CBS

Summary

CBS (cystathionine beta-synthase, HGNC:1550) is a protein-coding gene on chromosome 21q22.3, encoding Cystathionine beta-synthase (P35520). Hydro-lyase catalyzing the first step of the transsulfuration pathway, where the hydroxyl group of L-serine is displaced by L-homocysteine in a beta-replacement reaction to form L-cystathionine, the precursor of L-cysteine.

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. This gene is a major contributor to cellular hydrogen sulfide production. Multiple alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 875 — RefSeq curated summary.

At a glance

• Gene–disease (curated): classic homocystinuria (Definitive, ClinGen)
• GWAS associations: 12
• Clinical variants (ClinVar): 1,465 total — 94 pathogenic, 141 likely-pathogenic (top 2% of genes corpus-wide)
• Regional missense constraint (gnomAD): 3 of 4 regions constrained (≈86% of expected missense variation)
• GTEx eGene: eQTL in 50 tissues, sQTL in 5 (q < 0.05)
• Phenotypes (HPO): 93
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• MANE Select transcript: NM_000071

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1550
Approved symbol	CBS
Name	cystathionine beta-synthase
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	HIP4
Ensembl gene	ENSG00000160200
Ensembl biotype	protein_coding
OMIM	613381
Entrez	875

Gene structure

Transcript identifiers

Ensembl transcripts: 82 — 66 protein_coding, 7 nonsense_mediated_decay, 5 retained_intron, 4 protein_coding_CDS_not_defined

MANE Select: ENST00000398165

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 5, TSL 2: 5, TSL 3: 4, TSL 5: 3

ENST00000398165, ENST00000352178, ENST00000359624, ENST00000398158, ENST00000430013, ENST00000441030, ENST00000451248, ENST00000458223, ENST00000461686, ENST00000462349, ENST00000465732, ENST00000470912, ENST00000478709, ENST00000486098, ENST00000488526, ENST00000491776, ENST00000496485, ENST00000886703, ENST00000886704, ENST00000886705, ENST00000886706, ENST00000886707, ENST00000886708, ENST00000886709, ENST00000886710, ENST00000886711, ENST00000886712, ENST00000886713, ENST00000886714, ENST00000886715, ENST00000886716, ENST00000886717, ENST00000886718, ENST00000886719, ENST00000886720, ENST00000886721, ENST00000886722, ENST00000886723, ENST00000886724, ENST00000886725, ENST00000886726, ENST00000886727, ENST00000886728, ENST00000886729, ENST00000886730, ENST00000886731, ENST00000939285, ENST00000939286, ENST00000939287, ENST00000939288, ENST00000939289, ENST00000939290, ENST00000939291, ENST00000939292, ENST00000939293, ENST00000939294, ENST00000939295, ENST00000939296, ENST00000939297, ENST00000939298, ENST00000939299, ENST00000939300, ENST00000961044, ENST00000961045, ENST00000961046, ENST00000961047, ENST00000961048, ENST00000961049, ENST00000974778, ENST00000974779, ENST00000974780, ENST00000974781, ENST00000974782, ENST00000974783, ENST00000974786, ENST00000974788, ENST00001026384, ENST00001026385, ENST00001026386, ENST00001026387, ENST00001026388, ENST00001131428

RefSeq mRNA: 5 — MANE Select: NM_000071 NM_000071, NM_001178008, NM_001178009, NM_001320298, NM_001321072

CCDS: CCDS13693

Canonical transcript exons

ENST00000398165 — 17 exons

Exon	Start	End
ENSE00000000269	43075770	43075835
ENSE00001270928	43073266	43073341
ENSE00003462667	43062953	43063078
ENSE00003478977	43071985	43072201
ENSE00003498748	43063900	43063991
ENSE00003525308	43060441	43060546
ENSE00003566517	43065203	43065272
ENSE00003589198	43068509	43068615
ENSE00003601456	43058145	43058253
ENSE00003643599	43056803	43056887
ENSE00003646251	43062311	43062395
ENSE00003646800	43058834	43058968
ENSE00003666431	43065387	43065521
ENSE00003682750	43059226	43059303
ENSE00003692007	43066243	43066377
ENSE00003790203	43065616	43065695
ENSE00003902413	43053191	43053983

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.82.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3226 / max 15.0808, expressed in 160 samples.

Highest expression (Bgee): lobe of liver, body of pancreas, liver, cortical plate, hemisphere of cerebellum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CBS is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 50 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 55 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	2.6e-66	-0.83	21:43028665:G:A
Esophagus Muscularis	eqtl	9.3e-51	-0.78	21:43028665:G:A
Nerve Tibial	eqtl	2.4e-49	-0.72	21:43028665:G:A
Skin Sun Exposed Lower leg	eqtl	2.6e-47	-0.65	21:43028653:G:C
Artery Tibial	eqtl	9.6e-46	-0.67	21:43028665:G:A
Thyroid	eqtl	1.1e-45	-0.68	21:43028665:G:A
Heart Atrial Appendage	eqtl	9.9e-43	-0.78	21:43028665:G:A
Whole Blood	eqtl	1.2e-37	+0.53	21:43034905:C:G
Adipose Visceral Omentum	eqtl	3.1e-37	-0.63	21:43028665:G:A
Lung	eqtl	7.4e-37	-0.60	21:43028665:G:A
Stomach	eqtl	5.7e-36	-0.74	21:43028653:G:C
Artery Aorta	eqtl	5.8e-36	-0.76	21:43028653:G:C
Skin Not Sun Exposed Suprapubic	eqtl	6.2e-36	-0.56	21:43028665:G:A
Adipose Subcutaneous	eqtl	6.9e-35	-0.55	21:43028665:G:A
Esophagus Gastroesophageal Junction	eqtl	8.3e-35	-0.76	21:43028653:G:C
Colon Transverse	eqtl	3.7e-33	-0.72	21:43028653:G:C
Esophagus Mucosa	eqtl	1.2e-32	-0.57	21:43028665:G:A
Muscle Skeletal	eqtl	4.5e-30	-0.54	21:43028653:G:C
Breast Mammary Tissue	eqtl	1.8e-29	-0.88	21:42993347:G:A
Brain Cerebellum	eqtl	1.3e-26	-0.96	21:43028653:G:C

FANTOM5 promoters

8 alternative TSS:

Promoter ID	TPM avg	Samples expressed
190676	0.2300	96
190677	0.0673	13
190680	0.0193	9
190679	0.0033	1
190678	0.0016	0
190672	0.0007	0
190671	0.0004	0
190681	0.0004	0

Top tissues by expression

showing 100 of 134 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.82	gold quality
body of pancreas	UBERON:0001150	98.20	gold quality
liver	UBERON:0002107	97.60	gold quality
cortical plate	UBERON:0005343	97.34	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.66	gold quality
cerebellum	UBERON:0002037	96.29	gold quality
cerebellar cortex	UBERON:0002129	96.25	gold quality
cerebellar hemisphere	UBERON:0002245	96.22	gold quality
ventricular zone	UBERON:0003053	95.73	gold quality
stromal cell of endometrium	CL:0002255	95.25	gold quality
tibial nerve	UBERON:0001323	95.22	gold quality
ganglionic eminence	UBERON:0004023	95.17	gold quality
temporal lobe	UBERON:0001871	94.33	gold quality
amygdala	UBERON:0001876	94.29	gold quality
left lobe of thyroid gland	UBERON:0001120	93.62	gold quality
right lobe of thyroid gland	UBERON:0001119	93.35	gold quality
right ovary	UBERON:0002118	93.33	gold quality
left ovary	UBERON:0002119	92.98	gold quality
hypothalamus	UBERON:0001898	92.91	gold quality
Ammon’s horn	UBERON:0001954	92.85	gold quality
thyroid gland	UBERON:0002046	92.78	gold quality
mucosa of stomach	UBERON:0001199	92.73	gold quality
right frontal lobe	UBERON:0002810	92.72	gold quality
ovary	UBERON:0000992	92.39	gold quality
brain	UBERON:0000955	92.06	gold quality
substantia nigra	UBERON:0002038	91.88	gold quality
primary visual cortex	UBERON:0002436	91.81	gold quality
cerebral cortex	UBERON:0000956	91.80	gold quality
frontal cortex	UBERON:0001870	91.77	gold quality
putamen	UBERON:0001874	91.76	gold quality
anterior cingulate cortex	UBERON:0009835	91.68	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.42	gold quality
prefrontal cortex	UBERON:0000451	91.25	gold quality
superior frontal gyrus	UBERON:0002661	91.11	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.08	gold quality
sural nerve	UBERON:0015488	91.03	gold quality
nucleus accumbens	UBERON:0001882	90.87	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.74	gold quality
caudate nucleus	UBERON:0001873	90.11	gold quality
fundus of stomach	UBERON:0001160	90.10	gold quality
body of stomach	UBERON:0001161	89.71	gold quality
adenohypophysis	UBERON:0002196	89.49	gold quality
pancreas	UBERON:0001264	88.53	gold quality
pituitary gland	UBERON:0000007	88.47	gold quality
descending thoracic aorta	UBERON:0002345	88.35	gold quality
prostate gland	UBERON:0002367	88.17	gold quality
endocervix	UBERON:0000458	87.51	gold quality
upper lobe of left lung	UBERON:0008952	87.33	gold quality
thoracic aorta	UBERON:0001515	87.15	gold quality
stomach	UBERON:0000945	87.04	gold quality
ascending aorta	UBERON:0001496	87.04	gold quality
right lung	UBERON:0002167	85.00	gold quality
apex of heart	UBERON:0002098	83.92	gold quality
saliva-secreting gland	UBERON:0001044	83.50	gold quality
right atrium auricular region	UBERON:0006631	83.47	gold quality
minor salivary gland	UBERON:0001830	83.01	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	82.60	gold quality
ectocervix	UBERON:0012249	82.35	gold quality
lung	UBERON:0002048	82.15	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.87	gold quality
left uterine tube	UBERON:0001303	81.65	gold quality
lower esophagus muscularis layer	UBERON:0035833	81.55	gold quality
lower esophagus	UBERON:0013473	81.46	gold quality
multicellular organism	UBERON:0000468	81.44	gold quality
uterine cervix	UBERON:0000002	81.38	gold quality
small intestine	UBERON:0002108	81.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.82	gold quality
blood	UBERON:0000178	80.73	gold quality
heart	UBERON:0000948	80.53	gold quality
left coronary artery	UBERON:0001626	80.33	gold quality
heart left ventricle	UBERON:0002084	80.16	gold quality
corpus callosum	UBERON:0002336	80.08	gold quality
urinary bladder	UBERON:0001255	79.89	gold quality
metanephros cortex	UBERON:0010533	79.82	gold quality
omental fat pad	UBERON:0010414	79.48	gold quality
vagina	UBERON:0000996	78.77	gold quality
muscle layer of sigmoid colon	UBERON:0035805	78.74	gold quality
adipose tissue	UBERON:0001013	78.56	gold quality
transverse colon	UBERON:0001157	78.48	gold quality
right coronary artery	UBERON:0001625	78.35	gold quality
subcutaneous adipose tissue	UBERON:0002190	78.15	gold quality
fallopian tube	UBERON:0003889	78.09	gold quality
intestine	UBERON:0000160	77.93	gold quality
popliteal artery	UBERON:0002250	77.85	gold quality
tibial artery	UBERON:0007610	77.78	gold quality
colon	UBERON:0001155	77.56	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	77.15	gold quality
cortex of kidney	UBERON:0001225	77.09	gold quality
kidney	UBERON:0002113	76.77	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.95	gold quality
right adrenal gland	UBERON:0001233	75.88	gold quality
adult mammalian kidney	UBERON:0000082	75.81	gold quality
right adrenal gland cortex	UBERON:0035827	75.78	gold quality
tonsil	UBERON:0002372	75.35	gold quality
right uterine tube	UBERON:0001302	75.33	gold quality
esophagus	UBERON:0001043	75.24	gold quality
thoracic mammary gland	UBERON:0005200	74.47	gold quality
mucosa of transverse colon	UBERON:0004991	74.01	gold quality
duodenum	UBERON:0002114	73.56	gold quality
body of uterus	UBERON:0009853	73.51	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	21.25
E-MTAB-5061	yes	18.29
E-MTAB-8271	yes	7.47
E-ANND-3	yes	3.44
E-MTAB-6386	no	18.97

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	152.8	medium
Pancreas	tissue	128.1	medium
Hippocampus	tissue	64.8	medium
Locus coeruleus	tissue	59.6
Postcentral gyrus	tissue	49.2
Nucleus accumbens	tissue	37.0
Choroid plexus	tissue	32.2
Ovary	tissue	23.9	not detected
Caudate putamen	tissue	23.3
Frontal cortex	tissue	21.6
Thyroid gland	tissue	21.6	not detected
Salivary gland	tissue	18.7	not detected
Cervix	tissue	13.1	not detected
Thalamus	tissue	12.0
Prostate	tissue	11.9	not detected
Spinal cord	tissue	11.3
Superior colliculi	tissue	11.2
Seminal vesicle	tissue	9.5	not detected
Medulla oblongata	tissue	9.2
Pituitary gland	tissue	9.1
Cerebral cortex	tissue	9.1	low
Putamen	tissue	9.1
Hypothalamus	tissue	9.1
Somatosensory cortex	tissue	9.1
Septum	tissue	9.0
Pons	tissue	8.9
Periaqueductal gray	tissue	8.9
Midbrain	tissue	8.6
Temporal cortex	tissue	8.5
Motor cortex	tissue	8.4
Amygdala	tissue	8.4
Small intestine	tissue	8.4	not detected
Hippocampal formation	tissue	8.4
Entorhinal cortex	tissue	8.3
Olfactory bulb	tissue	8.1
Substantia nigra	tissue	7.9
Ventral forebrain	tissue	7.8
Basal ganglia	tissue	7.7	low
Occipital cortex	tissue	7.7
Insular cortex	tissue	7.4
Prefrontal cortex	tissue	7.2
Retrosplenial and cingulate cortex	tissue	6.8
Heart muscle	tissue	6.5	not detected
Vagina	tissue	6.2	not detected
Retrosplenial cortex	tissue	6.1
Fallopian tube	tissue	5.3	not detected
Duodenum	tissue	4.8	not detected
Parathyroid gland	tissue	4.4	not detected
Corpus callosum	tissue	4.1
Adrenal gland	tissue	4.0	not detected
Stomach 1	tissue	3.6	not detected
Lung	tissue	3.4	not detected
Retina	tissue	3.3
Cerebellum	tissue	2.8	medium
Kidney	tissue	2.7	not detected
Lymph node	tissue	2.6	not detected
Urinary bladder	tissue	2.5	not detected
Adipose tissue	tissue	2.2	not detected
Colon	tissue	2.2	not detected
Smooth muscle	tissue	2.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Cerebellar cortex (112.5), Flocculonodular lobe (104.8), Vermis (94.2), Habenula (83.3), Ventral posteromedial thalamic nucleus (78.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, MYC, NFYA, RELA, SP1, SP3, USF1

miRNA regulators (miRDB)

Targeting CBS by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 31 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-154-5P	98.92	66.65	733
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-198	98.70	67.32	920
HSA-MIR-6529-3P	98.68	66.76	1020
HSA-MIR-4317	98.49	67.09	987
HSA-MIR-4782-5P	98.35	69.33	1474
HSA-MIR-5706	98.35	69.33	1463
HSA-MIR-5088-5P	97.97	64.28	487
HSA-MIR-6508-3P	96.73	65.48	576
HSA-MIR-2909	96.36	67.30	562
HSA-MIR-3918	96.13	64.65	1300
HSA-MIR-6777-3P	95.35	64.30	699
HSA-MIR-483-5P	93.53	65.81	111

Functional genomics

Regional missense constraint (gnomAD)

ENST00000398165 splits into 4 regions with different missense tolerance; 3 are missense-constrained (≈86% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
21:43,053,883–43,065,253	0 / 24.7	0.00	yes (p 6.7e-07)
21:43,065,254–43,066,300	16 / 66.0	0.24	yes (p 7.5e-10)
21:43,066,301–43,066,347	0 / 16.5	0.00	yes (p 4.9e-05)
21:43,066,348–43,072,193	11 / 17.5	0.63	no

Literature-anchored findings (GeneRIF, showing 40)

• Selective biochemical screening may ascertain only approximately 25% of all homocystinuric patients. (PMID:11748855)
• A novel class of missense mutations in homocystinurics is described, located in the non-catalytic C-terminal region of CBS yielding enzymes that are catalytically active but deficient in their response to S-adenosylmethionine (AdoMet). (PMID:12007221)
• Proteins with seven novel and 20 known mutations detected in cystathionine beta-synthase (CBS) deficiency completely lack CBS catalytic activity. (PMID:12124992)
• Deletion of the heme-binding domain but not mutagenesis of the cysteines in the CXXC oxidoreductase motif of cystathionine beta-synthase is correlated with loss of redox sensitivity of its catalytic activity. (PMID:12173932)
• Human CBS has a frequent polymorphism- a duplication has generated a gene re-arrangement at the 3’ splice site where two GGGG runs have been brought close to each other (PMID:12228232)
• The activation domain mutation D444N reduces the steady-state levels of cystathionine beta-synthase 4-fold and drastically increases the activation response to AdoMet (by ~100-fold) so that it can no longer be activated at physiological concentrations. (PMID:12269827)
• investigation of functional organization of the catalytic and regulatory regions of this enzyme (PMID:12379655)
• results of this study with clinically relevant cell line models suggest potential mechanisms for disparate patterns of cystathionine beta synthase gene expression in Down syndrome and non-down syndrome megakaryocytic leukemia (PMID:12393509)
• confirms the important transactivating role of NF-YA isofoms for the 1b promoter via synergism with Sp1 (PMID:12427542)
• we did not find any indication that genetic variation in the CBS gene is associated with increased homocysteine concentrations. (PMID:12529702)
• number of 31 bp repeat elements in the CBS gene influences homocysteine levels (PMID:12649066)
• Five novel mutations causing amino acid substitutions have been identified in the CBS gene in 16 homocystinuric patients from Spain and Portugal. (PMID:12815602)
• study showed that the c.844ins68 variant in CBS gene decreases the risk of clinically manifested coronary artery disease (PMID:12855221)
• Sp1 has a critical and indispensable role in tissue-specific regulation of cystathionine beta-synthase (PMID:14670973)
• Mutation in cystathionine beta-synthase is not obviously correlated with stroke and is not associated with categories of stroke. (PMID:15009965)
• The expression of cystathionine beta-synthase was investigated by quantitative analysis in fetal Down syndrome (DS) brain. Levels were comparable between DS and control brain. (PMID:15082224)
• 4 new CBS mutations c.451G>A (p.Gly151?), c.740_769del (p.Lys247_Gly256del), c.862G>C (p.Ala288Pro) and c.1135C>T (p.Arg379Trp)were found. The CBS c.1224-2A>C allele confers vitamin B6 nonresponsiveness. (PMID:15365998)
• results confirm the ability of CBS to produce H2S, but show in contrast to prior reports that the major mechanism is via beta-replacement and not cysteine hydrolysis (PMID:15520012)
• The heme of cystathionine beta-synthase regulates activity through changes in redox state, because the heme prefers to be in the ferric state at physiological pH. (PMID:15544339)
• CBS, MTHFR, and SLC19a1 are involved in metabolism of folate and lung cancer risk in China (PMID:15922487)
• Our results show that elevated tHcy per se is not responsible for the neonatal lethality observed in Cbs-/- animals and suggests that CBS protein may have a function in addition to its role in homocysteine catabolism (PMID:15972722)
• 844ins68 mutation and VNTR allele 19 are independent risk factors for Alzheimer disease development in subjects aged 75 years or more. (PMID:15975077)
• Mutation analysis of the CBS gene in Korean patients with homocystinuria was performed. Eight mutations were identified, including four known mutations (T257M, R336C, T353M, and G347S) and four novel mutations (L154Q, A155V, del234D, and A288T). (PMID:16205833)
• over-expression of CBS may cause the developmental abnormality in cognition in Down’s syndrome (PMID:16274669)
• Functional studies of CBS provide strong evidence that coordination of Cys52 to the heme iron is crucial for full activity in this enzyme. (PMID:16363792)
• analysis of CBS p.T191M mutation in homocystinuric patients from Colombia (PMID:16470595)
• A mutation of the CBS gene is highly prevalent among homocytinuric patients from Spain, Portugal, and Colombia. (PMID:16479318)
• The mechanism of the inhibitory effect of carbon monoxide on CBS is reported. (PMID:16505479)
• production of several lines of transgenic mice expressing the human CBS gene to produce an animal disease model of Down syndrome. (PMID:16541333)
• cystathionine beta-synthase may have a role in kidney function (PMID:16601865)
• 31 bp VNTR in CBS is genetic determinant of post-methionine load tHcy concentrations. Since post-methionine load tHcy concentrations are found to be associated with increased risk for cardiovascular disease, this 31 bp VNTR may be risk factor for CVD. (PMID:16791140)
• These results suggested that maternal MTHFR 677TT genotype was one of the risks to the occurrence of congenital heart disease (CHD) in offspring but parents’ CBS gene 833 T–>C mutation did not get involved in CHD (PMID:16792904)
• The cystathionine beta-synthase variant (insertion allele of CBS c.844_845ins68) protects against CNS demyelination in X-linked adrenoleukodystrophy. (PMID:16941496)
• C431 is directly involved in AdoMet binding (PMID:16953589)
• Mutation within the CBS gene is associated with the development of congenital heart disease. (PMID:17319270)
• plasma Hcy-thiolactone is elevated 59-fold and 72-fold in human patients with hyperhomocysteinemia secondary to mutations in methylenetetrahydrofolate reductase and cystathionine beta-synthase genes, respectively (PMID:17327360)
• this is the first example of mutations in the catalytic core of cystathionine beta-synthase that result in failure of S-adenosylmethionine-dependent regulation. (PMID:17352495)
• Chemical chaperones present during the initial folding process may facilitate proper folding of several mutant CBS proteins and suggest it may be possible to treat some inborn errors of metabolism with agents that enhance proper protein folding. (PMID:17540596)
• These results not only highlight the involvement of the MSR and CBS genes in the etiology of cardiovascular disease, but also emphasize the strength of haplotype analyses in association studies. (PMID:17553479)
• Base pair variable numbeer tandem repeaets does not contribute to the etiology of mental reteardation. (PMID:17621169)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	cbsb	ENSDARG00000010946
danio_rerio	cbsa	ENSDARG00000053500
mus_musculus	Cbs	ENSMUSG00000024039
rattus_norvegicus	Cbs	ENSRNOG00000029528
drosophila_melanogaster	Cbs	FBGN0031148
caenorhabditis_elegans		WBGENE00013866
caenorhabditis_elegans		WBGENE00018783

Paralogs (5): SDS (ENSG00000135094), SDSL (ENSG00000139410), THNSL2 (ENSG00000144115), SRR (ENSG00000167720), THNSL1 (ENSG00000185875)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:88285) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 101 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased circulating homocysteine level	7
decreased body size	3
premature death	3
decreased body weight	2
postnatal growth retardation	2
female infertility	2
abnormal maternal decidual layer morphology	2
decreased placenta weight	2
abnormal pregnancy	2
kyphoscoliosis	1
kyphosis	1
abnormal cartilage development	1
abnormal long bone hypertrophic chondrocyte zone	1
extramedullary hematopoiesis	1
blood vessel congestion	1
abnormal heart development	1
abnormal hair follicle morphology	1
pointed snout	1
delayed kidney development	1
kinked tail	1
short tail	1
enlarged liver	1
pale liver	1
abnormal hepatocyte morphology	1
enlarged sebaceous gland	1

