CTPS2

protein-coding

CTP synthase 2, the group of Glutamine amidotransferase class 1 domain containing|MicroRNA protein coding host genes

Gene summary

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]

MANE transcript

NM_175859.3

Inheritance

—

ClinVar variants

U:171B:6

Top phenotype

CYTIDINE 5-PRIME TRIPHOSPHATE SYNTHETASE 2 deficiency

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chrX:16,587,999-16,712,936

External References & Databases

Ensembl (ENSG00000047230)

Transcript & Mutation Effects

hg38 • Region Span ~124.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CTPS2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 37

not providedTotal: 4

CYTIDINE 5-PRIME TRIPHOSPHATE SYNTHETASE 2 deficiencyTotal: 1

Laterality defects, autosomal dominantTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_175859.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			22 clinvar	2 clinvar	1 clinvar	25
missense			103 clinvar	2 clinvar	1 clinvar	106
nonsense			14 clinvar			14
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			32 clinvar			32
Total	0	0	171	4	2	177

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 83 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_175859.3	RefSeq	NP_787055.1	17	MANE Select
ENST00000359276.9	Ensembl	ENSP00000352222.4	17	MANE Select
NM_001144002.2	RefSeq	NP_001137474.1	17	Standard
NM_019857.5	RefSeq	NP_062831.3	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pyrimidine metabolism - Homo sapiens (human)
Pyrimidine metabolism
UTP and CTP dephosphorylation I
UTP and CTP <i>de novo</i> biosynthesis
Metabolism of nucleotides

Biological Process

pyrimidine nucleotide metabolic process
CTP biosynthetic process
glutamine metabolic process
nucleobase-containing small molecule interconversion
pyrimidine nucleobase biosynthetic process

Molecular Function

CTP synthase activity
protein binding
ATP binding
identical protein binding

Cellular Component

cytoplasm
cytosol
cytoophidium

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000443824
Coding exons: 17
Length: 124934
Individuals with no LoFs: 125740
Homozygous LoFs: 3
Heterozygous LoFs: 4
Defined: 125747
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.59	116	225	0.515	0.0000169	3870
Missense (PolyPhen)		30	105.98	0.28308		1771
Synonymous	0.604	79	86.1	0.917	0.00000719	1090
Loss of Function	3.70	4	23.2	0.172	0.00000169	415

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000076	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000072	0.000054	rare
Finnish	0.00013	0.000092	rare
European (Non-Finnish)	0.000038	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as the source of nitrogen. Constitutes the rate-limiting enzyme in the synthesis of cytosine nucleotides. {ECO:0000269|PubMed:10899599, ECO:0000269|PubMed:16179339}.;

Recessive Scores

pRec: 0.161

Intolerance Scores

LoFtool: 0.311
RVIS EVS: -0.18
RVIS percentile EVS: 39.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.846

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium