CTPS1

Chr 1AR

CTP synthase 1

Also known as: CTPS, GATD5, GATD5A, IMD24

NCBI Gene: 1503ENSG00000171793UniProt: P17812OMIM: 123860

This enzyme catalyzes the conversion of UTP to CTP, which is essential for DNA, RNA and phospholipid synthesis, and plays a crucial role in lymphocyte proliferation and immune function. Mutations cause autosomal recessive immunodeficiency 24, characterized by recurrent infections due to impaired immune cell function. The gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.29), indicating that heterozygous loss-of-function is typically not tolerated.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.291 OMIM phenotype
Clinical Summary— CTPS1
🧬
Gene-Disease Validity (ClinGen)
severe combined immunodeficiency due to CTPS1 deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
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 unique Pathogenic / Likely Pathogenic· 145 VUS of 367 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
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
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
LoF OE0.14 (0.07–0.29)
0≤0.351.4
Missense OE0.43 (0.37–0.49)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 5 / 36.7Missense obs/exp: 141 / 329.7Syn Z: 0.39
DN
0.3793th %ile
GOF
0.3887th %ile
LOF
0.67top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.29

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

367 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic3
VUS145
Likely Benign175
Benign19
Conflicting3
9
Pathogenic
3
Likely Pathogenic
145
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
113
23
5
145
Likely Benign
0
1
77
97
175
Benign
0
0
15
4
19
Conflicting
—3
Total5114126106354

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients