TDG

thymine DNA glycosylase, the group of DNA glycosylases

Basic information

Region (hg38): 12:103965821-103988874

Links

ENSG00000139372 ∙ NCBI:6996 ∙ OMIM:601423 ∙ HGNC:11700 ∙ Uniprot:Q13569 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

• Inborn genetic diseases (8 variants)
• Hereditary breast ovarian cancer syndrome (1 variants)

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			8			8
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region						0
non coding						0
Total	0	0	9	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)
12-103980016-G-A		not specified	Uncertain significance (Feb 15, 2023)
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)
12-103984824-A-C		not specified	Uncertain significance (Dec 07, 2023)
12-103984824-A-G		not specified	Uncertain significance (Jun 01, 2023)
12-103984867-G-A		not specified	Uncertain significance (Aug 22, 2023)
12-103985623-G-A		not specified	Uncertain significance (Dec 21, 2023)
12-103985728-A-ATTGAGAGC		Hereditary breast ovarian cancer syndrome	Uncertain significance (Aug 01, 2020)

GnomAD

Source: gnomAD

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: dbNSFP

• 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