TYMS
thymidylate synthetase
Basic information
Region (hg38): 18:657653-673578
Previous symbols: [ "TS" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
Clinical Genomic Database
Source:
| 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
- not_specified (10 variants)
- Dyskeratosis_congenita (7 variants)
- not_provided (6 variants)
- Dyskeratosis_congenita,_digenic (4 variants)
- TYMS-related_disorder (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. These statistics are base on transcript: NM_000001071.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 6 | |||||
| missense | 13 | |||||
| nonsense | 3 | |||||
| start loss | 0 | |||||
| frameshift | 2 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 6 | 0 | 9 | 9 | 1 |
Highest pathogenic variant AF is 0.00000615748
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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
- Phenotype
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