CTPS1

Chr 1AR

CTP synthase 1

Also known as: CTPS, GATD5, GATD5A, IMD24

NCBI Gene: 1503 ENSG00000171793 UniProt: P17812 OMIM: 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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.291 OMIM phenotype

Clinical Summary— CTPS1

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Gene-Disease Validity (ClinGen)

severe combined immunodeficiency due to CTPS1 deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 140 VUS of 351 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 OE?0.14 (0.07–0.29)

0≤0.351.4

Missense OE?0.43 (0.37–0.49)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 5 / 36.7Missense obs/exp: 141 / 329.7Syn Z: 0.39

This gene — mechanism propensity

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

351 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS140

Likely Benign175

Benign19

Conflicting3

Pathogenic

140

VUS

175

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	0	0	0	0	0
VUS	4	113	18	5	140
Likely Benign	0	1	77	97	175
Benign	0	0	15	4	19
Conflicting	—				3
Total	5	114	110	106	338

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap CTPS1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →