CTPS1 (CTP synthase 1)

Gene

• Entrez ID: 1503
• Gene name: CTP synthase 1
• Gene symbol: CTPS1
• Synonyms (NCBI Gene): CTPS, GATD5, GATD5A, IMD24
• Chromosome: 1
• Chromosome location: 1p34.2
• Summary: 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 importa

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs145092287	G>C	Pathogenic	Splice acceptor variant, genic downstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT023253	hsa-miR-122-5p	Microarray	17612493
MIRT032244	hsa-let-7b-5p	Proteomics	18668040
MIRT044987	hsa-miR-186-5p	CLASH	23622248
MIRT044690	hsa-miR-320a	CLASH	23622248
MIRT042068	hsa-miR-484	CLASH	23622248
MIRT040360	hsa-miR-615-3p	CLASH	23622248
MIRT052704	hsa-miR-1260b	CLASH	23622248
MIRT704422	hsa-let-7d-5p	HITS-CLIP	23313552
MIRT704421	hsa-let-7g-5p	HITS-CLIP	23313552
MIRT704420	hsa-let-7a-5p	HITS-CLIP	23313552
MIRT032244	hsa-let-7b-5p	HITS-CLIP	23313552
MIRT704419	hsa-let-7c-5p	HITS-CLIP	23313552
MIRT704418	hsa-let-7e-5p	HITS-CLIP	23313552
MIRT704417	hsa-let-7f-5p	HITS-CLIP	23313552
MIRT704416	hsa-miR-98-5p	HITS-CLIP	23313552
MIRT704415	hsa-miR-4500	HITS-CLIP	23313552
MIRT704414	hsa-miR-4458	HITS-CLIP	23313552
MIRT704413	hsa-let-7i-5p	HITS-CLIP	23313552
MIRT704412	hsa-miR-523-3p	HITS-CLIP	23313552
MIRT704411	hsa-miR-196a-5p	HITS-CLIP	23313552
MIRT704410	hsa-miR-196b-5p	HITS-CLIP	23313552
MIRT704409	hsa-miR-1322	HITS-CLIP	23313552
MIRT704408	hsa-miR-4742-5p	HITS-CLIP	23313552
MIRT704407	hsa-miR-4772-3p	HITS-CLIP	23313552
MIRT704406	hsa-miR-2276-3p	HITS-CLIP	23313552
MIRT704405	hsa-miR-381-5p	HITS-CLIP	23313552
MIRT704404	hsa-miR-621	HITS-CLIP	23313552
MIRT704403	hsa-miR-4703-3p	HITS-CLIP	23313552
MIRT704402	hsa-miR-580-3p	HITS-CLIP	23313552
MIRT704401	hsa-miR-106a-3p	HITS-CLIP	23313552
MIRT704400	hsa-miR-4737	HITS-CLIP	23313552
MIRT440861	ebv-miR-BART13-3p	HITS-CLIP	22473208
MIRT440861	ebv-miR-BART13-3p	HITS-CLIP	22473208
MIRT704422	hsa-let-7d-5p	HITS-CLIP	23313552
MIRT704421	hsa-let-7g-5p	HITS-CLIP	23313552
MIRT704420	hsa-let-7a-5p	HITS-CLIP	23313552
MIRT032244	hsa-let-7b-5p	HITS-CLIP	23313552
MIRT704419	hsa-let-7c-5p	HITS-CLIP	23313552
MIRT704418	hsa-let-7e-5p	HITS-CLIP	23313552
MIRT704417	hsa-let-7f-5p	HITS-CLIP	23313552
MIRT704416	hsa-miR-98-5p	HITS-CLIP	23313552
MIRT704415	hsa-miR-4500	HITS-CLIP	23313552
MIRT704414	hsa-miR-4458	HITS-CLIP	23313552
MIRT704413	hsa-let-7i-5p	HITS-CLIP	23313552
MIRT704412	hsa-miR-523-3p	HITS-CLIP	23313552
MIRT704411	hsa-miR-196a-5p	HITS-CLIP	23313552
MIRT704410	hsa-miR-196b-5p	HITS-CLIP	23313552
MIRT704409	hsa-miR-1322	HITS-CLIP	23313552
MIRT704408	hsa-miR-4742-5p	HITS-CLIP	23313552
MIRT704407	hsa-miR-4772-3p	HITS-CLIP	23313552
MIRT704406	hsa-miR-2276-3p	HITS-CLIP	23313552
MIRT704405	hsa-miR-381-5p	HITS-CLIP	23313552
MIRT704404	hsa-miR-621	HITS-CLIP	23313552
MIRT704403	hsa-miR-4703-3p	HITS-CLIP	23313552
MIRT704402	hsa-miR-580-3p	HITS-CLIP	23313552
MIRT704401	hsa-miR-106a-3p	HITS-CLIP	23313552
MIRT704400	hsa-miR-4737	HITS-CLIP	23313552

