CTPS1

Summary

CTPS1 (CTP synthase 1, HGNC:2519) is a protein-coding gene on chromosome 1p34.2, encoding CTP synthase 1 (P17812). CTP synthase involved in the de novo synthesis of CTP, a precursor of DNA, RNA and phospholipids. It is a selective cancer dependency (DepMap: 63.2% of cell lines).

This gene encodes an enzyme responsible for the catalytic conversion of UTP (uridine triphosphate) to CTP (cytidine triphospate). This reaction is an important step in the biosynthesis of phospholipids and nucleic acids. Activity of this proten is important in the immune system, and loss of function of this gene has been associated with immunodeficiency. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 1503 — RefSeq curated summary.

At a glance

• Gene–disease (curated): severe combined immunodeficiency due to CTPS1 deficiency (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 346 total — 1 pathogenic
• Phenotypes (HPO): 18
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 63.2% of screened cell lines
• MANE Select transcript: NM_001905

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2519
Approved symbol	CTPS1
Name	CTP synthase 1
Location	1p34.2
Locus type	gene with protein product
Status	Approved
Aliases	GATD5A
Ensembl gene	ENSG00000171793
Ensembl biotype	protein_coding
OMIM	123860
Entrez	1503

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 18 protein_coding, 7 retained_intron, 5 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000372616, ENST00000463285, ENST00000463423, ENST00000464283, ENST00000470271, ENST00000475060, ENST00000479480, ENST00000480420, ENST00000486889, ENST00000498694, ENST00000648020, ENST00000648801, ENST00000648914, ENST00000649124, ENST00000649215, ENST00000649864, ENST00000650070, ENST00000650634, ENST00000696070, ENST00000696107, ENST00000696108, ENST00000696109, ENST00000696110, ENST00000696111, ENST00000870152, ENST00000870153, ENST00000870154, ENST00000870155, ENST00000923258, ENST00000923259, ENST00000960813

RefSeq mRNA: 2 — MANE Select: NM_001905 NM_001301237, NM_001905

CCDS: CCDS459, CCDS90924

Canonical transcript exons

ENST00000650070 — 19 exons

Exon	Start	End
ENSE00001458238	41011658	41012565
ENSE00003464047	41006051	41006094
ENSE00003486465	41002160	41002254
ENSE00003541110	40991165	40991248
ENSE00003541185	40997394	40997526
ENSE00003583058	41003114	41003176
ENSE00003605301	40995917	40996068
ENSE00003608740	41007449	41007545
ENSE00003623111	41001029	41001117
ENSE00003627187	41008659	41008714
ENSE00003834843	40979696	40979829
ENSE00003965938	40991765	40991845
ENSE00003966020	40984821	40984991
ENSE00003966027	41008794	41008890
ENSE00003966028	40988594	40988710
ENSE00003966029	41010161	41010254
ENSE00003966031	40983278	40983456
ENSE00003966032	40987372	40987472
ENSE00003966035	41009445	41009589

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 95.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.1214 / max 838.8102, expressed in 1810 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2411	32.2075	1797
2412	11.3786	1641
2413	0.7784	498
2414	0.3979	208
2418	0.1771	18
2416	0.0527	3
2417	0.0500	11
2415	0.0368	17
2419	0.0228	11
2420	0.0196	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	95.63	gold quality
ascending aorta	UBERON:0001496	95.08	gold quality
thoracic aorta	UBERON:0001515	95.05	gold quality
left uterine tube	UBERON:0001303	94.24	gold quality
right coronary artery	UBERON:0001625	94.23	gold quality
left coronary artery	UBERON:0001626	94.14	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.65	gold quality
aorta	UBERON:0000947	93.60	gold quality
body of uterus	UBERON:0009853	93.15	gold quality
coronary artery	UBERON:0001621	92.99	gold quality
popliteal artery	UBERON:0002250	92.72	gold quality
tibial artery	UBERON:0007610	92.70	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.68	gold quality
descending thoracic aorta	UBERON:0002345	92.51	gold quality
right lobe of liver	UBERON:0001114	91.89	gold quality
smooth muscle tissue	UBERON:0001135	91.84	gold quality
stromal cell of endometrium	CL:0002255	90.27	gold quality
ventricular zone	UBERON:0003053	89.96	gold quality
ectocervix	UBERON:0012249	89.69	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.41	gold quality
embryo	UBERON:0000922	89.36	gold quality
myometrium	UBERON:0001296	89.08	gold quality
ganglionic eminence	UBERON:0004023	89.08	gold quality
sural nerve	UBERON:0015488	88.96	gold quality
liver	UBERON:0002107	88.87	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.77	gold quality
sigmoid colon	UBERON:0001159	88.65	gold quality
sperm	CL:0000019	88.51	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.39	gold quality
lower esophagus	UBERON:0013473	88.35	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-124858	no	472.35
E-MTAB-6142	no	467.76
E-CURD-112	no	3.59
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, TWIST1, TWIST2

miRNA regulators (miRDB)

41 targeting CTPS1, 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-3163	100.00	77.23	8605
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-4796-5P	99.34	70.06	810
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-122B-3P	99.21	68.90	1333
HSA-MIR-21-3P	99.21	68.95	1312
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-6876-3P	98.97	65.69	765
HSA-MIR-5001-3P	98.91	67.28	1394
HSA-MIR-626	98.89	66.21	762
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-29B-1-5P	98.86	68.35	1364

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 63.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 15)

• CTP synthetase is phosphorylated by protein kinase A (PMID:16179339)
• Data indicate that protein kinase C phosphorylation at Ser(462) stimulates human CTP synthetase 1 activity, whereas phosphorylation at Thr(455) inhibits activity. (PMID:17463002)
• analysis of phosphorylation and regulation of human CTPS1 in human cells shows that GSK3 is a novel regulator of CTPS activity (PMID:17681942)
• studies provide novel information on the potential interacting proteins that may regulate CTPS1 function or intracellular localization (PMID:18600551)
• analysis of the kinetic properties of hCTPS1 and hCTPS2, and determination that Ser(68) is a major site of CTPS2 regulation by phosphorylation (PMID:20739275)
• Rods and rings (RR) are protein assemblies composed of CTPS1 and IMPDH2. Glutamine deprivation initiates reversible assembly of mammalian rods and rings. (PMID:24477477)
• results highlight a key and specific role of CTPS1 in the immune system by its capacity to sustain the proliferation of activated lymphocytes during the immune response (PMID:24870241)
• The filament structures elucidate allosteric mechanisms of assembly and regulation that rely on a conserved conformational equilibrium. The findings may provide a mechanism for increasing human CTP synthase activity in response to metabolic state and challenge the assumption that metabolic filaments are generally storage forms of inactive enzymes. (PMID:28459447)
• CTP synthase forms the cytoophidium in human hepatocellular carcinoma. (PMID:29097181)
• Impaired lymphocyte function and differentiation in CTPS1-deficient patients result from a hypomorphic homozygous mutation. (PMID:32161190)
• Energy deficiency caused by CTPS downregulation in decidua may contribute to pre-eclampsia by impairing decidualization. (PMID:33576499)
• CTPS1 promotes malignant progression of triple-negative breast cancer with transcriptional activation by YBX1. (PMID:34991621)
• CTPS1 inhibition suppresses proliferation and migration in colorectal cancer cells. (PMID:35912542)
• The role of cytidine 5’-triphosphate synthetase 1 in metabolic rewiring during epithelial-to-mesenchymal transition in non-small-cell lung cancer. (PMID:39030877)
• MiR-519e-5p regulates malignant phenotype of breast cancer cells through binding to CTPS1. (PMID:39197579)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ctps1a	ENSDARG00000030700
danio_rerio	ctps1b	ENSDARG00000098386
mus_musculus	Ctps1	ENSMUSG00000028633
rattus_norvegicus	Ctps1	ENSRNOG00000009963
drosophila_melanogaster	Ctps	FBGN0266452
caenorhabditis_elegans		WBGENE00012316

Paralogs (1): CTPS2 (ENSG00000047230)

Protein

Protein identifiers

CTP synthase 1 — P17812 (reviewed: P17812)

Alternative names: CTP synthetase 1, Protein-asparagine deamidase CTPS1, UTP–ammonia ligase 1

All UniProt accessions (12): P17812, A0A3B3IRI2, A0A3B3IRQ8, A0A3B3ISY3, A0A3B3ITB8, A0A3B3ITF6, A0A3B3ITH9, A0A8Q3WKZ7, A0A8Q3WL00, A0A8Q3WL12, A0A8Q3WL40, B4E1E0

UniProt curated annotations — full annotation on UniProt →

Function. CTP synthase involved in the de novo synthesis of CTP, a precursor of DNA, RNA and phospholipids. Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as a source of nitrogen. CTPS1 CTP synthase activity plays a crucial role in the proliferation of activated lymphocytes and immunity; additional CTP being required to meet increased demand for DNA, RNA and lipid membrane biosynthesis in proliferating lymphocytes. In addition to CTP synthase activity, also acts as a protein deamidase that catalyzes the side chain deamidation of specific asparagine residues of proteins to aspartate. Acts as a negative regulator of innate immunity by mediating deamidation of ‘Asn-85’ of IRF3, preventing IRF3 from binding DNA. Facilitates chromatin relaxation in response to DNA damage by mediating deamidation of ‘Asn-76’ and ‘Asn-77’ of histone H1, thereby promoting subsequent acetylation of histone H1 at ‘Lys-75’ (H1K75ac), increasing chromatin accessibility to facilitate the recruitment of DNA repair proteins.

Subunit / interactions. Homotetramer. Polymerizes into filaments of stacked tetramers through conserved intertetramer interactions, leading to increased CTP synthase activity upon substrate-binding.

Subcellular location. Cytoplasm. Cytosol. Nucleus. Chromosome.

Tissue specificity. Widely expressed at low level, except in activated T-cells where it is highly expressed.

Post-translational modifications. Phosphorylation at Thr-455 by PKA and PKC inhibits the CTP synthase activity. Phosphorylation at Ser-462 by PKC increases the CTP synthase activity. Phosphorylation by GSK3-beta (GSK3B) inhibits both the CTP synthase and protein deamidase activities. Phosphorylation at Ser-571 by GSK3-beta (GSK3B) constitutes the major phosphorylation site, while phosphorylation at Ser-575 may by required for priming phosphorylation at Ser-571. Phosphorylation at Ser-575 by GSK3-beta (GSK3B) inhibits its ability to mediate deamination of IRF3.

Disease relevance. Immunodeficiency 24 (IMD24) [MIM:615897] A life-threatening immunodeficiency, characterized by an impaired capacity of activated T and B cells to proliferate in response to antigen receptor-mediated activation. Patients have early onset of severe chronic viral infections, mostly caused by herpes viruses, including EBV and varicella zooster virus (VZV), and also suffer from recurrent encapsulated bacterial infections, a spectrum of infections typical of a combined deficiency of adaptive immunity. The disease is caused by variants affecting the gene represented in this entry. A unique and recessive G to C hypomorphic mutation affecting a splice donor site at the junction of intron 17-18 and exon 18 has been identified in all patients. It results in expression of an abnormal transcript lacking exon 18 and a 80%-90% reduction of protein expression and CTP synthase activity.

Activity regulation. Polymerizes into filaments upon substrate-binding, increasing the CTP synthase activity. In contrast to CTPS2, only weakly inhibited by CTP; CTP synthase activity at higher CTP concentrations is consistent with its critical role in expanding nucleotide pools in proliferating cells. Activated by GTP. Specifically inhibited by small compound R80.

Induction. Up-regulated in T-cells and B-cells activated through the TCR and the BCR respectively (at protein level).

Pathway. Pyrimidine metabolism; CTP biosynthesis via de novo pathway; CTP from UDP: step 2/2.

Similarity. Belongs to the CTP synthase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P17812-1	1	yes
P17812-2	2

RefSeq proteins (2): NP_001288166, NP_001896* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004468	CTP_synthase	Family
IPR017456	CTP_synthase_N	Domain
IPR017926	GATASE	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR029062	Class_I_gatase-like	Homologous_superfamily
IPR033828	GATase1_CTP_Synthase	Domain

Pfam: PF00117, PF06418

Catalyzed reactions (Rhea), 2 shown:

• UTP + L-glutamine + ATP + H2O = CTP + L-glutamate + ADP + phosphate + 2 H(+) (RHEA:26426)
• L-asparaginyl-[protein] + H2O = L-aspartyl-[protein] + NH4(+) (RHEA:57416)

UniProt features (126 total): binding site 32, helix 27, strand 22, mutagenesis site 16, modified residue 11, turn 7, active site 3, sequence conflict 2, chain 1, domain 1, region of interest 1, compositionally biased region 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
2VO1	X-RAY DIFFRACTION	2.8
7MGZ	ELECTRON MICROSCOPY	2.8
7MIG	ELECTRON MICROSCOPY	2.9
7MIF	ELECTRON MICROSCOPY	3.1
9VMM	ELECTRON MICROSCOPY	3.3
5U03	ELECTRON MICROSCOPY	6.1
7MH0	ELECTRON MICROSCOPY	6.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17812-F1	91.46	0.83

Functional residue map

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

Catalytic / active sites (3): 399 (for gatase and protein-asparagine deamidase activities); 526 (for gatase and protein-asparagine deamidase activities); 528 (for gatase and protein-asparagine deamidase activities)

Ligand- & substrate-binding residues (32): 15; 15; 16; 16; 18; 21; 38; 40; 70; 70; 71; 112 …

Post-translational modifications (11): 100, 455, 462, 562, 568, 571, 573, 574, 575, 578, 587

Mutagenesis-validated functional residues (16):

Position	Phenotype
83	does not affect the ctp synthase activity.
161	localizes to cystolic filament structures.
219	does not affect the ctp synthase activity.
250	abolished inhibition by small compound r80.
355	abolished ability to polymerize into filaments in presence of substrates, leading to decreased ctp synthase activity.
378	does not affect the ctp synthase activity.
399	abolished protein-asparagine deamidase activity; when associated with 526-a–a-528.
455	increased ctp synthase activity.
462	decreased ctp synthase activity.
526–528	abolished protein-asparagine deamidase activity; when associated witha-399.
552	does not affect the ctp synthase activity.
562	does not affect the ctp synthase activity.
566	does not affect the ctp synthase activity.
571	decreased phosphorylation by gsk3-beta.
573	does not affect the ctp synthase activity.
575	decreased phosphorylation by gsk3-beta.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-499943	Interconversion of nucleotide di- and triphosphates

MSigDB gene sets: 403 (showing top): GOBP_CHROMOSOME_ORGANIZATION, ELVIDGE_HYPOXIA_DN, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, BASSO_B_LYMPHOCYTE_NETWORK, GOBP_B_CELL_ACTIVATION, FISCHER_G1_S_CELL_CYCLE, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_B_CELL_PROLIFERATION, GOBP_PYRIMIDINE_NUCLEOSIDE_TRIPHOSPHATE_BIOSYNTHETIC_PROCESS, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_NEGATIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, MODULE_453

GO Biological Process (13): nucleobase-containing compound metabolic process (GO:0006139), CTP biosynthetic process (GO:0006241), response to xenobiotic stimulus (GO:0009410), pyrimidine nucleobase biosynthetic process (GO:0019856), negative regulation of type I interferon production (GO:0032480), T cell proliferation (GO:0042098), B cell proliferation (GO:0042100), ‘de novo’ CTP biosynthetic process (GO:0044210), DNA repair-dependent chromatin remodeling (GO:0140861), negative regulation of chromosome condensation (GO:1902340), immune system process (GO:0002376), pyrimidine nucleotide biosynthetic process (GO:0006221), small molecule metabolic process (GO:0044281)

GO Molecular Function (8): CTP synthase activity (GO:0003883), ATP binding (GO:0005524), identical protein binding (GO:0042802), protein asparagine deamidase activity (GO:0160260), histone H1N76/N77 asparagine deamidase activity (GO:0160264), nucleotide binding (GO:0000166), protein binding (GO:0005515), ligase activity (GO:0016874)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), cytoophidium (GO:0097268)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of nucleotides	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
pyrimidine-containing compound biosynthetic process	2
lymphocyte proliferation	2
primary metabolic process	1
pyrimidine ribonucleoside triphosphate biosynthetic process	1
pyrimidine ribonucleotide biosynthetic process	1
CTP metabolic process	1
response to chemical	1
pyrimidine nucleobase metabolic process	1
nucleobase biosynthetic process	1
negative regulation of cytokine production	1
regulation of type I interferon production	1
type I interferon production	1
T cell activation	1
B cell activation	1
CTP biosynthetic process	1
chromatin remodeling	1
DNA damage response	1
chromosome condensation	1
regulation of chromosome condensation	1
negative regulation of chromosome organization	1
biological_process	1
pyrimidine nucleotide metabolic process	1
nucleotide biosynthetic process	1
metabolic process	1
ligase activity, forming carbon-nitrogen bonds	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	1
catalytic activity, acting on a protein	1
histone H1 asparagine deamidase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
chromosome	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

3786 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTPS1	IMPDH2	P12268	816
CTPS1	GMPS	P49915	731
CTPS1	UMPS	P11172	721
CTPS1	PPAT	Q06203	641
CTPS1	DHODH	Q02127	640
CTPS1	PFAS	O15067	635
CTPS1	TYMS	P04818	626
CTPS1	MAGT1	Q9H0U3	603
CTPS1	CAD	P27708	588
CTPS1	ASNS	P08184	588
CTPS1	CMPK1	P30085	578
CTPS1	STXBP2	Q15833	572
CTPS1	DCTD	P32321	566
CTPS1	CST8	O60676	558
CTPS1	CDA	P32320	555

IntAct

114 interactions, top by confidence:

A	B	Type	Score
CTPS2	CTPS1	psi-mi:“MI:0915”(physical association)	0.850
CTPS1	CTPS2	psi-mi:“MI:0915”(physical association)	0.850
CTPS2	CTPS1	psi-mi:“MI:0914”(association)	0.850
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CTPS1	CTPS1	psi-mi:“MI:0915”(physical association)	0.670
TIGD3	CTPS1	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
CTPS1	H2AC14	psi-mi:“MI:0915”(physical association)	0.400
CTPS1	YWHAZ	psi-mi:“MI:0915”(physical association)	0.400
OTUB1		psi-mi:“MI:0914”(association)	0.350
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350

BioGRID (244): CTPS1 (Two-hybrid), CTBP2 (Co-fractionation), CTPS1 (Co-fractionation), CTPS1 (Co-fractionation), CTPS1 (Co-fractionation), CTPS1 (Co-fractionation), CTPS1 (Co-fractionation), CTPS1 (Co-fractionation), CTPS1 (Co-fractionation), CTPS1 (Co-fractionation), CTPS1 (Co-fractionation), CTPS1 (Co-fractionation), CTPS1 (Co-fractionation), CTPS1 (Co-fractionation), CTPS1 (Co-fractionation)

ESM2 similar proteins: A0A286LEZ7, A0A498JQK2, B4JRX2, B6K4Q2, B8C6V3, B9KHF1, C6SZ50, C6TA59, C9SB02, D0A8W2, D7TCD0, G5EDZ2, O74731, P0DPA9, P17812, P21264, P33751, P47044, P78963, P94063, Q0ITU1, Q1RMS2, Q2GLS9, Q383H9, Q5B590, Q5BPS0, Q5PBX6, Q5TKP8, Q5ZC82, Q68EH8, Q69K55, Q75B78, Q7XDB8, Q84MC2, Q851C7, Q8GW29, Q8H7U8, Q8L8B8, Q8LBB7, Q8LR50

Diamond homologs: A0B7H6, A0RLC3, A2SSJ7, A3DGR3, A6LQF6, A6UTE4, A6ZQ59, A7GV88, A7Z9T4, A8FIE5, A9VSD6, B0CBC7, B0R6G2, B4U6A9, B6YTF0, B7HFN6, B7HY98, B7IQZ1, B7JHG1, B8HNM9, B8I598, B9IRX1, C1F0R6, C3LFL2, C3P2A0, C5A7F1, G0HV10, O29987, O42644, O59456, O74638, P13242, P17812, P28274, P38627, P50547, P70303, P70698, Q0SQX5, Q0TNA4

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
PRKCA	up-regulates	CTPS1	phosphorylation
PRKCA	down-regulates	CTPS1	phosphorylation
TWIST2	“up-regulates quantity by expression”	CTPS1	“transcriptional regulation”
TWIST1	“up-regulates quantity by expression”	CTPS1	“transcriptional regulation”
GSK3B	“down-regulates activity”	CTPS1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 110 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RAF activation	5	21.5×	4e-04
Signaling by RAF1 mutants	6	21.4×	9e-05
Signaling by high-kinase activity BRAF mutants	5	20.3×	5e-04
Signaling by moderate kinase activity BRAF mutants	6	19.5×	9e-05
Paradoxical activation of RAF signaling by kinase inactive BRAF	6	19.5×	9e-05
Signaling downstream of RAS mutants	6	19.5×	9e-05
MAP2K and MAPK activation	5	18.3×	6e-04
Signaling by BRAF and RAF1 fusions	6	13.1×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
intrinsic apoptotic signaling pathway	6	21.7×	9e-05
autophagosome maturation	6	21.3×	9e-05
mitophagy	5	16.1×	2e-03
autophagosome assembly	7	15.9×	9e-05
G1/S transition of mitotic cell cycle	6	12.2×	2e-03
MAPK cascade	6	9.3×	6e-03
protein ubiquitination	11	4.6×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	137
Likely benign	169
Benign	19

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
140454	NM_001905.4(CTPS1):c.1692-1G>C	Pathogenic

SpliceAI

2861 predictions. Top by Δscore:

Variant	Effect	Δscore
1:40983272:TTCCA:T	acceptor_loss	1.0000
1:40983273:TCCAG:T	acceptor_loss	1.0000
1:40983274:CCA:C	acceptor_loss	1.0000
1:40983275:CAG:C	acceptor_loss	1.0000
1:40983276:A:AG	acceptor_gain	1.0000
1:40983277:G:GC	acceptor_loss	1.0000
1:40983277:G:GG	acceptor_gain	1.0000
1:40983452:GCATG:G	donor_gain	1.0000
1:40983455:TGGT:T	donor_loss	1.0000
1:40983458:T:G	donor_loss	1.0000
1:40984809:T:TA	acceptor_gain	1.0000
1:40984814:A:AG	acceptor_gain	1.0000
1:40984814:ACT:A	acceptor_gain	1.0000
1:40984816:T:A	acceptor_gain	1.0000
1:40984816:TGCAG:T	acceptor_loss	1.0000
1:40984817:GCAGG:G	acceptor_loss	1.0000
1:40984818:CAG:C	acceptor_loss	1.0000
1:40984819:A:AG	acceptor_gain	1.0000
1:40984819:A:T	acceptor_loss	1.0000
1:40984819:AG:A	acceptor_gain	1.0000
1:40984819:AGGT:A	acceptor_gain	1.0000
1:40984819:AGGTG:A	acceptor_gain	1.0000
1:40984820:G:GA	acceptor_gain	1.0000
1:40984820:GG:G	acceptor_gain	1.0000
1:40984820:GGT:G	acceptor_gain	1.0000
1:40984820:GGTG:G	acceptor_gain	1.0000
1:40984820:GGTGA:G	acceptor_gain	1.0000
1:40984939:G:GG	donor_gain	1.0000
1:40984956:A:T	donor_gain	1.0000
1:40984988:CAAG:C	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000054079 (1:41000166 T>C), RS1000282398 (1:40985633 T>C), RS1000333946 (1:40979413 C>T), RS1000362346 (1:41012911 C>T), RS1000366503 (1:40979586 G>A,C,T), RS1000515586 (1:40990520 C>A,T), RS1000611578 (1:40985406 T>A,C), RS1000666788 (1:40978322 G>A), RS1000738544 (1:40981883 G>A), RS1000749212 (1:40978497 A>C,G), RS1000817476 (1:41003294 A>C,G), RS1000884114 (1:40999296 T>G), RS1000935878 (1:41004054 C>A,T), RS1001021790 (1:40984075 T>C), RS1001028853 (1:41002109 T>C)

Disease associations

OMIM: gene MIM:123860 | disease phenotypes: MIM:615897

GenCC curated gene-disease

Disease	Classification	Inheritance
combined immunodeficiency due to CTPS1 deficiency	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
severe combined immunodeficiency due to CTPS1 deficiency	Definitive	AR

Mondo (1): combined immunodeficiency due to CTPS1 deficiency (MONDO:0014391)

Orphanet (1): Severe combined immunodeficiency due to CTPS1 deficiency (Orphanet:420573)

HPO phenotypes

18 total (18 of 18 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001888	Decreased total lymphocyte count
HP:0002721	Immunodeficiency
HP:0004315	Decreased circulating IgG concentration
HP:0004429	Recurrent viral infections
HP:0005523	Lymphoproliferative disorder
HP:0008348	Decreased circulating IgG2 concentration
HP:0011947	Respiratory tract infection
HP:0012476	Decreased specific pneumococcal antibody level
HP:0030374	Decreased proportion of memory B cells
HP:0031379	Abnormal T cell proliferation
HP:0031402	Reduced antigen-specific T cell proliferation
HP:0031691	Severe viral infection
HP:0032170	Severe varicella zoster infection
HP:0032248	Persistent viremia
HP:0033222	Inverted CD4:CD8 ratio
HP:0410297	Partial absence of specific antibody response to tetanus vaccine
HP:4000039	Decreased mucosal-associated invariant T cell proportion

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006979_874	Heel bone mineral density	5.000000e-17
GCST011771_2	Rapid response to perioperative phenylephrine (change in mean arterial pressure)	6.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0006943	blood pressure change measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5291523 (SINGLE PROTEIN)

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4364871	CTPS1		0.00	0
rs11577910	CTPS1		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Nucleotide turnover

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 27 [PMID: 36449304]	Inhibition	7.49	pIC50

Binding affinities (BindingDB)

45 measured of 279 human assays (279 total across all organisms); most potent 45 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[1-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]cyclopropyl]naphthalene-2-carboxamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[2-[[6-(6-ethoxypyrazin-2-yl)-3-oxo-1H-isoindol-2-yl]methyl]-4-pyridinyl]cyclopropanesulfonamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[[4-(cyclopropylsulfonylamino)-2-pyridinyl]methyl]-4-(6-ethoxypyrazin-2-yl)piperazine-1-carboxamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[2-[(2R)-1-[4-(6-ethoxypyrazin-2-yl)-2-fluorobenzoyl]pyrrolidin-2-yl]-4-pyridinyl]cyclopropanesulfonamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[4-[1-[6-(6-ethoxypyrazin-2-yl)-3-oxo-1H-isoindol-2-yl]cyclopropyl]-1,3-thiazol-2-yl]cyclopropanesulfonamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[[4-(cyclopropylsulfonylamino)-2-pyridinyl]methyl]-6-methyl-5-[3-(trifluoromethyl)piperidin-1-yl]pyrazine-2-carboxamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[2-[(2R)-1-[2-(6-ethoxypyrazin-2-yl)-1,3-thiazole-5-carbonyl]pyrrolidin-2-yl]-4-pyridinyl]cyclopropanesulfonamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[4-[(1R)-1-[6-(6-ethoxypyrazin-2-yl)-3-oxo-1H-isoindol-2-yl]propyl]-1,3-thiazol-2-yl]cyclopropanesulfonamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[2-[(2R)-1-[4-(6-ethoxypyrazin-2-yl)benzoyl]pyrrolidin-2-yl]-4-pyridinyl]cyclopropanesulfonamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[2-[[5-(6-ethoxypyrazin-2-yl)-1,3-dioxoisoindol-2-yl]methyl]-4-pyridinyl]cyclopropanesulfonamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[[4-(cyclopropylsulfonylamino)-2-pyridinyl]methyl]-6-methyl-5-[(2R)-2-propylazetidin-1-yl]pyrazine-2-carboxamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[[4-(cyclopropylsulfonylamino)-2-pyridinyl]methyl]-6-(6-ethoxypyrazin-2-yl)-2-oxo-1H-pyridine-3-carboxamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[[2-(cyclopropylsulfonylamino)-4-pyridinyl]methyl]-4-(6-ethoxypyrazin-2-yl)benzamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[[3-(cyclopropylsulfonylamino)phenyl]methyl]-5-(6-ethoxypyrazin-2-yl)pyridine-2-carboxamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
2-[3-(cyclopropylsulfonylamino)pyrazol-1-yl]-N-[5-(6-ethoxypyrazin-2-yl)-2-pyridinyl]-2-methylpropanamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
4-(cyclopropylsulfonylamino)-N-[[5-(6-ethoxypyrazin-2-yl)-2-pyridinyl]methyl]pyridine-2-carboxamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[[4-(cyclopropylsulfonylamino)-2-pyridinyl]methyl]-4-(6-pyrrolidin-1-ylpyrazin-2-yl)benzamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
5-(6-chloroimidazo[1,2-a]pyridin-3-yl)-N-[[4-(cyclopropylsulfonylamino)-2-pyridinyl]methyl]-1,3-thiazole-2-carboxamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[2-[(2S)-1-[5-(6-ethoxypyrazin-2-yl)-1,3-thiazole-2-carbonyl]piperazin-2-yl]-4-pyridinyl]cyclopropanesulfonamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[(2R)-2-[4-(cyclopropylsulfonylamino)-2-pyridinyl]-4-methoxybutan-2-yl]-5-(6-ethoxypyrazin-2-yl)-1,3-thiazole-2-carboxamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[2-[1-[5-(6-ethoxypyrazin-2-yl)-1,3-thiazole-2-carbonyl]-4-methylpiperazin-2-yl]-4-pyridinyl]cyclopropanesulfonamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
5-(6-chloropyrazolo[1,5-a]pyridin-3-yl)-N-[[4-(cyclopropylsulfonylamino)-2-pyridinyl]methyl]-1,3-thiazole-2-carboxamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[(1R)-1-[4-(cyclopropylsulfonylamino)-2-pyridinyl]-3-piperidin-1-ylpropyl]-5-(6-ethoxypyrazin-2-yl)-1,3-thiazole-2-carboxamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[[4-(cyclopropylsulfonylamino)-2-pyridinyl]methyl]-2-fluoro-4-[6-(trifluoromethyl)pyrazin-2-yl]benzamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[[4-(cyclopropylsulfonylamino)-2-pyridinyl]methyl]-2-methyl-4-oxo-5H-pyrrolo[1,2-a]quinoxaline-8-carboxamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[[4-(cyclopropylsulfonylamino)-1,3-thiazol-2-yl]methyl]-5-(6-ethoxypyrazin-2-yl)pyridine-2-carboxamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[[4-(cyclopropylsulfonylamino)-2-pyridinyl]methyl]-5-[5-(trifluoromethyl)-3-pyridinyl]-1,3-thiazole-2-carboxamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[[4-(cyclopropylsulfonylamino)-2-pyridinyl]methyl]-5-pyrrolo[1,2-b]pyridazin-3-yl-1,3-thiazole-2-carboxamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[[4-(cyclopropylsulfonylamino)-2-pyridinyl]methyl]-1-(6-ethoxypyrazin-2-yl)pyrazole-4-carboxamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[(2R)-2-[4-(cyclopropylsulfonylamino)-2-pyridinyl]-1-methoxypropan-2-yl]-5-(6-ethoxypyrazin-2-yl)-1,3-thiazole-2-carboxamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[[4-(cyclopropylsulfonylamino)-2-pyridinyl]methyl]-1-(6-ethoxypyrazin-2-yl)imidazole-4-carboxamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
5-(6-chlorobenzimidazol-1-yl)-N-[[4-(cyclopropylsulfonylamino)-2-pyridinyl]methyl]-1,3-thiazole-2-carboxamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[4-[(2R)-1-[4-(6-ethoxypyrazin-2-yl)-2-fluorobenzoyl]pyrrolidin-2-yl]pyrimidin-2-yl]cyclopropanesulfonamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[[4-(cyclopropylsulfonylamino)-2-pyridinyl]methyl]-5-(2-methylpyrazolo[1,5-c]pyrimidin-4-yl)-1,3-thiazole-2-carboxamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[[4-(cyclopropylsulfonylamino)-2-pyridinyl]methyl]-5-pyrazolo[1,5-a]pyridin-3-yl-1,3-thiazole-2-carboxamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[[4-(cyclopropylsulfonylamino)-2-pyridinyl]methyl]-3-[(dimethylamino)methyl]-5-(6-ethoxypyrazin-2-yl)pyridine-2-carboxamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[(1S)-1-[4-(cyclopropylsulfonylamino)-2-pyridinyl]-2-[(2S)-1-methylpiperidin-2-yl]ethyl]-5-(6-ethoxypyrazin-2-yl)-1,3-thiazole-2-carboxamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[6-[(2S)-1-[5-(6-ethoxypyrazin-2-yl)-1,3-thiazole-2-carbonyl]pyrrolidin-2-yl]-2-pyridinyl]cyclopropanesulfonamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[4-[1-[5-(6-ethoxypyrazin-2-yl)-1,3-thiazole-2-carbonyl]piperazin-2-yl]pyrimidin-2-yl]cyclopropanesulfonamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[5-[(2S)-1-[5-(6-ethoxypyrazin-2-yl)-1,3-thiazole-2-carbonyl]pyrrolidin-2-yl]-3-pyridinyl]cyclopropanesulfonamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[2-[4-(cyclopropylsulfonylamino)-2-pyridinyl]-4-methoxybutan-2-yl]-5-(6-ethoxypyrazin-2-yl)-1,3-thiazole-2-carboxamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[(1S)-2-(azetidin-1-yl)-1-[4-(cyclopropylsulfonylamino)-2-pyridinyl]ethyl]-5-(6-ethoxypyrazin-2-yl)-1,3-thiazole-2-carboxamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[4-[(2R)-1-[5-(6-ethoxypyrazin-2-yl)-1,3-thiazole-2-carbonyl]pyrrolidin-2-yl]pyrimidin-2-yl]cyclopropanesulfonamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[2-[1-[5-(6-ethoxypyrazin-2-yl)-1,3-thiazole-2-carbonyl]piperazin-2-yl]-4-pyridinyl]cyclopropanesulfonamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof
N-[4-[(2S)-1-[5-(6-ethoxypyrazin-2-yl)-1,3-thiazole-2-carbonyl]piperazin-2-yl]pyrimidin-2-yl]cyclopropanesulfonamide	IC50	550 nM	US-12331046: CTPS1 inhibitors and uses thereof

