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26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CTPS1
CTP synthase 1
Chromosome 1 · 1p34.2
NCBI Gene: 1503Ensembl: ENSG00000171793.17HGNC: HGNC:2519UniProt: A0A3B3IRQ8
187PubMed Papers
21Diseases
0Drugs
1Pathogenic Variants
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
CTP synthase activityprotein bindingidentical protein bindinghistone H1N76/N77 asparagine deamidase activitycombined immunodeficiency due to CTPS1 deficiencyhyperpituitarismandrogenetic alopeciaAbnormality of the skeletal system
✦AI Summary

CTPS1 (CTP synthase 1) is a crucial enzyme that catalyzes the de novo synthesis of cytidine triphosphate (CTP), a precursor essential for DNA, RNA, and phospholipid biosynthesis 1. The enzyme converts UTP to CTP through ATP-dependent amination using glutamine or ammonia as nitrogen sources 1. CTPS1 plays a particularly important role in immune cell proliferation, as activated lymphocytes require increased CTP for enhanced DNA, RNA, and membrane synthesis 2. Beyond its metabolic function, CTPS1 exhibits protein deamidase activity that regulates immune responses and DNA repair. Specifically, CTPS1 deamidates asparagine-85 of IRF3, preventing its DNA binding and suppressing interferon induction, thereby negatively regulating innate immunity 3. Additionally, CTPS1 facilitates chr1 relaxation during DNA repair by deamidating histones H1 at asparagines-76 and -77, promoting subsequent acetylation and increasing chr1 accessibility for DNA repair proteins 4. Clinically, CTPS1 deficiency causes immunodeficiency-24, characterized by impaired T and B cell expansion 2. CTPS1 is also implicated in cancer progression and drug resistance, making it a potential therapeutic target in multiple myeloma, colorectal cancer, and other malignancies 15.

Sources cited
1
CTPS1 catalyzes de novo CTP synthesis and is essential in multiple myeloma
PMID: 37898670
2
CTPS1 is crucial for lymphocyte proliferation and immune cell maintenance
PMID: 38438357
3
CTPS1 deamidates IRF3 to suppress interferon induction and innate immunity
PMID: 39719712
4
CTPS1 deamidates histone H1 to facilitate chromatin relaxation for DNA repair
PMID: 40240600
5
CTPS1 promotes colorectal cancer progression through cell cycle pathways
PMID: 35912542
Disease Associationsⓘ21
combined immunodeficiency due to CTPS1 deficiencyOpen Targets
0.73Strong
hyperpituitarismOpen Targets
0.26Weak
androgenetic alopeciaOpen Targets
0.24Weak
Abnormality of the skeletal systemOpen Targets
0.09Suggestive
cardiac arrhythmiaOpen Targets
0.09Suggestive
triple-negative breast cancerOpen Targets
0.08Suggestive
breast carcinomaOpen Targets
0.08Suggestive
Miyoshi myopathyOpen Targets
0.07Suggestive
chronic obstructive pulmonary diseaseOpen Targets
0.07Suggestive
atrial fibrillationOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.06Suggestive
breast cancerOpen Targets
0.04Suggestive
cancerOpen Targets
0.04Suggestive
cardioembolic strokeOpen Targets
0.03Suggestive
gastric cancerOpen Targets
0.03Suggestive
open-angle glaucomaOpen Targets
0.03Suggestive
lung cancerOpen Targets
0.02Suggestive
nervous system diseaseOpen Targets
0.02Suggestive
non-small cell lung carcinomaOpen Targets
0.02Suggestive
risk-taking behaviourOpen Targets
0.02Suggestive
Immunodeficiency 24UniProt
Pathogenic Variants1
NM_001905.4(CTPS1):c.1692-1G>CPathogenic
Combined immunodeficiency due to CTPS1 deficiency|not provided|Ovarian serous cystadenocarcinoma|Papillary renal cell carcinoma type 1
★★☆☆2025
View on ClinVar ↗
Related Genes
EPRS1Protein interaction100%POLR1BProtein interaction100%NME1Protein interaction99%NME2Protein interaction97%NME1-NME2Protein interaction96%ITPAProtein interaction95%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
36%
Brain
35%
Lung
33%
Ovary
26%
Heart
18%
Gene Interaction Network
Click a node to explore
CTPS1EPRS1POLR1BNME1NME2NME1-NME2ITPA
PROTEIN STRUCTURE
Preparing viewer…
PDB2VO1 · 2.80 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.42Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.29 [0.20–0.42]
RankingsWhere CTPS1 stands among ~20K protein-coding genes
  • #2,288of 20,598
    Most Researched187 · top quartile
  • #4,736of 5,498
    Most Pathogenic Variants1
  • #2,245of 17,882
    Most Constrained (LOEUF)0.42 · top quartile
Genes detectedCTPS1
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
IDH2 stabilizes HIF-1α-induced metabolic reprogramming and promotes chemoresistance in urothelial cancer.
PMID: 36637036
EMBO J · 2023
1.00
2
Histone H1 deamidation facilitates chromatin relaxation for DNA repair.
PMID: 40240600
Nature · 2025
0.90
3
Pyrimidine synthesis enzyme CTP synthetase 1 suppresses antiviral interferon induction by deamidating IRF3.
PMID: 39719712
Immunity · 2025
0.80
4
When to suspect inborn errors of immunity in Epstein-Barr virus-related lymphoproliferative disorders.
PMID: 36209991
Clin Microbiol Infect · 2023
0.76
5
An automated network-based tool to search for metabolic vulnerabilities in cancer.
PMID: 39394196
Nat Commun · 2024
0.72