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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

CBS Gene

protein-coding GIFtS: 72
GCID: GC21M044473

cystathionine-beta-synthase

Explore 133 diseases affiliated with
CBS via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, and/or ¹¹Nature:405,311-319 and CroW21)
About This Section

Aliases
Cystathionine-Beta-Synthase¹		Beta-Thionase¹
HIP4¹ ²		Cystathionine Beta-Synthase²
Serine Sulfhydrase² ³		Methylcysteine Synthase²
EC 4.2.1.22³ ⁸		Beta-Thionase¹
Human Cystathionine-Beta-Synthase, EC 4.2.1.2211

External Ids:	HGNC: 1550¹	Entrez Gene: 875²	Ensembl: ENSG00000160200⁷	OMIM: 613381⁵	UniProtKB: P35520³

Export aliases for CBS gene to outside databases

Previous GC identifers: GC21M041021 GC21M043367 GC21M043346 GC21M029891

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for CBS:

The protein encoded by this gene acts as a homotetramer to catalyze the conversion of homocysteine to cystathionine,

the first step in the transsulfuration pathway. The encoded protein is allosterically activated by adenosyl-methionine

and uses pyridoxal phosphate as a cofactor. Defects in this gene can cause cystathionine beta-synthase deficiency

(CBSD), which can lead to homocystinuria. Multiple alternatively spliced transcript variants have been found for this

gene. (provided by RefSeq, May 2010)

UniProtKB/Swiss-Prot: CBS_HUMAN, P35520

Function: Only known pyridoxal phosphate-dependent enzyme that contains heme. Important regulator of hydrogen sulfide,

especially in the brain, utilizing cysteine instead of serine to catalyze the formation of hydrogen sulfide. Hydrogen

sulfide is a gastratransmitter with signaling and cytoprotective effects such as acting as a neuromodulator in the

brain to protect neurons against hypoxic injury (By similarity)

Gene Wiki entry for CBS (Cystathionine beta synthase)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics, Whole Chromsome Sequence According to Nature (Cited Here with Permission):405,311-319 and CroW21)
About This Section

RefSeq DNA sequence:

NC_000021.8 NC_018932.1 NT_011515.12

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the CBS gene promoter:
GR Sp1 Ik-3 Arnt FOXJ2 (long isoform) GR-alpha ZIC2/Zic2 FOXJ2
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): CBS promoter sequence

Search SABiosciences Chromatin IP Primers for CBS

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat CBS

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 21q22.3 Ensembl cytogenetic band: 21q22.3 HGNC cytogenetic band: 21q22.3
Nature(405: 311-319) cytogenetic band: 21q22.3

CBS Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CBS gene location

GeneLoc information about chromosome 21 GeneLoc Exon Structure

(about GC identifiers)

GC21M044473:	GeneLoc	Nature:405,311-319
Start:	44,473,301 bp from pter	30,020,629 bp from centromere
End:	44,497,053 bp from pter	30,035,840 bp from centromere
Size:	23,753 bases	15,212 bases
Orientation:	minus strand	minus strand

Whole chromosome sequencing:
cDNA sequence:	L00972
genomic clones:	KB1151C12 KB2007G4

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: CBS_HUMAN, P35520 (See protein sequence)

Recommended Name: Cystathionine beta-synthase

Size: 551 amino acids; 60587 Da

Cofactor: Pyridoxal phosphate

Subunit: Homotetramer

Subcellular location: Cytoplasm. Nucleus

2 PDB 3D structures from and Proteopedia for CBS:

1JBQ (3D)

1M54 (3D)

Secondary accessions: B2R993 D3DSK4 Q99425 Q9BWC5

Alternative splicing: 2 isoforms: P35520-1 P35520-2

Explore the universe of human proteins at neXtProt for CBS: NX_P35520

Post-translational modifications:

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P35520

4/11 DME Specific Peptides for CBS (P35520) (see all 11)

SNPLAHYD

LSAPLTVLPT

KSPKILPDIL

EIPNSHILDQY

CBS Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (3 alternative transcripts):

NP_000062.1 NP_001171479.1 NP_001171480.1

ENSEMBL proteins:

ENSP00000381225 ENSP00000381231 ENSP00000352643 ENSP00000344460 ENSP00000402823

ENSP00000408014 ENSP00000405929 ENSP00000388235 ENSP00000381234 ENSP00000439332

Reactome Protein details: P35520
Human Recombinant Protein Products:

	Browse Purified and Recombinant Proteins at EMD Millipore
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	Browse recombinant and purified proteins available from Enzo Life Sciences
	OriGene Purified Protein: CBS OriGene Protein Over-expression Lysate: CBS OriGene Custom Protein Services for CBS
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	Novus Biologicals CBS Proteins Novus Biologicals CBS Lysates
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Browse Proteins at Uscn

Gene Ontology (GO): 5/6 cellular component terms (GO ID links to tree view) (see all 6): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005625	soluble fraction	--	--
GO:0005634	nucleus	IDA	17087506
GO:0005730	nucleolus	IDA	--
GO:0005737	cytoplasm	--	--
GO:0005829	cytosol	TAS	--

CBS for ontologies About GeneDecksing

CBS Antibody Products:

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	Abcam antibodies for CBS
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	ThermoFisher Antibody for CBS

Assay Products for CBS:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
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	GenScript Custom Assay Services for CBS
	Browse Enzo Life Sciences for kits & assays
	Browse ELISAs and CLIAs at Uscn

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

CBS for domains About GeneDecksing

4 InterPro domains/families:

IPR005857 Cysta_beta_synth

IPR000644 Cysta_beta_synth_core

IPR001216 Cys_synth_BS

IPR001926 Trp_syn_b_sub_like_PLP_eny_SF

Graphical View of Domain Structure for InterPro Entry P35520

ProtoNet protein and cluster: P35520

2 Blocks protein families:

IPB000644 CBS domain

IPB001926 Pyridoxal-5'-phosphate-dependent enzyme

UniProtKB/Swiss-Prot: CBS_HUMAN, P35520

Similarity: Belongs to the cysteine synthase/cystathionine beta-synthase family

Similarity: Contains 1 CBS domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: CBS_HUMAN, P35520

Function: Only known pyridoxal phosphate-dependent enzyme that contains heme. Important regulator of hydrogen sulfide,

especially in the brain, utilizing cysteine instead of serine to catalyze the formation of hydrogen sulfide. Hydrogen

sulfide is a gastratransmitter with signaling and cytoprotective effects such as acting as a neuromodulator in the

brain to protect neurons against hypoxic injury (By similarity)

Catalytic activity: L-serine + L-homocysteine = L-cystathionine + H(2)O

Enzyme regulation: Allosterically activated by adenosyl-methionine (AdoMet)

Genatlas biochemistry entry for CBS:

cystathionine beta synthase gene with several transcripts,alternatively spliced in 5',sulfur aminoacid

metabolism,susceptibility gene to neural tube defect in association with MTHFR,no evidence of association with NTD in

Netherlands and U.K.,interacting with huntingtin

Enzyme Number (IUBMB): EC 4.2.1.22¹ ²

miRNA Products:		OriGene 3'-UTR Clone: CBS Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat CBS
		1 QIAGEN miScript miRNA Assays for microRNA that regulate CBS:
		hsa-miR-494
		SwitchGear 3'UTR luciferase reporter plasmid: CBS 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for CBS (see all 7) OriGene shRNA RFP: CBS OriGene siRNA: CBS
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat CBS

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for CBS

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for CBS (see all 6) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for CBS (see all 4) OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 3): CBS (NM_000071)
		Browse Sino Biological Human cDNA Clones
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for CBS
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat CBS

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for CBS
		Search LifeMap BioReagents cell lines for CBS

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CBS

Gene Ontology (GO): 5/11 molecular function terms (GO ID links to tree view) (see all 11): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004122	cystathionine beta-synthase activity	TAS	--
GO:0004124	cysteine synthase activity	--	--
GO:0005515	protein binding	IPI	17087506
GO:0016740	transferase activity	--	--
GO:0019899	enzyme binding	IPI	17087506

CBS for ontologies About GeneDecksing

2 GenomeRNAi human phenotypes for CBS:

Decreased Salmonella enterica

Synthetic lethal with Ras

Animal Models:
Mouse knock-out Cbs^tm1Unc for CBS
15/19 MGI mutant phenotypes (inferred from 1 allele) (MGI details for Cbs) (see all 19):

behavior/neurological	cardiovascular system	cellular	craniofacial	embryogenesis
endocrine/exocrine gland	growth/size	hematopoietic system	homeostasis/metabolism	immune system
integument	limbs/digits/tail	liver/biliary system	mortality/aging	muscle

CBS for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/8 super-pathways (see all 8) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Methionine metabolism

	Methionine metabolism	1.00			cysteine biosynthesis III (mammalia)	0.44
	Methionine metabolism	1.00			superpathway of methionine degradation	0.38

Antimetabolite Pathway - Folate Cycle, Pharmacodynamics

	Antimetabolite Pathway - Folate Cycle, Pharmacodynamics	1.00			Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics	0.36
	Methotrexate Pathway (Cancer Cell), Pharmacodynamics	0.45

Sulfur amino acid metabolism

Sulfur amino acid metabolism

1.00

Cysteine and methionine metabolism

0.36

Cysteine formation from homocysteine

cysteine biosynthesis/homocysteine degradation

1.00

Cysteine formation from homocysteine

1.00

Metabolism

Metabolism

1.00

Metabolic pathways

0.38

Pathway sources
See GeneCards unified pathways
Show all pathways

1 EMD Millipore Pathway for CBS

Methionine metabolism

1 GeneGo (Thomson Reuters) Pathway for CBS

Methionine metabolism

4 BioSystems Pathways for CBS

	Selenium Pathway
	cysteine biosynthesis III (mammalia)
	superpathway of methionine degradation
	cysteine biosynthesis/homocysteine degradation

4 Reactome Pathways for CBS

	Metabolism
	Sulfur amino acid metabolism
	Metabolism of amino acids and derivatives
	Cysteine formation from homocysteine

3 PharmGKB Pathways for CBS

	Antimetabolite Pathway - Folate Cycle, Pharmacodynamics
	Methotrexate Pathway (Cancer Cell), Pharmacodynamics
	Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics

3 Kegg Pathways (Kegg details for CBS):

	Glycine, serine and threonine metabolism
	Cysteine and methionine metabolism
	Metabolic pathways

UniProtKB/Swiss-Prot: CBS_HUMAN, P35520

Pathway: Amino-acid biosynthesis; L-cysteine biosynthesis; L-cysteine from L-homocysteine and L-serine: step 1/2

CBS for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for CBS

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/282 Interacting proteins for CBS (P35520^{2, 3} ENSP00000344460⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 282)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
HIST1H4A	P62805³	I2D: score=2
HIST1H4B	P62805³	I2D: score=2
HIST1H4C	P62805³	I2D: score=2
HIST1H4D	P62805³	I2D: score=2
HIST1H4E	P62805³	I2D: score=2

About this table

Gene Ontology (GO): 5/26 biological process terms (GO ID links to tree view) (see all 26): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000096	sulfur amino acid metabolic process	TAS	--
GO:0001958	endochondral ossification	IEA	--
GO:0001974	blood vessel remodeling	IEA	--
GO:0006535	cysteine biosynthetic process from serine	IEA	--
GO:0006563	L-serine metabolic process	IDA	19010420

CBS for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

CBS for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for CBS

10/13 HMDB Compounds for CBS (see all 13) About this table

Compound	Synonyms	CAS #	PubMed Ids
Allocystathionine	DL-Allocystathionine (see all 4)	535-34-2	--
Heme	(protoporphyrinato)iron (see all 19)	14875-96-8	--
Homocysteine	(+-)-homocysteine (see all 22)	454-29-5	--
Hydrogen sulfide	Dihydrogen disulfide (see all 24)	7783-06-4	--
L-Cystathionine	L-(+)-Cystathionine (see all 6)	56-88-2	--
L-Cysteine	(+)-2-Amino-3-mercaptopropionic acid (see all 37)	52-90-4	--
L-Serine	(-)-Serine (see all 26)	56-45-1	--
Pyridoxal 5'-phosphate	Apolon B6 (see all 27)	54-47-7	--
Pyridoxine	2-Methyl-3-hydroxy-4,5-bis(hydroxymethyl)pyridine (see all 16)	65-23-6	--
S-Adenosylmethionine	(3S)-5'-[(3-amino-3-carboxypropyl)methylsulfonio]-5'-deoxyadenosine (see all 16)	29908-03-0	--

6 DrugBank Compounds for CBS About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
L-Cysteine	(R)-2-Amino-3-mercaptopropanoic acid (see all 13)	52-90-4	target	--	16428267 17377202 17488480 15671155 16781459
Pyridoxal Phosphate	Codecarboxylase (see all 9)	54-47-7	target	cofactor	15196993 15365998 12644499 11948191 12173932
Pyridoxine	Pyridoxol (see all 2)	65-23-6	target	cofactor	17377202 16479318 16363792 16857832 16479441
S-Adenosylmethionine	Acylcarnitine (see all 6)	29908-03-0	target	activator	12163655 12269827 11559709 11524006
Heme	--	--	target	--	17139284 17016423
L-Serine	(-)-Serine (see all 11)	56-45-1	target	--	17352495 17629356

10/63 Novoseek chemical compound relationships for CBS gene (see all 63) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
cystathionine	99.2	1037	10052944 (7), 2011158 (5), 11042162 (4), 11742888 (4) (see all 99)
homocysteine	94.4	421	17971175 (5), 9357926 (4), 10363126 (4), 12529702 (4) (see all 99)
methionine	87.7	226	8134195 (3), 17937607 (3), 10954028 (2), 11216902 (2) (see all 99)
vitamin b6	85.8	49	9928444 (2), 9361025 (2), 7981678 (2), 15365998 (2) (see all 27)
folate	84.4	75	10833331 (3), 19633202 (2), 11569694 (2), 11585023 (2) (see all 49)
pyridoxal 5-phosphate	81.9	76	10052942 (5), 7929220 (4), 10052944 (4), 11042162 (1) (see all 27)
s-adenosylmethionine	81.5	91	16614071 (5), 11524006 (4), 8755636 (4), 16953589 (4) (see all 34)
betaine	76.8	21	12828591 (2), 15017331 (2), 9211201 (1), 9357926 (1) (see all 13)
vitamin b12	76.2	20	9235230 (1), 11481906 (1), 17686644 (1), 10758367 (1) (see all 15)
propargylglycine	75.4	4	19631409 (2), 17101327 (1)

Search CenterWatch for drugs/clinical trials and news about CBS

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for CBS gene (3 alternative transcripts):

NM_000071.2 NM_001178008.1 NM_001178009.1

Unigene Cluster for CBS:

Cystathionine-beta-synthase

Hs.533013 [show with all ESTs]

Unigene Representative Sequence: L00972

18/19 Ensembl transcripts including schematic representations, and UCSC links where relevant (see all 19):

ENST00000461686(uc002zcs.1) ENST00000398158 ENST00000398165(uc002zcu.2 uc002zct.2)

ENST00000359624(uc002zcw.3) ENST00000352178(uc002zcv.2) ENST00000451248

ENST00000462349 ENST00000491776 ENST00000458223 ENST00000430013 ENST00000496485

ENST00000486098 ENST00000441030 ENST00000470912 ENST00000465732 ENST00000488526

ENST00000478709 ENST00000398168

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		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat CBS
		1 QIAGEN miScript miRNA Assays for microRNA that regulate CBS:
		hsa-miR-494
		SwitchGear 3'UTR luciferase reporter plasmid: CBS 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for CBS (see all 7) OriGene shRNA RFP: CBS OriGene siRNA: CBS
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat CBS

Clone Products:		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for CBS (see all 6) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for CBS (see all 4) OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 3): CBS (NM_000071)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for CBS
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat CBS

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for CBS Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat CBS
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat CBS
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat CBS

Additional cDNA sequence:

AK294608.1 AK301063.1 AK313691.1 AL137314.1 BC000440.2 BC007257.1 BC010242.1 BC011381.1

BC012319.1 BT007154.1 L00972.1 L14577.1 L19501.1 X82166.1

21 DOTS entries:

DT.452726 DT.100810615 DT.97859672 DT.100810602 DT.121131733 DT.100810619 DT.121131732 DT.100810621

DT.70103884 DT.121131710 DT.121131727 DT.75182069 DT.95149090 DT.100810612 DT.100810614 DT.121131709

DT.91646095 DT.95149085 DT.97859673 DT.99995100 DT.121131717

24/312 AceView cDNA sequences (see all 312):

BF507816 AW071777 BQ691100 AI494295 AL522542 BQ720498 AI369768 CR624541

CA446196 BQ691794 BX101034 BQ051298 CR613114 BX117844 BQ225465 CR605513

BE898248 BU508699 BM471614 CD674556 BU552809 AI494305 AW247430 BE297756

GeneLoc Exon Structure

5/18 Alternative Splicing Database (ASD) splice patterns (SP) for CBS (see all 18) About this scheme

ExUns:	1	^	2a	·	2b	·	2c	^	3a	·	3b	·	3c	·	3d	·	3e	^	4a	·	4b	·	4c	·	4d	^	5	^	6a	·	6b	·	6c	^	7a	·	7b	^	8a	·	8b	^	9	^	10	^	11	^	12a	·	12b	^
SP1:									-		-		-		-		-		-														-		-		-												-
SP2:									-		-		-		-		-		-														-		-		-												-
SP3:																	-		-														-		-		-												-
SP4:																	-		-		-		-										-		-		-												-
SP5:																																																	-

ExUns:	13a	·	13b	^	14a	·	14b	^	15a	·	15b	·	15c	·	15d	^	16a	·	16b	·	16c	^	17	^	18	^	19	^	20	^	21a	·	21b	·	21c	^	22a	·	22b	·	22c
SP1:	-						-								-		-												-
SP2:	-						-								-		-												-
SP3:	-						-								-		-												-
SP4:	-						-								-		-												-
SP5:	-						-								-		-												-

ECgene alternative splicing isoforms for CBS

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

CBS expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: GCTTCCTAAA

About this image
See CBS Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for CBS

SOURCE GeneReport for Unigene cluster: Hs.533013

UniProtKB/Swiss-Prot: CBS_HUMAN, P35520

Tissue specificity: In the adult strongly expressed in liver and pancreas, some expression in heart and brain, weak

expression in lung and kidney. In the fetus, expressed in brain, liver and kidney

SABiosciences Expression via Pathway-Focused PCR Array including CBS:

Amino Acid Metabolism I in human mouse rat

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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the last universal common ancestor (LUCA).

Orthologs for CBS gene from 11/38 species (see all 38) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Cbs^{1 , 5}	cystathionine beta-synthase^{1, 5}	82.66(n)¹ 84.8(a)¹		17 (16.93 cM)⁵ 12411¹ NM_178224.2¹ NP_835742.1¹ 31612623⁵
chicken (Gallus gallus)	Aves	CBS¹	cystathionine-beta-synthase	73.75(n) 78.75(a)		418545 XM_416752.2 XP_416752.2
lizard (Anolis carolinensis)	Reptilia	CBS⁶	--	78(a)	1 ↔ 1	3(137228682-137258197)
African clawed frog (Xenopus laevis)	Amphibia	cbs-prov²	cystathionine-beta-synthase	75.8(n)		BC044091.1
zebrafish (Danio rerio)	Actinopterygii	wufq06c06²	wufq06c06	76.9(n)		335753 BI704255.1
fruit fly (Drosophila melanogaster)	Insecta	CG1753^{1 , 3}	cystathione beta-synthase³ CG1753¹	51(a)³ 59.71(n)¹ 52.76(a)¹		19E7³ 33081¹ NM_134580.2¹ NP_608424.1¹
worm (Caenorhabditis elegans)	Secernentea	F54A3.4³	--	55(a) (best of 4)		II(2220000-2223540) --
baker's yeast (Saccharomyces cerevisiae)	Saccharomycetes	CYS4(YGR155W)⁴ CYS4¹	Cystathionine beta-synthase, catalyzes synthesis of cystathionine from serine and homocysteine, the first committed step in cysteine biosynthesis; responsible for hydrogen sulfide generation; mutations in human ortholog cause homocystinuria less⁴ Cys4p¹	50.98(n)¹ 49.51(a)¹		7(798543-800066)⁴ 853059^{1, 4} NP_011671.3¹ NP_011671.1⁴
thale cress (Arabidopsis thaliana)	eudicotyledons	AT1G55880⁶	cysteine synthase A	25(a)	1 ↔ 1	1(20898898-20901183)
rice (Oryza sativa)	Liliopsida	Os06g0564500¹	hypothetical protein	47.51(n) 43.18(a)		4341321 NM_001064419.1 NP_001057884.1

ENSEMBL Gene Tree for CBS (if available)
TreeFam Gene Tree for CBS (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 21 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs121964968^1,2	C,	pathogenic	44474030(-)	`TGACTC/TGCTGA`	6	S L	mis¹		0	--	--	--	--
rs121964972^1,2	C	pathogenic	44480638(-)	`CAGCAC/TGGTGG`	6	T M	mis¹		1		NA	4432
rs121964962^1,2	C	pathogenic	44483098(-)	`GGATCA/GGCTAC`	6	S G	mis¹		0	--	--	--	--
rs5742905^1,2	C,F,H,	pathogenic	44483184(-)	`GATCAT/CTGGGG`	6	/T /I	mis¹ ese³		9		NS EA NA EU	7411
rs121964964^1,2	C,F	pathogenic	44486463(-)	`CAACGC/TGGGCG`	6	A V	mis¹		1		NA	4550
rs182162260^1,2		--	44472833(+)	`ACAAAA/GATACA`	3	--	int¹ ds500¹		0	--	--	--	--
rs79074528^1,2	C,	--	44472860(+)	`AGTGGT/CGCACA`	3	--	ds500¹ int¹		2		WA NA	122
rs141345089^1,2		--	44472953(+)	`TGCCAC/TTGTAC`	3	--	int¹ ds500¹		0	--	--	--	--
rs56291828^1,2	C	--	44472991(+)	`AAAAA-/AAAA AAAAAATTAAA`	3	--	ds500¹ int¹		1		NA	2
rs186857140^1,2		--	44473018(+)	`TAAACA/GTGGAG`	3	--	ds500¹ int¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for CBS (44473301 - 44497053 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV) variations for CBS: --
Human Gene Mutation Database (HGMD): CBS

Locus Specific Mutation Databases (LSDB): CBS

SABiosciences Cancer Mutation PCR Assays

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DNA2.0 Custom Variant and Variant Library Synthesis for CBS

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

CBS for disorders           About GeneDecksing

OMIM gene information: 613381
OMIM disorders: 236200
UniProtKB/Swiss-Prot: CBS_HUMAN, P35520

Defects in CBS are the cause of cystathionine beta-synthase deficiency (CBSD) [MIM:236200]. CBSD is an

enzymatic deficiency resulting in altered sulfur metabolism and homocystinuria. The clinical features of untreated

homocystinuria due to CBS deficiency include myopia, ectopia lentis, mental retardation, skeletal anomalies resembling

Marfan syndrome, and thromboembolic events. Light skin and hair can also be present. Biochemical features include

increased urinary homocystine and methionine

20/133 diseases for CBS (see all 133): About MalaCards

homocystinuria glycine n-methyltransferase deficiency ectopia lentis methionine adenosyltransferase deficiency

neural tube defect homocystinuria due to cbs deficiency thrombosis, hyperhomocysteinemic homocysteine

tinea manuum lens subluxation diffuse large b-cell lymphoma cleft lip/palate

methylmalonic aciduria and homocystinuria pityriasis versicolor deep vein thrombosis spina bifida

arterial occlusive disease b-cell lymphomas mthfr deficiency retinal vein occlusion

12 diseases from the University of Copenhagen DISEASES database for CBS:

Homocystinuria Hyperhomocysteinemia Apraxia Progressive supranuclear palsy

Frontotemporal dementia Aphasia Tinea manuum Ideomotor apraxia

Tinea corporis Neurodegenerative disease Pityriasis versicolor Trichosporonosis

10/64 Novoseek disease relationships for CBS gene (see all 64) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
homocystinuria	97.4	249	8744616 (4), 11338767 (3), 14744647 (3), 12007221 (3) (see all 99)
hyperhomocysteinemia	91.9	86	2011158 (4), 15386278 (3), 18987302 (2), 16375773 (2) (see all 51)
hypermethioninemia	85.8	6	12765841 (1), 10674710 (1), 15972722 (1)
ectopia lentis	81.5	2	11596648 (1), 10564686 (1)
homocysteinemia	81.4	7	9587026 (1), 2407253 (1), 1445498 (1), 8364009 (1) (see all 6)
vascular diseases	73.7	35	2011158 (3), 11216902 (2), 9712328 (2), 9848890 (2) (see all 23)
folate deficiency	71	8	2007933 (1), 11569694 (1), 16575899 (1), 8364009 (1) (see all 6)
neural tube defects	67.1	5	9712534 (1), 10517251 (1), 12725044 (1), 9084933 (1)
down syndrome	60.4	28	11391481 (2), 16541333 (2), 16115349 (1), 11415440 (1) (see all 13)
mental retardation	55.8	11	11596648 (1), 14744647 (1), 16160063 (1), 16274669 (1) (see all 8)

Genatlas disease: CBS

homocystinuria,pyridoxine responsive or not responsive forms,neural tube defect,no evidence of association with NTD in

Netherlands and U.K.,interacting with huntingtin

GeneTests: CBS

Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency

Genetic Association Database (GAD): CBS
Human Genome Epidemiology (HuGE) Navigator: CBS (180 documents)

Export disorders for CBS gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for CBS gene, integrated from 9 sources (see all 653):
(articles sorted by number of sources associating them with CBS)

Utopia: connect your pdf to the dynamic
world of online information

The human cystathionine beta-synthase (CBS) gene: complete sequence, alternative splicing, and polymorphisms. (PubMed id 9790750)^{1, 2, 3, 9} Kraus J.P.... Kozich V. (1998)
The cystathionine beta-synthase (CBS) mutation c.1224-2A>C in Central Europe: vitamin B6 nonresponsiveness and a common ancestral haplotype. (PubMed id 15365998)^{1, 2, 7, 9} Linnebank M.... Koch H.G. (2004)
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. (PubMed id 12173932)^{1, 2, 7, 9} Taoka S.... Banerjee R. (2002)
A missense mutation (I278T) in the cystathionine beta-synthase gene prevalent in pyridoxine-responsive homocystinuria and associated with mild clinical phenotype. (PubMed id 7611293)^{1, 2, 4, 9} Shih V.E.... Ramesh V. (1995)
High homocysteine and thrombosis without connective tissue disorders are associated with a novel class of cystathionine beta-synthase (CBS) mutations. (PubMed id 12007221)^{1, 2, 9} Maclean K.N.... Kraus J.P. (2002)
Human cystathionine beta-synthase is a target for sumoylation. (PubMed id 17087506)^{1, 2, 9} Kabil O.... Banerjee R. (2006)
A 31 bp VNTR in the cystathionine beta-synthase (CBS) gene is associated with reduced CBS activity and elevated post-load homocysteine levels. (PubMed id 11528503)^{1, 4, 9} Lievers K.J....Blom H.J. (2001)
Cystathionine beta-synthase polymorphisms and hyperhomocysteinaemia: an association study. (PubMed id 12529702)^{1, 4, 9} Lievers K.J....Blom H.J. (2003)
A yeast assay for functional detection of mutations in the human cystathionine beta-synthase gene. (PubMed id 8528202)^{1, 2, 9} Kruger W.D. and Cox D.R. (1995)
Identical genotypes in siblings with different homocystinuric phenotypes: identification of three mutations in cystathionine beta- synthase using an improved bacterial expression system. (PubMed id 7981678)^{1, 2, 9} de Franchis R.... Kraus J.P. (1994)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 875	HGNC: 1550	AceView: CBS	Ensembl:ENSG00000160200	euGenes: HUgn875
ECgene: CBS	Kegg: 875	H-InvDB: CBS

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for CBS	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for CBS	Genetics and Cytogenetics in Oncology and Haematology
CBS mutation database	http://cbs.lf1.cuni.cz/index.php
GeneReviews	http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CBS

Intellectual Property for CBS gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for CBS gene:
Search GeneIP for patents involving CBS

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

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Fatty Liver
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CBS Gene

cystathionine-beta-synthase

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