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): 1,445 total — 95 pathogenic, 136 likely-pathogenic
• Phenotypes (HPO): 93
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• 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: 68 — 59 protein_coding, 5 retained_intron, 4 protein_coding_CDS_not_defined

ENST00000352178, ENST00000359624, ENST00000398158, ENST00000398165, 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

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.

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

134 total, 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

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

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

31 targeting CBS, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

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

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)

Protein

Protein identifiers

Cystathionine beta-synthase — P35520 (reviewed: P35520)

Alternative names: Beta-thionase, Serine sulfhydrase

All UniProt accessions (5): P35520, C9JMA6, 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), 1 shown:

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

UniProt features (182 total): sequence variant 113, helix 25, 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)

19 structures.

PDB	Method	Resolution (Å)
4UUU	X-RAY DIFFRACTION	1.71
4COO	X-RAY DIFFRACTION	2
8STW	X-RAY DIFFRACTION	2.4
1JBQ	X-RAY DIFFRACTION	2.6
4L28	X-RAY DIFFRACTION	2.63
7QGT	X-RAY DIFFRACTION	2.69
5MMS	X-RAY DIFFRACTION	2.8
1M54	X-RAY DIFFRACTION	2.9
4L0D	X-RAY DIFFRACTION	2.97
8S5I	ELECTRON MICROSCOPY	3.1
4L27	X-RAY DIFFRACTION	3.39
4PCU	X-RAY DIFFRACTION	3.58
4L3V	X-RAY DIFFRACTION	3.63
9HIF	X-RAY DIFFRACTION	3.65
8S5H	ELECTRON MICROSCOPY	3.7
8S5K	ELECTRON MICROSCOPY	3.8
8S5L	ELECTRON MICROSCOPY	3.8
8S5J	ELECTRON MICROSCOPY	3.9
8S5M	ELECTRON MICROSCOPY	4

Predicted structure (AlphaFold)

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

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): 52 (axial binding residue); 65 (axial binding residue); 149; 256–260; 349

Post-translational modifications (4): 119, 199, 211, 27

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

6 pathways

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

MSigDB gene sets: 0 (showing top):

GO Biological Process (28): endochondral ossification (GO:0001958), blood vessel remodeling (GO:0001974), obsolete L-cysteine biosynthetic process from L-serine (GO:0006535), L-serine metabolic process (GO:0006563), L-serine catabolic process (GO:0006565), superoxide metabolic process (GO:0006801), obsolete regulation of nitric oxide mediated signal transduction (GO:0010749), obsolete L-cysteine biosynthetic process via L-cystathionine (GO:0019343), L-cysteine biosynthetic process (GO:0019344), transsulfuration (GO:0019346), L-cysteine catabolic process (GO:0019448), cerebellum morphogenesis (GO:0021587), DNA protection (GO:0042262), negative regulation of apoptotic process (GO:0043066), L-homocysteine catabolic process (GO:0043418), regulation of JNK cascade (GO:0046328), homocysteine metabolic process (GO:0050667), response to folic acid (GO:0051593), maternal process involved in female pregnancy (GO:0060135), cartilage development involved in endochondral bone morphogenesis (GO:0060351), hydrogen sulfide biosynthetic process (GO:0070814), cellular response to hypoxia (GO:0071456), blood vessel diameter maintenance (GO:0097746), obsolete cysteine metabolic process (GO:0006534), amino acid biosynthetic process (GO:0008652), obsolete serine family amino acid metabolic process (GO:0009069), response to nutrient levels (GO:0031667), 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

Rollup of top-4 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
L-amino acid catabolic process	3
small molecule binding	3
endochondral bone morphogenesis	2
L-amino acid metabolic process	2
proteinogenic amino acid metabolic process	2
proteinogenic amino acid catabolic process	2
homocysteine metabolic process	2
sulfur amino acid catabolic process	2
protein binding	2
cation binding	2
binding	2
cellular anatomical structure	2
replacement ossification	1
tissue remodeling	1
L-serine metabolic process	1
reactive oxygen species metabolic process	1
sulfur amino acid biosynthetic process	1
serine family amino acid biosynthetic process	1
L-amino acid biosynthetic process	1
proteinogenic amino acid biosynthetic process	1
anatomical structure morphogenesis	1
cerebellum development	1
hindbrain morphogenesis	1
DNA metabolic process	1
cellular response to stress	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
non-proteinogenic amino acid catabolic process	1
JNK cascade	1
regulation of MAPK cascade	1
sulfur amino acid metabolic process	1
non-proteinogenic amino acid metabolic process	1
response to vitamin	1
response to nitrogen compound	1
response to oxygen-containing compound	1
female pregnancy	1
multicellular organismal reproductive process	1
cartilage development	1
hydro-lyase activity	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

160 interactions, top by confidence:

A	B	Type	Score
CBS	CBS	psi-mi:“MI:0915”(physical association)	0.850
UBE2I	CBS	psi-mi:“MI:0915”(physical association)	0.720
CBS	UBE2I	psi-mi:“MI:0915”(physical association)	0.720
PSMA1	CBS	psi-mi:“MI:0915”(physical association)	0.670
UBASH3A	CBS	psi-mi:“MI:0915”(physical association)	0.670
EHHADH	CBS	psi-mi:“MI:0915”(physical association)	0.670
CBS	PIN1	psi-mi:“MI:0915”(physical association)	0.670
CBS	UBASH3A	psi-mi:“MI:0915”(physical association)	0.670
CBS	EHHADH	psi-mi:“MI:0915”(physical association)	0.670
PIN1	CBS	psi-mi:“MI:0915”(physical association)	0.670
FXR2	CBS	psi-mi:“MI:0915”(physical association)	0.670
CBS	FXR2	psi-mi:“MI:0915”(physical association)	0.670
PRKAG1	CBS	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (186): CBS (Two-hybrid), EHHADH (Two-hybrid), PIN1 (Two-hybrid), PRKAG1 (Two-hybrid), PSMA1 (Two-hybrid), UBE2I (Two-hybrid), UBASH3A (Two-hybrid), CBS (Two-hybrid), VTA1 (Two-hybrid), FXR2 (Two-hybrid), HID1 (Two-hybrid), CBS (Two-hybrid), AP1B1 (Co-fractionation), CARS (Co-fractionation), CBS (Co-fractionation)

ESM2 similar proteins: A2AV36, A3KP77, A4IHY0, A8E7D2, B1AS42, D3ZG52, P00387, P17571, P20070, P32232, P35520, Q05B89, Q07G10, Q0CT94, Q13057, Q2UM43, Q3UZW7, Q4V7D6, Q4WN24, Q502I6, Q58DM7, Q58E95, Q58H57, Q5B5L3, Q5EB81, Q5R4D2, Q5RCH4, Q5U378, Q60HG4, Q6ING7, Q6IPT4, Q6JQN1, Q6ZQJ5, Q7T0L7, Q7T0X7, Q7T291, Q7ZW24, Q8AWD2, Q8K4Z3, Q8VE38

Diamond homologs: A5INY7, A6QDA0, A6TXQ1, A7WX68, A8YZ41, C7M8J5, D0K799, D1GUM7, D2N3G7, D3ERF5, F4K5T2, G5EFH8, O01592, O05393, O23733, O23735, O32978, O34476, O45679, O59701, O67507, O81154, O81155, P0A1E3, P0A1E4, P0A535, P0ABK5, P0ABK6, P16703, P29848, P31300, P32232, P32260, P32582, P35520, P37887, P38076, P45040, P46794, P47998

SIGNOR signaling

7 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”

Disease & clinical

Clinical variants and AI predictions

ClinVar

1445 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	95
Likely pathogenic	136
Uncertain significance	338
Likely benign	599
Benign	77

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1073191	NM_000071.3(CBS):c.1397C>A (p.Ser466Ter)	Pathogenic
1076335	NC_000021.8:g.(?44488599)(44492323_?)del	Pathogenic
1076336	NC_000021.8:g.(?44478245)(44485815_?)del	Pathogenic
117	NM_000071.3(CBS):c.919G>A (p.Gly307Ser)	Pathogenic
120	NM_000071.3(CBS):c.833T>C (p.Ile278Thr)	Pathogenic
128	NM_000071.3(CBS):c.1224-2A>C	Pathogenic
131	NM_000071.3(CBS):c.1058C>T (p.Thr353Met)	Pathogenic
132	NM_000071.3(CBS):c.572C>T (p.Thr191Met)	Pathogenic
1326932	NM_000071.3(CBS):c.667-1G>C	Pathogenic
1339663	NM_000071.3(CBS):c.1039+1G>T	Pathogenic
1351168	NM_000071.3(CBS):c.829-249_878del	Pathogenic
1356572	NC_000021.8:g.(?44492085)(44496976_?)del	Pathogenic
1361476	NM_000071.3(CBS):c.532-1G>A	Pathogenic
1376358	NM_000071.3(CBS):c.1169G>A (p.Trp390Ter)	Pathogenic
1402639	NM_000071.3(CBS):c.702del (p.Asp234fs)	Pathogenic
1449016	NM_000071.3(CBS):c.256del (p.Asp86fs)	Pathogenic
1452001	NM_000071.3(CBS):c.456_477del (p.Ile152fs)	Pathogenic
1452782	NM_000071.3(CBS):c.624G>A (p.Trp208Ter)	Pathogenic
1456891	NM_000071.3(CBS):c.444dup (p.Asn149fs)	Pathogenic
1458301	NM_000071.3(CBS):c.184dup (p.Glu62fs)	Pathogenic
1458882	NM_000071.3(CBS):c.427dup (p.Ile143fs)	Pathogenic
1459487	NC_000021.8:g.(?44479686)(44483266_?)del	Pathogenic
1482701	NM_000071.3(CBS):c.736+1G>A	Pathogenic
1492630	NM_000071.3(CBS):c.194A>G (p.His65Arg)	Pathogenic
188784	NM_000071.3(CBS):c.1566del (p.Lys523fs)	Pathogenic
188787	NM_000071.3(CBS):c.346G>A (p.Gly116Arg)	Pathogenic
188801	NM_000071.3(CBS):c.1039G>A (p.Gly347Ser)	Pathogenic
188825	NM_000071.3(CBS):c.1136G>A (p.Arg379Gln)	Pathogenic
188829	NM_000071.3(CBS):c.689del (p.Leu230fs)	Pathogenic
189081	NM_000071.3(CBS):c.1358+1G>A	Pathogenic

SpliceAI

3861 predictions. Top by Δscore:

Variant	Effect	Δscore
21:43053980:TGGT:T	acceptor_gain	1.0000
21:43053981:GGT:G	acceptor_gain	1.0000
21:43053984:C:CC	acceptor_gain	1.0000
21:43056801:A:AC	donor_gain	1.0000
21:43056801:A:C	donor_loss	1.0000
21:43056802:C:CG	donor_gain	1.0000
21:43056802:C:CT	donor_gain	1.0000
21:43056802:CA:C	donor_gain	1.0000
21:43058252:CC:C	acceptor_gain	1.0000
21:43058253:CC:C	acceptor_gain	1.0000
21:43058832:AC:A	donor_gain	1.0000
21:43058833:CC:C	donor_gain	1.0000
21:43058833:CCCCG:C	donor_gain	1.0000
21:43059221:CTTAC:C	donor_loss	1.0000
21:43059222:TTAC:T	donor_loss	1.0000
21:43059222:TTACC:T	donor_loss	1.0000
21:43059223:TA:T	donor_loss	1.0000
21:43059224:A:AC	donor_gain	1.0000
21:43059224:A:T	donor_loss	1.0000
21:43059225:C:A	donor_loss	1.0000
21:43059225:C:CC	donor_gain	1.0000
21:43060437:TTA:T	donor_loss	1.0000
21:43060438:TAC:T	donor_loss	1.0000
21:43060439:A:AC	donor_gain	1.0000
21:43060439:ACATG:A	donor_loss	1.0000
21:43060440:C:CC	donor_gain	1.0000
21:43060440:C:CT	donor_gain	1.0000
21:43060543:CCAC:C	acceptor_gain	1.0000
21:43060544:CAC:C	acceptor_gain	1.0000
21:43060544:CACC:C	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000276530 (21:43078679 GTAAAA>G,GTAAAATAAAA), RS1000307882 (21:43078389 C>T), RS1000697114 (21:43063962 C>T), RS1000757478 (21:43059217 C>G,T), RS1001187359 (21:43056209 A>G), RS1001989321 (21:43059710 A>T), RS1002082633 (21:43059901 G>A), RS1002410035 (21:43077899 ACG>A), RS1002588458 (21:43066583 C>T), RS1002604875 (21:43055309 C>T), RS1002762442 (21:43057052 G>T), RS1003149769 (21:43061752 C>G), RS1003349832 (21:43070003 C>G), RS1003603227 (21:43065765 CAG>C), RS1003981491 (21:43057502 C>T)

Disease associations

OMIM: gene MIM:613381 | disease phenotypes: MIM:607086, MIM:236200, MIM:603174, MIM:117000

GenCC curated gene-disease

Disease	Classification	Inheritance
classic homocystinuria	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
classic homocystinuria	Definitive	AR

Mondo (7): familial thoracic aortic aneurysm and aortic dissection (MONDO:0019625), classic homocystinuria (MONDO:0009352), homocystinuria (MONDO:0004737), intellectual disability (MONDO:0001071), connective tissue disorder (MONDO:0003900), hyperhomocysteinemia (MONDO:0004743), congenital myopathy (MONDO:0019952)

Orphanet (4): Familial thoracic aortic aneurysm and aortic dissection (Orphanet:91387), Homocystinuria due to cystathionine beta-synthase deficiency (Orphanet:394), Congenital myopathy (Orphanet:97245), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

93 total (30 of 93 shown, 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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST000367_2	Homocysteine levels	3.000000e-10
GCST001762_514	Obesity-related traits	4.000000e-06
GCST002039_9	Blood trace element (Se levels)	5.000000e-06
GCST002087_18	Homocysteine levels	2.000000e-12
GCST002087_7	Homocysteine levels	4.000000e-24
GCST002391_2	Plasma homocysteine levels (post-methionine load test)	3.000000e-26
GCST002670_11	Blood and toenail selenium levels	3.000000e-08
GCST002670_12	Blood and toenail selenium levels	5.000000e-09
GCST002670_4	Blood and toenail selenium levels	4.000000e-09
GCST008758_84	Pre-treatment viral load in HIV-1 infection	1.000000e-15
GCST012020_508	Serum metabolite levels	9.000000e-21
GCST90002398_66	Neutrophil count	2.000000e-09

EFO canonical traits (3, from GWAS)

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

MeSH disease descriptors (4)

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3399911 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 16,266 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL286494	HYPERICIN	3	16,266

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs234709	CBS		0.00	0
rs4920037	CBS		0.00	0

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

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 116 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	increases expression, affects metabolic processing, affects response to substance, decreases expression, increases abundance (+1 more)	6
sodium arsenite	increases expression, decreases expression, increases abundance	4
Valproic Acid	affects cotreatment, 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	decreases expression, increases expression, affects cotreatment	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	affects cotreatment, increases abundance, increases expression	2
TAK-243	increases sumoylation	1
bufotalin	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	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

21 cell lines: 10 finite cell line, 10 transformed 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)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	PHASE4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	PHASE4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	PHASE4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	PHASE4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	PHASE4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT06247085	PHASE3	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	PHASE3	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	PHASE3	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	PHASE3	UNKNOWN	A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
NCT01196091	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01488708	PHASE3	TERMINATED	On Open-Label Study in Participants With Systemic Lupus Erythematosus
NCT03626688	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
NCT03683186	PHASE3	ENROLLING_BY_INVITATION	A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
NCT04084678	PHASE3	TERMINATED	A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH
NCT06716606	PHASE3	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	PHASE3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT00483314	PHASE2	COMPLETED	Homocystinuria: Treatment With N-Acetylcysteine
NCT02404337	PHASE2	COMPLETED	Betaine METABOLISM OF PATIENTS With Homocystinuria
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00004357	PHASE2	COMPLETED	Absorption of Corticosteroids in Children With Juvenile Dermatomyositis
NCT00005675	PHASE2	COMPLETED	Oral Type I Collagen for Relieving Scleroderma
NCT01808196	PHASE2	COMPLETED	Testing Effectiveness of Losartan in Patients With EoE With or Without a CTD
NCT02682511	PHASE2	ACTIVE_NOT_RECRUITING	Oral Ifetroban to Treat Diffuse Cutaneous Systemic Sclerosis (SSc) or SSc-associated Pulmonary Arterial Hypertension
NCT04993885	PHASE2	RECRUITING	Avatrombopag in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies
NCT05516758	PHASE2	TERMINATED	A Study of Peresolimab (LY3462817) in Participants With Moderately-to-Severely Active Rheumatoid Arthritis
NCT05998759	PHASE2	RECRUITING	Telitacicept for the Treatment of Connective Tissue Disease-associated Thrombocytopenia
NCT06104228	PHASE2	RECRUITING	129 Xenon MRI as a Biomarker for Diagnosis and Response to Therapy in Pulmonary Arterial Hypertension (PAH)
NCT05462132	PHASE1	COMPLETED	Safety, Tolerability and Pharmacodynamics of SYNB1353 in Healthy Adult Volunteers
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities