TDG
protein-codingthymine DNA glycosylase, the group of DNA glycosylases
Gene summary
The protein encoded by this gene belongs to the TDG/mug DNA glycosylase family. Thymine-DNA glycosylase (TDG) removes thymine moieties from G/T mismatches by hydrolyzing the carbon-nitrogen bond between the sugar-phosphate backbone of DNA and the mispaired thymine. With lower activity, this enzyme also removes thymine from C/T and T/T mispairings. TDG can also remove uracil and 5-bromouracil from mispairings with guanine. This enzyme plays a central role in cellular defense against genetic mutation caused by the spontaneous deamination of 5-methylcytosine and cytosine. This gene may have a pseudogene in the p arm of chromosome 12. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~23.1 kbGenCC 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 TDG variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003211.6. 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 | 0 | |||||
| missense | 46 | 1 | 47 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 9 | 9 | ||||
| Total | 0 | 0 | 55 | 1 | 0 | 56 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003202.3 | 10 | MANE Select | |
| Ensembl | ENSP00000376611.3 | 10 | MANE Select | |
| RefSeq | NP_001350541.1 | 7 | Standard | |
| Ensembl | ENSP00000266775.9 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Fluoropyrimidine Pathway, Pharmacodynamics
- Base excision repair - Homo sapiens (human)
- Fluoropyrimidine Activity
- miR-targeted genes in epithelium - TarBase
- miR-targeted genes in lymphocytes - TarBase
Biological Process
- negative regulation of transcription by RNA polymerase II
- base-excision repair
- base-excision repair, AP site formation
- mismatch repair
- chromatin organization
Molecular Function
- magnesium ion binding
- DNA binding
- damaged DNA binding
- double-stranded DNA binding
- transcription coregulator activity
Cellular Component
- nucleus
- nucleoplasm
- plasma membrane
- PML body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000392872
- Coding exons
- 10
- Length
- 23071
- Individuals with no LoFs
- 111720
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 14027
- Defined
- 125747
- p
- 0.0574
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.24 | 160 | 211 | 0.760 | 0.0000102 | 2653 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.11 | 0.10 | notable |
| Latino/Admixed American | 0.083 | 0.072 | notable |
| Ashkenazi Jewish | 0.064 | 0.060 | notable |
| East Asian | 0.12 | 0.11 | notable |
| Finnish | 0.017 | 0.016 | notable |
| European (Non-Finnish) | 0.044 | 0.041 | notable |
| South Asian | 0.079 | 0.074 | notable |
| Other | 0.078 | 0.070 | notable |
dbNSFP Gene Annotations
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}.;
Recessive Scores
- pRec
- 0.152
Intolerance Scores
- LoFtool
- 0.811
- RVIS EVS
- 0.13
- RVIS percentile EVS
- 63.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.773
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | Medium | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |