CTPS1

CTP synthase 1, the group of Glutamine amidotransferase class 1 domain containing

Basic information

Region (hg38): 1:40979299-41012565

Previous symbols: [ "CTPS" ]

Links

ENSG00000171793 ∙ NCBI:1503 ∙ OMIM:123860 ∙ HGNC:2519 ∙ Uniprot:P17812 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• severe combined immunodeficiency due to CTPS1 deficiency (Strong), mode of inheritance: AR
• severe combined immunodeficiency due to CTPS1 deficiency (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 24	AR	Allergy/Immunology/Infectious; Oncologic	Individuals are susceptible to frequent and severe viral and bacterial infections (as well as sequelae such as EBV-related lymphoma), and and antiinfectious prophylaxis and early and aggressive treatment of infections, as well as awareness of potential oncologic sequelae, may be beneficial; HSCT has been described	Allergy/Immunology/Infectious; Oncologic	24870241

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CTPS1 gene.

• Severe combined immunodeficiency due to CTPS1 deficiency (199 variants)
• not specified (16 variants)
• not provided (10 variants)
• Inborn genetic diseases (8 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CTPS1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	53	5	60
missense			76	2		78
nonsense						0
start loss			1			1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)	1		3			4
splice region			14	8	2	24
non coding				32	11	43
Total	1	0	82	87	16

Highest pathogenic variant AF is 0.000145

Variants in CTPS1

This is a list of pathogenic ClinVar variants found in the CTPS1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-40983293-G-T			Uncertain significance (Sep 05, 2017)
1-40983371-C-T		Severe combined immunodeficiency due to CTPS1 deficiency	Likely benign (May 11, 2023)
1-40983388-A-G		Severe combined immunodeficiency due to CTPS1 deficiency	Uncertain significance (Oct 12, 2021)
1-40983388-A-T		Severe combined immunodeficiency due to CTPS1 deficiency	Uncertain significance (Apr 01, 2022)
1-40983389-T-C		Severe combined immunodeficiency due to CTPS1 deficiency	Likely benign (Oct 13, 2023)
1-40983405-A-G		Severe combined immunodeficiency due to CTPS1 deficiency	Uncertain significance (Jan 27, 2022)
1-40983427-A-G		Severe combined immunodeficiency due to CTPS1 deficiency	Uncertain significance (Oct 13, 2023)
1-40983452-G-A		Severe combined immunodeficiency due to CTPS1 deficiency	Likely benign (Jan 12, 2023)
1-40983462-C-CA		Severe combined immunodeficiency due to CTPS1 deficiency	Likely benign (Apr 27, 2020)
1-40983471-T-G		Severe combined immunodeficiency due to CTPS1 deficiency	Likely benign (May 21, 2023)
1-40984806-C-G		Severe combined immunodeficiency due to CTPS1 deficiency	Likely benign (Jan 14, 2024)
1-40984808-C-T		Severe combined immunodeficiency due to CTPS1 deficiency	Likely benign (Jul 16, 2023)
1-40984816-T-C		Severe combined immunodeficiency due to CTPS1 deficiency	Likely benign (Aug 16, 2022)
1-40984845-G-A		Severe combined immunodeficiency due to CTPS1 deficiency	Uncertain significance (Mar 16, 2022)
1-40984852-A-G		Severe combined immunodeficiency due to CTPS1 deficiency	Likely benign (Aug 04, 2023)
1-40984875-A-G		Severe combined immunodeficiency due to CTPS1 deficiency	Uncertain significance (Nov 16, 2020)
1-40984876-T-C		Severe combined immunodeficiency due to CTPS1 deficiency	Likely benign (Sep 26, 2022)
1-40984887-T-G		not specified	Uncertain significance (Apr 25, 2023)
1-40984895-C-T		Severe combined immunodeficiency due to CTPS1 deficiency	Uncertain significance (Dec 09, 2020)
1-40984896-G-A		Severe combined immunodeficiency due to CTPS1 deficiency	Uncertain significance (Jun 08, 2022)
1-40984916-C-G		Severe combined immunodeficiency due to CTPS1 deficiency	Uncertain significance (Aug 02, 2022)
1-40984941-A-G		Severe combined immunodeficiency due to CTPS1 deficiency	Uncertain significance (Dec 31, 2019)
1-40984951-C-T		Severe combined immunodeficiency due to CTPS1 deficiency	Likely benign (Nov 02, 2018)
1-40984958-C-T		Severe combined immunodeficiency due to CTPS1 deficiency	Uncertain significance (Feb 01, 2024)
1-40984959-G-A		Severe combined immunodeficiency due to CTPS1 deficiency	Uncertain significance (Dec 11, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CTPS1	protein_coding	protein_coding	ENST00000372621	17	33229

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.993	0.00741	125712	0	36	125748	0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.69	141	330	0.428	0.0000173	3859
Missense in Polyphen		32	134.59	0.23776		1568
Synonymous	0.395	111	116	0.953	0.00000622	1118
Loss of Function	4.85	5	36.7	0.136	0.00000185	443

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.000552	0.000496
East Asian	0.0000544	0.0000544
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000220	0.000220
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: This enzyme is involved in the de novo synthesis of CTP, a precursor of DNA, RNA and phospholipids. Catalyzes the ATP- dependent amination of UTP to CTP with either L-glutamine or ammonia as a source of nitrogen. This enzyme and its product, CTP, play a crucial role in the proliferation of activated lymphocytes and therefore in immunity. {ECO:0000269|PubMed:16179339, ECO:0000269|PubMed:24870241}.
• Disease: DISEASE: Immunodeficiency 24 (IMD24) [MIM:615897]: A life- threatening immunodeficiency, characterized by an impaired capacity of activated T and B cells to proliferate in response to antigen receptor-mediated activation. Patients have early onset of severe chronic viral infections, mostly caused by herpes viruses, including EBV and varicella zooster virus (VZV), and also suffer from recurrent encapsulated bacterial infections, a spectrum of infections typical of a combined deficiency of adaptive immunity. {ECO:0000269|PubMed:24870241}. Note=The disease is caused by mutations affecting the gene represented in this entry. A unique and recessive G to C mutation probably affecting a splice donor site at the junction of intron 17-18 and exon 18 has been identified in all patients. It results in expression of an abnormal transcript lacking exon 18 and a complete loss of the expression of the protein. {ECO:0000269|PubMed:24870241}.
• Pathway: Pyrimidine metabolism - Homo sapiens (human);Pyrimidine Metabolism;UMP Synthase Deiciency (Orotic Aciduria);Gemcitabine Action Pathway;MNGIE (Mitochondrial Neurogastrointestinal Encephalopathy);Gemcitabine Metabolism Pathway;Beta Ureidopropionase Deficiency;Dihydropyrimidinase Deficiency;Pyrimidine metabolism;UTP and CTP dephosphorylation I;UTP and CTP <i>de novo</i> biosynthesis;Metabolism of nucleotides;Interconversion of nucleotide di- and triphosphates;UTP and CTP dephosphorylation II;Metabolism;superpathway of pyrimidine ribonucleotides <i>de novo</i> biosynthesis;Pyrimidine nucleotides nucleosides metabolism;superpathway of pyrimidine deoxyribonucleotides <i>de novo</i> biosynthesis (Consensus)

Recessive Scores

• pRec: 0.262

Intolerance Scores

• rvis_EVS: -0.74
• rvis_percentile_EVS: 13.94

Haploinsufficiency Scores

• pHI: 0.612
• hipred: Y
• hipred_score: 0.824
• ghis: 0.662

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ctps

Gene ontology

• Biological process: nucleobase-containing compound metabolic process;CTP biosynthetic process;glutamine metabolic process;nucleobase-containing small molecule interconversion;pyrimidine nucleobase biosynthetic process;T cell proliferation;B cell proliferation;response to drug;'de novo' CTP biosynthetic process
• Cellular component: cytoplasm;cytosol;membrane;cytoophidium
• Molecular function: CTP synthase activity;ATP binding;identical protein binding