Cystathionine beta-synthase

NameCystathionine beta-synthase
Synonyms
  • 4.2.1.22
  • Beta-thionase
  • Serine sulfhydrase
Gene NameCBS
OrganismHuman
Amino acid sequence
>lcl|BSEQ0036990|Cystathionine beta-synthase
MPSETPQAEVGPTGCPHRSGPHSAKGSLEKGSPEDKEAKEPLWIRPDAPSRCTWQLGRPA
SESPHHHTAPAKSPKILPDILKKIGDTPMVRINKIGKKFGLKCELLAKCEFFNAGGSVKD
RISLRMIEDAERDGTLKPGDTIIEPTSGNTGIGLALAAAVRGYRCIIVMPEKMSSEKVDV
LRALGAEIVRTPTNARFDSPESHVGVAWRLKNEIPNSHILDQYRNASNPLAHYDTTADEI
LQQCDGKLDMLVASVGTGGTITGIARKLKEKCPGCRIIGVDPEGSILAEPEELNQTEQTT
YEVEGIGYDFIPTVLDRTVVDKWFKSNDEEAFTFARMLIAQEGLLCGGSAGSTVAVAVKA
AQELQEGQRCVVILPDSVRNYMTKFLSDRWMLQKGFLKEEDLTEKKPWWWHLRVQELGLS
APLTVLPTITCGHTIEILREKGFDQAPVVDEAGVILGMVTLGNMLSSLLAGKVQPSDQVG
KVIYKQFKQIRLTDTLGRLSHILEMDHFALVVHEQIQYHSTGKSSQRQMVFGVVTAIDLL
NFVAAQERDQK
Number of residues551
Molecular Weight60586.05
Theoretical pI6.63
GO Classification
Functions
  • carbon monoxide binding
  • modified amino acid binding
  • oxygen binding
  • nitric oxide binding
  • cystathionine beta-synthase activity
  • S-adenosyl-L-methionine binding
  • metal ion binding
  • nitrite reductase (NO-forming) activity
  • enzyme binding
  • protein homodimerization activity
  • identical protein binding
  • ubiquitin protein ligase binding
  • heme binding
  • pyridoxal phosphate binding
Processes
  • cysteine biosynthetic process
  • cysteine biosynthetic process from serine
  • cysteine biosynthetic process via cystathionine
  • cellular nitrogen compound metabolic process
  • DNA protection
  • small molecule metabolic process
  • homocysteine catabolic process
  • homocysteine metabolic process
  • hydrogen sulfide biosynthetic process
  • L-serine catabolic process
  • oxidation-reduction process
  • L-serine metabolic process
  • transsulfuration
  • sulfur amino acid metabolic process
  • L-cysteine catabolic process
Components
  • cytoplasm
  • nucleus
  • cytosol
General FunctionUbiquitin protein ligase binding
Specific FunctionHydro-lyase catalyzing the first step of the transsulfuration pathway, where the hydroxyl group of L-serine is displaced by L-homocysteine in a beta-replacement reaction to form L-cystathionine, the precursor of L-cysteine. This catabolic route allows the elimination of L-methionine and the toxic metabolite L-homocysteine (PubMed:23981774, PubMed:20506325, PubMed:23974653). Also involved in the production of hydrogen sulfide, a gasotransmitter with signaling and cytoprotective effects on neurons (By similarity).
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID388716
UniProtKB IDP35520
UniProtKB Entry NameCBS_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0010085|Cystathionine beta-synthase (CBS)
ATGCCTTCTGAGACCCCCCAGGCAGAAGTGGGGCCCACAGGCTGCCCCCACCGCTCAGGG
CCACACTCGGCGAAGGGGAGCCTGGAGAAGGGGTCCCCAGAGGATAAGGAAGCCAAGGAG
CCCCTGTGGATCCGGCCCGATGCTCCGAGCAGGTGCACCTGGCAGCTGGGCCGGCCTGCC
TCCGAGTCCCCACATCACCACACTGCCCCGGCAAAATCTCCAAAAATCTTGCCAGATATT
CTGAAGAAAATCGGGGACACCCCTATGGTCAGAATCAACAAGATTGGGAAGAAGTTCGGC
CTGAAGTGTGAGCTCTTGGCCAAGTGTGAGTTCTTCAACGCGGGCGGGAGCGTGAAGGAC
CGCATCAGCCTGCGGATGATTGAGGATGCTGAGCGCGACGGGACGCTGAAGCCCGGGGAC
ACGATTATCGAGCCGACATCCGGGAACACCGGGATCGGGCTGGCCCTGGCTGCGGCAGTG
AGGGGCTATCGCTGCATCATCGTGATGCCAGAGAAGATGAGCTCCGAGAAGGTGGACGTG
CTGCGGGCACTGGGGGCTGAGATTGTGAGGACGCCCACCAATGCCAGGTTCGACTCCCCG
GAGTCACACGTGGGGGTGGCCTGGCGGCTGAAGAACGAAATCCCCAATTCTCACATCCTA
GACCAGTACCGCAACGCCAGCAACCCCCTGGCTCACTATGACACCACCGCTGATGAGATC
CTGCAGCAGTGTGATGGGAAGCTGGACATGCTGGTGGCTTCAGTGGGCACGGGCGGCACC
ATCACGGGCATTGCCAGGAAGCTGAAGGAGAAGTGTCCTGGATGCAGGATCATTGGGGTG
GATCCCGAAGGGTCCATCCTCGCAGAGCCGGAGGAGCTGAACCAGACGGAGCAGACAACC
TACGAGGTGGAAGGGATCGGCTACGACTTCATCCCCACGGTGCTGGACAGGACGGTGGTG
GACAAGTGGTTCAAGAGCAACGATGAGGAGGCGTTCACCTTTGCCCGCATGCTGATCGCG
CAAGAGGGGCTGCTGTGCGGTGGCAGTGCTGGCAGCACGGTGGCGGTGGCCGTGAAGGCC
GCGCAGGAGCTGCAGGAGGGCCAGCGCTGCGTGGTCATTCTGCCCGACTCAGTGCGGAAC
TACATGACCAAGTTCCTGAGCGACAGGTGGATGCTGCAGAAGGGCTTTCTGAAGGAGGAG
GACCTCACGGAGAAGAAGCCCTGGTGGTGGCACCTCCGTGTTCAGGAGCTGGGCCTGTCA
GCCCCGCTGACCGTGCTCCCGACCATCACCTGTGGGCACACCATCGAGATCCTCCGGGAG
AAGGGCTTCGACCAGGCGCCCGTGGTGGATGAGGCGGGGGTAATCCTGGGAATGGTGACG
CTTGGGAACATGCTCTCGTCCCTGCTTGCCGGGAAGGTGCAGCCGTCAGACCAAGTTGGC
AAAGTCATCTACAAGCAGTTCAAACAGATCCGCCTCACGGACACGCTGGGCAGGCTCTCG
CACATCCTGGAGATGGACCACTTCGCCCTGGTGGTGCACGAGCAGATCCAGTCGCAGGAC
CAGGCCTGGGCAGGCGTGGTGGGGGGGCCTGCAGACCACAGCACCGGGAAGTCCAGTCAG
CGGCAGATGGTGTTCGGGGTGGTCACCGCCATTGACTTGCTGAACTTCGTGGCCGCCCAG
GAGCGGGACCAGAAGTGA
GenBank Gene IDL19501
GeneCard IDNot Available
GenAtlas IDCBS
HGNC IDHGNC:1550
Chromosome Location21
LocusNot Available
References
  1. Kraus JP, Le K, Swaroop M, Ohura T, Tahara T, Rosenberg LE, Roper MD, Kozich V: Human cystathionine beta-synthase cDNA: sequence, alternative splicing and expression in cultured cells. Hum Mol Genet. 1993 Oct;2(10):1633-8. 7903580
  2. Chasse JF, Paly E, Paris D, Paul V, Sinet PM, Kamoun P, London J: Genomic organization of the human cystathionine beta-synthase gene: evidence for various cDNAs. Biochem Biophys Res Commun. 1995 Jun 26;211(3):826-32. 7598711
  3. Kruger WD, Cox DR: A yeast system for expression of human cystathionine beta-synthase: structural and functional conservation of the human and yeast genes. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6614-8. 8022826
  4. Chasse JF, Paul V, Escanez R, Kamoun P, London J: Human cystathionine beta-synthase: gene organization and expression of different 5' alternative splicing. Mamm Genome. 1997 Dec;8(12):917-21. 9383285
  5. Kraus JP, Oliveriusova J, Sokolova J, Kraus E, Vlcek C, de Franchis R, Maclean KN, Bao L, Bukovsk, Patterson D, Paces V, Ansorge W, Kozich V: The human cystathionine beta-synthase (CBS) gene: complete sequence, alternative splicing, and polymorphisms. Genomics. 1998 Sep 15;52(3):312-24. 9790750
  6. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  8. Kraus J, Packman S, Fowler B, Rosenberg LE: Purification and properties of cystathionine beta-synthase from human liver. Evidence for identical subunits. J Biol Chem. 1978 Sep 25;253(18):6523-8. 681363
  9. Kabil O, Zhou Y, Banerjee R: Human cystathionine beta-synthase is a target for sumoylation. Biochemistry. 2006 Nov 14;45(45):13528-36. 17087506
  10. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. 19413330
  11. Kozich V, Sokolova J, Klatovska V, Krijt J, Janosik M, Jelinek K, Kraus JP: Cystathionine beta-synthase mutations: effect of mutation topology on folding and activity. Hum Mutat. 2010 Jul;31(7):809-19. doi: 10.1002/humu.21273. 20506325
  12. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  13. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. 21406692
  14. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  15. Meier M, Janosik M, Kery V, Kraus JP, Burkhard P: Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein. EMBO J. 2001 Aug 1;20(15):3910-6. 11483494
  16. Taoka S, Lepore BW, Kabil O, Ojha S, Ringe D, Banerjee R: Human cystathionine beta-synthase is a heme sensor protein. Evidence that the redox sensor is heme and not the vicinal cysteines in the CXXC motif seen in the crystal structure of the truncated enzyme. Biochemistry. 2002 Aug 20;41(33):10454-61. 12173932
  17. Kraus JP, Janosik M, Kozich V, Mandell R, Shih V, Sperandeo MP, Sebastio G, de Franchis R, Andria G, Kluijtmans LA, Blom H, Boers GH, Gordon RB, Kamoun P, Tsai MY, Kruger WD, Koch HG, Ohura T, Gaustadnes M: Cystathionine beta-synthase mutations in homocystinuria. Hum Mutat. 1999;13(5):362-75. 10338090
  18. Kozich V, Kraus JP: Screening for mutations by expressing patient cDNA segments in E. coli: homocystinuria due to cystathionine beta-synthase deficiency. Hum Mutat. 1992;1(2):113-23. 1301198
  19. Kozich V, de Franchis R, Kraus JP: Molecular defect in a patient with pyridoxine-responsive homocystinuria. Hum Mol Genet. 1993 Jun;2(6):815-6. 8353501
  20. Hu FL, Gu Z, Kozich V, Kraus JP, Ramesh V, Shih VE: Molecular basis of cystathionine beta-synthase deficiency in pyridoxine responsive and nonresponsive homocystinuria. Hum Mol Genet. 1993 Nov;2(11):1857-60. 7506602
  21. de Franchis R, Kozich V, McInnes RR, Kraus JP: Identical genotypes in siblings with different homocystinuric phenotypes: identification of three mutations in cystathionine beta-synthase using an improved bacterial expression system. Hum Mol Genet. 1994 Jul;3(7):1103-8. 7981678
  22. Marble M, Geraghty MT, de Franchis R, Kraus JP, Valle D: Characterization of a cystathionine beta-synthase allele with three mutations in cis in a patient with B6 nonresponsive homocystinuria. Hum Mol Genet. 1994 Oct;3(10):1883-6. 7849717
  23. Kraus JP: Komrower Lecture. Molecular basis of phenotype expression in homocystinuria. J Inherit Metab Dis. 1994;17(4):383-90. 7967489
  24. Shih VE, Fringer JM, Mandell R, Kraus JP, Berry GT, Heidenreich RA, Korson MS, Levy HL, Ramesh V: A missense mutation (I278T) in the cystathionine beta-synthase gene prevalent in pyridoxine-responsive homocystinuria and associated with mild clinical phenotype. Am J Hum Genet. 1995 Jul;57(1):34-9. 7611293
  25. Sebastio G, Sperandeo MP, Panico M, de Franchis R, Kraus JP, Andria G: The molecular basis of homocystinuria due to cystathionine beta-synthase deficiency in Italian families, and report of four novel mutations. Am J Hum Genet. 1995 Jun;56(6):1324-33. 7762555
  26. Kluijtmans LA, Blom HJ, Boers GH, van Oost BA, Trijbels FJ, van den Heuvel LP: Two novel missense mutations in the cystathionine beta-synthase gene in homocystinuric patients. Hum Genet. 1995 Aug;96(2):249-50. 7635485
  27. Kruger WD, Cox DR: A yeast assay for functional detection of mutations in the human cystathionine beta-synthase gene. Hum Mol Genet. 1995 Jul;4(7):1155-61. 8528202
  28. Sperandeo MP, Panico M, Pepe A, Candito M, de Franchis R, Kraus JP, Andria G, Sebastio G: Molecular analysis of patients affected by homocystinuria due to cystathionine beta-synthase deficiency: report of a new mutation in exon 8 and a deletion in intron 11. J Inherit Metab Dis. 1995;18(2):211-4. 7564249
  29. Kluijtmans LA, Boers GH, Stevens EM, Renier WO, Kraus JP, Trijbels FJ, van den Heuvel LP, Blom HJ: Defective cystathionine beta-synthase regulation by S-adenosylmethionine in a partially pyridoxine responsive homocystinuria patient. J Clin Invest. 1996 Jul 15;98(2):285-9. 8755636
  30. Sperandeo MP, Candito M, Sebastio G, Rolland MO, Turc-Carel C, Giudicelli H, Dellamonica P, Andria G: Homocysteine response to methionine challenge in four obligate heterozygotes for homocystinuria and relationship with cystathionine beta-synthase mutations. J Inherit Metab Dis. 1996;19(3):351-6. 8803779
  31. Dawson PA, Cox AJ, Emmerson BT, Dudman NP, Kraus JP, Gordon RB: Characterisation of five missense mutations in the cystathionine beta-synthase gene from three patients with B6-nonresponsive homocystinuria. Eur J Hum Genet. 1997 Jan-Feb;5(1):15-21. 9156316
  32. Kim CE, Gallagher PM, Guttormsen AB, Refsum H, Ueland PM, Ose L, Folling I, Whitehead AS, Tsai MY, Kruger WD: Functional modeling of vitamin responsiveness in yeast: a common pyridoxine-responsive cystathionine beta-synthase mutation in homocystinuria. Hum Mol Genet. 1997 Dec;6(13):2213-21. 9361025
  33. Aral B, Coude M, London J, Aupetit J, Chasse JF, Zabot MT, Chadefaux-Vekemans B, Kamoun P: Two novel mutations (K384E and L539S) in the C-terminal moiety of the cystathionine beta-synthase protein in two French pyridoxine-responsive homocystinuria patients. Hum Mutat. 1997;9(1):81-2. 8990018
  34. Kozich V, Janosik M, Sokolova J, Oliveriusova J, Orendac M, Kraus JP, Elleder D: Analysis of CBS alleles in Czech and Slovak patients with homocystinuria: report on three novel mutations E176K, W409X and 1223 + 37 del99. J Inherit Metab Dis. 1997 Jul;20(3):363-6. 9266356
