TYMS

thymidylate synthetase

Basic information

Region (hg38): 18:657653-673578

Previous symbols: [ "TS" ]

Links

ENSG00000176890 ∙ NCBI:7298 ∙ OMIM:188350 ∙ HGNC:12441 ∙ Uniprot:P04818 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dyskeratosis congenita, digenic	Digenic	Allergy/Immunology/Infectious; Oncologic	Surveillance (eg, with regularly performed CBC as well as other measures in the presence of concern for hematologic sequelae) for bone marrow failure, as well as surveillance for multiple cancer types (eg, with self-examination and clinical examination) may allow early detection and treatment; Awareness of infectious risk may allow prompt diagnosis and treatment of infections	Allergy/Immunology/Infectious; Craniofacial; Dental; Dermatologic; Oncologic	35931051
Inheritance involves variants in TYMS as well a a specific haplotype in the ENOSF1 gene

ClinVar

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

• Dyskeratosis congenita (5 variants)
• Dyskeratosis congenita, digenic (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TYMS 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				4	1	5
missense			7	1	1	9
nonsense	3					3
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)	1					1
splice region						0
non coding					2	2
Total	5	0	7	5	4

Variants in TYMS

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

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

Position	Type	Phenotype	Significance	ClinVar
18-657752-G-T		not specified	Uncertain significance (Jul 15, 2021)
18-657785-C-T		TYMS-related disorder	Benign (Feb 21, 2019)
18-657812-C-A		not specified	Uncertain significance (Aug 02, 2021)
18-657827-G-A		not specified	Uncertain significance (Feb 10, 2022)
18-657838-G-A			Likely benign (Aug 05, 2018)
18-657878-A-C		TYMS-related disorder	Likely benign (Dec 29, 2022)
18-658147-C-A			Benign (Jun 01, 2024)
18-659694-G-A		Dyskeratosis congenita	Uncertain significance (Jun 22, 2022)
18-662209-C-T		Dyskeratosis congenita • Dyskeratosis congenita, digenic	Pathogenic (Jun 22, 2022)
18-662226-C-G		not specified	Uncertain significance (Jun 13, 2023)
18-662247-A-G		TYMS-related disorder	Benign (Oct 07, 2019)
18-669097-A-T		Dyskeratosis congenita • Dyskeratosis congenita, digenic	Uncertain significance (Jun 22, 2022)
18-669101-CAA-C		Dyskeratosis congenita • Dyskeratosis congenita, digenic	Pathogenic (Jun 22, 2022)
18-669151-C-CTG		Dyskeratosis congenita, digenic • Dyskeratosis congenita	Pathogenic (Jun 22, 2022)
18-669171-G-A		not specified	Likely benign (Sep 06, 2022)
18-669174-G-A		Dyskeratosis congenita	Pathogenic (Jun 22, 2022)
18-670825-C-T			Likely benign (Feb 01, 2023)
18-670845-T-C		not specified	Uncertain significance (May 18, 2023)
18-671433-C-T			Likely benign (Jun 08, 2018)
18-672866-C-T		Dyskeratosis congenita	Pathogenic (Jun 22, 2022)
18-673086-A-G			Benign (Jul 15, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TYMS	protein_coding	protein_coding	ENST00000323274	7	15975

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.722	0.277	125735	0	5	125740	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.58	71	164	0.433	0.00000846	2018
Missense in Polyphen		16	74.591	0.2145		886
Synonymous	0.366	63	66.8	0.943	0.00000398	611
Loss of Function	3.19	3	17.3	0.173	9.74e-7	184

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000177	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. {ECO:0000269|PubMed:21876188}.
• Pathway: Fluoropyrimidine Pathway, Pharmacodynamics;Antimetabolite Pathway - Folate Cycle, Pharmacodynamics;Pyrimidine metabolism - Homo sapiens (human);One carbon pool by folate - Homo sapiens (human);Fluoropyrimidine Pathway, Pharmacokinetics;Methotrexate Pathway (Cancer Cell), Pharmacodynamics;Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics;Pyrimidine Metabolism;Capecitabine Action Pathway;Capecitabine Metabolism Pathway;Fluorouracil Action Pathway;UMP Synthase Deiciency (Orotic Aciduria);Gemcitabine Action Pathway;MNGIE (Mitochondrial Neurogastrointestinal Encephalopathy);Fluorouracil Metabolism Pathway;Gemcitabine Metabolism Pathway;Beta Ureidopropionase Deficiency;Dihydropyrimidinase Deficiency;Fluoropyrimidine Activity;miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Mitotic G1-G1-S phases;One Carbon Metabolism;Retinoblastoma (RB) in Cancer;Trans-sulfuration and one carbon metabolism;One carbon metabolism and related pathways;Ethanol effects on histone modifications;Pyrimidine metabolism;pyrimidine deoxyribonucleotides <i>de novo</i> biosynthesis;Metabolism of nucleotides;Folate metabolism;Interconversion of nucleotide di- and triphosphates;Metabolism;dTMP <i>de novo</i> biosynthesis (mitochondrial);superpathway of pyrimidine deoxyribonucleoside salvage;Pyrimidine nucleotides nucleosides metabolism;superpathway of pyrimidine deoxyribonucleotides <i>de novo</i> biosynthesis;pyrimidine deoxyribonucleotides biosynthesis from CTP;pyrimidine deoxyribonucleosides salvage;E2F transcription factor network (Consensus)

Recessive Scores

• pRec: 0.618

Intolerance Scores

• loftool: 0.173
• rvis_EVS: -0.16
• rvis_percentile_EVS: 41.25

Haploinsufficiency Scores

• pHI: 0.941
• hipred: Y
• hipred_score: 0.831
• ghis: 0.731

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.763

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tyms

Zebrafish Information Network

• Gene name: tyms
• Affected structure: melanocyte
• Phenotype tag: abnormal
• Phenotype quality: quality

Gene ontology

• Biological process: regulation of transcription involved in G1/S transition of mitotic cell cycle;dTMP biosynthetic process;dTTP biosynthetic process;aging;circadian rhythm;nucleobase-containing small molecule interconversion;negative regulation of translation;immortalization of host cell by virus;uracil metabolic process;methylation;response to progesterone;response to vitamin A;response to cytokine;tetrahydrofolate interconversion;response to ethanol;dUMP metabolic process;response to organophosphorus;developmental growth;cartilage development;response to glucocorticoid;response to folic acid;intestinal epithelial cell maturation;DNA biosynthetic process;liver regeneration
• Cellular component: nucleus;nucleolus;cytoplasm;mitochondrion;mitochondrial inner membrane;mitochondrial matrix;cytosol
• Molecular function: nucleotide binding;translation repressor activity, mRNA regulatory element binding;thymidylate synthase activity;folic acid binding;protein homodimerization activity;cofactor binding;sequence-specific mRNA binding