CTH

Summary

CTH (cystathionine gamma-lyase, HGNC:2501) is a protein-coding gene on chromosome 1p31.1, encoding Cystathionine gamma-lyase (P32929). Catalyzes the last step in the trans-sulfuration pathway from L-methionine to L-cysteine in a pyridoxal-5’-phosphate (PLP)-dependent manner, which consists on cleaving the L,L-cystathionine molecule into L-cysteine, ammonia and 2-oxobutanoate.

This gene encodes a cytoplasmic enzyme in the trans-sulfuration pathway that converts cystathione derived from methionine into cysteine. Glutathione synthesis in the liver is dependent upon the availability of cysteine. Mutations in this gene cause cystathioninuria. Alternative splicing of this gene results in three transcript variants encoding different isoforms.

Source: NCBI Gene 1491 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cystathioninuria (Definitive, ClinGen)
• GWAS associations: 5
• Clinical variants (ClinVar): 112 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 9
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001902

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2501
Approved symbol	CTH
Name	cystathionine gamma-lyase
Location	1p31.1
Locus type	gene with protein product
Status	Approved
Aliases	CSE
Ensembl gene	ENSG00000116761
Ensembl biotype	protein_coding
OMIM	607657
Entrez	1491

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000346806, ENST00000370938, ENST00000411986, ENST00000464926, ENST00000482383, ENST00000896200, ENST00000896201, ENST00000896202, ENST00000896203, ENST00000896204, ENST00000896205, ENST00000896206, ENST00000916100

RefSeq mRNA: 3 — MANE Select: NM_001902 NM_001190463, NM_001902, NM_153742

CCDS: CCDS53333, CCDS650, CCDS651

Canonical transcript exons

ENST00000370938 — 12 exons

Exon	Start	End
ENSE00000774647	70435125	70435177
ENSE00000774649	70433828	70433949
ENSE00000798481	70417937	70418032
ENSE00000798485	70432083	70432235
ENSE00001066694	70439101	70439851
ENSE00003508976	70411268	70411583
ENSE00003511884	70424285	70424416
ENSE00003539495	70438688	70438826
ENSE00003565589	70429794	70429851
ENSE00003577173	70415956	70416037
ENSE00003648111	70430317	70430394
ENSE00003652860	70421566	70421675

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 95.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.6478 / max 727.4148, expressed in 1741 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3491	25.1473	1678
3490	2.3546	1206
3489	0.1459	46

Top tissues by expression

282 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	95.88	gold quality
liver	UBERON:0002107	95.65	gold quality
pigmented layer of retina	UBERON:0001782	90.90	gold quality
jejunal mucosa	UBERON:0000399	88.16	gold quality
sperm	CL:0000019	87.88	gold quality
cartilage tissue	UBERON:0002418	87.74	gold quality
left ovary	UBERON:0002119	86.63	gold quality
choroid plexus epithelium	UBERON:0003911	86.36	gold quality
nephron tubule	UBERON:0001231	85.95	gold quality
right ovary	UBERON:0002118	85.11	gold quality
male germ cell	CL:0000015	84.65	gold quality
duodenum	UBERON:0002114	82.41	gold quality
body of pancreas	UBERON:0001150	82.29	gold quality
ovary	UBERON:0000992	82.00	gold quality
mucosa of sigmoid colon	UBERON:0004993	81.62	gold quality
colonic mucosa	UBERON:0000317	81.30	gold quality
ventricular zone	UBERON:0003053	80.50	gold quality
adrenal tissue	UBERON:0018303	80.23	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.61	gold quality
kidney epithelium	UBERON:0004819	78.91	gold quality
hindlimb stylopod muscle	UBERON:0004252	78.84	gold quality
pancreas	UBERON:0001264	78.70	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.40	gold quality
right lobe of thyroid gland	UBERON:0001119	78.31	gold quality
tibia	UBERON:0000979	78.08	gold quality
mucosa of transverse colon	UBERON:0004991	77.94	gold quality
rectum	UBERON:0001052	77.88	gold quality
ganglionic eminence	UBERON:0004023	77.67	gold quality
renal glomerulus	UBERON:0000074	77.62	gold quality
left lobe of thyroid gland	UBERON:0001120	77.60	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6379	no	2.53
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

44 targeting CTH, 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-513A-5P	100.00	69.77	2465
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-5697	99.39	67.74	1249

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• two nonsense mutations, namely exon 8 c.940-941delCT and exon 11 c.1220delC, and two missense mutations, namely exon 2 c.356C>T (T67I) and exon 7 c.874C>G (Q240E)were found in four probands with cystathioninuria (PMID:12574942)
• Cystathionine gamma-lyase has a role in regulating cell proliferation via a H2S-dependent modulation of ERK1/2 phosphorylation and p21Cip/WAK-1 (PMID:15347670)
• Mutations weaken the affinity for pyridoxal-5-phosphate and suggest that cystathionuric patients with these mutations should be responsive to pyridoxine therapy. (PMID:18476726)
• The present study suggests that the SNPs rs482843 and rs1021737 of the CTH gene were not associated with essential hypertension in the Northern Chinese Han population. (PMID:18701025)
• porphyrin moiety of the heme plays a critical role in proper CBS folding and assembly, but the metal ion is not essential for this function or for allosteric regulation by S-adenosyl-L-methionine (PMID:18849566)
• structure of hCSE.PLP.PAG complex highlights the particular importance of Tyr(114) in hCSE and the mechanism of PAG-dependent inhibition of hCSE (PMID:19019829)
• H2S biogenesis by human cystathionine gamma-lyase leads to the novel sulfur metabolites lanthionine and homolanthionine and is responsive to the grade of hyperhomocysteinemia (PMID:19261609)
• These results demonstrate that cystathionase is a farnesoid X receptor-regulated gene and provide a new molecular explanation for the pathophysiology of portal hypertension. (PMID:19418582)
• no evidence that severe loss of CTH activity due to the mutations is accompanied by adverse clinical effects (PMID:19428278)
• cystathionine beta-synthase and gamma-cystathionase have roles in H2S biogenesis via alternative trans-sulfuration reactions (PMID:19531479)
• Cystathionine beta-synthase 844Ins68 polymorphism is not associated with the levels of homocysteine and cysteine in an Indian population (PMID:20175737)
• The investigations could aim at verifying whether the stimulation of CST, at the level of protein or gene expression, could change the proliferation of neoplastic cells. (PMID:20446008)
• the CTH p.T67I substitution could have an ancient common origin, which probably occurred in the Neolithic Era and spread throughout Europe. (PMID:20584029)
• The increased expression of cystathionine-gamma-lyase(CSE)/H2S pathway might be involved in the pathogenesis of viral myocarditis. (PMID:20849728)
• CTH 1208 GT genotype was associated with increased chance of pregnancy and smaller number of previously failed IVF cycles and genotype frequency was lower in IVF patients with three or more previously failed IVF treatments compared with fertile controls (PMID:21507721)
• transcript factor Sp1 is a critical regulator of the hCSE expression during SMC differentiation, and CSE/H(2)S system is essential for maintenance of SMC phenotype. (PMID:21659522)
• H(2)S generated by CSE and CBS locally exerts dual effects on the contractility of pregnant myometrium (PMID:21886822)
• Take together, these results suggest that miR-21 participates in CSE/H(2)S-mediated-SMC differentiation by targeting SP1. (PMID:22034194)
• CTH is present in prostatic tissues and both normal and malignant prostate cell lines, including stromal compartments and the stromal cell line WPMY-1. It is downregulated by dihydrotestosterone. (PMID:22310774)
• PI3K/AKT pathway increased the activity of cystathionine gamma-lyase gene promoter via Sp1. (PMID:22360859)
• Transgenic CTH plays a critical role in the preservation of cardiac function following transverse aortic constriction, i.e., in the setting of pressure overload-induced heart failure. (PMID:23393010)
• MicroRNA-21, which negatively regulates CSE expression, was increased in placentas with abnormal Doppler waveforms. (PMID:23410520)
• Endogenous H2S is required for healthy placental vasculature, and a decrease in cystathionine gamma-lyase/H2S activity may contribute to the pathogenesis of preeclampsia. (PMID:23704251)
• The up-regulation of cystathionine gamma-lyase expression during hypoxia may be useful for increasing the production and concentration of H2S in mammalian cells and indirectly protecting cells from hypoxia. (PMID:23852134)
• Overexpression of the gene encoding CTH in cells leads to increased production of H2S, which plays a role in neuron protection against oxidative stress, and stimulates increase in gamma-glutamylcysteine synthetase and an increase in level of GSH. (review) (PMID:24491890)
• demonstrates for the first time that both hyperglycemia and hyperketonemia mediate a reduction in CSE expression and activity, which can contribute to the impaired H2S signaling associated with diabetes (PMID:24610811)
• These results demonstrate that H2S/CSE and its downstream pathway contribute to the proliferation of hepatoma cells, and inhibition of this pathway strongly suppress the excessive growth of hepatoma cells by stimulating mitochondrial apoptosis (PMID:24657251)
• results of the present study provide molecular insights into the antioxidative activity of CSE and highlights the importance of the CSE/H2S system in maintaining cellular glutathione status (PMID:24707893)
• our data suggest that the NF-kappaB binding site on CSE promoter is critical for LPS-induced CSE expression in mammalian cells. (PMID:24866963)
• Studies indicate taht a number of transcript factors regulate cystathionine gamma-lyase (CSE) transcription through direct or indirect binding with CSE promoter. (PMID:24896355)
• CTH is distributed in the human fallopian tube epithelium. (PMID:24914509)
• Wnt pathway regulates CSE gene expression on transcriptional level and CSE/hydrogen sulfide plays important roles in colon cancer. (PMID:25193114)
• The miR-30 family are potentially important regulators of cystathionine gamma-lyase gene expression. (PMID:25203395)
• The l-cysteine/cystathionine gamma lyase/hydrogen sulfide pathway is involved in melanoma progression. (PMID:25205294)
• Substantial portion of Huntington’s disease neurotoxicity appears to be attributable to cystathionine gamma-lyase deficiency. (PMID:25486189)
• An increase of placental mRNA levels in the pre-eclampsia group was observed for methionine synthase and cystathionine gamma-lyase. (PMID:25801727)
• CTH observed relationship between the rs482843 polymorphism and the risk of preeclampsia. (PMID:25807836)
• GPBAR1 plays a role in secondary bile acid induced vasodilation via reglation of cystathionine gamma-lyase. The GPBAR1/CSE pathway might contribute to endothelial dysfunction and hyperdynamic circulation in liver cirrhosis. (PMID:25934094)
• The expression of CSE was positively correlated with the severity of gastric ulcer (PMID:26060478)
• 3-Mercaptopyruvate sulphurtransferase and not cystathionine gamma-lyase is the primary regulator of coronary artery hydrogen sulfide production and function. (PMID:26519030)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	cthl	ENSDARG00000032206
danio_rerio	cth	ENSDARG00000074301
mus_musculus	Cth	ENSMUSG00000028179
rattus_norvegicus	Cth	ENSRNOG00000010658
drosophila_melanogaster	Cth	FBGN0000566
caenorhabditis_elegans		WBGENE00009048
caenorhabditis_elegans		WBGENE00022856

Protein

Protein identifiers

Cystathionine gamma-lyase — P32929 (reviewed: P32929)

Alternative names: Cysteine desulfhydrase, Cysteine-protein sulfhydrase, Gamma-cystathionase, Homocysteine desulfhydrase

All UniProt accessions (1): P32929

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the last step in the trans-sulfuration pathway from L-methionine to L-cysteine in a pyridoxal-5’-phosphate (PLP)-dependent manner, which consists on cleaving the L,L-cystathionine molecule into L-cysteine, ammonia and 2-oxobutanoate. Part of the L-cysteine derived from the trans-sulfuration pathway is utilized for biosynthesis of the ubiquitous antioxidant glutathione. Besides its role in the conversion of L-cystathionine into L-cysteine, it utilizes L-cysteine and L-homocysteine as substrates (at much lower rates than L,L-cystathionine) to produce the endogenous gaseous signaling molecule hydrogen sulfide (H2S). In vitro, it converts two L-cysteine molecules into lanthionine and H2S, also two L-homocysteine molecules to homolanthionine and H2S, which can be particularly relevant under conditions of severe hyperhomocysteinemia (which is a risk factor for cardiovascular disease, diabetes, and Alzheimer’s disease). Lanthionine and homolanthionine are structural homologs of L,L-cystathionine that differ by the absence or presence of an extra methylene group, respectively. Acts as a cysteine-protein sulfhydrase by mediating sulfhydration of target proteins: sulfhydration consists of converting -SH groups into -SSH on specific cysteine residues of target proteins such as GAPDH, PTPN1 and NF-kappa-B subunit RELA, thereby regulating their function. By generating the gasotransmitter H2S, it participates in a number of physiological processes such as vasodilation, bone protection, and inflammation. Plays an essential role in myogenesis by contributing to the biogenesis of H2S in skeletal muscle tissue. Can also accept homoserine as substrate. Catalyzes the elimination of selenocystathionine (which can be derived from the diet) to yield selenocysteine, ammonia and 2-oxobutanoate.

Subunit / interactions. Homotetramer. Interacts with CALM in a calcium-dependent manner.

Subcellular location. Cytoplasm.

Tissue specificity. Highly expressed in liver. Also in muscle and lower expression in most tissues except heart, pituitary gland, spleen, thymus, and vascular tissue, where it is hardly detected.

Disease relevance. Cystathioninuria (CSTNU) [MIM:219500] Autosomal recessive phenotype characterized by abnormal accumulation of plasma cystathionine, leading to increased urinary excretion. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by propargylglycine, trifluoroalanine and aminoethoxyvinylglycine.

Induction. Estrogen receptor alpha (ESR1) regulates CSE promoter activity and induces protein expression in human osteoblasts.

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

Similarity. Belongs to the trans-sulfuration enzymes family.

Isoforms (3)

UniProt ID	Names	Canonical?
P32929-1	1	yes
P32929-2	2
P32929-3	3

RefSeq proteins (3): NP_001177392, NP_001893, NP_714964 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000277	Cys/Met-Metab_PyrdxlP-dep_enz	Family
IPR015421	PyrdxlP-dep_Trfase_major	Homologous_superfamily
IPR015422	PyrdxlP-dep_Trfase_small	Homologous_superfamily
IPR015424	PyrdxlP-dep_Trfase	Homologous_superfamily
IPR054542	Cys_met_metab_PP	Conserved_site

Pfam: PF01053

Enzyme classification (BRENDA):

• EC 4.4.1.1 — cystathionine gamma-lyase (BRENDA: 70 organisms, 145 substrates, 139 inhibitors, 128 Km, 71 kcat entries)

Substrate kinetics (BRENDA)

23 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-CYSTATHIONINE	0.204–25.5	35
L-CYSTEINE	0.09–7.7	29
O-ACETYL-L-SERINE	0.7–5.3	10
BETA-CHLORO-L-ALANINE	0.1–11.77	8
L-CYSTINE	0.032–1.29	8
L-HOMOCYSTEINE	1.2–8	5
D-ALANINE	0.76–25.3	4
L-ALANINE	1–20	4
DJENKOLIC ACID	0.51–1.5	3
DL-CYSTATHIONINE	3.27–3.4	3
(DL)-HOMOCYSTEINE	1.153–1.417	2
L-CYS	0.029–0.069	2
3-CHLORO-DL-ALANINE	28.41	1
BETA-CHLORO-L-ALA	2.39	1
CYS	3.4	1

Catalyzed reactions (Rhea), 5 shown:

• L,L-cystathionine + H2O = 2-oxobutanoate + L-cysteine + NH4(+) (RHEA:14005)
• L-homocysteine + H2O = 2-oxobutanoate + hydrogen sulfide + NH4(+) + H(+) (RHEA:14501)
• L-homoserine = 2-oxobutanoate + NH4(+) (RHEA:24923)
• L-cysteine + H2O = hydrogen sulfide + pyruvate + NH4(+) + H(+) (RHEA:24931)
• L-selenocystathionine + H2O = L-selenocysteine + 2-oxobutanoate + NH4(+) (RHEA:31151)

UniProt features (49 total): strand 16, helix 15, turn 7, binding site 4, sequence variant 3, splice variant 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
3COG	X-RAY DIFFRACTION	2
9KHN	X-RAY DIFFRACTION	2
5TSU	X-RAY DIFFRACTION	2.2
3ELP	X-RAY DIFFRACTION	2.4
6NBA	X-RAY DIFFRACTION	2.5
2NMP	X-RAY DIFFRACTION	2.6
5EIG	X-RAY DIFFRACTION	2.7
6OVG	X-RAY DIFFRACTION	2.72
5TT2	X-RAY DIFFRACTION	2.95

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P32929-F1	95.91	0.93

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 (4): 62; 114; 119; 339

Post-translational modifications (1): 212

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1614558	Degradation of cysteine and homocysteine
R-HSA-1614603	Cysteine formation from homocysteine
R-HSA-2408508	Metabolism of ingested SeMet, Sec, MeSec into H2Se

MSigDB gene sets: 292 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, MULLIGHAN_NPM1_SIGNATURE_3_UP, DORSAM_HOXA9_TARGETS_UP, GOBP_PROTEIN_HOMOTETRAMERIZATION, GOBP_RESPONSE_TO_PEPTIDE, RORA1_01, GOBP_REGULATION_OF_SMOOTH_MUSCLE_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_SMOOTH_MUSCLE_CELL_DIFFERENTIATION, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS

GO Biological Process (16): obsolete cysteine metabolic process (GO:0006534), lipid metabolic process (GO:0006629), protein-pyridoxal-5-phosphate linkage via peptidyl-N6-pyridoxal phosphate-L-lysine (GO:0018272), obsolete L-cysteine biosynthetic process via L-cystathionine (GO:0019343), L-cysteine biosynthetic process (GO:0019344), transsulfuration (GO:0019346), endoplasmic reticulum unfolded protein response (GO:0030968), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), protein sulfhydration (GO:0044524), protein homotetramerization (GO:0051289), hydrogen sulfide biosynthetic process (GO:0070814), positive regulation of aortic smooth muscle cell differentiation (GO:1904831), cellular response to leukemia inhibitory factor (GO:1990830), negative regulation of apoptotic signaling pathway (GO:2001234), amino acid biosynthetic process (GO:0008652), negative regulation of apoptotic process (GO:0043066)

GO Molecular Function (10): cystathionine gamma-lyase activity (GO:0004123), calmodulin binding (GO:0005516), pyridoxal phosphate binding (GO:0030170), identical protein binding (GO:0042802), L-cystine L-cysteine-lyase (deaminating) activity (GO:0044540), homocysteine desulfhydrase activity (GO:0047982), L-cysteine desulfhydrase activity (GO:0080146), selenocystathionine gamma-lyase activity (GO:0098606), protein binding (GO:0005515), lyase activity (GO:0016829)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Sulfur amino acid metabolism	2
Selenoamino acid metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
carbon-sulfur lyase activity	5
protein binding	2
cellular anatomical structure	2
primary metabolic process	1
peptidyl-lysine modification	1
protein-pyridoxal-5-phosphate linkage	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
homocysteine metabolic process	1
L-amino acid metabolic process	1
proteinogenic amino acid metabolic process	1
cellular response to unfolded protein	1
response to endoplasmic reticulum stress	1
intracellular signal transduction	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
protein modification process	1
protein homooligomerization	1
protein tetramerization	1
sulfur compound biosynthetic process	1
hydrogen sulfide metabolic process	1
aortic smooth muscle cell differentiation	1
regulation of aortic smooth muscle cell differentiation	1
positive regulation of vascular associated smooth muscle cell differentiation	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	1
negative regulation of signal transduction	1
negative regulation of apoptotic process	1
apoptotic signaling pathway	1
regulation of apoptotic signaling pathway	1
amino acid metabolic process	1
biosynthetic process	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
anion binding	1
vitamin B6 binding	1

Protein interactions and networks

STRING

2847 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTH	H7C2H4	H7C2H4	974
CTH	P0DN79	P0DN79	971
CTH	MPST	P25325	940
CTH	DGUOK	P78532	851
CTH	MTHFR	P42898	838
CTH	BHMT	Q93088	783
CTH	TST	Q16762	772
CTH	MTR	Q99707	760
CTH	SQOR	Q9Y6N5	741
CTH	AHCY	P23526	729
CTH	SUOX	P51687	717
CTH	CDO1	P78513	716
CTH	DAO	P14920	704
CTH	MAT1A	Q00266	681
CTH	ETHE1	O95571	669

IntAct

46 interactions, top by confidence:

A	B	Type	Score
CTH	CTH	psi-mi:“MI:0915”(physical association)	0.780
RECK	CTH	psi-mi:“MI:0915”(physical association)	0.720
CTH	RECK	psi-mi:“MI:0915”(physical association)	0.720
CTH	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
GUCD1	CTH	psi-mi:“MI:0915”(physical association)	0.560
CTH	GUCD1	psi-mi:“MI:0915”(physical association)	0.560
NTAQ1	CTH	psi-mi:“MI:0915”(physical association)	0.560
FSD1	UBFD1	psi-mi:“MI:0914”(association)	0.530
ZSCAN32	ZNF197	psi-mi:“MI:0914”(association)	0.530
GHITM	CCNB2	psi-mi:“MI:0914”(association)	0.530
CTH	GAPDHS	psi-mi:“MI:0915”(physical association)	0.400
YWHAZ	CTH	psi-mi:“MI:0915”(physical association)	0.400
CTH	SDCBP2	psi-mi:“MI:0915”(physical association)	0.370
FOXI2	DDX39A	psi-mi:“MI:0914”(association)	0.350
ZDHHC5	HACD3	psi-mi:“MI:0914”(association)	0.350
SLC25A41	VPS37C	psi-mi:“MI:0914”(association)	0.350
KLHL20	KRBA1	psi-mi:“MI:0914”(association)	0.350
MPL	FAM171A2	psi-mi:“MI:0914”(association)	0.350
FGB	KIF2A	psi-mi:“MI:0914”(association)	0.350
TMEM223	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
ZNF488	USO1	psi-mi:“MI:0914”(association)	0.350

BioGRID (94): CTH (Two-hybrid), RECK (Two-hybrid), WDYHV1 (Two-hybrid), GUCD1 (Two-hybrid), CTH (Affinity Capture-MS), CTH (Affinity Capture-MS), CTH (Affinity Capture-MS), CTH (Affinity Capture-MS), CTH (Two-hybrid), ACLY (Co-fractionation), CTBP1 (Co-fractionation), CTH (Co-fractionation), CTH (Co-fractionation), CTH (Co-fractionation), CTH (Co-fractionation)

ESM2 similar proteins: A3QK15, F6V515, O46560, O55052, O88958, P14174, P29401, P30904, P32929, P34884, P36959, P40142, P50137, P80177, P80928, P82197, Q02960, Q0II59, Q0II68, Q1ZZU7, Q259G4, Q2KHU0, Q3T186, Q3ZBV9, Q4R549, Q5R4C1, Q5R8T8, Q5ZJ01, Q5ZLG0, Q60HG7, Q64422, Q6DCC5, Q6DEY3, Q6DN04, Q6P8M1, Q6PA43, Q6UWP2, Q71R50, Q7XPW5, Q7ZV22

Diamond homologs: A0A0D2YG02, A0A0J6G7P5, A0A0M3VI47, A2RM21, A8CEI3, O05394, O13326, O31631, O31632, O94350, P00935, P06106, P0A4K2, P0C2T9, P13254, P18757, P24601, P31373, P32929, P44502, P46807, P50125, P53780, P55216, P55218, P56069, P66876, P94890, P9WGB4, P9WGB5, P9WGB6, P9WGB7, Q19QT7, Q1M0P5, Q55DV9, Q58DW2, Q5MNH8, Q5SJ58, Q5SK88, Q60HG7

SIGNOR signaling

13 interactions.