  35. Tsai MY, Wong PW, Garg U, Hanson NQ, Schwichtenberg K: Two Novel Mutations in the Cystathionine beta-synthase Gene of Homocystinuric Patients. Mol Diagn. 1997 Jun;2(2):129-133. 10462600
  36. Gordon RB, Cox AJ, Dawson PA, Emmerson BT, Kraus JP, Dudman NP: Mutational analysis of the cystathionine beta-synthase gene: a splicing mutation, two missense mutations and an insertion in patients with homocystinuria. Mutations in brief no. 120. Online. Hum Mutat. 1998;11(4):332. 10215408
  37. Gallagher PM, Naughten E, Hanson NQ, Schwichtenberg K, Bignell M, Yuan M, Ward P, Yap S, Whitehead AS, Tsai MY: Characterization of mutations in the cystathionine beta-synthase gene in Irish patients with homocystinuria. Mol Genet Metab. 1998 Dec;65(4):298-302. 9889017
  38. de Franchis R, Kraus E, Kozich V, Sebastio G, Kraus JP: Four novel mutations in the cystathionine beta-synthase gene: effect of a second linked mutation on the severity of the homocystinuric phenotype. Hum Mutat. 1999;13(6):453-7. 10408774
  39. Gat-Yablonski G, Mandel H, Fowler B, Taleb O, Sela BA: Homocystinuria in the Arab population of Israel: identification of two novel mutations using DGGE analysis. Hum Mutat. 2000 Oct;16(4):372. 11013450
  40. Janosik M, Oliveriusova J, Janosikova B, Sokolova J, Kraus E, Kraus JP, Kozich V: Impaired heme binding and aggregation of mutant cystathionine beta-synthase subunits in homocystinuria. Am J Hum Genet. 2001 Jun;68(6):1506-13. Epub 2001 May 15. 11359213
  41. Castro R, Heil SG, Rivera I, Jakobs C, de Almeida IT, Blom HJ: Molecular genetic analysis of the cystathionine beta-synthase gene in Portuguese homocystinuria patients: three novel mutations. Clin Genet. 2001 Aug;60(2):161-3. 11553052
  42. Maclean KN, Gaustadnes M, Oliveriusova J, Janosik M, Kraus E, Kozich V, Kery V, Skovby F, Rudiger N, Ingerslev J, Stabler SP, Allen RH, Kraus JP: High homocysteine and thrombosis without connective tissue disorders are associated with a novel class of cystathionine beta-synthase (CBS) mutations. Hum Mutat. 2002 Jun;19(6):641-55. 12007221
  43. Gaustadnes M, Wilcken B, Oliveriusova J, McGill J, Fletcher J, Kraus JP, Wilcken DE: The molecular basis of cystathionine beta-synthase deficiency in Australian patients: genotype-phenotype correlations and response to treatment. Hum Mutat. 2002 Aug;20(2):117-26. 12124992
  44. Urreizti R, Balcells S, Rodes M, Vilarinho L, Baldellou A, Couce ML, Munoz C, Campistol J, Pinto X, Vilaseca MA, Grinberg D: Spectrum of CBS mutations in 16 homocystinuric patients from the Iberian Peninsula: high prevalence of T191M and absence of I278T or G307S. Hum Mutat. 2003 Jul;22(1):103. 12815602
  45. Kruger WD, Wang L, Jhee KH, Singh RH, Elsas LJ 2nd: Cystathionine beta-synthase deficiency in Georgia (USA): correlation of clinical and biochemical phenotype with genotype. Hum Mutat. 2003 Dec;22(6):434-41. 14635102
  46. Orendae M, Pronicka E, Kubalska J, Janosik M, Sokolova J, Linnebank M, Koch HG, Kozich V: Identification and functional analysis of two novel mutations in the CBS gene in Polish patients with homocystinuria. Hum Mutat. 2004 Jun;23(6):631. 15146473
  47. Linnebank M, Janosik M, Kozich V, Pronicka E, Kubalska J, Sokolova J, Linnebank A, Schmidt E, Leyendecker C, Klockgether T, Kraus JP, Koch HG: The cystathionine beta-synthase (CBS) mutation c.1224-2A>C in Central Europe: Vitamin B6 nonresponsiveness and a common ancestral haplotype. Hum Mutat. 2004 Oct;24(4):352-3. 15365998
  48. Porto MP, Galdieri LC, Pereira VG, Vergani N, da Rocha JC, Micheletti C, Martins AM, Perez AB, Almeida VD: Molecular analysis of homocystinuria in Brazilian patients. Clin Chim Acta. 2005 Dec;362(1-2):71-8. Epub 2005 Jul 5. 15993874
  49. Lee SJ, Lee DH, Yoo HW, Koo SK, Park ES, Park JW, Lim HG, Jung SC: Identification and functional analysis of cystathionine beta-synthase gene mutations in patients with homocystinuria. J Hum Genet. 2005;50(12):648-54. Epub 2005 Oct 5. 16205833
  50. Urreizti R, Asteggiano C, Cozar M, Frank N, Vilaseca MA, Grinberg D, Balcells S: Functional assays testing pathogenicity of 14 cystathionine-beta synthase mutations. Hum Mutat. 2006 Feb;27(2):211. 16429402
  51. Cozar M, Urreizti R, Vilarinho L, Grosso C, Dodelson de Kremer R, Asteggiano CG, Dalmau J, Garcia AM, Vilaseca MA, Grinberg D, Balcells S: Identification and functional analyses of CBS alleles in Spanish and Argentinian homocystinuric patients. Hum Mutat. 2011 Jul;32(7):835-42. doi: 10.1002/humu.21514. Epub 2011 Jun 7. 21520339
  52. Kwok JS, Fung SL, Lui GC, Law EL, Chan MH, Leung CB, Tang NL: CBS gene mutations found in a Chinese pyridoxine-responsive homocystinuria patient. Pathology. 2011 Jan;43(1):81-3. doi: 10.1097/PAT.0b013e3283419dbb. 21240075
  53. Smith AT, Su Y, Stevens DJ, Majtan T, Kraus JP, Burstyn JN: Effect of the disease-causing R266K mutation on the heme and PLP environments of human cystathionine beta-synthase. Biochemistry. 2012 Aug 14;51(32):6360-70. Epub 2012 Jul 31. 22738154
  54. Casique L, Kabil O, Banerjee R, Martinez JC, De Lucca M: Characterization of two pathogenic mutations in cystathionine beta-synthase: different intracellular locations for wild-type and mutant proteins. Gene. 2013 Nov 15;531(1):117-24. doi: 10.1016/j.gene.2013.08.021. Epub 2013 Aug 24. 23981774
  55. Mendes MI, Santos AS, Smith DE, Lino PR, Colaco HG, de Almeida IT, Vicente JB, Salomons GS, Rivera I, Blom HJ, Leandro P: Insights into the regulatory domain of cystathionine Beta-synthase: characterization of six variant proteins. Hum Mutat. 2014 Oct;35(10):1195-202. doi: 10.1002/humu.22616. Epub 2014 Jul 31. 25044645
  56. Mendes MI, Colaco HG, Smith DE, Ramos RJ, Pop A, van Dooren SJ, Tavares de Almeida I, Kluijtmans LA, Janssen MC, Rivera I, Salomons GS, Leandro P, Blom HJ: Reduced response of Cystathionine Beta-Synthase (CBS) to S-Adenosylmethionine (SAM): Identification and functional analysis of CBS gene mutations in Homocystinuria patients. J Inherit Metab Dis. 2014 Mar;37(2):245-54. doi: 10.1007/s10545-013-9647-6. Epub 2013 Aug 23. 23974653