2nz2

Structural highlights

Disease

[ASSY_HUMAN] Defects in ASS1 are the cause of citrullinemia type 1 (CTLN1) [MIM:215700]. Citrullinemia belongs to the urea cycle disorders. It is an autosomal recessive disease characterized primarily by elevated serum and urine citrulline levels. Ammonia intoxication is another manifestation. CTLN1 usually manifests in the first few days of life. Affected infants appear normal at birth, but as ammonia builds up in the body they present symptoms such as lethargy, poor feeding, vomiting, seizures and loss of consciousness. Less commonly, a milder CTLN1 form can develop later in childhood or adulthood.^{[1] [2] [3] [4] [5] [6] [7] [8] [9]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Haberle J, Pauli S, Linnebank M, Kleijer WJ, Bakker HD, Wanders RJ, Harms E, Koch HG. Structure of the human argininosuccinate synthetase gene and an improved system for molecular diagnostics in patients with classical and mild citrullinemia. Hum Genet. 2002 Apr;110(4):327-33. Epub 2002 Mar 1. PMID:11941481 doi:10.1007/s00439-002-0686-6
2. ↑ Kobayashi K, Jackson MJ, Tick DB, O'Brien WE, Beaudet AL. Heterogeneity of mutations in argininosuccinate synthetase causing human citrullinemia. J Biol Chem. 1990 Jul 5;265(19):11361-7. PMID:2358466
3. ↑ Kobayashi K, Rosenbloom C, Beaudet AL, O'Brien WE. Additional mutations in argininosuccinate synthetase causing citrullinemia. Mol Biol Med. 1991 Feb;8(1):95-100. PMID:1943692
4. ↑ Kobayashi K, Shaheen N, Terazono H, Saheki T. Mutations in argininosuccinate synthetase mRNA of Japanese patients, causing classical citrullinemia. Am J Hum Genet. 1994 Dec;55(6):1103-12. PMID:7977368
5. ↑ Shaheen N, Kobayashi K, Terazono H, Fukushige T, Horiuchi M, Saheki T. Characterization of human wild-type and mutant argininosuccinate synthetase proteins expressed in bacterial cells. Enzyme Protein. 1994-1995;48(5-6):251-64. PMID:8792870
6. ↑ Vilaseca MA, Kobayashi K, Briones P, Lambruschini N, Campistol J, Tabata A, Alomar A, Rodes M, Lluch M, Saheki T. Phenotype and genotype heterogeneity in Mediterranean citrullinemia. Mol Genet Metab. 2001 Nov;74(3):396-8. PMID:11708871 doi:10.1006/mgme.2001.3221
7. ↑ Gao HZ, Kobayashi K, Tabata A, Tsuge H, Iijima M, Yasuda T, Kalkanoglu HS, Dursun A, Tokatli A, Coskun T, Trefz FK, Skladal D, Mandel H, Seidel J, Kodama S, Shirane S, Ichida T, Makino S, Yoshino M, Kang JH, Mizuguchi M, Barshop BA, Fuchinoue S, Seneca S, Zeesman S, Knerr I, Rodes M, Wasant P, Yoshida I, De Meirleir L, Abdul Jalil M, Begum L, Horiuchi M, Katunuma N, Nakagawa S, Saheki T. Identification of 16 novel mutations in the argininosuccinate synthetase gene and genotype-phenotype correlation in 38 classical citrullinemia patients. Hum Mutat. 2003 Jul;22(1):24-34. PMID:12815590 doi:10.1002/humu.10230
8. ↑ Haberle J, Pauli S, Schmidt E, Schulze-Eilfing B, Berning C, Koch HG. Mild citrullinemia in Caucasians is an allelic variant of argininosuccinate synthetase deficiency (citrullinemia type 1). Mol Genet Metab. 2003 Nov;80(3):302-6. PMID:14680976 doi:10.1016/j.ymgme.2003.08.002
9. ↑ Kleijer WJ, Garritsen VH, van der Sterre ML, Berning C, Haberle J, Huijmans JG. Prenatal diagnosis of citrullinemia and argininosuccinic aciduria: evidence for a transmission ratio distortion in citrullinemia. Prenat Diagn. 2006 Mar;26(3):242-7. PMID:16475226 doi:10.1002/pd.1390
10. ↑ Karlberg T, Collins R, van den Berg S, Flores A, Hammarstrom M, Hogbom M, Holmberg Schiavone L, Uppenberg J. Structure of human argininosuccinate synthetase. Acta Crystallogr D Biol Crystallogr. 2008 Mar;64(Pt 3):279-86. Epub 2008, Feb 20. PMID:18323623 doi:http://dx.doi.org/S0907444907067455