TDG
thymine DNA glycosylase, the group of DNA glycosylases
Basic information
Region (hg38): 12:103965822-103988874
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TDG 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 | 0 | |||||
| missense | 17 | 17 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 18 | 0 | 0 |
Variants in TDG
This is a list of pathogenic ClinVar variants found in the TDG region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 12-103966044-G-C | not specified | Uncertain significance (Jan 30, 2024) | ||
| 12-103966047-G-A | not specified | Uncertain significance (Feb 06, 2024) | ||
| 12-103966054-C-G | not specified | Uncertain significance (May 06, 2022) | ||
| 12-103976947-A-G | not specified | Uncertain significance (Jan 24, 2024) | ||
| 12-103976980-C-G | not specified | Uncertain significance (Dec 19, 2023) | ||
| 12-103977022-A-T | not specified | Uncertain significance (Nov 21, 2023) | ||
| 12-103977023-A-T | not specified | Uncertain significance (Nov 21, 2023) | ||
| 12-103977034-C-G | not specified | Uncertain significance (Jun 24, 2022) | ||
| 12-103979959-A-C | not specified | Uncertain significance (Dec 15, 2023) | ||
| 12-103979993-G-A | not specified | Uncertain significance (Aug 12, 2024) | ||
| 12-103980016-G-A | not specified | Uncertain significance (Feb 15, 2023) | ||
| 12-103982822-C-T | not specified | Uncertain significance (Sep 26, 2024) | ||
| 12-103982831-G-A | not specified | Uncertain significance (Oct 21, 2024) | ||
| 12-103982854-T-A | not specified | Uncertain significance (Jan 17, 2023) | ||
| 12-103982894-A-G | not specified | Uncertain significance (Jan 10, 2023) | ||
| 12-103983330-G-A | not specified | Uncertain significance (Aug 16, 2021) | ||
| 12-103984806-G-A | not specified | Uncertain significance (Oct 29, 2024) | ||
| 12-103984824-A-C | not specified | Uncertain significance (Dec 07, 2023) | ||
| 12-103984824-A-G | not specified | Uncertain significance (Jun 01, 2023) | ||
| 12-103984830-C-A | not specified | Uncertain significance (Nov 12, 2024) | ||
| 12-103984867-G-A | not specified | Uncertain significance (Aug 22, 2023) | ||
| 12-103985623-G-A | not specified | Uncertain significance (Dec 21, 2023) | ||
| 12-103985644-C-T | not specified | Uncertain significance (Jul 30, 2024) | ||
| 12-103985686-C-A | not specified | Uncertain significance (Nov 13, 2024) | ||
| 12-103985728-A-ATTGAGAGC | Hereditary breast ovarian cancer syndrome | Uncertain significance (Aug 01, 2020) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| TDG | protein_coding | protein_coding | ENST00000392872 | 10 | 23071 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.000563 | 0.994 | 111720 | 0 | 14027 | 125747 | 0.0574 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.24 | 160 | 211 | 0.760 | 0.0000102 | 2653 |
| Missense in Polyphen | 23 | 38.22 | 0.60179 | 479 | ||
| Synonymous | 1.09 | 61 | 72.8 | 0.838 | 0.00000386 | 724 |
| Loss of Function | 2.46 | 9 | 21.2 | 0.424 | 0.00000106 | 274 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.190 | 0.185 |
| Ashkenazi Jewish | 0.0640 | 0.0602 |
| East Asian | 0.122 | 0.110 |
| Finnish | 0.0169 | 0.0164 |
| European (Non-Finnish) | 0.0439 | 0.0413 |
| Middle Eastern | 0.122 | 0.110 |
| South Asian | 0.0793 | 0.0740 |
| Other | 0.0782 | 0.0704 |
dbNSFP
Source:
- Function
- FUNCTION: DNA glycosylase that plays a key role in active DNA demethylation: specifically recognizes and binds 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) in the context of CpG sites and mediates their excision through base-excision repair (BER) to install an unmethylated cytosine. Cannot remove 5- hydroxymethylcytosine (5hmC). According to an alternative model, involved in DNA demethylation by mediating DNA glycolase activity toward 5-hydroxymethyluracil (5hmU) produced by deamination of 5hmC. Also involved in DNA repair by acting as a thymine-DNA glycosylase that mediates correction of G/T mispairs to G/C pairs: in the DNA of higher eukaryotes, hydrolytic deamination of 5- methylcytosine to thymine leads to the formation of G/T mismatches. Its role in the repair of canonical base damage is however minor compared to its role in DNA demethylation. It is capable of hydrolyzing the carbon-nitrogen bond between the sugar- phosphate backbone of the DNA and a mispaired thymine. In addition to the G/T, it can remove thymine also from C/T and T/T mispairs in the order G/T >> C/T > T/T. It has no detectable activity on apyrimidinic sites and does not catalyze the removal of thymine from A/T pairs or from single-stranded DNA. It can also remove uracil and 5-bromouracil from mispairs with guanine. {ECO:0000269|PubMed:21862836, ECO:0000269|PubMed:22327402, ECO:0000269|PubMed:22573813, ECO:0000269|PubMed:22962365, ECO:0000269|PubMed:8127859, ECO:0000269|PubMed:8407958, ECO:0000269|PubMed:8662714}.;
- Pathway
- Fluoropyrimidine Pathway, Pharmacodynamics;Base excision repair - Homo sapiens (human);Fluoropyrimidine Activity;miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;TET1,2,3 and TDG demethylate DNA;DNA Repair;Epigenetic regulation of gene expression;Gene expression (Transcription);SUMOylation of DNA damage response and repair proteins;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;Recognition and association of DNA glycosylase with site containing an affected pyrimidine;Cleavage of the damaged pyrimidine ;Depyrimidination;Base-Excision Repair, AP Site Formation;SUMOylation;Resolution of Abasic Sites (AP sites);Base Excision Repair;Displacement of DNA glycosylase by APEX1
(Consensus)
Recessive Scores
- pRec
- 0.152
Intolerance Scores
- loftool
- 0.811
- rvis_EVS
- 0.13
- rvis_percentile_EVS
- 63.2
Haploinsufficiency Scores
- pHI
- 0.388
- hipred
- Y
- hipred_score
- 0.712
- ghis
- 0.615
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.773
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | Medium | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |
Mouse Genome Informatics
- Gene name
- Tdg
- Phenotype
- cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); liver/biliary system phenotype; embryo phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype;
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;base-excision repair;base-excision repair, AP site formation;mismatch repair;chromatin organization;negative regulation of protein binding;oxidative DNA demethylation;negative regulation of chromatin binding;regulation of gene expression, epigenetic;depyrimidination;regulation of embryonic development;DNA demethylation;regulation of DNA N-glycosylase activity
- Cellular component
- nucleus;nucleoplasm;plasma membrane;PML body
- Molecular function
- magnesium ion binding;DNA binding;damaged DNA binding;double-stranded DNA binding;transcription coregulator activity;uracil DNA N-glycosylase activity;protein kinase C binding;protein binding;ATP binding;transcription factor binding;pyrimidine-specific mismatch base pair DNA N-glycosylase activity;DNA N-glycosylase activity;protein domain specific binding;mismatched DNA binding;sodium ion binding;chloride ion binding;SUMO binding;protein homodimerization activity;protein self-association;G/U mismatch-specific uracil-DNA glycosylase activity