CTPS2

Chr X

CTP synthase 2

Also known as: GATD5B

NCBI Gene: 56474 ENSG00000047230 UniProt: Q9NRF8 OMIM: 300380

CTP synthase 2 catalyzes the rate-limiting step in cytosine nucleotide synthesis, converting UTP to CTP for DNA, RNA, and phospholipid production. Biallelic mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, refractory seizures, and cortical visual impairment. The gene is highly constrained against loss-of-function variants, reflecting its essential role in nucleotide metabolism.

OMIM ResearchSummary from UniProt

The protein encoded by this gene catalyzes the formation of CTP from UTP with the concomitant deamination of glutamine to glutamate. This protein is the rate-limiting enzyme in the synthesis of cytosine nucleotides, which play an important role in various metabolic processes and provide the precursors necessary for the synthesis of RNA and DNA. Cancer cells that exhibit increased cell proliferation also exhibit an increased activity of this encoded protein. Thus, this protein is an attractive target for selective chemotherapy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

OMIM ResearchGenerating clinical summary…

LOEUF 0.39

Clinical Summary— CTPS2

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.82) — some intolerance to loss-of-function variants.

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ClinVar Variants

32 VUS of 196 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.39LOEUF

pLI 0.819

Z-score 3.70

OE 0.17 (0.08–0.39)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.59Z-score

OE missense 0.51 (0.44–0.60)

116 obs / 225.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.17 (0.08–0.39)

0≤0.351.4

Missense OE?0.51 (0.44–0.60)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 4 / 23.2Missense obs/exp: 116 / 225.4Syn Z: 0.60

ClinVar Variant Classifications

196 submitted variants in ClinVar

ClinVar

Classification Summary

VUS32

Likely Benign4

Benign2

Conflicting1

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	32	0	0	32
Likely Benign	0	1	1	2	4
Benign	0	1	0	1	2
Conflicting	—				1
Total	0	34	1	3	39

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

View in ClinVar →

95 pathogenic / likely-pathogenic (of 104) ClinVar copy-number / structural variants overlap CTPS2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →