AiPD: Autoinhibited Protein Database

P35520

Gene name	CBS
Protein name	Cystathionine beta-synthase
Names	Beta-thionase, Serine sulfhydrase
Species	Homo sapiens (Human)
KEGG Pathway	hsa:875
EC number	4.2.1.22: Hydro-lyases
Protein Class	CYSTATHIONINE BETA-SYNTHASE (PTHR10314)

Descriptions

Cystathionine beta-synthase (CBS) is a key regulatory point in the biosynthesis of cysteine via the transsulfuration pathway. CBS is activated by S-adenosyl-L-methionine (AdoMet) by inducing a conformational change involving a noncatalytic C-terminal region spanning residues 414-551. The discovery of mutants (S466L and I435T) from patients represents the autoinhibitory role of the C-terminal region.

Autoinhibitory domains (AIDs)

Target domain	37-413 (Catalytic domain)
Relief mechanism	Ligand binding, Cleavage, Others
Assay	Deletion assay, Mutagenesis experiment, Structural analysis

AID

414-551 (C-terminal autoinhibitory domain)

Target domain

37-413 (Catalytic domain)

Relief mechanism

Ligand binding (S-adenosyl-L-methionine binding), Cleavage (Proteolytic cleavage of autoinhibitory domain), Others (Thermal denaturation)

Assay

Deletion assay, Mutagenesis experiment, Structural analysis

Accessory elements

No accessory elements

References

Janosík M et al. (2001) "Regulation of human cystathionine beta-synthase by S-adenosyl-L-methionine: evidence for two catalytically active conformations involving an autoinhibitory domain in the C-terminal region", Biochemistry, 40, 10625-33

Ereño-Orbea J et al. (2014) "Structural insight into the molecular mechanism of allosteric activation of human cystathionine β-synthase by S-adenosylmethionine", Proceedings of the National Academy of Sciences of the United States of America, 111, E3845-52

Autoinhibited structure

Activated structure

13 structures for P35520

Entry ID	Method	Resolution	Chain	Position	Source
1JBQ	X-ray	260 A	A/B/C/D/E/F	2-413	PDB
1M54	X-ray	290 A	A/B/C/D/E/F	44-406	PDB
4COO	X-ray	200 A	A/B	1-551	PDB
4L0D	X-ray	297 A	A/B	1-551	PDB
4L27	X-ray	339 A	A/B/C/D	2-551	PDB
4L28	X-ray	263 A	A/B/C/D	2-551	PDB
4L3V	X-ray	363 A	A/B/C	2-551	PDB
4PCU	X-ray	358 A	A/B	1-551	PDB
4UUU	X-ray	171 A	A/B	406-547	PDB
5MMS	X-ray	280 A	A/B/C/D/E/F	1-408	PDB
7QGT	X-ray	269 A	A/B	1-551	PDB
8STW	X-ray	240 A	A/B/C/D/E/F	44-406	PDB
AF-P35520-F1	Predicted				AlphaFoldDB

523 variants for P35520

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
CA324871 rs546530618 RCV001241147 RCV000200313	2	P>L	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
RCV000478091 rs748695461 RCV000409151	7	Q>missing	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
rs1057516552 RCV000409242	9	E>missing	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
rs779250698 RCV000723446 RCV000279971	10	V>missing	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
RCV000251012 rs201827340 RCV000359251 CA10587951 VAR_046921 COSM1031138 RCV000466468	18	R>C	associated with 1/3 to 2/3 the enzyme activity of the wild-type Classic homocystinuria endometrium [UniProt, ClinVar, Cosmic]	Yes	ClinGen cosmic curated ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV000648122 RCV000197426 CA321891 rs763151207	22	H>R	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV001833697 rs759682004 CA321104045 COSM3785473 RCV001091466	24	A>V	pancreas Classic homocystinuria [Cosmic, ClinVar]	Yes	ClinGen cosmic curated ClinVar ExAC dbSNP gnomAD
RCV001855274 CA321103958 RCV000617634 rs904453895	36	K>E	HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP gnomAD
RCV000229516 RCV000620035 rs759502207 CA10583892 RCV001658051	45	R>Q	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
VAR_008049 rs148865119 CA325105	49	P>L	CBSD; decreased expression; no effect on cystathionine beta-synthase activity; increased homotetramer formation [UniProt]	Yes	ClinGen UniProt ESP ExAC TOPMed dbSNP gnomAD
RCV000674825 rs1555876784	51	R>missing	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
CA321707 RCV000409663 rs199948079	54	W>*	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
CA321103816 rs555959266 VAR_008050	58	R>W	CBSD; linked with V-114; 18% of activity [UniProt]	Yes	ClinGen UniProt ExAC dbSNP gnomAD
CA410602253 VAR_021790 rs1191141364	65	H>R	CBSD; decreased cystathionine beta-synthase activity; inhibited by AdoMet and AdoHcy; decreased homotetramer formation [UniProt]	Yes	ClinGen UniProt dbSNP gnomAD
rs2229413 CA323808 RCV000199276 RCV000691905	70	P>L	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
RCV001546889 rs762862715 CA321100449 RCV001248604 RCV000621470	74	P>L	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs786204608 VAR_002171 CA274218 RCV000169367	78	P>R	CBSD; severe form; associated in cis with N-102; decreased cystathionine beta-synthase activity; decreased homotetramer formation Classic homocystinuria [UniProt, ClinVar]	Yes	ClinGen ClinVar UniProt dbSNP gnomAD
rs863223435 CA319849 VAR_008051 RCV000195506	85	G>R	CBSD; loss of cystathionine beta-synthase activity [UniProt]	Yes	ClinGen ClinVar UniProt dbSNP gnomAD
RCV000557426 CA410602047 rs1347662650	95	I>T	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP gnomAD
RCV001854831 rs749697783 CA10583890 RCV000229409	99	F>L	Classic homocystinuria HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV001704553 RCV000459701 CA16616548 RCV000497848 rs112029370	99	F>Y	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
rs786204757 VAR_021791 CA274473 RCV000169617	101	L>P	CBSD; common mutation in Irish population; loss of activity Classic homocystinuria [UniProt, ClinVar]	Yes	ClinGen ClinVar UniProt TOPMed dbSNP
rs369644531 RCV000310277 CA10653007	101	L>V	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
VAR_002173 RCV000169368 rs786204609 CA274220	102	K>N	CBSD; associated in cis with R-78; decreased cystathionine beta-synthase activity; decreased homotetramer formation Classic homocystinuria [UniProt, ClinVar]	Yes	ClinGen ClinVar UniProt dbSNP gnomAD
RCV000199752 RCV000248928 RCV000588375 RCV000535881 rs778220779 CA324303 VAR_021792	109	C>R	Homocystinuria Classic homocystinuria CBSD; loss of activity [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt TOPMed dbSNP gnomAD
RCV000200823 CA113878 RCV000590659 COSM300854 rs121964964 VAR_002174 RCV000000140 RCV000490533	114	A>V	Homocystinuria large_intestine Classic homocystinuria Homocystinuria, pyridoxine-responsive CBSD; mild form; when linked with W-58 severe form; decreased cystathionine beta-synthase activity; decreases homotetramer formation by promoting formation of larger aggregates [ClinVar, Cosmic, UniProt]	Yes	ClinGen cosmic curated ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA273957 RCV000169116 VAR_008053 rs760214620	116	G>R	Classic homocystinuria CBSD [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC dbSNP gnomAD
RCV001138042 rs1982753226	117	S>C	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
rs763385546 CA10644745 RCV000368495	118	V>M	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
RCV001344817 rs1982750491	120	D>G	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
CA321269 RCV000475484 VAR_008054 rs775992753 RCV000196859	121	R>C	Classic homocystinuria CBSD [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC dbSNP gnomAD
CA274172 RCV000169322 rs770095972 VAR_008055 COSM1031132	121	R>H	Classic homocystinuria endometrium CBSD [ClinVar, Cosmic, UniProt]	Yes	ClinGen cosmic curated ClinVar UniProt ExAC TOPMed dbSNP gnomAD
RCV001857669 rs770095972 CA275933 RCV000190373 VAR_008056	121	R>L	Classic homocystinuria HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED CBSD; mild form [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC TOPMed dbSNP gnomAD
CA410601850 rs1555875387 RCV000550221	123	S>R	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
CA275291 RCV000178709 VAR_002175 RCV000723426 rs781444670	125	R>Q	Classic homocystinuria CBSD; severe form; when linked with D-131 moderate form; loss of cystathionine beta-synthase activity; decreased homotetramer formation [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC TOPMed dbSNP gnomAD
CA10644742 RCV000667483 rs886057100 VAR_008057	125	R>W	Classic homocystinuria CBSD; exhibits an activity lower than 4% of the wild-type enzyme; absent capacity to form multimeric quaternary structure [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt dbSNP gnomAD
RCV000669819 rs755625628	126	M>missing	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
CA410601821 VAR_008059 rs374593242	128	E>D	CBSD [UniProt]	Yes	ClinGen UniProt ExAC dbSNP gnomAD
VAR_002176 RCV000534364 rs1555875351 CA410601785	131	E>D	Classic homocystinuria CBSD; linked with Q-125; loss of activity [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA16616276 rs779011920 RCV000462847	132	R>H	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV001833290 rs140002610 CA10587954 RCV001859452 RCV000247887	132	R>S	Classic homocystinuria HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
RCV000198043 rs539326697 CA322517 RCV000243532 RCV001271170	133	D>N	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
RCV001231415 CA323396 rs766958673 RCV000198867	134	G>A	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV000648115 CA321097659 rs147474549	134	G>R	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA320927 RCV000196511 RCV000469139 rs147474549	134	G>R	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs1555875325 RCV000674577	135	T>missing	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
rs1057517083 RCV000411736	135	T>missing	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
RCV000549296 CA321097621 rs144832032	135	T>M	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
rs121964965 RCV000000143 CA113883 VAR_008060	139	G>R	Homocystinuria, pyridoxine-responsive CBSD; mild form [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ESP ExAC TOPMed dbSNP gnomAD
VAR_021793 rs370167302 CA410601680	143	I>M	CBSD; 4% of activity; stable [UniProt]	Yes	ClinGen UniProt ExAC TOPMed dbSNP gnomAD
rs121964966 RCV001264024	144	E>*	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
rs121964966 RCV000723427 RCV000000144 RCV000169074 VAR_002177 CA113885	144	E>K	CBSD; loss of cystathionine beta-synthase activity; impaired stimulation by AdoMet and AdoHcy; decreased homotetramer formation Classic homocystinuria Homocystinuria, pyridoxine-responsive [UniProt, ClinVar]	Yes	ClinGen ClinVar UniProt ExAC TOPMed dbSNP gnomAD
RCV000538588 RCV001755867 CA321097472 rs121964966	144	E>Q	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV000625555 RCV000000139 rs121964963 VAR_002178 CA113876	145	P>L	Classic homocystinuria Homocystinuria, pyridoxine-responsive CBSD [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt dbSNP gnomAD
RCV000411624 CA16042005 VAR_008061 rs755952006	148	G>R	Classic homocystinuria CBSD; loss of cystathionine beta-synthase activity; impaired stimulation by AdoMet and AdoHcy; loss of homotetramer formation [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC TOPMed dbSNP gnomAD
rs373782713 CA321097418 VAR_008062	151	G>R	CBSD [UniProt]	Yes	ClinGen UniProt ESP ExAC TOPMed dbSNP gnomAD
RCV000689266 CA320011 rs745704046	153	G>R	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
rs1429138569 VAR_008065 CA410601506	155	A>T	CBSD; complete loss of activity; severely affects homotetramer formation by promoting formation of larger aggregates [UniProt]	Yes	ClinGen UniProt dbSNP gnomAD
RCV000412346 rs767036273	156	L>missing	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
rs199817801 RCV000527354 CA10587952 RCV000242064 RCV001589301	157	A>T	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar 1000Genomes dbSNP gnomAD
RCV000704014 rs1234354755 CA410601405	165	C>G	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
rs1347651454 VAR_002179 CA410601403	165	C>Y	CBSD; severe form; protein expression is comparable to wild-type; loss of cystathionine beta-synthase activity; no effect on homotetramer formation [UniProt]	Yes	ClinGen UniProt dbSNP gnomAD
VAR_002180 RCV000458159 CA113895 rs121964970 RCV000250042 RCV000000150 RCV000179250	168	V>M	Classic homocystinuria Homocystinuria, pyridoxine-responsive CBSD [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC TOPMed dbSNP gnomAD
VAR_008066 rs762065361 CA410601279	176	E>K	CBSD; severe form; loss of cystathionine beta-synthase activity; inhibited by AdoMet; severely decreases homotetramer formation by promoting formation of larger aggregates [UniProt]	Yes	ClinGen UniProt ExAC dbSNP gnomAD
RCV001264023 rs1982601982	177	K>*	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
rs370843514 RCV000279590 CA10650559	178	V>M	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ESP dbSNP gnomAD
RCV000675172 rs794727835 RCV000413538	179	D>missing	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
VAR_008067 RCV000672889 CA410601186 rs1555875010	180	V>A	CBSD; decreased cystathionine beta-synthase activity; decreases homotetramer formation Classic homocystinuria [UniProt, ClinVar]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA321096193 rs138314784 RCV000813541	182	R>Q	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ESP ExAC dbSNP gnomAD
rs374464810 RCV000251610 RCV000541664 CA10587946	183	A>V	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ESP TOPMed dbSNP gnomAD
VAR_008068 rs121964973 RCV000589097 RCV000576767 RCV000195441 RCV000000155 CA113904	191	T>M	CBSD; moderate and severe forms; loss of cystathionine beta-synthase activity; absent capacity to form multimeric quaternary structure Homocystinuria Classic homocystinuria Homocystinuria, pyridoxine-nonresponsive [UniProt, ClinVar]	Yes	ClinGen ClinVar UniProt TOPMed dbSNP gnomAD
CA321096025 RCV000700809 rs555751528	196	R>S	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC dbSNP gnomAD
CA321095994 VAR_066099 rs758712880	200	P>L	CBSD [UniProt]	Yes	ClinGen UniProt ExAC TOPMed dbSNP gnomAD
RCV001276191 RCV000197936 CA322403 rs372679328	204	V>M	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA324707 RCV000648123 rs369220569 RCV000200147	206	V>M	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
CA16616544 RCV000786286 RCV000457277 rs1060500683	208	W>R	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP gnomAD
RCV001242770 rs201118737 CA321095900	211	K>R	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC dbSNP gnomAD
RCV001276190 rs2298758 RCV000196277 CA320697	212	N>K	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs758703098 RCV001264022	213	E>*	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
rs758703098 RCV000997830 RCV001858865 COSM1031122 CA321095865	213	E>K	endometrium HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED [Cosmic, ClinVar]	Yes	ClinGen cosmic curated ClinVar ExAC TOPMed dbSNP gnomAD
RCV000673555 rs1555874874 CA410600786	217	S>F	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
CA410600738 rs1568932262 RCV000778918	222	Q>*	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs139456571 COSM1031120 CA322963 RCV000243693 RCV000556147 RCV000726462	224	R>C	Classic homocystinuria endometrium [ClinVar, Cosmic]	Yes	ClinGen cosmic curated ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
VAR_002181 CA321095515 rs761647392	224	R>H	CBSD [UniProt]	Yes	ClinGen UniProt ExAC dbSNP gnomAD
CA16042003 VAR_008070 rs763835246 RCV000412334	226	A>T	Classic homocystinuria CBSD; presents 20% of the wild-type activity; dramatically reduced capacity to form multimeric quaternary structure [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC dbSNP gnomAD
RCV001175076 RCV001833732 VAR_021794 rs1464223176	228	N>K	CBSD; loss of cystathionine beta-synthase activity; decreased homotetramer formation Homocystinuria Classic homocystinuria [UniProt, ClinVar]	Yes	ClinVar UniProt dbSNP
RCV001193391 CA410600615 rs1464223176	228	N>K	Homocystinuria [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP gnomAD
VAR_046928 RCV000669206 CA410600619 rs1555874803	228	N>S	CBSD; has significantly decreased levels of enzyme activity Classic homocystinuria [UniProt, ClinVar]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000198642 RCV000169175 rs775351239	230	L>missing	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
COSM3423979 rs773734233 CA324489 VAR_008071	234	D>N	large_intestine CBSD; decreased cystathionine beta-synthase activity; changed localization; decreased interaction with pyridoxal 5'-phosphate; no effect on homotetramer formation [Cosmic, UniProt]	Yes	ClinGen cosmic curated UniProt ExAC TOPMed dbSNP gnomAD
rs1057517435 RCV000409103	236	T>missing	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
CA410600518 RCV000688536 rs1568931765	237	A>V	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV001264021 rs1982493665	239	E>*	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
RCV001277493 rs746892057	247	K>N	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
CA321094365 RCV000691790 rs767397847	249	D>N	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
CA322755 RCV000800742 rs863223431 RCV000198250	250	M>I	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
rs1176770868 CA410600363 RCV000671309	251	L>P	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
rs1982371715 RCV001277492	255	V>L	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
CA274140 rs758236584 VAR_002183 RCV000169294 RCV000197988	257	T>M	Classic homocystinuria CBSD; moderate to severe form; protein expression is comparable to wild-type; significant decrease of enzyme activity [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC TOPMed dbSNP gnomAD
VAR_008072 RCV000200469 rs149119723 RCV000180461 CA275440	262	T>M	Classic homocystinuria CBSD; moderate form [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ESP ExAC TOPMed dbSNP gnomAD
CA113891 RCV000621987 RCV000000147 RCV000469164 rs121964969 VAR_008074	266	R>K	CBSD; mild form; decreased cystathionine beta-synthase activity; decreased homotetramer formation; no effect on heme-binding; decreased stability Classic homocystinuria Homocystinuria, pyridoxine-responsive [UniProt, ClinVar]	Yes	ClinGen ClinVar UniProt dbSNP gnomAD
CA321094214 RCV000673238 RCV000507871 rs528689432	272	C>*	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs5742905 VAR_002184 CA113880	278	I>T	CBSD; mild to severe form; common mutation; decreased expression; loss of cystathionine beta-synthase activity; impaired stimulation by AdoMet and AdoHcy; severely affects homotetramer formation by promoting formation of larger aggregates [UniProt]	Yes	ClinGen UniProt 1000Genomes ESP TOPMed dbSNP
COSM725043 CA321091525 rs765811825 RCV000678282 RCV001572365	283	E>K	lung Classic homocystinuria [Cosmic, ClinVar]	Yes	ClinGen cosmic curated ClinVar ExAC dbSNP gnomAD
RCV000243626 RCV001276188 rs1555874223	283	E>S	Classic homocystinuria [ClinVar]	Yes	ClinVar Ensembl dbSNP
CA323231 rs147040567 RCV000731875 RCV000648120	286	I>V	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
VAR_046933 CA321091505 rs141502207 RCV000671575	288	A>T	CBSD; protein expression is comparable to wild-type; significant decrease of enzyme activity Classic homocystinuria [UniProt, ClinVar]	Yes	ClinGen ClinVar UniProt ESP ExAC dbSNP gnomAD
CA321091497 rs760912339 VAR_002185	290	P>L	CBSD [UniProt]	Yes	ClinGen UniProt ExAC TOPMed dbSNP gnomAD
CA321091405 RCV000558244 rs562530775	296	T>M	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC dbSNP gnomAD
RCV001140939 CA321091411 rs562530775	296	T>R	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC dbSNP gnomAD
RCV000411137 rs746575551 CA16042000	301	Y>*	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs779270933 VAR_008076 CA321091356	302	E>K	CBSD; no effect on cystathionine beta-synthase activity; inhibited by AdoHcy and impaired activation by AdoMet; no effect on homotetramer formation [UniProt]	Yes	ClinGen UniProt ExAC TOPMed dbSNP gnomAD
VAR_002186 CA113874 rs121964962 COSM444547	307	G>S	CBSD; moderate to severe form; linked with D-534; common mutation; loss of cystathionine beta-synthase activity; impaired stimulation by AdoMet and AdoHcy; no effect on homotetramer formation breast [UniProt, Cosmic]	Yes	ClinGen cosmic curated UniProt ESP ExAC TOPMed dbSNP gnomAD
CA321091315 RCV000802038 rs540013184	309	D>N	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
CA410599956 rs1438933819 RCV001257457	314	V>A	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
rs769541394 RCV000468076 RCV000755893 CA16616303	318	T>M	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
VAR_008078 RCV000780081 RCV001000797 CA16041998 RCV001861384 rs781567152 RCV000410016	320	V>A	Homocystinuria CBSD; has 36% of wild-type enzyme activity Classic homocystinuria HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC dbSNP gnomAD
CA321445 RCV000363392 rs863223432 RCV000197013	323	W>*	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
RCV000755891 rs758447354 RCV000665455 CA321090579	328	D>N	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
VAR_008079 rs777919630 CA323703	331	A>E	CBSD [UniProt]	Yes	ClinGen UniProt TOPMed dbSNP gnomAD
CA239449 RCV000173977 RCV001252181 VAR_002187 rs777919630	331	A>V	Intellectual disability CBSD [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt TOPMed dbSNP gnomAD
RCV000670102 rs1555873925	336	R>*	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
VAR_002188 rs398123151 CA274154	336	R>C	CBSD; protein expression is comparable to wild-type; loss of activity; absent capacity to form multimeric quaternary structure [UniProt]	Yes	ClinGen UniProt ExAC dbSNP gnomAD
CA16041997 VAR_008080 RCV000409189 rs760417941	336	R>H	Classic homocystinuria CBSD; mild form; no effect on expression; exhibits an activity lower than 4% of the wild-type enzyme; altered stimulation by AdoMet; absent capacity to form multimeric quaternary structure [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC dbSNP gnomAD