A	Effect	B	Mechanism
CTH	“up-regulates quantity”	“L-cysteine zwitterion”	“chemical modification”
CTH	“up-regulates quantity”	hydrosulfide	“chemical modification”
CTH	“up-regulates quantity”	pyruvate	“chemical modification”
CTH	“up-regulates quantity”	“L-selenocysteine zwitterion”	“chemical modification”
CTH	“down-regulates quantity”	“L-cystathionine dizwitterion”	“chemical modification”
CTH	“down-regulates quantity”	“L-selenocystathionine zwitterion”	“chemical modification”
CTH	“down-regulates quantity”	“L-cysteine zwitterion”	“chemical modification”
CTH	“down-regulates quantity”	“L-homocysteine zwitterion”	“chemical modification”
AMPK	“up-regulates activity”	CTH	phosphorylation
PRKG2	“down-regulates activity”	CTH	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	84
Likely benign	8
Benign	4

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2937	NM_001902.6(CTH):c.784_785del (p.Leu262fs)	Pathogenic
2940	NM_001902.6(CTH):c.718C>G (p.Gln240Glu)	Pathogenic
225330	NM_001902.6(CTH):c.793C>T (p.Arg265Ter)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2659 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:70415965:T:C	Y60H	0.998
1:70429840:A:T	K212I	0.997
1:70415982:T:A	N65K	0.996
1:70415982:T:G	N65K	0.996
1:70430325:G:C	D219H	0.996
1:70432128:G:C	R257P	0.996
1:70435161:A:C	S346R	0.996
1:70435163:C:A	S346R	0.996
1:70435163:C:G	S346R	0.996
1:70411554:T:C	F47L	0.995
1:70411556:C:A	F47L	0.995
1:70411556:C:G	F47L	0.995
1:70429837:C:T	T211I	0.995
1:70430317:G:A	G216D	0.995
1:70424291:T:A	W155R	0.994
1:70424291:T:C	W155R	0.994
1:70430337:G:C	G223R	0.994
1:70432114:T:G	C252W	0.994
1:70435143:A:C	S340R	0.994
1:70435145:C:A	S340R	0.994
1:70435145:C:G	S340R	0.994
1:70415971:C:A	R62S	0.993
1:70430322:A:C	S218R	0.993
1:70430324:T:A	S218R	0.993
1:70430324:T:G	S218R	0.993
1:70415968:A:C	S61R	0.992
1:70415970:C:A	S61R	0.992
1:70415970:C:G	S61R	0.992
1:70430317:G:T	G216V	0.992
1:70430326:A:T	D219V	0.992

dbSNP variants (sampled 300 via entrez): RS1000044904 (1:70422796 G>A), RS1000382414 (1:70428865 A>T), RS1000474668 (1:70415856 T>A,C), RS1000489845 (1:70435062 A>C,G), RS1000561253 (1:70411078 T>G), RS1000775690 (1:70411344 A>G,T), RS1000894187 (1:70420369 A>G,T), RS1000926548 (1:70430311 T>G), RS1001093930 (1:70424227 G>A), RS1001124098 (1:70438337 A>G), RS1001169503 (1:70427391 G>A), RS1001192077 (1:70423534 G>A), RS1001276038 (1:70423936 A>G), RS1001285490 (1:70427009 T>C), RS1001366166 (1:70416467 A>T)

Disease associations

OMIM: gene MIM:607657 | disease phenotypes: MIM:219500

GenCC curated gene-disease

Disease	Classification	Inheritance
cystathioninuria	Moderate	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
cystathioninuria	Definitive	AR

Mondo (1): cystathioninuria (MONDO:0009058)

Orphanet (1): Cystathioninuria (Orphanet:212)

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000377	Abnormal pinna morphology
HP:0000787	Nephrolithiasis
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001337	Tremor
HP:0001762	Talipes equinovarus
HP:0003153	Cystathioninuria
HP:0003286	Cystathioninemia

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002178_1	Adverse response to chemotherapy in breast cancer (alopecia) (cyclophosphamide+doxorubicin+/-5FU)	2.000000e-06
GCST004797_11	Brain volume in infants (grey matter)	9.000000e-07
GCST007102_2	Seasonality and depression	8.000000e-06
GCST010916_2	Proportion of activated microglia (inferior temporal cortex)	3.000000e-06
GCST012147_2	Declining hemoglobin trajectory in blood donors	4.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008368	infant grey matter volume measurement
EFO:0006876	seasonality measurement
EFO:0600027	hemoglobin change measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295745 (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: 1,860 (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
CHEMBL1454910	NITROXOLINE	4	1,860

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1021737	Toxicity	3	busulfan;cyclophosphamide	Hematopoietic stem cell transplantation

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1021737	CTH	3	3.00	1	busulfan;cyclophosphamide
rs648743	CTH		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 (4 total), top 4:

Ligand	Action	Affinity	Parameter
aminoethoxyvinylglycine	Inhibition	6.0	pIC50
aminooxyacetic acid	Inhibition	5.96	pIC50
β-Cyano-L-alanine	Inhibition	5.85	pIC50
propargylglycine	Inhibition	4.4	pIC50

Binding affinities (BindingDB)

18 measured of 71 human assays (71 total across all organisms); most potent 18 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-(3,4-DIHYDROXYPHENYL)-2-METHYL-L-ALANINE	IC50	50000 nM
3-[amino(2H-tetrazol-5-yl)amino]-N,N-dimethylpropan-1-amine	IC50	55000 nM	US-9725426: Cystathionine-γ-lyase (CSE) inhibitors
1-(2-methoxyethyl)-1-(2H-tetrazol-5-yl)hydrazine	IC50	55000 nM	US-9725426: Cystathionine-γ-lyase (CSE) inhibitors
1-propyl-1-(2H-tetrazol-5-yl)hydrazine	IC50	55000 nM	US-9725426: Cystathionine-γ-lyase (CSE) inhibitors
2-[amino(2H-tetrazol-5-yl)amino]-N-methylethanamine	IC50	55000 nM	US-9725426: Cystathionine-γ-lyase (CSE) inhibitors
1-(2H-tetrazol-5-yl)-1-[3-(2H-tetrazol-5-yl)propyl]hydrazine	IC50	55000 nM	US-9725426: Cystathionine-γ-lyase (CSE) inhibitors
N-[(E)-benzylideneamino]tetrazolidin-5-amine	IC50	55000 nM	US-9725426: Cystathionine-γ-lyase (CSE) inhibitors
N-[(E)-[4-(dimethylamino)phenyl]methylideneamino]-2H-tetrazol-5-amine	IC50	55000 nM	US-9725426: Cystathionine-γ-lyase (CSE) inhibitors
N-[(E)-[4-(dimethylamino)phenyl]methylideneamino]-N-methyltetrazolidin-5-amine	IC50	55000 nM	US-9725426: Cystathionine-γ-lyase (CSE) inhibitors
3-[amino(methyl)amino]-1,2,4-oxadiazolidin-5-one	IC50	55000 nM	US-9725426: Cystathionine-γ-lyase (CSE) inhibitors
2-(2-propan-2-ylidenehydrazinyl)acetic acid	IC50	55000 nM	US-9725426: Cystathionine-γ-lyase (CSE) inhibitors
N,N-dimethyl-4-[[2-(tetrazolidin-5-yl)hydrazinyl]methyl]aniline	IC50	55000 nM	US-9725426: Cystathionine-γ-lyase (CSE) inhibitors
N-[(E)-[4-(diethylamino)phenyl]methylideneamino]tetrazolidin-5-amine	IC50	55000 nM	US-9725426: Cystathionine-γ-lyase (CSE) inhibitors
4-[(E)-(tetrazolidin-5-ylhydrazinylidene)methyl]phenol	IC50	55000 nM	US-9725426: Cystathionine-γ-lyase (CSE) inhibitors
2H-tetrazol-5-ylhydrazine	IC50	55000 nM	US-9725426: Cystathionine-γ-lyase (CSE) inhibitors
(2S)-2-amino-N-(2H-tetrazol-5-yl)pent-4-ynamide	IC50	125000 nM	US-10227314: Cystathionine-gamma-lyase (CSE) inhibitors
(2S)-2-amino-N-(benzenesulfonyl)pent-4-ynamide	IC50	125000 nM	US-10227314: Cystathionine-gamma-lyase (CSE) inhibitors
(2S)-2-amino-N-methylsulfonylpent-4-ynamide	IC50	125000 nM	US-10227314: Cystathionine-gamma-lyase (CSE) inhibitors

ChEMBL bioactivities

44 potent at pChembl≥5 of 74 total, top 42 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.24	IC50	570	nM	CARBOXYMETHOXYLAMINE
6.22	Ki	600	nM	AURINTRICARBOXYLIC ACID
6.22	IC50	600	nM	AURINTRICARBOXYLIC ACID
5.96	IC50	1100	nM	CHEMBL1619821
5.92	IC50	1200	nM	CHEMBL4163832
5.77	IC50	1700	nM	AURINTRICARBOXYLIC ACID
5.75	IC50	1800	nM	AURINTRICARBOXYLIC ACID
5.72	IC50	1900	nM	CHEMBL4159854
5.70	IC50	2000	nM	CHEMBL4162824
5.70	IC50	2000	nM	CHEMBL4171052
5.70	IC50	2000	nM	CHEMBL4160453
5.70	IC50	2000	nM	CHEMBL4166278
5.68	IC50	2100	nM	CHEMBL4168463
5.60	IC50	2500	nM	CHEMBL4167775
5.58	IC50	2600	nM	AURINTRICARBOXYLIC ACID
5.57	IC50	2700	nM	CHEMBL4166122
5.52	IC50	3000	nM	CHEMBL4176894
5.52	IC50	3000	nM	CHEMBL4169541
5.48	IC50	3300	nM	AURINTRICARBOXYLIC ACID
5.47	Kd	3400	nM	AURINTRICARBOXYLIC ACID
5.46	IC50	3500	nM	CHEMBL4170080
5.42	Kd	3800	nM	CHEMBL4761159
5.40	IC50	4000	nM	CARBOXYMETHOXYLAMINE
5.31	Ki	4900	nM	CHEMBL4761159
5.30	IC50	5000	nM	CHEMBL4170257
5.30	IC50	5000	nM	CHEMBL4177072
5.22	IC50	6000	nM	CHEMBL3318351
5.22	IC50	6000	nM	CHEMBL4160479
5.22	IC50	6000	nM	CHEMBL4159631
5.22	IC50	6000	nM	CHEMBL4169868
5.22	IC50	6000	nM	CHEMBL4173530
5.22	IC50	6000	nM	CHEMBL4176749
5.22	IC50	6000	nM	CHEMBL4174491
5.22	IC50	6000	nM	CHEMBL4159463
5.22	IC50	6000	nM	NITROXOLINE
5.21	IC50	6200	nM	CHEMBL4761159
5.20	IC50	6300	nM	CHEMBL1985550
5.16	IC50	7000	nM	CHEMBL4162997
5.13	IC50	7400	nM	CHEMBL4761159
5.10	IC50	8000	nM	NITROXOLINE
5.00	IC50	1e+04	nM	CHEMBL4161944
5.00	IC50	1e+04	nM	CHEMBL4167285

PubChem BioAssay actives

44 with measured affinity, of 147 total; 31 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
2-aminooxyacetic acid	1506493: Inhibition of N-terminal His-tagged CSE extracted from human HepG2 cells expressed in Escherichia coli BL21 (DE3) using methylcysteine as substrate measured for 10 mins by CPM probe-based fluorescence assay	ic50	0.5700	uM
5-[(3-carboxy-4-hydroxyphenyl)-(3-carboxy-4-oxocyclohexa-2,5-dien-1-ylidene)methyl]-2-hydroxybenzoic acid	1680637: Competitive inhibition of human CSE using varying levels of L-Cys as substrate and fixed PLP levels	ki	0.6000	uM
(E,2S)-2-amino-4-(2-aminoethoxy)but-3-enoic acid	1504913: Inhibition of cystathionine gamma-lyase (unknown origin)	ic50	1.1000	uM
[2-(4-methoxyanilino)-2-oxoethyl] N-[(E)-(3-fluoro-2-pyridinyl)methylideneamino]carbamodithioate	1504918: Inhibition of cystathionine gamma-lyase (unknown origin) assessed as reduction in cysteine formation from CPM using L-cystathionine pre-incubated for 15 min followed by L-cystathionine and CPM addition and measured after 7 mins by fluorescence-based primary assay	ic50	1.2000	uM
[2-(4-methoxyanilino)-2-oxoethyl] N-[(E)-(6-methyl-2-pyridinyl)methylideneamino]carbamodithioate	1504918: Inhibition of cystathionine gamma-lyase (unknown origin) assessed as reduction in cysteine formation from CPM using L-cystathionine pre-incubated for 15 min followed by L-cystathionine and CPM addition and measured after 7 mins by fluorescence-based primary assay	ic50	1.9000	uM
[2-(4-tert-butylanilino)-2-oxoethyl] N-[(E)-(3-fluoro-2-pyridinyl)methylideneamino]carbamodithioate	1504918: Inhibition of cystathionine gamma-lyase (unknown origin) assessed as reduction in cysteine formation from CPM using L-cystathionine pre-incubated for 15 min followed by L-cystathionine and CPM addition and measured after 7 mins by fluorescence-based primary assay	ic50	2.0000	uM
[2-(4-methoxyanilino)-2-oxoethyl] N-[(E)-pyridin-2-ylmethylideneamino]carbamodithioate	1504918: Inhibition of cystathionine gamma-lyase (unknown origin) assessed as reduction in cysteine formation from CPM using L-cystathionine pre-incubated for 15 min followed by L-cystathionine and CPM addition and measured after 7 mins by fluorescence-based primary assay	ic50	2.0000	uM
[2-(4-methylanilino)-2-oxoethyl] N-[(E)-(3-fluoro-2-pyridinyl)methylideneamino]carbamodithioate	1504918: Inhibition of cystathionine gamma-lyase (unknown origin) assessed as reduction in cysteine formation from CPM using L-cystathionine pre-incubated for 15 min followed by L-cystathionine and CPM addition and measured after 7 mins by fluorescence-based primary assay	ic50	2.0000	uM
[2-(4-methylanilino)-2-oxoethyl] N-[(E)-pyridin-2-ylmethylideneamino]carbamodithioate	1504918: Inhibition of cystathionine gamma-lyase (unknown origin) assessed as reduction in cysteine formation from CPM using L-cystathionine pre-incubated for 15 min followed by L-cystathionine and CPM addition and measured after 7 mins by fluorescence-based primary assay	ic50	2.0000	uM
[2-(4-methoxyanilino)-2-oxoethyl] N-[(E)-1,3-thiazol-4-ylmethylideneamino]carbamodithioate	1504918: Inhibition of cystathionine gamma-lyase (unknown origin) assessed as reduction in cysteine formation from CPM using L-cystathionine pre-incubated for 15 min followed by L-cystathionine and CPM addition and measured after 7 mins by fluorescence-based primary assay	ic50	2.1000	uM
[2-(4-methylanilino)-2-oxoethyl] N-[(E)-(3-methyl-2-pyridinyl)methylideneamino]carbamodithioate	1504918: Inhibition of cystathionine gamma-lyase (unknown origin) assessed as reduction in cysteine formation from CPM using L-cystathionine pre-incubated for 15 min followed by L-cystathionine and CPM addition and measured after 7 mins by fluorescence-based primary assay	ic50	2.5000	uM
[2-(4-methoxyanilino)-2-oxoethyl] N-[(E)-(4-chloro-1-methylpyrazol-3-yl)methylideneamino]carbamodithioate	1504918: Inhibition of cystathionine gamma-lyase (unknown origin) assessed as reduction in cysteine formation from CPM using L-cystathionine pre-incubated for 15 min followed by L-cystathionine and CPM addition and measured after 7 mins by fluorescence-based primary assay	ic50	2.7000	uM
[2-(4-methylanilino)-2-oxoethyl] N-[(E)-(4-chloro-1-methylpyrazol-3-yl)methylideneamino]carbamodithioate	1504918: Inhibition of cystathionine gamma-lyase (unknown origin) assessed as reduction in cysteine formation from CPM using L-cystathionine pre-incubated for 15 min followed by L-cystathionine and CPM addition and measured after 7 mins by fluorescence-based primary assay	ic50	3.0000	uM
[2-(4-tert-butylanilino)-2-oxoethyl] N-[(E)-pyridin-2-ylmethylideneamino]carbamodithioate	1504918: Inhibition of cystathionine gamma-lyase (unknown origin) assessed as reduction in cysteine formation from CPM using L-cystathionine pre-incubated for 15 min followed by L-cystathionine and CPM addition and measured after 7 mins by fluorescence-based primary assay	ic50	3.0000	uM
[2-(4-methylanilino)-2-oxoethyl] N-[(E)-(6-methyl-2-pyridinyl)methylideneamino]carbamodithioate	1504918: Inhibition of cystathionine gamma-lyase (unknown origin) assessed as reduction in cysteine formation from CPM using L-cystathionine pre-incubated for 15 min followed by L-cystathionine and CPM addition and measured after 7 mins by fluorescence-based primary assay	ic50	3.5000	uM
2-[(1S,3R)-9-methoxy-1-methyl-5,10-dioxo-3,4-dihydro-1H-benzo[g]isochromen-3-yl]acetic acid	1680640: Binding affinity to human CSE by ITC analysis	kd	3.8000	uM
methyl N-[(E)-(3-fluoro-2-pyridinyl)methylideneamino]carbamodithioate	1504918: Inhibition of cystathionine gamma-lyase (unknown origin) assessed as reduction in cysteine formation from CPM using L-cystathionine pre-incubated for 15 min followed by L-cystathionine and CPM addition and measured after 7 mins by fluorescence-based primary assay	ic50	5.0000	uM
methyl N-[(E)-(6-methyl-2-pyridinyl)methylideneamino]carbamodithioate	1504918: Inhibition of cystathionine gamma-lyase (unknown origin) assessed as reduction in cysteine formation from CPM using L-cystathionine pre-incubated for 15 min followed by L-cystathionine and CPM addition and measured after 7 mins by fluorescence-based primary assay	ic50	5.0000	uM
(2-anilino-2-oxoethyl) N-[(E)-pyridin-2-ylmethylideneamino]carbamodithioate	1504918: Inhibition of cystathionine gamma-lyase (unknown origin) assessed as reduction in cysteine formation from CPM using L-cystathionine pre-incubated for 15 min followed by L-cystathionine and CPM addition and measured after 7 mins by fluorescence-based primary assay	ic50	6.0000	uM
[2-oxo-2-[4-(trifluoromethyl)anilino]ethyl] N-[(E)-(3-fluoro-2-pyridinyl)methylideneamino]carbamodithioate	1504918: Inhibition of cystathionine gamma-lyase (unknown origin) assessed as reduction in cysteine formation from CPM using L-cystathionine pre-incubated for 15 min followed by L-cystathionine and CPM addition and measured after 7 mins by fluorescence-based primary assay	ic50	6.0000	uM
methyl N-[(E)-(3-methyl-2-pyridinyl)methylideneamino]carbamodithioate	1504918: Inhibition of cystathionine gamma-lyase (unknown origin) assessed as reduction in cysteine formation from CPM using L-cystathionine pre-incubated for 15 min followed by L-cystathionine and CPM addition and measured after 7 mins by fluorescence-based primary assay	ic50	6.0000	uM
methyl N-[(E)-(4-chloro-1-methylpyrazol-3-yl)methylideneamino]carbamodithioate	1504918: Inhibition of cystathionine gamma-lyase (unknown origin) assessed as reduction in cysteine formation from CPM using L-cystathionine pre-incubated for 15 min followed by L-cystathionine and CPM addition and measured after 7 mins by fluorescence-based primary assay	ic50	6.0000	uM
[2-(4-tert-butylanilino)-2-oxoethyl] N-[(E)-(6-methyl-2-pyridinyl)methylideneamino]carbamodithioate	1504918: Inhibition of cystathionine gamma-lyase (unknown origin) assessed as reduction in cysteine formation from CPM using L-cystathionine pre-incubated for 15 min followed by L-cystathionine and CPM addition and measured after 7 mins by fluorescence-based primary assay	ic50	6.0000	uM
[2-(4-tert-butylanilino)-2-oxoethyl] N-[(E)-(4-chloro-1-methylpyrazol-3-yl)methylideneamino]carbamodithioate	1504918: Inhibition of cystathionine gamma-lyase (unknown origin) assessed as reduction in cysteine formation from CPM using L-cystathionine pre-incubated for 15 min followed by L-cystathionine and CPM addition and measured after 7 mins by fluorescence-based primary assay	ic50	6.0000	uM
5-nitroquinolin-8-ol	1680647: Inhibition of human CSE using H-Cys as the substrate by LC/MS/MS-based assay	ic50	6.0000	uM
5-methylsulfanyl-2-pyridin-2-yl-2,3-dihydro-1,3,4-thiadiazole	1504918: Inhibition of cystathionine gamma-lyase (unknown origin) assessed as reduction in cysteine formation from CPM using L-cystathionine pre-incubated for 15 min followed by L-cystathionine and CPM addition and measured after 7 mins by fluorescence-based primary assay	ic50	6.0000	uM
methyl N-[(E)-pyridin-2-ylmethylideneamino]carbamodithioate	1504918: Inhibition of cystathionine gamma-lyase (unknown origin) assessed as reduction in cysteine formation from CPM using L-cystathionine pre-incubated for 15 min followed by L-cystathionine and CPM addition and measured after 7 mins by fluorescence-based primary assay	ic50	6.0000	uM
7-amino-5-imino-1H-quinoline-2,8-dione	1504913: Inhibition of cystathionine gamma-lyase (unknown origin)	ic50	6.3000	uM
methyl N-[(E)-1,3-thiazol-4-ylmethylideneamino]carbamodithioate	1504918: Inhibition of cystathionine gamma-lyase (unknown origin) assessed as reduction in cysteine formation from CPM using L-cystathionine pre-incubated for 15 min followed by L-cystathionine and CPM addition and measured after 7 mins by fluorescence-based primary assay	ic50	7.0000	uM
[2-(4-methylanilino)-2-oxoethyl] N-[(E)-(6-bromo-2-pyridinyl)methylideneamino]carbamodithioate	1504918: Inhibition of cystathionine gamma-lyase (unknown origin) assessed as reduction in cysteine formation from CPM using L-cystathionine pre-incubated for 15 min followed by L-cystathionine and CPM addition and measured after 7 mins by fluorescence-based primary assay	ic50	10.0000	uM
methyl N-[(E)-(5-bromo-2-pyridinyl)methylideneamino]carbamodithioate	1504918: Inhibition of cystathionine gamma-lyase (unknown origin) assessed as reduction in cysteine formation from CPM using L-cystathionine pre-incubated for 15 min followed by L-cystathionine and CPM addition and measured after 7 mins by fluorescence-based primary assay	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	7
Valproic Acid	affects expression, decreases expression, increases expression	5
Aflatoxin B1	affects expression, decreases expression, decreases methylation	5
sodium arsenite	increases expression	4
Arsenic Trioxide	affects binding, decreases reaction, increases expression	3
Acetaminophen	decreases expression, increases expression	3
Benzo(a)pyrene	decreases expression	3
Cisplatin	affects response to substance, increases expression	3
Formaldehyde	increases expression	3
Particulate Matter	increases abundance, increases expression, decreases expression, affects cotreatment	3
tungsten carbide	affects cotreatment, decreases expression, increases expression	2
cobaltous chloride	increases expression	2
nickel chloride	affects binding, decreases reaction, increases expression, decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
Rosiglitazone	decreases expression, increases expression	2
Zoledronic Acid	decreases expression	2
Air Pollutants	increases abundance, increases expression, decreases expression	2
Carbamazepine	affects expression	2
Cobalt	decreases expression, increases expression, affects cotreatment	2
Oxygen	decreases expression, affects cotreatment	2
Silicon Dioxide	decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Tunicamycin	increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
bismuth tripotassium dicitrate	increases expression	1
urushiol	increases expression	1
chloroacetaldehyde	affects expression	1
ethylbenzene	increases expression	1

ChEMBL screening assays

31 unique, capped per target: 31 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4136611	Binding	Inhibition of cystathionine gamma-lyase (unknown origin)	2-Arylidene Hydrazinecarbodithioates as Potent, Selective Inhibitors of Cystathionine γ-Lyase (CSE). — ACS Med Chem Lett

Cellosaurus cell lines

11 cell lines: 7 transformed cell line, 3 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_9R62	GM01565	Transformed cell line	Female
CVCL_D1VY	Abcam A-549 CTH KO	Cancer cell line	Male
CVCL_D6RK	WIMRi002-A	Induced pluripotent stem cell	Female
CVCL_EJ27	GM01456	Transformed cell line	Female
CVCL_EJ28	GM01461	Transformed cell line	Female
CVCL_EJ30	GM01868	Transformed cell line	Male
CVCL_GY16	GM01454	Transformed cell line	Male
CVCL_GY17	GM01566	Transformed cell line	Female
CVCL_GY18	GM01781	Transformed cell line	Female
CVCL_SK07	HAP1 CTH (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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