+76 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Staphylococcus aureus subsp. aureus JH9	A5INY7	100.0%	Diamond
Staphylococcus aureus subsp. aureus str. Newman	A6QDA0	100.0%	Diamond
Staphylococcus aureus subsp. aureus JH1	A6TXQ1	100.0%	Diamond
Staphylococcus aureus subsp. aureus Mu3	A7WX68	100.0%	Diamond
Staphylococcus aureus subsp. aureus USA300_TCH1516	A8YZ41	100.0%	Diamond
Staphylococcus aureus subsp. aureus ED98	D0K799	100.0%	Diamond
Staphylococcus aureus subsp. aureus TW20	D1GUM7	100.0%	Diamond
Staphylococcus aureus subsp. aureus ST398	D2N3G7	100.0%	Diamond
Staphylococcus aureus 04-02981	D3ERF5	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Typhimurium str. LT2	P0A1E3	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Typhi	P0A1E4	100.0%	Diamond
Mycobacterium tuberculosis variant bovis AF2122/97	P0A535	100.0%	Diamond
Escherichia coli K-12	P0ABK5	100.0%	Diamond
Escherichia coli O157:H7	P0ABK6	100.0%	Diamond
Staphylococcus aureus subsp. aureus Mu50	P63870	100.0%	Diamond
Staphylococcus aureus subsp. aureus N315	P63871	100.0%	Diamond
Staphylococcus aureus subsp. aureus MW2	P63872	100.0%	Diamond
Mycobacterium tuberculosis CDC1551	P9WP50	100.0%	Diamond
Mycobacterium tuberculosis H37Rv	P9WP51	100.0%	Diamond
Staphylococcus aureus subsp. aureus USA300	Q2FKE3	100.0%	Diamond
Staphylococcus aureus subsp. aureus NCTC 8325	Q2G1N3	100.0%	Diamond
Staphylococcus aureus subsp. aureus COL	Q5HIG2	100.0%	Diamond
Staphylococcus epidermidis RP62A	Q5HRP1	100.0%	Diamond
Staphylococcus aureus subsp. aureus MSSA476	Q6GBX5	100.0%	Diamond
Staphylococcus aureus subsp. aureus MRSA252	Q6GJF8	100.0%	Diamond
Staphylococcus epidermidis ATCC 12228	Q8CMT6	100.0%	Diamond
Staphylococcus aureus RF122	Q2YUU0	98.8%	Diamond
Macaca fascicularis	Q58H57	96.9%	Diamond
Brassica juncea	O23733	96.6%	Diamond
Arabidopsis thaliana	P47998	96.6%	Diamond
Malus domestica	Q1KLZ1	94.7%	Diamond
Helicobacter pylori 26695	P56067	93.8%	Diamond
Helicobacter pylori J99	Q9ZMW6	93.8%	Diamond
Staphylococcus haemolyticus	Q59918	90.3%	Diamond
Triticum aestivum	P38076	90.2%	Diamond
Zea mays	P80608	90.2%	Diamond
Oryza sativa Japonica Group	Q9XEA6	90.2%	Diamond
Solanum tuberosum	O81155	88.9%	Diamond
Capsicum annuum	P31300	88.9%	Diamond
Pseudomonas syringae pv. syringae	P48028	88.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
FRGCA	ncRNA	106481742
CRYAA	protein-coding	1409
U2AF1	protein-coding	7307
MIR5692B	ncRNA	100847013
PKNOX1	protein-coding	5316

Protein

Protein identifiers

Cystathionine beta-synthase — P35520 (reviewed: P35520)

Alternative names: Beta-thionase, Serine sulfhydrase

All UniProt accessions (5): C9JMA6, P35520, H7C1W6, H7C2H4, H7C2W0

UniProt curated annotations — full annotation on UniProt →

Function. Hydro-lyase catalyzing the first step of the transsulfuration pathway, where the hydroxyl group of L-serine is displaced by L-homocysteine in a beta-replacement reaction to form L-cystathionine, the precursor of L-cysteine. This catabolic route allows the elimination of L-methionine and the toxic metabolite L-homocysteine. Also involved in the production of hydrogen sulfide, a gasotransmitter with signaling and cytoprotective effects on neurons.

Subunit / interactions. Homotetramer.

Subcellular location. Cytoplasm. Nucleus.

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.

Disease relevance. Cystathionine beta-synthase deficiency (CBSD) [MIM:236200] 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. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Allosterically activated by S-adenosyl-methionine/AdoMet. Activated by S-adenosylhomocysteine/AdoHcy. Binds non-covalently to a heme group that may control the redox sensitivity of the enzyme.

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

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

Isoforms (2)

UniProt ID	Names	Canonical?
P35520-1	1, Major	yes
P35520-2	2, Minor

RefSeq proteins (12): NP_000062, NP_001171479, NP_001171480, NP_001307227, NP_001308001, NP_001308002, NP_001340935, NP_001340936, NP_001340937, NP_001340938, NP_001340939, NP_001340941 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000644	CBS_dom	Domain
IPR001216	P-phosphate_BS	Binding_site
IPR001926	TrpB-like_PALP	Domain
IPR005857	Cysta_beta_synth	Family
IPR036052	TrpB-like_PALP_sf	Homologous_superfamily
IPR046342	CBS_dom_sf	Homologous_superfamily
IPR046353	CBS_C	Domain
IPR050214	Cys_Synth/Cystath_Beta-Synth	Family

Pfam: PF00291, PF00571

Enzyme classification (BRENDA)

• EC 4.2.1.22 — cystathionine beta-synthase (BRENDA: 46 organisms, 83 substrates, 57 inhibitors, 150 Km, 98 kcat entries)

Substrate kinetics (BRENDA)

12 substrates with measured Km, best-characterized 12. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-SERINE	0.42–27.1	42
L-HOMOCYSTEINE	0.16–20	35
HOMOCYSTEINE	0.05–67	26
L-CYSTEINE	1–37	19
L-SER	0.91–8	9
2-MERCAPTOETHANOL	1.72–24	4
L-CYSTATHIONINE	0.083–0.9	4
L-CYS	0.13–36	3
CYSTEAMINE	5.6–6.6	2
H2S	4.7–5.02	2
O-ACETYL-L-SERINE	1.3–2.8	2
DL-HOMOCYSTEINE	68	1

Catalyzed reactions (Rhea)

• L-homocysteine + L-serine = L,L-cystathionine + H2O (RHEA:10112)

UniProt features (188 total): sequence variant 113, helix 31, strand 23, binding site 5, turn 4, modified residue 3, mutagenesis site 2, chain 1, domain 1, cross-link 1, sequence conflict 1, splice variant 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

28 structures by resolution:

PDB	Title	Method	Resolution (Å)
4UUU	1.7 A resolution structure of human cystathionine beta-synthase regulatory domain (del …	X-RAY DIFFRACTION	1.71
4COO	Crystal structure of human cystathionine beta-synthase (delta516-525) at 2.0 angstrom …	X-RAY DIFFRACTION	2
9SHM	Structure of trans-basal conformer of human CBS trapped in PLP-aminoacrylate intermediate …	ELECTRON MICROSCOPY	2
9SHN	Structure of trans-basal conformer of human CBS trapped in PLP-serine external aldemine …	ELECTRON MICROSCOPY	2.18
8STW	K384N HUMAN CYSTATHIONINE BETA-SYNTHASE (delta 411-551)	X-RAY DIFFRACTION	2.4
9SI8	Structure of trans-basal conformer of human CBS trapped in PLP-aminoacrylate intermediate …	ELECTRON MICROSCOPY	2.47
1JBQ	STRUCTURE OF HUMAN CYSTATHIONINE BETA-SYNTHASE: A UNIQUE PYRIDOXAL 5’-PHOSPHATE DEPENDENT …	X-RAY DIFFRACTION	2.6
4L28	Crystal structure of delta516-525 human cystathionine beta-synthase D444N mutant …	X-RAY DIFFRACTION	2.63
7QGT	Crystal structure of human cystathionine beta-synthase (delta516-525) in complex with …	X-RAY DIFFRACTION	2.69
9SQ0	Structure of trans-basal conformer of wild-type human CBS alone (internal aldemine)- by …	ELECTRON MICROSCOPY	2.74
9SML	Structure of trans-basal conformer of human CBS trapped in PLP-serine external aldemine …	ELECTRON MICROSCOPY	2.78
5MMS	Human cystathionine beta-synthase (CBS) p.P49L delta409-551 variant	X-RAY DIFFRACTION	2.8
1M54	CYSTATHIONINE-BETA SYNTHASE: REDUCED VICINAL THIOLS	X-RAY DIFFRACTION	2.9
4L0D	Crystal structure of delta516-525 human cystathionine beta-synthase containing C-terminal …	X-RAY DIFFRACTION	2.97
9SQQ	Structure of trans-basal conformer of wild-type human CBS enzyme in absence of substrate …	ELECTRON MICROSCOPY	3
9VTF	Structural basis for the inhibition of cystathionine-b-synthase by isoflurane	X-RAY DIFFRACTION	3.03
8S5I	Full-length human cystathionine beta-synthase with C-terminal 6xHis-tag, basal state …	ELECTRON MICROSCOPY	3.1
4L27	Crystal structure of delta1-39 and delta516-525 human cystathionine beta-synthase D444N …	X-RAY DIFFRACTION	3.39
4PCU	Crystal structure of delta516-525 E201S human cystathionine beta-synthase with AdoMet	X-RAY DIFFRACTION	3.58
4L3V	Crystal structure of delta516-525 human cystathionine beta-synthase	X-RAY DIFFRACTION	3.63
9HIF	Crystal Structure of Human cystathionine beta-synthase variant R336C	X-RAY DIFFRACTION	3.65
8S5H	Full-length human cystathionine beta-synthase with C-terminal 6xHis-tag, basal state …	ELECTRON MICROSCOPY	3.7
8S5K	Full-length human cystathionine beta-synthase, basal state, single particle reconstruction	ELECTRON MICROSCOPY	3.8
8S5L	Full-length human cystathionine beta-synthase, basal state, partially degraded tetramer	ELECTRON MICROSCOPY	3.8
8S5J	Full-length human cystathionine beta-synthase, basal state, helical reconstruction	ELECTRON MICROSCOPY	3.9
8S5M	Full-length human cystathionine beta-synthase with C-terminal 6xHis-tag, SAM bound …	ELECTRON MICROSCOPY	4
9SPV	focused structure of regulatory domains of cis-basal conformer of human CBS induced by …	ELECTRON MICROSCOPY	4.04
9SPW	Structure of cis-basal conformer of human CBS induced by non-activating allosteric SAO …	ELECTRON MICROSCOPY	4.11

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35520-F1	90.15	0.75

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Lyases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of amino acid metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles; nucleoli

Antibody reliability (HPA): IH enhanced · IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5)

Position	Role
52	heme
65	heme
149	pyridoxal 5’-phosphate
256–260	pyridoxal 5’-phosphate
349	pyridoxal 5’-phosphate

Post-translational modifications (4)

Type	Positions
N6-(pyridoxal phosphate)lysine	119
Phosphoserine	199, 27
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo)	211

Mutagenesis-validated functional residues (2)

Position	Phenotype
272	reduced heme content and cystathionine beta-synthase activity.
275	reduced heme content and cystathionine beta-synthase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 6; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

6 pathways:

ID	Pathway	Evidence
R-HSA-1614603	Cysteine formation from homocysteine	curated
R-HSA-1430728	Metabolism	—
R-HSA-71291	Metabolism of amino acids and derivatives	—
R-HSA-2408508	Metabolism of ingested SeMet, Sec, MeSec into H2Se	electronic
R-HSA-2408522	Selenoamino acid metabolism	—
R-HSA-1614635	Sulfur amino acid metabolism	—

MSigDB gene sets: 0 (showing top):

GO Biological Process (15): L-serine metabolic process (GO:0006563), L-serine catabolic process (GO:0006565), L-cysteine biosynthetic process (GO:0019344), transsulfuration (GO:0019346), L-cysteine catabolic process (GO:0019448), response to nutrient levels (GO:0031667), DNA protection (GO:0042262), negative regulation of apoptotic process (GO:0043066), L-homocysteine catabolic process (GO:0043418), homocysteine metabolic process (GO:0050667), hydrogen sulfide biosynthetic process (GO:0070814), cellular response to hypoxia (GO:0071456), amino acid biosynthetic process (GO:0008652), cellular response to insulin stimulus (GO:0032869), sulfur compound biosynthetic process (GO:0044272)

GO Molecular Function (17): cystathionine beta-synthase activity (GO:0004122), oxygen binding (GO:0019825), enzyme binding (GO:0019899), heme binding (GO:0020037), pyridoxal phosphate binding (GO:0030170), ubiquitin protein ligase binding (GO:0031625), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), metal ion binding (GO:0046872), nitrite reductase (NO-forming) activity (GO:0050421), carbon monoxide binding (GO:0070025), nitric oxide binding (GO:0070026), modified amino acid binding (GO:0072341), S-adenosyl-L-methionine binding (GO:1904047), catalytic activity (GO:0003824), protein binding (GO:0005515), lyase activity (GO:0016829)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

4 top-level categories:

Category	Pathways
Metabolism of amino acids and derivatives	2
Sulfur amino acid metabolism	1
Selenoamino acid metabolism	1
Metabolism	1

GO top-level categories

47 GO namespaces:

Category	Terms
amino acid catabolic process	3
small molecule binding	3
proteinogenic amino acid metabolic process	2
proteinogenic amino acid catabolic process	2
homocysteine metabolic process	2
sulfur amino acid catabolic process	2
cellular response to stress	2
biosynthetic process	2
protein binding	2
cation binding	2
binding	2
cellular anatomical structure	2
L-serine metabolic process	1
sulfur amino acid biosynthetic process	1
serine family amino acid biosynthetic process	1
proteinogenic amino acid biosynthetic process	1
response to stimulus	1
DNA metabolic process	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
non-proteinogenic amino acid catabolic process	1
sulfur amino acid metabolic process	1
non-proteinogenic amino acid metabolic process	1
sulfur compound biosynthetic process	1
hydrogen sulfide metabolic process	1
response to hypoxia	1
cellular response to decreased oxygen levels	1
amino acid metabolic process	1
response to insulin	1
cellular response to peptide hormone stimulus	1
sulfur compound metabolic process	1
hydro-lyase activity	1
tetrapyrrole binding	1
anion binding	1
vitamin B6 binding	1
ubiquitin-like protein ligase binding	1
identical protein binding	1
protein dimerization activity	1
oxidoreductase activity, acting on other nitrogenous compounds as donors, cytochrome as acceptor	1
nitrite reductase activity	1
sulfur compound binding	1
molecular_function	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 24 of 38 annotations. The rest are phylogenetic / computational / electronic (IEA).

24 experimentally-supported GO terms:

GO term	NS	Evidence
DNA protection	BP	mutant phenotype
L-cysteine biosynthetic process	BP	direct assay
L-cysteine catabolic process	BP	direct assay
L-homocysteine catabolic process	BP	direct assay
L-serine catabolic process	BP	direct assay
L-serine metabolic process	BP	direct assay
homocysteine metabolic process	BP	direct assay
hydrogen sulfide biosynthetic process	BP	direct assay
cytoplasm	CC	direct assay
cytosol	CC	high-throughput assay
nucleus	CC	direct assay
S-adenosyl-L-methionine binding	MF	direct assay
carbon monoxide binding	MF	direct assay
cystathionine beta-synthase activity	MF	direct assay
enzyme binding	MF	physical interaction
heme binding	MF	direct assay
identical protein binding	MF	physical interaction
modified amino acid binding	MF	direct assay
nitric oxide binding	MF	direct assay
nitrite reductase (NO-forming) activity	MF	direct assay
oxygen binding	MF	direct assay
protein homodimerization activity	MF	direct assay
pyridoxal phosphate binding	MF	direct assay
ubiquitin protein ligase binding	MF	physical interaction

Protein interactions and networks

IntAct

Human interaction partners of CBS in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 50 partners by confidence:

Partner	Interaction type	MIscore	Records
UBE2I	physical association	0.720	7
EHHADH	physical association	0.670	4
PIN1	physical association	0.670	4
PSMA1	physical association	0.670	4
UBASH3A	physical association	0.670	4
FXR2	physical association	0.670	3
HTT	physical association	0.560	12
PIAS2	physical association	0.560	4
ZMYM5	physical association	0.560	4
ARO4	physical association	0.560	3
CAMK2A	physical association	0.560	3
CTNNB1	physical association	0.560	3
CYTH1	physical association	0.560	3
FAA2	physical association	0.560	3
FKBP6	physical association	0.560	3
FYN	physical association	0.560	3
GAL	physical association	0.560	3
GCD7	physical association	0.560	3
KAT5	physical association	0.560	3
PRKACA	physical association	0.560	3
PRKAG1	physical association	0.560	3
SRP1	physical association	0.560	3
TAE1	physical association	0.560	3
HID1	physical association	0.550	2
VTA1	physical association	0.550	2
NTAQ1	physical association	0.490	2
EIF3B	physical association	0.400	1
TPM1	physical association	0.400	1
CERT1	physical association	0.370	1
DAXX	physical association	0.370	1

BioGRID (191 interactions; top human partners by supporting records): UBE2I (Two-hybrid; 5 records), FXR2 (Two-hybrid; 2 records), OTUD5 (Affinity Capture-MS; 2 records), PIAS2 (Two-hybrid; 2 records), ZMYM5 (Two-hybrid; 2 records), AAR2 (Affinity Capture-MS), ABAT (Co-fractionation), ACE2 (Affinity Capture-MS), AIMP2 (Affinity Capture-MS), AP1B1 (Co-fractionation), ARHGAP11B (Affinity Capture-MS), ARHGAP24 (Affinity Capture-MS), ARHGAP26 (Affinity Capture-MS), ARHGAP29 (Affinity Capture-MS), ARHGAP32 (Affinity Capture-MS)

SIGNOR signaling

7 signaling interactions:

A	Effect	B	Mechanism
SP1	“up-regulates quantity by expression”	CBS	“transcriptional regulation”
SP3	“up-regulates quantity by expression”	CBS	“transcriptional regulation”
USF1	“up-regulates quantity by expression”	CBS	“transcriptional regulation”
NFYA	“up-regulates quantity by expression”	CBS	“transcriptional regulation”
CBS	“down-regulates quantity”	“L-homocysteine zwitterion”	“chemical modification”
CBS	“down-regulates quantity”	“L-serine zwitterion”	“chemical modification”
CBS	“up-regulates quantity”	“L-cystathionine dizwitterion”	“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 50 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transmission across Chemical Synapses	5	11.5×	4e-03

Disease & clinical

Genetic variants

Variant evidence for CBS: 1,465 ClinVar records (235 pathogenic / likely pathogenic); 12 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

1,465 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	94
Likely pathogenic	141
Uncertain significance	342
Likely benign	609
Benign	72

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 235 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
120	NM_000071.3(CBS):c.833T>C (p.Ile278Thr)	Pathogenic	criteria provided, multiple submitters, no conflicts	41
117	NM_000071.3(CBS):c.919G>A (p.Gly307Ser)	Pathogenic	criteria provided, multiple submitters, no conflicts	23
128	NM_000071.3(CBS):c.1224-2A>C	Pathogenic	criteria provided, multiple submitters, no conflicts	18
132	NM_000071.3(CBS):c.572C>T (p.Thr191Met)	Pathogenic	criteria provided, multiple submitters, no conflicts	16
197625	NM_000071.3(CBS):c.374G>A (p.Arg125Gln)	Pathogenic	criteria provided, multiple submitters, no conflicts	16
92423	NM_000071.3(CBS):c.1006C>T (p.Arg336Cys)	Pathogenic	criteria provided, multiple submitters, no conflicts	14
131	NM_000071.3(CBS):c.1058C>T (p.Thr353Met)	Pathogenic	criteria provided, multiple submitters, no conflicts	12
188801	NM_000071.3(CBS):c.1039G>A (p.Gly347Ser)	Pathogenic	criteria provided, multiple submitters, no conflicts	11
371345	NM_000071.3(CBS):c.19dup (p.Gln7fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	9
188829	NM_000071.3(CBS):c.689del (p.Leu230fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
863694	NM_000071.3(CBS):c.451G>A (p.Gly151Arg)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
188784	NM_000071.3(CBS):c.1566del (p.Lys523fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
188825	NM_000071.3(CBS):c.1136G>A (p.Arg379Gln)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
212874	NM_000071.3(CBS):c.253G>A (p.Gly85Arg)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
370105	NM_000071.3(CBS):c.738del	Pathogenic	criteria provided, multiple submitters, no conflicts	6

Per-variant reference — Sugi Variant

Explore CBS’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 42 predictions of 2,012):

Position(s)	Effect	Δscore	Sites
21:43056801–43056802	donor_loss	1.0000	5
21:43059224–43059225	donor_loss	1.0000	5
21:43060439–43060440	donor_loss	1.0000	3
21:43060547–43060548	acceptor_loss	1.0000	6
21:43062309–43062310	donor_loss	1.0000	5
21:43065201–43065202	donor_loss	1.0000	4
21:43065273–43065274	acceptor_loss	1.0000	6
21:43065277	acceptor_gain	1.0000
21:43065385–43065386	donor_loss	1.0000	5
21:43065522–43065523	acceptor_loss	1.0000	2

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Liver Hepatocellular Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Pancreatic Adenocarcinoma (validation)	unfavorable	1.03e-05
Lung Adenocarcinoma (validation)	unfavorable	1.31e-05
Liver Hepatocellular Carcinoma (TCGA)	favorable	6.1e-05
Colon Adenocarcinoma (TCGA)	unfavorable	0.000977

Disease associations

OMIM: gene MIM:613381 | disease phenotypes: MIM:236200, MIM:607086, MIM:603174

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
classic homocystinuria	Definitive	Autosomal recessive	7

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
classic homocystinuria	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (12 panels, 11 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

12 panels:

Panel	Rating
DDG2P	green
Ehlers Danlos syndrome with a likely monogenic cause	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Paediatric disorders	green
Structural eye disease	green
Thoracic aortic aneurysm or dissection (GMS)	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green
Thoracic aortic aneurysm or dissection	amber

Mondo (7): classic homocystinuria (MONDO:0009352), familial thoracic aortic aneurysm and aortic dissection (MONDO:0019625), homocystinuria (MONDO:0004737), intellectual disability (MONDO:0001071), connective tissue disorder (MONDO:0003900), hyperhomocysteinemia (MONDO:0004743), inborn errors of metabolism (MONDO:0019052)

Orphanet (4): Homocystinuria due to cystathionine beta-synthase deficiency (Orphanet:394), Familial thoracic aortic aneurysm and aortic dissection (Orphanet:91387), Rare inborn errors of metabolism (Orphanet:68367), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

showing 60 of 93 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000098	Tall stature
HP:0000218	High palate
HP:0000486	Strabismus
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000541	Retinal detachment
HP:0000545	Myopia
HP:0000577	Exotropia
HP:0000646	Amblyopia
HP:0000648	Optic atrophy
HP:0000678	Dental crowding
HP:0000708	Atypical behavior
HP:0000709	Psychosis
HP:0000716	Depression
HP:0000729	Autistic behavior
HP:0000739	Anxiety
HP:0000767	Pectus excavatum
HP:0000768	Pectus carinatum
HP:0000822	Hypertension
HP:0000939	Osteoporosis
HP:0000965	Cutis marmorata
HP:0001010	Hypopigmentation of the skin
HP:0001025	Urticaria
HP:0001083	Ectopia lentis
HP:0001132	Lens subluxation
HP:0001166	Arachnodactyly
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001297	Stroke
HP:0001300	Parkinsonism
HP:0001328	Specific learning disability
HP:0001332	Dystonia
HP:0001376	Limitation of joint mobility
HP:0001387	Joint stiffness
HP:0001397	Hepatic steatosis
HP:0001508	Failure to thrive
HP:0001519	Disproportionate tall stature
HP:0001634	Mitral valve prolapse
HP:0001658	Myocardial infarction
HP:0001733	Pancreatitis
HP:0001761	Pes cavus
HP:0001907	Thromboembolism
HP:0001933	Subcutaneous hemorrhage
HP:0002039	Anorexia
HP:0002040	Esophageal varix
HP:0002071	Abnormality of extrapyramidal motor function
HP:0002156	Homocystinuria
HP:0002160	Hyperhomocystinemia
HP:0002170	Intracranial hemorrhage
HP:0002204	Pulmonary embolism
HP:0002209	Sparse scalp hair
HP:0002239	Gastrointestinal hemorrhage
HP:0002240	Hepatomegaly
HP:0002299	Brittle hair

GWAS associations

12 associations:

