shapiro, L.J. Somat. Cell Mol. Genet. (1999) [Pubmed]
  23. Enzymological and mutational analysis of a complex primary hyperoxaluria type 1 phenotype involving alanine:glyoxylate aminotransferase peroxisome-to-mitochondrion mistargeting and intraperoxisomal aggregation. Danpure, C.J., Purdue, P.E., Fryer, P., Griffiths, S., Allsop, J., Lumb, M.J., Guttridge, K.M., Jennings, P.R., Scheinman, J.I., Mauer, S.M. Am. J. Hum. Genet. (1993) [Pubmed]
  24. The peroxisomal targeting sequence type 1 receptor, Pex5p, and the peroxisomal import efficiency of alanine:glyoxylate aminotransferase. Knott, T.G., Birdsey, G.M., Sinclair, K.E., Gallagher, I.M., Purdue, P.E., Danpure, C.J. Biochem. J. (2000) [Pubmed]
  25. Characterization and chromosomal mapping of a genomic clone encoding human alanine:glyoxylate aminotransferase. Purdue, P.E., Lumb, M.J., Fox, M., Griffo, G., Hamon-Benais, C., Povey, S., Danpure, C.J. Genomics (1991) [Pubmed]
  26. Primary hyperoxaluria type 1 and peroxisome-to-mitochondrion mistargeting of alanine:glyoxylate aminotransferase. Danpure, C.J. Biochimie (1993) [Pubmed]
  27. Biochemical and genetic diagnosis of the primary hyperoxalurias: a review. Rumsby, G. Molecular urology. (2000) [Pubmed]
  28. Crystal structure of alanine:glyoxylate aminotransferase and the relationship between genotype and enzymatic phenotype in primary hyperoxaluria type 1. Zhang, X., Roe, S.M., Hou, Y., Bartlam, M., Rao, Z., Pearl, L.H., Danpure, C.J. J. Mol. Biol. (2003) [Pubmed]
  29. Inhibition of telomerase activity in malignant glioma cells correlates with their sensitivity to temozolomide. Kanzawa, T., Germano, I.M., Kondo, Y., Ito, H., Kyo, S., Kondo, S. Br. J. Cancer (2003) [Pubmed]
  30. A glycine-to-glutamate substitution abolishes alanine:glyoxylate aminotransferase catalytic activity in a subset of patients with primary hyperoxaluria type 1. Purdue, P.E., Lumb, M.J., Allsop, J., Minatogawa, Y., Danpure, C.J. Genomics (1992) [Pubmed]
  31. Peroxisomal import of human alanine:glyoxylate aminotransferase requires ancillary targeting information remote from its C terminus. Huber, P.A., Birdsey, G.M., Lumb, M.J., Prowse, D.T., Perkins, T.J., Knight, D.R., Danpure, C.J. J. Biol. Chem. (2005) [Pubmed]
  32. Evaluation of mutation screening as a first line test for the diagnosis of the primary hyperoxalurias. Rumsby, G., Williams, E., Coulter-Mackie, M. Kidney Int. (2004) [Pubmed]
  33. Identification of a novel splice site mutation of CLCN5 gene and characterization of a new alternative 5' UTR end of ClC-5 mRNA in human renal tissue and leukocytes. Forino, M., Graziotto, R., Tosetto, E., Gambaro, G., D'Angelo, A., Anglani, F. J. Hum. Genet. (2004) [Pubmed]
  34. Site-specific oxidation of angiotensin I by copper(II) and L-ascorbate: conversion of histidine residues to 2-imidazolones. Uchida, K., Kawakishi, S. Arch. Biochem. Biophys. (1990) [Pubmed]
  35. Rates of evolution of pyridoxal-5'-phosphate-dependent enzymes. Salzmann, D., Christen, P., Mehta, P.K., Sandmeier, E. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  36. Presentation and role of transplantation in adult patients with type 1 primary hyperoxaluria and the I244T AGXT mutation: Single-center experience. Lorenzo, V., Alvarez, A., Torres, A., Torregrosa, V., Hernández, D., Salido, E. Kidney Int. (2006) [Pubmed]
  37. Polymorphisms in the alanine:glyoxylate aminotransferase gene and their application to the prenatal diagnosis of primary hyperoxaluria type 1. Rumsby, G., Mandel, H., Avey, C., Geraerts, A. Nephrol. Dial. Transplant. (1995) [Pubmed]
  38. Molecular analysis of the AGXT gene in Italian patients with primary hyperoxaluria type 1 (PH1). Ferrettini, C., Pirulli, D., Cosseddu, D., Marangella, M., Petrarulo, M., Mazzola, G., Vatta, S., Amoroso, A. J. Nephrol. (1998) [Pubmed]
  39. Enzymological diagnosis of primary hyperoxaluria type 1 by measurement of hepatic alanine: glyoxylate aminotransferase activity. Danpure, C.J., Jennings, P.R., Watts, R.W. Lancet (1987) [Pubmed]
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