RCV000199004 RCV001276187 rs372822486 CA323553	337	M>L	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ESP ExAC dbSNP gnomAD
RCV000196067 RCV001828020 RCV000243887 rs372822486 CA320468	337	M>V	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ESP ExAC dbSNP gnomAD
VAR_021798 COSM1740703 CA273978 RCV000197584 RCV000169132 rs771298943	347	G>S	CBSD; protein expression is comparable to wild-type; loss of activity Classic homocystinuria haematopoietic_and_lymphoid_tissue [UniProt, ClinVar, Cosmic]	Yes	ClinGen cosmic curated ClinVar UniProt ExAC dbSNP gnomAD
VAR_008082 CA113902 rs121964972	353	T>M	CBSD; protein expression is comparable to wild-type; significant decrease of enzyme activity [UniProt]	Yes	ClinGen UniProt ESP ExAC TOPMed dbSNP gnomAD
RCV000667592 rs863223436	354	V>missing	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
CA321689843 VAR_008083 rs267606146	354	V>M	CBSD [UniProt]	Yes	ClinGen UniProt Ensembl dbSNP
VAR_021800 CA410398205 rs1192581453	355	A>P	CBSD [UniProt]	Yes	ClinGen UniProt dbSNP gnomAD
CA321689820 RCV000618875 rs370163789 RCV001275692	356	V>A	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
RCV000473415 CA324052 rs863223437 RCV000199512	357	A>G	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP gnomAD
VAR_046934 rs745764562 CA321689765	361	A>T	CBSD [UniProt]	Yes	ClinGen UniProt ExAC TOPMed dbSNP gnomAD
RCV000648114 CA658799452 rs1555873407	361	A>T	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs370851632 RCV000576355 CA321689756	361	A>V	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ESP TOPMed dbSNP gnomAD
rs117687681 VAR_008084 CA324371	369	R>C	CBSD; when linked with C-491 severe form; decreased cystathionine beta-synthase activity; decreased homotetramer formation [UniProt]	Yes	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
VAR_002189 CA321689739 rs11700812	369	R>H	CBSD [UniProt]	Yes	ClinGen UniProt ExAC dbSNP gnomAD
rs757920190 RCV000482454 VAR_008085 CA16621012	370	C>Y	CBSD [UniProt]	Yes	ClinGen ClinVar UniProt ExAC dbSNP gnomAD
RCV000196393 CA320805 RCV000410135 VAR_002190 rs372010465	371	V>M	Classic homocystinuria CBSD [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ESP ExAC TOPMed dbSNP gnomAD
rs775354680 CA324632 RCV001835719 RCV000200072	372	V>F	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA410397989 VAR_046935 rs1170128038	376	D>N	CBSD; has significantly decreased levels of enzyme activity [UniProt]	Yes	ClinGen UniProt dbSNP gnomAD
RCV000480748 VAR_021801 RCV000169171 rs763036586 CA274005	379	R>Q	Classic homocystinuria CBSD; exhibits an activity lower than 4% of the wild-type enzyme; absent capacity to form multimeric quaternary structure [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC dbSNP gnomAD
rs769080151 RCV000763061 VAR_046936 RCV000196320 CA320740	379	R>W	Classic homocystinuria CBSD [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC dbSNP gnomAD
RCV000000145 rs121964967 VAR_002191 CA113887	384	K>E	CBSD; severe form Homocystinuria, pyridoxine-responsive [UniProt, ClinVar]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA410397847 RCV001540545 rs1304669003 RCV001004615	384	K>N	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
RCV000396187 rs745438246	400	E>missing	Homocystinuria [ClinVar]	Yes	ClinVar dbSNP
rs371214833 CA321688584 RCV000555545	402	L>P	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ESP ExAC dbSNP gnomAD
RCV001861821 RCV000673393 rs1555872822	404	E>missing	Classic homocystinuria HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED [ClinVar]	Yes	ClinVar dbSNP
RCV001264020 rs1981682654	404	E>*	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
RCV001275691 rs780555741 RCV000486837	406	K>missing	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
RCV000174443 rs794727083 RCV000724407 RCV001852126	406	K>missing	Classic homocystinuria HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED [ClinVar]	Yes	ClinVar dbSNP
RCV000588547 rs1361324844 RCV000666270	408	W>missing	Homocystinuria Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
RCV000196138 CA320559 RCV001275690 rs863223433	408	W>*	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV000675050 CA113898 RCV000000152 rs28934892 VAR_021802 RCV000522394	422	P>L	Classic homocystinuria HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED CBSD; changed cystathionine beta-synthase activity; impaired stimulation by AdoMet; does not affect homotetramer formation [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt dbSNP gnomAD
RCV000197292 RCV000584030 VAR_074592 CA321746 rs863223434	427	P>L	CBSD; no effect on cystathionine beta-synthase activity; altered stimulation by AdoMet [UniProt]	Yes	ClinGen ClinVar UniProt dbSNP gnomAD
VAR_008088 CA410397130 rs1555872506 RCV000667146	434	T>N	Classic homocystinuria CBSD [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000666335 CA410397108 rs1282119406	435	I>T	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
RCV000169494 rs756467921 RCV000587586 CA274364 VAR_008090	439	R>Q	CBSD; no effect on cystathionine beta-synthase activity; increased homotetramer formation Classic homocystinuria [UniProt, ClinVar]	Yes	ClinGen ClinVar UniProt ExAC dbSNP gnomAD
CA321688011 RCV001592989 rs780508029 RCV000801252	439	R>W	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
RCV000412412 CA16041996 rs1057516645	441	K>*	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
VAR_002192 CA113893 rs28934891	444	D>N	CBSD; decreased expression; no effect on cystathionine beta-synthase activity; altered stimulation by AdoMet; increased homotetramer formation [UniProt]	Yes	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs757347527 CA321687985 RCV000688358	446	A>V	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
RCV000490064 RCV001856890 CA321687971 rs865989946 RCV001273208	448	V>M	Classic homocystinuria HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP gnomAD
CA322659 rs367962613 RCV000198168 RCV001853129 RCV000764259	451	E>D	Classic homocystinuria HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED [ClinVar]	Yes	ClinGen ClinVar ESP ExAC dbSNP gnomAD
RCV000248732 CA10587940 RCV000990350 rs886039146	453	G>E	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
CA10653005 RCV000339973 rs886057099	453	G>W	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
rs752596508 CA321687493 RCV000688137 COSM327387	460	T>M	Classic homocystinuria haematopoietic_and_lymphoid_tissue [ClinVar, Cosmic]	Yes	ClinGen cosmic curated ClinVar ExAC dbSNP gnomAD
VAR_008091 RCV000000153 RCV000675119 CA113900 rs121964971	466	S>L	CBSD; increased cystathionine beta-synthase activity; impaired stimulation by AdoMet and AdoHcy; decreased homotetramer formation Classic homocystinuria HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED [UniProt, ClinVar]	Yes	ClinGen ClinVar UniProt ExAC TOPMed dbSNP gnomAD
CA324881 RCV000764258 RCV000200328 rs201098477	471	G>R	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs886038933 CA10587935 RCV000253951 RCV001273207	479	V>A	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
RCV000403386 rs886057098 CA10653004	485	K>E	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs1339830457 CA410395895 VAR_008092	491	R>C	CBSD; linked with C-369 [UniProt]	Yes	ClinGen UniProt dbSNP gnomAD
RCV000483442 CA10587936 RCV001299974 RCV000249170 rs747419767	491	R>H	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV000482429 RCV000463603 CA16616512 rs772344567	495	T>M	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV000593857 RCV001867959 RCV000984247 rs1555871188	500	S>missing	Classic homocystinuria HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED [ClinVar]	Yes	ClinVar dbSNP
CA321686665 rs755106884 VAR_074594	500	S>L	CBSD; no effect on cystathionine beta-synthase activity; altered stimulation by AdoMet [UniProt]	Yes	ClinGen UniProt ExAC TOPMed dbSNP gnomAD
rs1060500680 RCV000467733 COSM1682018 CA16616509	509	A>T	large_intestine Classic homocystinuria [Cosmic, ClinVar]	Yes	ClinGen cosmic curated ClinVar TOPMed dbSNP gnomAD
RCV000669346 rs1555871095	516	I>missing	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
RCV000819074 rs201916339 CA321684767	522	G>R	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
RCV000169113 rs786204466	523	K>missing	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
rs1555869958 CA410394837 RCV000672976	526	Q>*	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV000594688 CA321684717 rs748953468 RCV000696029	532	G>R	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
rs1555869934 RCV000666158	535	T>missing	Classic homocystinuria [ClinVar]	Yes	ClinVar dbSNP
VAR_002194 CA113889 rs121964968 RCV000000146 RCV000675072	539	L>S	Classic homocystinuria Homocystinuria, pyridoxine-responsive CBSD; loss of cystathionine beta-synthase activity; impaired stimulation by AdoMet and AdoHcy; loss of homotetramer formation [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt 1000Genomes ExAC dbSNP gnomAD
rs1365095601 CA410394475 RCV000674493	552	K>C	Classic homocystinuria [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
RCV000176975 rs769766030	1	M>T		No	ClinVar dbSNP
rs748832676 CA321104211	4	E>D		No	ClinGen ExAC
CA321104208 rs528184368	6	P>S		No	ClinGen 1000Genomes ExAC gnomAD
CA321104173 rs919403971	8	A>G		No	ClinGen TOPMed gnomAD
CA410602597 rs758092887	9	E>K		No	ClinGen ExAC gnomAD
rs758092887 CA321104168	9	E>Q		No	ClinGen ExAC gnomAD
CA410602591 rs1479837105	10	V>M		No	ClinGen gnomAD
rs1205411379 CA410602584	11	G>R		No	ClinGen gnomAD
CA321523 rs558259739	12	P>S		No	ClinGen ExAC gnomAD
rs1371674515 CA410602565	14	G>V		No	ClinGen gnomAD
CA321104115 rs750850447	15	C>F		No	ClinGen ExAC gnomAD
CA321104113 rs768172160	17	H>L		No	ClinGen ExAC
rs755850396 CA321104101	18	R>H		No	ClinGen gnomAD
rs201827340 CA321104102	18	R>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA321104095 rs764399291	19	S>L		No	ClinGen ExAC gnomAD
rs775785018 CA321104075	23	S>L		No	ClinGen ExAC TOPMed gnomAD
CA410602515 rs1378750597	23	S>T		No	ClinGen gnomAD
rs1484147890 CA410602498	25	K>N		No	ClinGen gnomAD
rs746782366 CA321104037	26	G>A		No	ClinGen ExAC TOPMed gnomAD
rs746782366 CA321104038	26	G>E		No	ClinGen ExAC TOPMed gnomAD
CA410602489 rs771748290	27	S>I		No	ClinGen ExAC gnomAD
CA321104017 rs771748290	27	S>N		No	ClinGen ExAC gnomAD
rs530296903 CA321104010	27	S>R		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA321103977 rs778653743	29	E>K		No	ClinGen ExAC
CA410602464 rs1226779462	31	G>E		No	ClinGen gnomAD
CA321103971 rs753430439	32	S>P		No	ClinGen ExAC gnomAD
rs563211474 CA321103967	33	P>S		No	ClinGen 1000Genomes ExAC gnomAD
rs757899237 CA321103963	34	E>G		No	ClinGen ExAC gnomAD
CA410602444 rs368471318	35	D>N		No	ClinGen ESP ExAC TOPMed gnomAD
CA321103959 rs368471318	35	D>Y		No	ClinGen ESP ExAC TOPMed gnomAD
rs1064795253 CA410602421	38	A>P		No	ClinGen gnomAD
rs1064795253 CA16621018 RCV000483422	38	A>T		No	ClinGen ClinVar dbSNP gnomAD
CA321103957 rs764487170	40	E>D		No	ClinGen ExAC gnomAD
rs1315746924 CA410602398	41	P>L		No	ClinGen gnomAD
rs763389870 CA321103954	41	P>S		No	ClinGen ExAC gnomAD
rs1375321603 CA410602384	43	W>C		No	ClinGen gnomAD
rs1334019279 CA410602377	44	I>M		No	ClinGen gnomAD
rs201372812 RCV000198945 CA323483	45	R>W		No	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs148865119 CA321103880	49	P>R		No	ClinGen ESP ExAC TOPMed gnomAD
rs370983323 CA16621017 RCV000486724	51	R>K		No	ClinGen ClinVar ESP ExAC dbSNP gnomAD
rs748795053 CA410602336	51	R>S		No	ClinGen ExAC gnomAD
rs779777933 CA321103843	52	C>Y		No	ClinGen ExAC gnomAD
CA321103836 rs564501381	53	T>I		No	ClinGen Ensembl
CA410602314 rs1292304665	55	Q>K		No	ClinGen gnomAD
CA410602304 rs1180472259	56	L>P		No	ClinGen gnomAD
CA410602299 rs1295461215	57	G>D		No	ClinGen Ensembl
CA410602301 rs1480938544	57	G>S		No	ClinGen gnomAD
rs758648251 CA321103808	58	R>Q		No	ClinGen ExAC gnomAD
rs376496085 CA321103799	59	P>S		No	ClinGen ESP ExAC gnomAD
rs765352771 CA321103781	60	A>V		No	ClinGen ExAC gnomAD
rs1392721766 CA410602281	61	S>P		No	ClinGen gnomAD
CA321103764 rs199507134	62	E>K		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA410602241 rs1248573959	67	H>Y		No	ClinGen gnomAD
rs760770298 CA321103755	68	T>I		No	ClinGen ExAC gnomAD
rs17849313 CA321103747 VAR_046922	69	A>P		No	ClinGen UniProt Ensembl dbSNP
CA321103742 rs2229413	70	P>R		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA321100463 rs761878715	71	A>E		No	ClinGen ExAC gnomAD
rs761878715 CA410602201	71	A>V		No	ClinGen ExAC gnomAD
CA320825 rs192232907	72	K>I		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs763892068 CA321100454	73	S>C		No	ClinGen ExAC gnomAD
rs1170538361 CA410602186	74	P>S		No	ClinGen gnomAD
rs552179536 CA321100444	75	K>N		No	ClinGen 1000Genomes ExAC gnomAD
CA410602175 rs1601375965	76	I>V		No	ClinGen Ensembl
rs769608918 CA321100441	80	I>V		No	ClinGen ExAC gnomAD
rs1480481730 CA410602142	81	L>V		No	ClinGen TOPMed
CA321100408 rs71322504	82	K>N		No	ClinGen ExAC gnomAD
CA321100406 rs71322504	82	K>N		No	ClinGen ExAC gnomAD
rs776259258 CA321100394	86	D>N		No	ClinGen ExAC gnomAD
CA410602100 rs1239864776	87	T>I		No	ClinGen gnomAD
rs748617584 CA321100365	89	M>I		No	ClinGen ExAC gnomAD
rs772450760 CA322220 RCV001090985	89	M>K		No	ClinGen ClinVar ExAC dbSNP gnomAD
rs71322503 CA321100363	91	R>K		No	ClinGen Ensembl
rs779297627 CA410602053	94	K>N		No	ClinGen ExAC TOPMed gnomAD
rs1347662650 CA410602048	95	I>N		No	ClinGen TOPMed gnomAD
CA410602019 rs112029370	99	F>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs1310019343 CA410602016	100	G>S		No	ClinGen TOPMed gnomAD
CA302971 rs34040148 VAR_008052	102	K>Q		No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs1601375543 CA410601983	105	L>V		No	ClinGen Ensembl
CA321097886 rs121964964	114	A>G		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs377708532 CA321097892	114	A>S		No	ClinGen ExAC gnomAD
rs377708532 CA321097898	114	A>T		No	ClinGen ExAC gnomAD
rs772768738 CA321097853	117	S>I		No	ClinGen ExAC gnomAD
rs1251292223 CA410601874	120	D>N		No	ClinGen gnomAD
rs746251495 CA321097819	124	L>R		No	ClinGen ExAC gnomAD
rs199824647 CA410601828	127	I>M		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs771108045 CA321097797	127	I>T		No	ClinGen ExAC gnomAD
rs892948151 CA321097798	127	I>V		No	ClinGen TOPMed gnomAD
rs1308193541 CA410601827	128	E>K		No	ClinGen gnomAD
CA410601812 rs1373078731	129	D>V		No	ClinGen gnomAD
rs1301672360 CA410601798 RCV000622233	130	A>V		No	ClinGen ClinVar dbSNP gnomAD
CA410601794 rs1360154930	131	E>K		No	ClinGen gnomAD
rs140002610 CA320193	132	R>C		No	ClinGen ESP ExAC TOPMed gnomAD
rs766958673 CA321097649	134	G>E		No	ClinGen ExAC TOPMed gnomAD
rs775937459 CA321097579	136	L>P		No	ClinGen ExAC gnomAD
rs765702034 CA410601736	138	P>A		No	ClinGen ExAC TOPMed gnomAD
rs765702034 CA321097561	138	P>S		No	ClinGen ExAC TOPMed gnomAD
CA321097517 rs771178320	141	T>M		No	ClinGen ExAC gnomAD
rs772225410 CA321097495	143	I>T		No	ClinGen ExAC gnomAD
CA410601650 rs1458998509	146	T>I		No	ClinGen gnomAD
rs373782713 CA321097412	151	G>W		No	ClinGen ESP ExAC TOPMed gnomAD
rs780799772 CA321096729	156	L>P		No	ClinGen ExAC gnomAD
rs1376851289 CA410601475	158	A>E		No	ClinGen gnomAD
CA410601473 rs1376851289	158	A>V		No	ClinGen gnomAD
rs1452995855 CA410601470	159	A>T		No	ClinGen gnomAD
rs751064748 CA321096685	162	G>S		No	ClinGen ExAC
rs1216829353 CA410601414	164	R>C		No	ClinGen gnomAD
CA321096667 rs757935417	164	R>H		No	ClinGen ExAC TOPMed gnomAD
rs1234354755 CA410601408	165	C>S		No	ClinGen gnomAD
rs754246295 CA410601373	167	I>M		No	ClinGen ExAC TOPMed gnomAD
rs121964970 CA410601371	168	V>L		No	ClinGen ExAC TOPMed gnomAD
rs1371228792 CA410601362	169	M>L		No	ClinGen gnomAD
CA321096619 rs750879576	173	M>I		No	ClinGen ExAC gnomAD
CA410601301 rs1172978385	174	S>N		No	ClinGen gnomAD
CA324559 rs762065361	176	E>*		No	ClinGen ExAC gnomAD
rs1064795022 RCV000478922 CA16621016	177	K>N		No	ClinGen ClinVar dbSNP gnomAD
rs1472673650 CA410601263	177	K>T		No	ClinGen gnomAD
CA410601213 rs370843514	178	V>L		No	ClinGen ESP gnomAD
rs759402521 CA321096210	180	V>M		No	ClinGen ExAC gnomAD
rs149649130 CA321096200	182	R>W		No	ClinGen ESP ExAC TOPMed gnomAD
rs374464810 CA321096163	183	A>G		No	ClinGen ESP TOPMed gnomAD
rs772705832 CA321096183	183	A>T		No	ClinGen ExAC gnomAD
CA410601125 rs1435269264	187	E>G		No	ClinGen gnomAD
RCV000497733 CA410601079 rs121964973	191	T>K		No	ClinGen ClinVar TOPMed dbSNP gnomAD
CA321096062 rs754553273	192	P>L		No	ClinGen ExAC gnomAD
rs370089875 CA321096051	194	N>D		No	ClinGen ESP ExAC gnomAD
CA321096036 rs911670352	194	N>S		No	ClinGen TOPMed gnomAD
rs537027536 CA321096003	198	D>N		No	ClinGen 1000Genomes ExAC gnomAD
CA410600914 rs1367873681	205	G>E		No	ClinGen gnomAD
CA410600904 rs1369398275	206	V>A		No	ClinGen gnomAD
CA410600899 rs1462927996 COSM1031124	207	A>T	endometrium [Cosmic]	No	ClinGen cosmic curated gnomAD
CA410600884 rs774174074	208	W>*		No	ClinGen ExAC TOPMed gnomAD
rs774174074 CA321095930	208	W>C		No	ClinGen ExAC TOPMed gnomAD
rs781759129 CA321095905	209	R>Q		No	ClinGen ExAC gnomAD
CA321095924 rs137939628	209	R>W		No	ClinGen ESP ExAC TOPMed gnomAD
rs1481588195 CA410600837	213	E>G		No	ClinGen TOPMed gnomAD
rs1034007575 CA321095812	215	P>L		No	ClinGen TOPMed
CA321095830 rs765471315	215	P>S		No	ClinGen ExAC gnomAD
rs755015303 CA321095810	216	N>S		No	ClinGen ExAC gnomAD
rs1264692707 CA410600764	219	I>T		No	ClinGen gnomAD
rs1455474151 CA410600680	223	Y>D		No	ClinGen gnomAD
rs761647392 CA410600665	224	R>L		No	ClinGen ExAC gnomAD
CA321095500 rs763835246	226	A>P		No	ClinGen ExAC gnomAD
CA321095484 rs775293525	229	P>R		No	ClinGen ExAC TOPMed gnomAD
CA321095493 rs375730175	229	P>T		No	ClinGen ESP ExAC gnomAD
rs1411597530 CA410600601	230	L>Q		No	ClinGen TOPMed
CA321095438 rs981981270	236	T>I		No	ClinGen TOPMed
rs1226723382 CA410600525	237	A>T		No	ClinGen gnomAD
rs1364919198 CA410600508	238	D>A		No	ClinGen gnomAD
CA410600479 rs1601359306	240	I>S		No	ClinGen Ensembl
rs1388788227 CA410600454	242	Q>H		No	ClinGen gnomAD
CA321095385 rs749466749	243	Q>H		No	ClinGen ExAC gnomAD
CA410600396 rs1441519122	246	G>E		No	ClinGen gnomAD
CA410600368 rs863223431	250	M>I		No	ClinGen gnomAD
rs1555874564 CA410600371	250	M>K		No	ClinGen Ensembl
CA321094346 rs777884368	250	M>L		No	ClinGen ExAC TOPMed gnomAD
CA410600348 rs1470764055	254	S>P		No	ClinGen gnomAD
rs1409259346 CA410600340	255	V>G		No	ClinGen gnomAD
rs1000697114 CA321094327	256	G>S		No	ClinGen TOPMed
rs1157774154 CA410600333	256	G>V		No	ClinGen gnomAD
CA410600319 rs1242898623	259	G>D		No	ClinGen gnomAD
rs143124288 CA321094274	259	G>S		No	ClinGen ESP ExAC gnomAD
CA321094265 rs760212248	264	I>T		No	ClinGen ExAC gnomAD
rs1351478245 CA410600283	265	A>V		No	ClinGen gnomAD
rs1337180584 CA410600252	270	E>K		No	ClinGen gnomAD
CA410600237 rs1601355972	272	C>R		No	ClinGen Ensembl
CA410600225 rs1386009525	273	P>L		No	ClinGen gnomAD
CA410600212 rs764638041	275	C>*		No	ClinGen ExAC gnomAD
rs1400846504 CA410600207	276	R>K		No	ClinGen gnomAD
rs756816076 CA321091605	277	I>L		No	ClinGen ExAC
CA410600170 rs1170192852	280	V>A		No	ClinGen gnomAD
CA16043118 rs1057518515 RCV000413391	282	P>S		No	ClinGen ClinVar Ensembl dbSNP
rs786200967 RCV000152935	283	E>K		No	ClinVar Ensembl dbSNP
rs1480171482 CA410600148	284	G>R		No	ClinGen gnomAD
rs1060500681 CA16616516	286	I>T		No	ClinGen Ensembl
CA321091499 rs141502207	288	A>S		No	ClinGen ESP ExAC gnomAD
rs1601352415 CA410600118	289	E>G		No	ClinGen Ensembl
rs760912339 CA410600110	290	P>Q		No	ClinGen ExAC TOPMed gnomAD
rs201155833 CA321091454	291	E>D		No	ClinGen 1000Genomes TOPMed
CA321091438 rs761995096	292	E>*		No	ClinGen ExAC gnomAD
COSM725045 rs761995096 CA321091443	292	E>K	lung [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA16621015 RCV000482632 rs1064795178	292	E>L		No	ClinGen ClinVar Ensembl dbSNP
CA321091423 rs774134517	292	E>V		No	ClinGen ExAC gnomAD
CA321091414 rs562885611	295	Q>E		No	ClinGen 1000Genomes TOPMed
CA410600070 rs1298089659	297	E>*		No	ClinGen gnomAD
CA410600060 rs1568929121	298	Q>P		No	ClinGen Ensembl
rs780856971 CA321091398	300	T>A		No	ClinGen ExAC gnomAD
rs746575551 RCV001268903	301	Y>*		No	ClinVar dbSNP
rs1601352057 CA410600031	303	V>M		No	ClinGen Ensembl
CA410600015 rs1178687976	305	G>W		No	ClinGen gnomAD
CA410599974 rs1323813663	311	I>L		No	ClinGen gnomAD
rs761787042 CA321091300	312	P>H		No	ClinGen ExAC gnomAD
CA321091293 rs774557878	313	T>M		No	ClinGen ExAC gnomAD
CA321091271 rs762823766	314	V>M		No	ClinGen ExAC gnomAD
rs775432669 CA321091261	317	R>G		No	ClinGen ExAC gnomAD
CA410599904 rs1225612737	321	D>G		No	ClinGen gnomAD
rs757588995 CA321090605	322	K>E		No	ClinGen ExAC gnomAD
rs751768786 CA321090592	322	K>T		No	ClinGen ExAC gnomAD
CA321090571 rs765151853	329	E>D		No	ClinGen ExAC gnomAD
rs1165948778 CA410599843	329	E>G		No	ClinGen gnomAD
rs1194877209 CA410599830	331	A>S		No	ClinGen gnomAD
rs1064793703 CA16621014	336	R>C		No	ClinGen Ensembl
CA410599797 rs760417941	336	R>L		No	ClinGen ExAC gnomAD
CA321090519 rs771910579	337	M>R		No	ClinGen ExAC gnomAD
rs1321607022 COSM1031116 CA410599778	340	A>T	endometrium [Cosmic]	No	ClinGen cosmic curated gnomAD
rs1282760211 CA410599773	340	A>V		No	ClinGen gnomAD
CA321090508 rs771298943	347	G>C		No	ClinGen ExAC gnomAD
CA321689884 rs763890444	349	S>G		No	ClinGen ExAC gnomAD
CA321689876 rs973369208	349	S>T		No	ClinGen TOPMed
rs762513900 CA321689870	350	A>S		No	ClinGen ExAC gnomAD
rs1400722415 CA410398252	350	A>V		No	ClinGen gnomAD
CA410398246 rs1160971811	351	G>D		No	ClinGen gnomAD
CA320282 rs774926464 RCV000195902	351	G>R		No	ClinGen ClinVar ExAC dbSNP gnomAD
rs773726723 CA321689841	354	V>A		No	ClinGen ExAC gnomAD
rs1192581453 CA410398206	355	A>T		No	ClinGen gnomAD
CA321689840 RCV000598006 rs772384826	355	A>V		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA410398190 rs370163789	356	V>G		No	ClinGen gnomAD
CA410398197 rs1220129204	356	V>M		No	ClinGen gnomAD
rs1292263120 CA410398188	357	A>T		No	ClinGen gnomAD
CA410398183 rs863223437	357	A>V		No	ClinGen TOPMed gnomAD
rs148589243 CA410398178	358	V>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA239721 rs148589243	358	V>M		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs779940364 CA321689781	359	K>M		No	ClinGen ExAC TOPMed gnomAD
CA410398160 rs1300646763	359	K>N		No	ClinGen gnomAD
CA410398152 rs1365464994	360	A>D		No	ClinGen gnomAD
CA410398157 rs1423323590	360	A>T		No	ClinGen gnomAD
CA410398148 rs1365464994	360	A>V		No	ClinGen gnomAD
RCV000482968 rs1064794540	363	E>missing		No	ClinVar dbSNP
CA410398119 rs1478217276	363	E>K		No	ClinGen gnomAD
rs1265455165 CA410398105	364	L>P		No	ClinGen gnomAD
rs757098275 CA321689743	366	E>K		No	ClinGen ExAC gnomAD
CA410398074 rs1269436351	367	G>S		No	ClinGen gnomAD
rs1601343848 CA410398063	368	Q>*		No	ClinGen Ensembl
CA321689733 rs11700812	369	R>P		No	ClinGen ExAC gnomAD
CA410398046 rs1192694513	370	C>R		No	ClinGen gnomAD
rs372010465 CA410398031	371	V>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs775354680 CA321689710	372	V>I		No	ClinGen ExAC TOPMed gnomAD
rs868467561 CA321689674	375	P>S		No	ClinGen Ensembl
CA321689656 rs920511437	377	S>T		No	ClinGen TOPMed
rs547713475 CA321689653	378	V>L		No	ClinGen 1000Genomes ExAC gnomAD
rs267606145 CA321689644	381	Y>N		No	ClinGen Ensembl
CA410397853 rs1568924550	383	T>I		No	ClinGen Ensembl
rs1421332904 CA410397823	388	D>G		No	ClinGen gnomAD
rs375513996 CA321688595 COSM1534608	388	D>N	lung [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
rs375513996 CA321688594	388	D>Y		No	ClinGen ESP ExAC TOPMed gnomAD
rs1383178636 CA410397815	389	R>K		No	ClinGen gnomAD
CA410397816 rs1383178636 RCV000620693 RCV000596015	389	R>T		No	ClinGen ClinVar dbSNP gnomAD
rs1424033329 CA410397762	394	K>R		No	ClinGen gnomAD
rs1257759867 CA410397747	395	G>V		No	ClinGen gnomAD
CA410397715 rs1485255027	399	E>K		No	ClinGen gnomAD
rs763217939 CA321688585	402	L>I		No	ClinGen ExAC gnomAD
rs886042297 CA10604053 RCV000372121	403	T>M		No	ClinGen ClinVar dbSNP gnomAD
CA321688560 rs376942014	404	E>D		No	ClinGen ESP ExAC TOPMed gnomAD
rs570121873 CA410397650	405	K>*		No	ClinGen 1000Genomes ExAC gnomAD
CA321688542 rs570121873	405	K>Q		No	ClinGen 1000Genomes ExAC gnomAD
CA321688536 rs992398873	406	K>Q		No	ClinGen TOPMed gnomAD
CA321688532 rs766523013	406	K>R		No	ClinGen ExAC gnomAD
rs1555872796 CA410397624	407	P>S		No	ClinGen Ensembl
CA410397470 rs1445695397	408	W>C		No	ClinGen gnomAD
rs376916741 CA321688102	409	W>*		No	ClinGen ExAC gnomAD
CA410397457 rs1332950288	409	W>*		No	ClinGen gnomAD
rs376916741 CA321688098	409	W>L		No	ClinGen ExAC gnomAD
rs1467814360 CA410397444	410	W>*		No	ClinGen gnomAD
CA410397439 rs1404697104	411	H>N		No	ClinGen gnomAD
CA321688091 rs767595472	413	R>C		No	ClinGen ExAC gnomAD
CA321688083 rs574577579	413	R>H		No	ClinGen 1000Genomes ExAC gnomAD
rs1379816380 CA410397410	414	V>I		No	ClinGen gnomAD
CA410397397 rs1180174934	415	Q>R		No	ClinGen gnomAD
rs751477766 CA321688081	416	E>Q		No	ClinGen ExAC gnomAD
CA410397365 rs1460109011	418	G>D		No	ClinGen gnomAD
CA410397372 rs1200734227	418	G>S		No	ClinGen gnomAD
CA410397360 rs1460109011	418	G>V		No	ClinGen gnomAD
CA10587938 RCV000248108 rs886039021	421	A>D		No	ClinGen ClinVar dbSNP gnomAD
rs28934892 CA410397325	422	P>R		No	ClinGen gnomAD
rs138211175 CA410397285	425	V>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs138211175 CA325175	425	V>M		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1311066540 CA410397267	426	L>F		No	ClinGen gnomAD
CA410397251 rs1450044796	427	P>S		No	ClinGen gnomAD
rs776175674 CA321688051	428	T>N		No	ClinGen ExAC gnomAD
CA410397224 rs1405061619	429	I>V		No	ClinGen gnomAD
rs947698557 CA321688049	430	T>A		No	ClinGen TOPMed
rs1381340460 CA410397185	431	C>Y		No	ClinGen gnomAD
rs1180854779 CA410397172	432	G>R		No	ClinGen gnomAD
CA410397157 rs1237063529	433	H>P		No	ClinGen gnomAD
CA410397110 rs1282119406	435	I>N		No	ClinGen gnomAD
rs1354271840 COSM1031114 CA410397096	436	E>K	endometrium [Cosmic]	No	ClinGen cosmic curated gnomAD
rs1243421704 CA410397058	438	L>F		No	ClinGen gnomAD
CA410397042 rs1449634173	440	E>Q		No	ClinGen gnomAD
CA410397009 rs1324151005	442	G>D		No	ClinGen gnomAD
CA410396949 rs1413430493	446	A>T		No	ClinGen gnomAD
CA321687980 rs764165836	447	P>T		No	ClinGen ExAC gnomAD
rs865989946 CA321687970	448	V>L		No	ClinGen TOPMed gnomAD
rs1220059415 CA410396889	451	E>G		No	ClinGen gnomAD
CA410396878 rs201585750	452	A>E		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA321687965 COSM1031112 rs201585750	452	A>V	endometrium [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
CA410396871 rs886057099	453	G>R		No	ClinGen gnomAD
rs1398459455 CA410396822	454	V>A		No	ClinGen gnomAD
rs751797189 CA321687519	455	I>N		No	ClinGen ExAC gnomAD
CA321687499 rs758500477	458	M>T		No	ClinGen ExAC gnomAD
CA321687485 rs902200637	461	L>F		No	ClinGen TOPMed
CA321687482 rs141428279	464	M>T		No	ClinGen ESP ExAC
rs1237233267 CA410396742	467	S>F		No	ClinGen gnomAD
CA321687439 rs562625029	474	Q>*		No	ClinGen 1000Genomes
CA321687435 rs367711379	475	P>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA410396681 rs1555871920 RCV000617298	477	D>E		No	ClinGen ClinVar Ensembl dbSNP
CA321687420 rs746393838	483	I>T		No	ClinGen ExAC gnomAD
rs1555871913 CA410396619	484	Y>C		No	ClinGen Ensembl
rs1555871913 CA410396618	484	Y>F		No	ClinGen Ensembl
CA410396608 rs1318731229	485	K>R		No	ClinGen Ensembl
rs996249907 CA321686674	493	T>M		No	ClinGen TOPMed gnomAD
rs1292687681 CA410395845	495	T>A		No	ClinGen gnomAD
rs772344567 CA410395837	495	T>K		No	ClinGen ExAC TOPMed gnomAD
rs1265746216 CA410395733	503	L>V		No	ClinGen gnomAD
CA321686659 rs200613751	505	M>I		No	ClinGen 1000Genomes gnomAD
CA410395701 rs1317348103	506	D>N		No	ClinGen gnomAD
rs794727161 CA240632 RCV000174986	509	A>V		No	ClinGen ClinVar Ensembl dbSNP
CA410395646 rs1387121972	511	V>M		No	ClinGen gnomAD
rs187828882 RCV000424660 CA16608554	513	H>Q		No	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
CA410395613 rs1328834710	513	H>R		No	ClinGen gnomAD
CA321686639 rs145228319	514	E>K		No	ClinGen ESP ExAC gnomAD
CA410395590 rs145228319	514	E>Q		No	ClinGen ESP ExAC gnomAD
rs1463986810 CA410395566	515	Q>*		No	ClinGen gnomAD
CA321686636 rs750311684	517	Q>H		No	ClinGen ExAC gnomAD
rs1198678305 CA410395514	518	Y>H		No	ClinGen gnomAD
CA321684761 rs747984710	524	S>P		No	ClinGen ExAC gnomAD
CA410394851 rs1359693246	525	S>N		No	ClinGen gnomAD
CA321684735 rs551198487	527	R>Q		No	ClinGen Ensembl
CA410394820 rs1455031864	527	R>W		No	ClinGen gnomAD
CA321684726 rs768230991	531	F>L		No	ClinGen ExAC gnomAD
CA410394732 rs1568916218	533	V>L		No	ClinGen Ensembl
rs779569366 CA321684714 RCV001312009	534	V>I		No	ClinGen ClinVar ExAC dbSNP gnomAD
rs747522167 CA321684705	536	A>T		No	ClinGen ExAC gnomAD
CA321684668 rs753183931	543	V>M		No	ClinGen ExAC gnomAD
CA321684647 rs754031824	545	A>G		No	ClinGen ExAC gnomAD
CA321684653 rs139651937	545	A>S		No	ClinGen ESP ExAC gnomAD
CA324952 rs150828989 VAR_046938	548	R>Q	presents 60% of the wild-type activity; highly reduced capacity to form multimeric quaternary structure [UniProt]	No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA321684636 rs766444814	548	R>W		No	ClinGen ExAC TOPMed gnomAD
CA321684617 rs767500762	552	K>G		No	ClinGen ExAC gnomAD

1 associated diseases with P35520

[MIM: 236200]: Cystathionine beta-synthase deficiency (CBSD)

An enzymatic deficiency resulting in altered sulfur metabolism and homocystinuria. The clinical features of untreated homocystinuria due to CBS deficiency include myopia, ectopia lentis, intellectual disability, skeletal anomalies resembling Marfan syndrome, and thromboembolic events. Light skin and hair can also be present. Biochemical features include increased urinary homocystine and methionine. {ECO:0000269|PubMed:10215408, ECO:0000269|PubMed:10408774, ECO:0000269|PubMed:10462600, ECO:0000269|PubMed:11013450, ECO:0000269|PubMed:11359213, ECO:0000269|PubMed:11553052, ECO:0000269|PubMed:12007221, ECO:0000269|PubMed:12124992, ECO:0000269|PubMed:12815602, ECO:0000269|PubMed:1301198, ECO:0000269|PubMed:14635102, ECO:0000269|PubMed:15146473, ECO:0000269|PubMed:15365998, ECO:0000269|PubMed:15993874, ECO:0000269|PubMed:16205833, ECO:0000269|PubMed:16429402, ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:21240075, ECO:0000269|PubMed:21520339, ECO:0000269|PubMed:22738154, ECO:0000269|PubMed:23974653, ECO:0000269|PubMed:23981774, ECO:0000269|PubMed:25044645, ECO:0000269|PubMed:7506602, ECO:0000269|PubMed:7564249, ECO:0000269|PubMed:7611293, ECO:0000269|PubMed:7635485, ECO:0000269|PubMed:7762555, ECO:0000269|PubMed:7849717, ECO:0000269|PubMed:7967489, ECO:0000269|PubMed:7981678, ECO:0000269|PubMed:8353501, ECO:0000269|PubMed:8528202, ECO:0000269|PubMed:8755636, ECO:0000269|PubMed:8803779, ECO:0000269|PubMed:8990018, ECO:0000269|PubMed:9156316, ECO:0000269|PubMed:9266356, ECO:0000269|PubMed:9361025, ECO:0000269|PubMed:9889017}. Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

An enzymatic deficiency resulting in altered sulfur metabolism and homocystinuria. The clinical features of untreated homocystinuria due to CBS deficiency include myopia, ectopia lentis, intellectual disability, skeletal anomalies resembling Marfan syndrome, and thromboembolic events. Light skin and hair can also be present. Biochemical features include increased urinary homocystine and methionine. {ECO:0000269|PubMed:10215408, ECO:0000269|PubMed:10408774, ECO:0000269|PubMed:10462600, ECO:0000269|PubMed:11013450, ECO:0000269|PubMed:11359213, ECO:0000269|PubMed:11553052, ECO:0000269|PubMed:12007221, ECO:0000269|PubMed:12124992, ECO:0000269|PubMed:12815602, ECO:0000269|PubMed:1301198, ECO:0000269|PubMed:14635102, ECO:0000269|PubMed:15146473, ECO:0000269|PubMed:15365998, ECO:0000269|PubMed:15993874, ECO:0000269|PubMed:16205833, ECO:0000269|PubMed:16429402, ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:21240075, ECO:0000269|PubMed:21520339, ECO:0000269|PubMed:22738154, ECO:0000269|PubMed:23974653, ECO:0000269|PubMed:23981774, ECO:0000269|PubMed:25044645, ECO:0000269|PubMed:7506602, ECO:0000269|PubMed:7564249, ECO:0000269|PubMed:7611293, ECO:0000269|PubMed:7635485, ECO:0000269|PubMed:7762555, ECO:0000269|PubMed:7849717, ECO:0000269|PubMed:7967489, ECO:0000269|PubMed:7981678, ECO:0000269|PubMed:8353501, ECO:0000269|PubMed:8528202, ECO:0000269|PubMed:8755636, ECO:0000269|PubMed:8803779, ECO:0000269|PubMed:8990018, ECO:0000269|PubMed:9156316, ECO:0000269|PubMed:9266356, ECO:0000269|PubMed:9361025, ECO:0000269|PubMed:9889017}. Note=The disease is caused by variants affecting the gene represented in this entry.

4 regional properties for P35520

Type	Name	Position	InterPro Accession
domain	CBS domain	418 - 476	IPR000644
binding_site	Cysteine synthase/cystathionine beta-synthase, pyridoxal-phosphate attachment site	108 - 126	IPR001216
domain	Tryptophan synthase beta chain-like, PALP domain	82 - 376	IPR001926
domain	Cystathionine beta-synthase, C-terminal domain	412 - 542	IPR046353

Functions

		Description
EC Number	4.2.1.22	Hydro-lyases
Subcellular Localization	Cytoplasm Nucleus
PANTHER Family	PTHR10314	CYSTATHIONINE BETA-SYNTHASE
PANTHER Subfamily	PTHR10314:SF194	CYSTATHIONINE BETA-SYNTHASE
PANTHER Protein Class	lyase
PANTHER Pathway Category	Cysteine biosynthesis O-Acetylserine-lyase

3 GO annotations of cellular component

Name	Definition
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
nucleus	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.

14 GO annotations of molecular function

Name	Definition
carbon monoxide binding	Binding to carbon monoxide (CO).
cystathionine beta-synthase activity	Catalysis of the reaction: L-serine + L-homocysteine = cystathionine + H2O.
enzyme binding	Binding to an enzyme, a protein with catalytic activity.
heme binding	Binding to a heme, a compound composed of iron complexed in a porphyrin (tetrapyrrole) ring.
identical protein binding	Binding to an identical protein or proteins.
metal ion binding	Binding to a metal ion.
modified amino acid binding	Binding to a modified amino acid.
nitric oxide binding	Binding to nitric oxide (NO).
nitrite reductase (NO-forming) activity	Catalysis of the reaction: nitric oxide + H2O + ferricytochrome c = nitrite + ferrocytochrome c + 2 H+.
oxygen binding	Binding to oxygen (O2).
protein homodimerization activity	Binding to an identical protein to form a homodimer.
pyridoxal phosphate binding	Binding to pyridoxal 5' phosphate, 3-hydroxy-5-(hydroxymethyl)-2-methyl4-pyridine carboxaldehyde 5' phosphate, the biologically active form of vitamin B6.
S-adenosyl-L-methionine binding	Binding to S-adenosyl-L-methionine.
ubiquitin protein ligase binding	Binding to a ubiquitin protein ligase enzyme, any of the E3 proteins.

10 GO annotations of biological process

Name	Definition
cysteine biosynthetic process	The chemical reactions and pathways resulting in the formation of cysteine, 2-amino-3-mercaptopropanoic acid.
cysteine biosynthetic process from serine	The chemical reactions and pathways resulting in the formation of cysteine from other compounds, including serine.
cysteine biosynthetic process via cystathionine	The chemical reactions and pathways resulting in the formation of cysteine, via the intermediate cystathionine.
DNA protection	Any process in which DNA is protected from damage by, for example, oxidative stress.
homocysteine catabolic process	The chemical reactions and pathways resulting in the breakdown of homocysteine, the amino acid alpha-amino-gamma-mercaptobutanoic acid.
homocysteine metabolic process	The chemical reactions and pathways involving homocysteine, the amino acid alpha-amino-gamma-mercaptobutanoic acid. Homocysteine is an important intermediate in the metabolic reactions of its S-methyl derivative, methionine.
hydrogen sulfide biosynthetic process	The chemical reactions and pathways resulting in the formation of hydrogen sulfide, H2S.
L-cysteine catabolic process	The chemical reactions and pathways resulting in the breakdown of L-cysteine, the L-enantiomer of 2-amino-3-mercaptopropanoic acid, i.e. (2R)-2-amino-3-mercaptopropanoic acid.
L-serine catabolic process	The chemical reactions and pathways resulting in the breakdown of L-serine, the L-enantiomer of serine, i.e. (2S)-2-amino-3-hydroxypropanoic acid.
L-serine metabolic process	The chemical reactions and pathways involving L-serine, the L-enantiomer of serine, i.e. (2S)-2-amino-3-hydroxypropanoic acid.

3 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
P32582	CYS4	Cystathionine beta-synthase	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	PR
Q91WT9	Cbs	Cystathionine beta-synthase	Mus musculus (Mouse)	SS
P32232	Cbs	Cystathionine beta-synthase	Rattus norvegicus (Rat)	SS

10	20	30	40	50	60
MPSETPQAEV	GPTGCPHRSG	PHSAKGSLEK	GSPEDKEAKE	PLWIRPDAPS	RCTWQLGRPA
70	80	90	100	110	120
SESPHHHTAP	AKSPKILPDI	LKKIGDTPMV	RINKIGKKFG	LKCELLAKCE	FFNAGGSVKD
130	140	150	160	170	180
RISLRMIEDA	ERDGTLKPGD	TIIEPTSGNT	GIGLALAAAV	RGYRCIIVMP	EKMSSEKVDV
190	200	210	220	230	240
LRALGAEIVR	TPTNARFDSP	ESHVGVAWRL	KNEIPNSHIL	DQYRNASNPL	AHYDTTADEI
250	260	270	280	290	300
LQQCDGKLDM	LVASVGTGGT	ITGIARKLKE	KCPGCRIIGV	DPEGSILAEP	EELNQTEQTT
310	320	330	340	350	360
YEVEGIGYDF	IPTVLDRTVV	DKWFKSNDEE	AFTFARMLIA	QEGLLCGGSA	GSTVAVAVKA
370	380	390	400	410	420
AQELQEGQRC	VVILPDSVRN	YMTKFLSDRW	MLQKGFLKEE	DLTEKKPWWW	HLRVQELGLS
430	440	450	460	470	480
APLTVLPTIT	CGHTIEILRE	KGFDQAPVVD	EAGVILGMVT	LGNMLSSLLA	GKVQPSDQVG
490	500	510	520	530	540
KVIYKQFKQI	RLTDTLGRLS	HILEMDHFAL	VVHEQIQYHS	TGKSSQRQMV	FGVVTAIDLL
550
NFVAAQERDQ	K