Study	Trait	p-value
GCST002391_2	Plasma homocysteine levels (post-methionine load test)	3e-26
GCST002087_7	Homocysteine levels	4e-24
GCST012020_231	Serum metabolite levels	9e-21
GCST008758_78	Pre-treatment viral load in HIV-1 infection	1e-15
GCST002087_18	Homocysteine levels	2e-12
GCST000367_2	Homocysteine levels	3e-10
GCST90002398_235	Neutrophil count	2e-9
GCST002670_4	Blood and toenail selenium levels	4e-9
GCST002670_12	Blood and toenail selenium levels	5e-9
GCST002670_11	Blood and toenail selenium levels	3e-8
GCST001762_489	Obesity-related traits	4e-6
GCST002039_9	Blood trace element (Se levels)	5e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0004578	homocysteine measurement
EFO:0010125	viral load
EFO:0004833	neutrophil count

MeSH disease descriptors

5 disease descriptors:

Descriptor	Name	Tree numbers
D003240	Connective Tissue Diseases	C17.300
D006712	Homocystinuria	C10.228.140.163.100.365; C16.320.565.100.480.500; C16.320.565.189.365; C17.300.428; C18.452.132.100.365; C18.452.648.100.480.500; C18.452.648.189.365
D020138	Hyperhomocysteinemia	C16.320.565.100.480; C18.452.603.378; C18.452.648.100.480; C18.654.521.500.133.699.418
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008661	Metabolism, Inborn Errors	C16.320.565; C18.452.648

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3399911 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 16,388 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL286494	HYPERICIN	3	16,388

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

4 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs915854		Other	Allele C is associated with increased expression of PKNOX1 as compared to allele T.	PMID:27060151
rs915854	bortezomib	Toxicity	Genotype TT is associated with increased likelihood of Peripheral Nervous System Diseases, Pain and neuropathic pain when treated with bortezomib in people with Multiple Myeloma as compared to genotypes CC + CT.	PMID:37194045
rs234709	Arsenic compounds	Toxicity, Metabolism/PK	Genotypes CT + TT are associated with increased metabolism of Arsenic compounds as compared to genotype CC.	PMID:20670920
rs4920037	Arsenic compounds	Toxicity, Metabolism/PK	Genotypes AA + AG are associated with increased metabolism of Arsenic compounds as compared to genotype GG.	PMID:20670920

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Hydrogen sulphide synthesis

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
aminooxyacetic acid	Inhibition	5.07	pIC50
benserazide	Inhibition	4.52	pIC50

Binding affinities (BindingDB)

11 measured of 11 human assays (11 total across all organisms); most potent 11 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM
MLS002153482	IC50	3200 nM
CHEMBL3403661	IC50	83000 nM
CHEMBL3403662	IC50	87000 nM
CHEMBL4757665	KD	94000 nM
Rubrolide A	IC50	108000 nM
CHEMBL1956805	IC50	125000 nM
CHEMBL3403663	IC50	136000 nM
4,5-dibromopyrrole-2-carboxamide	IC50	156000 nM
CHEMBL1956777	IC50	170000 nM
CHEMBL1957775	IC50	187000 nM

ChEMBL bioactivities

18 potent at pChembl≥5 of 31 total, top 18 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.05	IC50	900	nM	SIKOKIANIN C
6.00	IC50	1000	nM	CARBOXYMETHOXYLAMINE
5.85	IC50	1400	nM	SIKOKIANIN C
5.52	IC50	3000	nM	AURINTRICARBOXYLIC ACID
5.51	IC50	3100	nM	HYPERICIN
5.40	IC50	4000	nM	CARBOXYMETHOXYLAMINE
5.32	Kd	4841	nM	CHEMBL5653589
5.32	ED50	4841	nM	CHEMBL5653589
5.26	IC50	5500	nM	SIKOKIANIN C
5.23	IC50	5900	nM	CHEMBL4160717
5.21	IC50	6200	nM	CHEMBL4167976
5.13	IC50	7400	nM	CHEMBL455348
5.12	IC50	7500	nM	CARBOXYMETHOXYLAMINE
5.11	IC50	7800	nM	CHEMBL4164543
5.09	IC50	8100	nM	CHEMBL4172426
5.07	IC50	8600	nM	CARBOXYMETHOXYLAMINE
5.05	IC50	8900	nM	PODOCARPUSFLAVONE A
5.04	IC50	9200	nM	SIKOKIANIN C

PubChem BioAssay actives

33 with measured affinity, of 94 total; 11 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S,3R)-3-[(2S,3R)-5,7-dihydroxy-2-(4-methoxyphenyl)-4-oxo-2,3-dihydrochromen-3-yl]-5,7-dihydroxy-2-(4-hydroxyphenyl)-2,3-dihydrochromen-4-one	1412123: Inhibition of full-length GST-fused human CBS assessed as reduction in H2S production using 2 mM S-methylcysteine as substrate preincubated for 3 mins followed by substrate addition	ic50	0.9000	uM
2-aminooxyacetic acid	1506492: Inhibition of full-length GST-fused human CBS using methylcysteine as substrate measured for 10 mins by CPM probe-based fluorescence assay	ic50	1.0000	uM
5-[(3-carboxy-4-hydroxyphenyl)-(3-carboxy-4-oxocyclohexa-2,5-dien-1-ylidene)methyl]-2-hydroxybenzoic acid	1680643: Inhibition of CBS (unknown origin) by AzMC based fluorescence assay	ic50	3.0000	uM
9,11,13,16,18,20-hexahydroxy-5,24-dimethyloctacyclo[13.11.1.12,10.03,8.04,25.019,27.021,26.014,28]octacosa-1(26),2,4(25),5,8,10,12,14(28),15(27),16,18,20,23-tridecaene-7,22-dione	1506494: Inhibition of full-length GST-fused human CBS using cysteine/homocysteine as substrate assessed as decrease in H2S production preincubated for 3 mins in presence of homocysteine and lead nitrate followed by cysteine addition	ic50	3.1000	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148004: Binding affinity to human CBS incubated for 45 mins by Kinobead based pull down assay	kd	4.8413	uM
(10R,11R,18S,19S)-3,11,19-tris(4-hydroxyphenyl)-4,12,20-trioxaheptacyclo[16.6.1.12,5.110,13.021,25.09,27.017,26]heptacosa-1(25),2,5,7,9(27),13,15,17(26),21,23-decaene-7,15,23-triol	1506494: Inhibition of full-length GST-fused human CBS using cysteine/homocysteine as substrate assessed as decrease in H2S production preincubated for 3 mins in presence of homocysteine and lead nitrate followed by cysteine addition	ic50	5.9000	uM
[(2S,3R,4R,5R,6S)-6-[5,7-dihydroxy-2-(4-hydroxyphenyl)-4-oxochromen-3-yl]oxy-4-hydroxy-5-[(Z)-3-(4-hydroxyphenyl)prop-2-enoyl]oxy-2-methyloxan-3-yl] (Z)-3-(4-hydroxyphenyl)prop-2-enoate	1506494: Inhibition of full-length GST-fused human CBS using cysteine/homocysteine as substrate assessed as decrease in H2S production preincubated for 3 mins in presence of homocysteine and lead nitrate followed by cysteine addition	ic50	6.2000	uM
5-[(Z)-14-(3,5-dihydroxyphenyl)tetradec-10-enyl]benzene-1,3-diol	1506494: Inhibition of full-length GST-fused human CBS using cysteine/homocysteine as substrate assessed as decrease in H2S production preincubated for 3 mins in presence of homocysteine and lead nitrate followed by cysteine addition	ic50	7.4000	uM
8-[(2R,3S)-2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxo-2,3-dihydrochromen-3-yl]-7-hydroxy-2-(4-hydroxyphenyl)-5-methoxychromen-4-one	1506494: Inhibition of full-length GST-fused human CBS using cysteine/homocysteine as substrate assessed as decrease in H2S production preincubated for 3 mins in presence of homocysteine and lead nitrate followed by cysteine addition	ic50	7.8000	uM
9-phenyl-1-(2,4,6-trihydroxyphenyl)nonan-1-one	1506494: Inhibition of full-length GST-fused human CBS using cysteine/homocysteine as substrate assessed as decrease in H2S production preincubated for 3 mins in presence of homocysteine and lead nitrate followed by cysteine addition	ic50	8.1000	uM
8-[5-(5,7-dihydroxy-4-oxochromen-2-yl)-2-hydroxyphenyl]-5,7-dihydroxy-2-(4-methoxyphenyl)chromen-4-one	1506494: Inhibition of full-length GST-fused human CBS using cysteine/homocysteine as substrate assessed as decrease in H2S production preincubated for 3 mins in presence of homocysteine and lead nitrate followed by cysteine addition	ic50	8.9000	uM

CTD chemical–gene interactions

92 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects methylation, increases expression, affects metabolic processing, affects response to substance, decreases expression (+1 more)	6
Valproic Acid	decreases expression, decreases reaction, affects cotreatment, increases expression	5
sodium arsenite	decreases expression, increases abundance, increases expression	4
Cyclosporine	affects expression, increases expression	4
methylmercuric chloride	increases expression, affects cotreatment	3
bisphenol A	affects expression, decreases expression, increases expression	3
trichostatin A	affects cotreatment, increases expression	3
Tretinoin	decreases expression	3
deoxynivalenol	decreases expression	2
entinostat	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
(+)-JQ1 compound	decreases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Cisplatin	increases expression, affects cotreatment	2
Hydrogen Sulfide	affects secretion, increases chemical synthesis, decreases response to substance	2
Tetrachlorodibenzodioxin	decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
tert-Butylhydroperoxide	increases methylation, decreases expression	2
Particulate Matter	increases expression, affects cotreatment, increases abundance	2
TAK-243	increases sumoylation	1
bufotalin	decreases expression	1
alpha-pinene	increases expression, increases abundance, affects cotreatment	1
glycidyl methacrylate	increases expression	1
4-hydroxyphenylacetic acid	decreases activity, decreases reaction	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
manganese chloride	decreases expression, increases abundance	1
hydroquinone	increases expression	1
1-nitropyrene	increases expression	1

ChEMBL screening assays

22 unique, capped per target: 22 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3404160	Binding	Inhibition of full-length wild-type cystathionine beta-synthase (unknown origin) assessed as inhibition of H2S production by fluorescence assay in presence of S-adenosylmethionine	Marine natural products as inhibitors of cystathionine beta-synthase activity. — *Bioorg Med Chem Lett*

Cellosaurus cell lines

22 cell lines: 11 transformed cell line, 10 finite cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_2G96	GM00584	Finite cell line	Male
CVCL_2G97	GM00585	Finite cell line	Male
CVCL_2H01	GM00751	Finite cell line	Male
CVCL_2H02	GM00752	Finite cell line	Male
CVCL_2H03	GM00753	Finite cell line	Male
CVCL_2H09	GM00885	Finite cell line	Male
CVCL_2H11	GM01128	Finite cell line	Female
CVCL_2H13	GM01374	Finite cell line	Female
CVCL_2H15	GM01376	Finite cell line	Male
CVCL_2H18	GM01463	Transformed cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT05657860	Phase 4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	Phase 4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	Phase 4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	Phase 4	RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT01042158	Phase 4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	Phase 4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	Phase 4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	Phase 4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	Phase 4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	Phase 4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	Phase 4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	Phase 4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT06247085	Phase 3	RECRUITING	A Study to Investigate Efficacy and Safety of Pegtibatinase Compared With Placebo in Participants ≥12 to ≤65 Years of Age With Classical Homocystinuria (HCU) Due to Cystathionine Beta Synthase Deficiency Receiving Standard of Care Treatment
NCT06431893	Phase 3	ENROLLING_BY_INVITATION	A Long-term Extension Study to Assess the Long-term Safety and Efficacy of Pegtibatinase Treatment in Participants ≥5 to ≤65 Years of Age With Classical Homocystinuria (HCU) (ENSEMBLE)
NCT02270736	Phase 3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00864201	Phase 3	UNKNOWN	A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
NCT01196091	Phase 3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438	Phase 3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01488708	Phase 3	TERMINATED	On Open-Label Study in Participants With Systemic Lupus Erythematosus
NCT03626688	Phase 3	COMPLETED	A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
NCT03683186	Phase 3	ENROLLING_BY_INVITATION	A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
NCT06716606	Phase 3	RECRUITING	A Study to Investigate the Long-term Safety and Efficacy of Belimumab in Adults With Interstitial Lung Disease (ILD) Associated With Systemic Sclerosis (SSc) and Other Connective Tissue Diseases (CTD) (BLISSconneCTD-OLE)
NCT06917690	Phase 3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT00483314	Phase 2	COMPLETED	Homocystinuria: Treatment With N-Acetylcysteine
NCT02404337	Phase 2	COMPLETED	Betaine METABOLISM OF PATIENTS With Homocystinuria
NCT02304302	Phase 2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	Phase 2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	Phase 2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	Phase 2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00004357	Phase 2	COMPLETED	Absorption of Corticosteroids in Children With Juvenile Dermatomyositis
NCT00005675	Phase 2	COMPLETED	Oral Type I Collagen for Relieving Scleroderma
NCT01808196	Phase 2	COMPLETED	Testing Effectiveness of Losartan in Patients With EoE With or Without a CTD
NCT02682511	Phase 2	ACTIVE_NOT_RECRUITING	Oral Ifetroban to Treat Diffuse Cutaneous Systemic Sclerosis (SSc) or SSc-associated Pulmonary Arterial Hypertension
NCT04993885	Phase 2	RECRUITING	Avatrombopag in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies
NCT05516758	Phase 2	TERMINATED	A Study of Peresolimab (LY3462817) in Participants With Moderately-to-Severely Active Rheumatoid Arthritis
NCT05998759	Phase 2	RECRUITING	Telitacicept for the Treatment of Connective Tissue Disease-associated Thrombocytopenia
NCT06104228	Phase 2	RECRUITING	129 Xenon MRI as a Biomarker for Diagnosis and Response to Therapy in Pulmonary Arterial Hypertension (PAH)
NCT05462132	Phase 1	COMPLETED	Safety, Tolerability and Pharmacodynamics of SYNB1353 in Healthy Adult Volunteers
NCT05273320	Phase 1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	Phase 1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	Phase 1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	Phase 1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	Phase 1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01093911	Phase 1	COMPLETED	Safety Study of CDP7657 in Healthy Volunteers and Patients With Systemic Lupus Erythematosus (SLE)
NCT01764594	Phase 1	COMPLETED	Safety Study of CDP7657 in Patients With Systemic Lupus Erythematosus
NCT02392130	Phase 1	COMPLETED	A Clinical Trial to Assess the Potential of LEO 130852A Gel to Reduce Steroid Induced Skin Atrophy on Healthy Skin
NCT03337165	Phase 1	COMPLETED	Autologous Tolerogenic Dendritic Cells for Treatment of Patients With Rheumatoid Arthritis
NCT03929120	Phase 1	COMPLETED	Allogeneic Bone Marrow Mesenchymal Stem Cells for Patients With Interstitial Lung Disease (ILD) & Connective Tissue Disorders (CTD)
NCT04015557	Phase 1/2	SUSPENDED	Effect of Acetaminophen and N-Acetylcysteine on Liver Metabolism on Homocystinuria
NCT05154890	Phase 1/2	TERMINATED	A Multiple Ascending Dose Study of ACN00177 (Pegtarviliase) in Subjects With CBS Deficiency
NCT02998710	Not specified	COMPLETED	Natural History Study of Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency (ACAPPELLA)
NCT03440697	Not specified	ACTIVE_NOT_RECRUITING	Pathogenetic Basis of Aortopathy and Aortic Valve Disease
NCT06783803	Not specified	ACTIVE_NOT_RECRUITING	Application of Linkage Analysis in the Identification of Novel Hereditary Factors in Familial Aneurysms
NCT01192828	Phase 1/2	COMPLETED	Oxidative Stress Markers In Inherited Homocystinuria And The Impact Of Taurine
NCT03406611	Phase 1/2	RECRUITING	Pegtibatinase as a Treatment for Patients With Classical Homocystinuria (HCU) (Also Known as the COMPOSE Study)
NCT00004356	Not specified	COMPLETED	Study of Homocysteine Metabolism in Homocystinuria
NCT03655223	Not specified	ACTIVE_NOT_RECRUITING	Early Check: Expanded Screening in Newborns
NCT04021732	Not specified	COMPLETED	Effects of Exercise on Metabolic Parameters in Classical Homocystinuria
NCT05051657	Not specified	COMPLETED	Evaluation of the Express Plus Range
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CBS across ~30M SureChEMBL compounds — explore on Sugi Predict.