ChEMBL bioactivities

156 potent at pChembl≥5 of 167 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.89	IC50	13	nM	CHEMBL5267968
7.50	IC50	32	nM	CHEMBL5283284
7.38	IC50	42	nM	CHEMBL5277468
7.00	IC50	100	nM	CHEMBL5093311
7.00	IC50	100	nM	CHEMBL5080689
7.00	IC50	100	nM	CHEMBL5093592
7.00	IC50	100	nM	CHEMBL5077083
7.00	IC50	100	nM	CHEMBL5087963
7.00	IC50	100	nM	CHEMBL5090744
7.00	IC50	100	nM	CHEMBL5080768
7.00	IC50	100	nM	CHEMBL5077185
7.00	IC50	100	nM	CHEMBL5080729
7.00	IC50	100	nM	CHEMBL5082964
7.00	IC50	100	nM	CHEMBL5081939
7.00	IC50	100	nM	CHEMBL5089582
7.00	IC50	100	nM	CHEMBL5093918
7.00	IC50	100	nM	CHEMBL5079488
7.00	IC50	100	nM	CHEMBL5093988
7.00	IC50	100	nM	CHEMBL5089802
7.00	IC50	100	nM	CHEMBL5086441
7.00	IC50	100	nM	CHEMBL5078712
7.00	IC50	100	nM	CHEMBL5082908
7.00	IC50	100	nM	CHEMBL5090660
7.00	IC50	100	nM	CHEMBL5090201
7.00	IC50	100	nM	CHEMBL5076467
7.00	IC50	100	nM	CHEMBL5079127
7.00	IC50	100	nM	CHEMBL5088022
7.00	IC50	100	nM	CHEMBL5090371
7.00	IC50	100	nM	CHEMBL5090733
7.00	IC50	100	nM	CHEMBL5087545
7.00	IC50	100	nM	CHEMBL5090170
7.00	IC50	100	nM	CHEMBL5078318
7.00	IC50	100	nM	CHEMBL5090641
7.00	IC50	100	nM	CHEMBL5404302
7.00	IC50	100	nM	CHEMBL5094917
7.00	IC50	100	nM	CHEMBL5076555
7.00	IC50	100	nM	CHEMBL5077807
7.00	IC50	100	nM	CHEMBL5090866
7.00	IC50	100	nM	CHEMBL5072618
7.00	IC50	100	nM	CHEMBL5081101
7.00	IC50	100	nM	CHEMBL5087209
7.00	IC50	100	nM	CHEMBL5086616
7.00	IC50	100	nM	CHEMBL5090929
7.00	IC50	100	nM	CHEMBL5091742
7.00	IC50	100	nM	CHEMBL5080300
7.00	IC50	100	nM	CHEMBL5094948
7.00	IC50	100	nM	CHEMBL5087269
7.00	IC50	100	nM	CHEMBL5085030
7.00	IC50	100	nM	CHEMBL5093362
7.00	IC50	100	nM	CHEMBL5088443

PubChem BioAssay actives

19 with measured affinity, of 47 total; 19 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-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]-N-[2-fluoro-4-[6-(trifluoromethyl)pyrazin-2-yl]phenyl]-2-methylpropanamide	1935767: Inhibition of human CTPS1 preincubated for 10 mins followed by substrate addition and measured after 30 to 60 mins by RFMS assay	ic50	0.0130	uM
2-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]-2-methyl-N-[5-[6-(trifluoromethyl)pyrazin-2-yl]-2-pyridinyl]propanamide	1935767: Inhibition of human CTPS1 preincubated for 10 mins followed by substrate addition and measured after 30 to 60 mins by RFMS assay	ic50	0.0320	uM
2-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]-2-methyl-N-(4-pyridin-3-ylphenyl)propanamide	1935767: Inhibition of human CTPS1 preincubated for 10 mins followed by substrate addition and measured after 30 to 60 mins by RFMS assay	ic50	0.0420	uM
N-(3-chlorophenyl)-2-[2-(ethylsulfonylamino)-1,3-thiazol-4-yl]acetamide	1935749: Inhibition of C-terminal FLAG-His8-tagged full length human CTPS1 preincubated for 10 mins followed by substrate addition by ADP-Glo assay	ic50	0.1800	uM
2-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]-N-(4-propoxyphenyl)acetamide	1935749: Inhibition of C-terminal FLAG-His8-tagged full length human CTPS1 preincubated for 10 mins followed by substrate addition by ADP-Glo assay	ic50	0.2100	uM
N-(3-chlorophenyl)-2-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]acetamide	1935749: Inhibition of C-terminal FLAG-His8-tagged full length human CTPS1 preincubated for 10 mins followed by substrate addition by ADP-Glo assay	ic50	0.2500	uM
2-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]-N-(3-phenylphenyl)acetamide	1935749: Inhibition of C-terminal FLAG-His8-tagged full length human CTPS1 preincubated for 10 mins followed by substrate addition by ADP-Glo assay	ic50	0.4200	uM
2-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]-N-(4-pyridin-3-ylphenyl)acetamide	1935749: Inhibition of C-terminal FLAG-His8-tagged full length human CTPS1 preincubated for 10 mins followed by substrate addition by ADP-Glo assay	ic50	0.4300	uM
2-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]-N-(5-phenyl-2-pyridinyl)acetamide	1935749: Inhibition of C-terminal FLAG-His8-tagged full length human CTPS1 preincubated for 10 mins followed by substrate addition by ADP-Glo assay	ic50	0.4400	uM
2-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]-N-(4-phenylphenyl)acetamide	1935749: Inhibition of C-terminal FLAG-His8-tagged full length human CTPS1 preincubated for 10 mins followed by substrate addition by ADP-Glo assay	ic50	0.4400	uM
N-(3-chlorophenyl)-2-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]-N-methylacetamide	1935749: Inhibition of C-terminal FLAG-His8-tagged full length human CTPS1 preincubated for 10 mins followed by substrate addition by ADP-Glo assay	ic50	0.5700	uM
2-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]-2-methyl-N-(4-propoxyphenyl)propanamide	1935767: Inhibition of human CTPS1 preincubated for 10 mins followed by substrate addition and measured after 30 to 60 mins by RFMS assay	ic50	0.5800	uM
2-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]-N-(3-propoxyphenyl)acetamide	1935749: Inhibition of C-terminal FLAG-His8-tagged full length human CTPS1 preincubated for 10 mins followed by substrate addition by ADP-Glo assay	ic50	0.9500	uM
N-(3-chlorophenyl)-2-[2-(methanesulfonamido)-1,3-thiazol-4-yl]acetamide	1935749: Inhibition of C-terminal FLAG-His8-tagged full length human CTPS1 preincubated for 10 mins followed by substrate addition by ADP-Glo assay	ic50	2.3000	uM
2-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]-N-(4-pyridin-4-ylphenyl)acetamide	1935749: Inhibition of C-terminal FLAG-His8-tagged full length human CTPS1 preincubated for 10 mins followed by substrate addition by ADP-Glo assay	ic50	4.4700	uM
N-(4-chlorophenyl)-2-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]acetamide	1935749: Inhibition of C-terminal FLAG-His8-tagged full length human CTPS1 preincubated for 10 mins followed by substrate addition by ADP-Glo assay	ic50	4.5000	uM
2-[2-(cyclopropylsulfonylamino)-1,3-thiazol-4-yl]-N-(4-pyridin-2-ylphenyl)acetamide	1935749: Inhibition of C-terminal FLAG-His8-tagged full length human CTPS1 preincubated for 10 mins followed by substrate addition by ADP-Glo assay	ic50	7.1800	uM
4-(4-methylpiperidin-1-yl)-3-nitrobenzamide	1935749: Inhibition of C-terminal FLAG-His8-tagged full length human CTPS1 preincubated for 10 mins followed by substrate addition by ADP-Glo assay	ic50	7.8200	uM
N-(3-chlorophenyl)-2-[2-(propylsulfonylamino)-1,3-thiazol-4-yl]acetamide	1935749: Inhibition of C-terminal FLAG-His8-tagged full length human CTPS1 preincubated for 10 mins followed by substrate addition by ADP-Glo assay	ic50	9.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	6
Valproic Acid	affects expression, decreases expression	6
sodium arsenite	increases abundance, increases expression, affects binding, increases reaction, decreases expression	5
Air Pollutants	increases oxidation, increases expression, affects cotreatment, decreases expression, increases abundance	3
Tretinoin	increases expression, decreases expression, affects cotreatment	3
trichostatin A	decreases expression	2
cobaltous chloride	decreases expression	2
Resveratrol	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Estradiol	increases expression	2
Nickel	increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
afuresertib	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
beauvericin	affects cotreatment, decreases expression	1
2,4,6-tribromophenol	increases expression	1
alpha-pinene	increases abundance, affects cotreatment, decreases expression, increases oxidation	1
propionaldehyde	increases expression	1
decabromobiphenyl ether	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	decreases methylation	1
nickel sulfate	increases expression	1
coumarin	increases phosphorylation	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression, increases oxidation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1

ChEMBL screening assays

11 unique, capped per target: 11 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5239154	Binding	Inhibition of C-terminal FLAG-His8-tagged full length human CTPS1 preincubated for 10 mins followed by substrate addition by ADP-Glo assay	Discovery and Optimization of Potent and Orally Available CTP Synthetase Inhibitors for Use in Treatment of Diseases Driven by Aberrant Immune Cell Proliferation. — J Med Chem

Clinical trials (associated diseases)

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