Transcription factors

Transcription factor	Regulation	Reference
TWIST1	Activation	19051271
TWIST2	Activation	19051271

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0002376	Process	Immune system process	IEA
GO:0003883	Function	CTP synthase activity	IBA
GO:0003883	Function	CTP synthase activity	IDA	16179339, 17189248, 17463002, 28459447
GO:0003883	Function	CTP synthase activity	IEA
GO:0003883	Function	CTP synthase activity	IGI	16179339
GO:0003883	Function	CTP synthase activity	IMP	24870241
GO:0003883	Function	CTP synthase activity	TAS	2113467
GO:0005515	Function	Protein binding	IPI	28514442, 32296183, 33961781, 35271311
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IDA	24503052
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IDA	24503052
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0006139	Process	Nucleobase-containing compound metabolic process	TAS	2113467
GO:0006221	Process	Pyrimidine nucleotide biosynthetic process	IEA
GO:0006241	Process	CTP biosynthetic process	IBA
GO:0006241	Process	CTP biosynthetic process	IDA	16179339, 28459447
GO:0006241	Process	CTP biosynthetic process	IEA
GO:0006241	Process	CTP biosynthetic process	IMP	24870241
GO:0009410	Process	Response to xenobiotic stimulus	TAS	7981751
GO:0016020	Component	Membrane	HDA	19946888
GO:0016874	Function	Ligase activity	IEA
GO:0019856	Process	Pyrimidine nucleobase biosynthetic process	IBA
GO:0042098	Process	T cell proliferation	IDA	8530356
GO:0042098	Process	T cell proliferation	IMP	24870241
GO:0042100	Process	B cell proliferation	IMP	24870241
GO:0042802	Function	Identical protein binding	IBA
GO:0042802	Function	Identical protein binding	IPI	25416956, 32296183
GO:0044210	Process	'de novo' CTP biosynthetic process	IEA
GO:0044281	Process	Small molecule metabolic process	IEA
GO:0097268	Component	Cytoophidium	IBA
GO:0097268	Component	Cytoophidium	IDA	24503052, 25223282

Other IDs

• MIM: 123860
• HGNC: 2519
• e!Ensembl: ENSG00000171793

Protein

• UniProt ID: P17812
• Protein name: CTP synthase 1 (EC 6.3.4.2) (CTP synthetase 1) (UTP--ammonia ligase 1)
• Protein function: This enzyme is 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. This enzyme and its product, CTP,
• PDB: 2VO1, 5U03, 7MGZ, 7MH0, 7MIF, 7MIG
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF06418	CTP_synth_N	2 → 272	CTP synthase N-terminus	Domain
  PF00117	GATase	309 → 546	Glutamine amidotransferase class-I	Domain

• Tissue specificity: TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:24870241}.
• Sequence:

  MKYILVTGGVISGIGKGIIASSVGTILKSCGLHVTSIKIDPYINIDAGTFSPYEHGEVFV
  LDDGGEVDLDLGNYERFLDIRLTKDNNLTTGKIYQYVINKERKGDYLGKTVQVVPHITDA
  IQEWVMRQALIPVDEDGLEPQVCVIELGGTVGDIESMPFIEAFRQFQFKVKRENFCNIHV
  SLVPQPSSTGEQKTKPTQNSVRELRGLGLSPDLVVCRCSNPLDTSVKEKISMFCHVEPEQ
  VICVHDVSSIYRVPLLLEEQGVVDYFLRRLDLPIERQPRKMLMKWKEMADRYDRLLETCS
  IALVGKYTKFSDSYASVIKALEHSALAINHKLEIKYIDSADLEPITSQEEPVRYHEAWQK
  LCSAHGVLVPGGFGVRGTEGKIQAIAWARNQKKPFLGVCLGMQLAVVEFSRNVLGWQDAN
  STEFDPTTSHPVVVDMPEHNPGQMGGTMRLGKRRTLFQTKNSVMRKLYGDADYLEERHRH
  RFEVNPVWKKCLEEQGLKFVGQDVEGERMEIVELEDHPFFVGVQYHPEFLSRPIKPSPPY
  FGLLLASVGRLSHYLQKGCRLSPRDTYSDRSGSSSPDSEITELKFPSINHD

• Sequence length: 591

Pathways

KEGG:

Pyrimidine metabolism
Metabolic pathways
Nucleotide metabolism
Biosynthesis of cofactors

Reactome:

Interconversion of nucleotide di- and triphosphates

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Combined immunodeficiency due to CTPS1 deficiency	Pathogenic	rs145092287	RCV000128633	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ovarian serous cystadenocarcinoma	Pathogenic	rs145092287	RCV005886893	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Papillary renal cell carcinoma type 1	Pathogenic	rs145092287	RCV005886892	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Chronic lymphocytic leukemia/small lymphocytic lymphoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CTPS1-related disorder	Likely benign; Benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial pancreatic carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
IMMUNODEFICIENCY 24	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SEVERE COMBINED IMMUNODEFICIENCY DUE TO CTPS1 DEFICIENCY	—	ClinGen, ClinVar, Orphanet ClinGen, ClinVar, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SEVERE COMBINED IMMUNODEFICIENCY DUE TO CYTIDINE 5-PRIME TRIPHOSPHATE SYNTHETASE 1 DEFICIENCY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute leukemia	Leukemia	BEFREE	8309250		★☆☆☆☆ Found in Text Mining only
Arteriosclerosis	Arteriosclerosis	BEFREE	30687225		★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	BEFREE	30687225		★☆☆☆☆ Found in Text Mining only
B-CELL MALIGNANCY, LOW-GRADE	Lymphocytic Leukemia	BEFREE	25956014		★☆☆☆☆ Found in Text Mining only
Chronic Lymphocytic Leukemia	Lymphocytic Leukemia	BEFREE	25956014		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	35912542	Associate	★☆☆☆☆ Found in Text Mining only
Diabetic Foot	Diabetic foot	Pubtator	38287255	Associate	★☆☆☆☆ Found in Text Mining only
Immune System Diseases	Immune system disease	Pubtator	34583994	Associate	★☆☆☆☆ Found in Text Mining only
IMMUNODEFICIENCY 24	Immunodeficiency	CLINVAR_DG	24870241, 27638562		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
IMMUNODEFICIENCY 24	Immunodeficiency	ORPHANET_DG	24870241		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
IMMUNODEFICIENCY 24	Immunodeficiency	GENOMICS_ENGLAND_DG	9536098		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
IMMUNODEFICIENCY 24	Immunodeficiency	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Immunologic Deficiency Syndromes	Immunologic Deficiency Syndromes	BEFREE	29176466		★☆☆☆☆ Found in Text Mining only
Immunologic Deficiency Syndromes	Immunologic Deficiency Syndromes	HPO_DG			★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	29097181		★☆☆☆☆ Found in Text Mining only
Lymphoma	Lymphoma	BEFREE	31402499		★☆☆☆☆ Found in Text Mining only
Lymphoma	Lymphoma	Pubtator	32161190	Associate	★☆☆☆☆ Found in Text Mining only
Lymphopenia	Lymphopenia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lymphoproliferative Disorders	Lymphoproliferative syndrome	Pubtator	34281398	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of pancreas	Pancreatic cancer	BEFREE	28697344		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	30988367		★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	Pubtator	39394196	Associate	★☆☆☆☆ Found in Text Mining only
Pancreatic carcinoma	Pancreatic carcinoma	BEFREE	28697344		★☆☆☆☆ Found in Text Mining only
Severe combined immunodeficiency due to CTPS1 deficiency	Severe combined immunodeficiency disease	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Severe combined immunodeficiency due to CTPS1 deficiency	Severe combined immunodeficiency disease	GENOMICS_ENGLAND_DG	9536098		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Stomach Neoplasms	Stomach neoplasms	Pubtator	36043523	Associate	★☆☆☆☆ Found in Text Mining only