CTPS1: CTP Synthase 1
Key enzyme in pyrimidine biosynthesis, linked to immunodeficiency and cancer
Gene Information Card
| Symbol | CTPS1 |
|---|---|
| Full Name | CTP synthase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 1p34.2 |
| NCBI Gene ID | 1503 ncbi.nlm.nih.gov/gene/1503 |
| Ensembl ID | ENSG00000117650 |
| UniProt ID | P17812 |
| OMIM ID | 123860 |
| HGNC ID | 2519 |
| Aliases | CTPS, CTPS1A, IMD49 |
Description
CTPS1 encodes CTP synthase 1, an enzyme that catalyzes the conversion of UTP to CTP, a rate-limiting step in pyrimidine nucleotide biosynthesis. This enzyme is essential for DNA and RNA synthesis, particularly in proliferating cells such as lymphocytes. Mutations in CTPS1 cause a primary immunodeficiency characterized by susceptibility to Epstein-Barr virus (EBV) and other infections. Overexpression is observed in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Immunodeficiency 49 (IMD49) | Loss-of-function mutations impair CTP production in activated T and B cells, leading to defective lymphocyte proliferation. | OMIM #617117; PMID: 25271327 |
| EBV susceptibility | Reduced CTP pools impair control of EBV-infected B cells. | ClinVar; PMID: 25271327 |
| Colorectal cancer | CTPS1 overexpression supports increased nucleotide demand in tumor cells. | COSMIC; PMID: 25944712 |
| Hepatocellular carcinoma | Upregulation correlates with poor prognosis. | PMID: 31065109 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | High |
| Spleen | 10.8 | High |
| Bone marrow | 8.2 | Medium |
| Testis | 7.1 | Medium |
| Brain | 2.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.0 | High expression |
| HeLa | 12.4 | High expression |
| K562 | 9.8 | Medium expression |
| HepG2 | 8.5 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1692G>A (p.Trp564*) | Nonsense | Rare (founder in consanguineous families) | Loss of function; truncated protein |
| c.758T>C (p.Leu253Pro) | Missense | Rare | Loss of function; reduced catalytic activity |
| c.1021C>T (p.Arg341Trp) | Missense | Rare | Loss of function; impaired CTP binding |
Mutation functional classification
Loss of Function (LOF)
Homozygous or compound heterozygous loss-of-function mutations cause IMD49 with defective lymphocyte proliferation.
Gain of Function (GOF)
Not reported in germline; somatic overexpression in cancers may act as gain-of-function.
Dominant Negative (DN)
Not described; recessive inheritance pattern.
View complete mutation data：
Gene Ontology (GO)
| • CTP synthase activity (GO:0003883) | • ATP binding (GO:0005524) |
| • pyrimidine nucleotide biosynthetic process (GO:0006221) | • cytoplasm (GO:0005737) |
| • cytosol (GO:0005829) |
Pathways
• Pyrimidine metabolism (KEGG: hsa00240)
• Metabolic pathways (KEGG: hsa01100)
Protein Summary
CTP synthase 1 (UniProt P17812) is a 591-amino acid protein that forms tetramers. It catalyzes the ATP-dependent amination of UTP to CTP using glutamine as the nitrogen source. The enzyme is allosterically regulated by CTP (feedback inhibition) and GTP (activation). It contains a glutaminase domain and an ATP-binding domain. Subcellular localization is cytoplasmic.
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