CTPS1

Chr 1AR

CTP synthase 1

Also known as: CTPS, GATD5, GATD5A, IMD24

NCBI Gene: 1503ENSG00000171793UniProt: P17812

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. [provided by RefSeq, Jul 2014]

Primary Disease Associations & Inheritance

Immunodeficiency 24MIM #615897
AR
366
ClinVar variants
12
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— CTPS1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 144 VUS of 366 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.29LOEUF
pLI 0.993
Z-score 4.85
OE 0.14 (0.07–0.29)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.69Z-score
OE missense 0.43 (0.37–0.49)
141 obs / 329.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.14 (0.07–0.29)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.43 (0.37–0.49)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.95
0≤1.21.6
LoF obs/exp: 5 / 36.7Missense obs/exp: 141 / 329.7Syn Z: 0.39

ClinVar Variant Classifications

366 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic3
VUS144
Likely Benign175
Benign19
Conflicting3
9
Pathogenic
3
Likely Pathogenic
144
VUS
175
Likely Benign
19
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
8
0
9
Likely Pathogenic
0
0
3
0
3
VUS
4
112
23
5
144
Likely Benign
0
1
77
97
175
Benign
0
0
15
4
19
Conflicting
—3
Total5113126106353

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CTPS1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Immunodeficiency 24

MIM #615897

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Histone H1 deamidation facilitates chromatin relaxation for DNA repair.
Tian Y et al.·Nature
2025
MYC-induced cytidine metabolism regulates survival and drug resistance via cGas-STING pathway in mantle cell lymphoma.
Liang JH et al.·Br J Haematol
2023
When to suspect inborn errors of immunity in Epstein-Barr virus-related lymphoproliferative disorders.
Sacco KA et al.·Clin Microbiol Infect
2023Review
A Novel Synthetic Lethal Approach to Target MYC-Driven Cancers.
Chabanon RM et al.·Cancer Res
2022
H1N76/77 deamidation facilitates chromatin remodelling and genome stability during DNA damage repair.
Feng T et al.·Clin Transl Med
2025Functional
MiR-519e-5p regulates malignant phenotype of breast cancer cells through binding to CTPS1.
Ma S et al.·Exp Cell Res
2024
Smooth muscle-specific drug targets for next-generation drug-eluting stent.
Tang R et al.·Expert Rev Cardiovasc Ther
2014Review
Advances in basic and clinical immunology in 2014.
Chinen J et al.·J Allergy Clin Immunol
2015Review
Primary immune regulatory disorders (PIRD): expanding the mutation spectrum in Turkey and identification of sixteen novel variants.
Aykut A et al.·Immunol Res
2024
Inhibitors of pyrimidine synthesis synergize with N4-hydroxycytidine to diminish influenza virus replication.
Schrell L et al.·Antiviral Res
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
INHBA promotes chemoresistance in pancreatic cancer by enhancing CTPS1 stability and mediating pyrimidine metabolism.
Sun X et al.·Cancer Cell Int
2025🔓 Open Access
CTPS2 regulates CTP synthetase activity by interacting with CTPS1.
Minet N et al.·Life Sci Alliance
2025🔓 Open Access
[Circ_0000437 promotes proliferation, invasion, migration and epithelial-mesenchymal transition of breast cancer cells by targeting the let-7b-5p/CTPS1 axis].
Ma S et al.·Nan Fang Yi Ke Da Xue Xue Bao
2025
Histone lactylation-mediated overexpression of RASD2 promotes endometriosis progression via upregulating the SUMOylation of CTPS1.
Wang Z et al.·Am J Physiol Cell Physiol
2025
Combined inhibition of CTPS1 and ATR is a metabolic vulnerability in p53-deficient myeloma cells.
Durand R et al.·Hemasphere
2024🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools