TET1
tet methylcytosine dioxygenase 1, the group of Zinc fingers CXXC-type|Tet methylcytosine dioxygenase family
Basic information
Region (hg38): 10:68560337-68694487
Previous symbols: [ "CXXC6" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (191 variants)
- not_provided (22 variants)
- TET1-related_disorder (21 variants)
- Neurodevelopmental_delay (1 variants)
- Hearing_impairment (1 variants)
- Hypothyroidism (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TET1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000030625.3. 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 | 12 | 19 | ||||
| missense | 180 | 18 | 205 | |||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 182 | 30 | 14 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| TET1 | protein_coding | protein_coding | ENST00000373644 | 11 | 133827 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 9.35e-8 | 125740 | 0 | 4 | 125744 | 0.0000159 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.62 | 970 | 1.12e+3 | 0.864 | 0.0000581 | 13990 |
| Missense in Polyphen | 136 | 239.78 | 0.56719 | 3015 | ||
| Synonymous | 0.0692 | 428 | 430 | 0.996 | 0.0000236 | 4247 |
| Loss of Function | 7.32 | 7 | 75.7 | 0.0925 | 0.00000426 | 989 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000615 | 0.0000615 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000265 | 0.0000264 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5- hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation. Also mediates subsequent conversion of 5hmC into 5- formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC). Conversion of 5mC into 5hmC, 5fC and 5caC probably constitutes the first step in cytosine demethylation. Methylation at the C5 position of cytosine bases is an epigenetic modification of the mammalian genome which plays an important role in transcriptional regulation. In addition to its role in DNA demethylation, plays a more general role in chromatin regulation. Preferentially binds to CpG-rich sequences at promoters of both transcriptionally active and Polycomb-repressed genes. Involved in the recruitment of the O-GlcNAc transferase OGT to CpG-rich transcription start sites of active genes, thereby promoting histone H2B GlcNAcylation by OGT. Also involved in transcription repression of a subset of genes through recruitment of transcriptional repressors to promoters. Involved in the balance between pluripotency and lineage commitment of cells it plays a role in embryonic stem cells maintenance and inner cell mass cell specification. Plays an important role in the tumorigenicity of glioblastoma cells. TET1-mediated production of 5hmC acts as a recruitment signal for the CHTOP-methylosome complex to selective sites on the chromosome, where it methylates H4R3 and activates the transcription of genes involved in glioblastomagenesis (PubMed:25284789). {ECO:0000269|PubMed:12124344, ECO:0000269|PubMed:19372391, ECO:0000269|PubMed:19372393, ECO:0000269|PubMed:21496894, ECO:0000269|PubMed:21778364, ECO:0000269|PubMed:25284789}.;
- Disease
- DISEASE: Note=A chromosomal aberration involving TET1 may be a cause of acute leukemias (PubMed:12646957). Translocation t(10;11)(q22;q23) with KMT2A/MLL1. This is a rare chromosomal translocation 5' KMT2A/MLL1-TET1 3' (PubMed:12124344, PubMed:12646957). {ECO:0000269|PubMed:12124344, ECO:0000269|PubMed:12646957}.;
- Pathway
- The oncogenic action of Succinate;The oncogenic action of Fumarate;The oncogenic action of 2-hydroxyglutarate;The oncogenic action of L-2-hydroxyglutarate in Hydroxygluaricaciduria;The oncogenic action of D-2-hydroxyglutarate in Hydroxygluaricaciduria ;Mesodermal Commitment Pathway;MECP2 and Associated Rett Syndrome;TET1,2,3 and TDG demethylate DNA;Epigenetic regulation of gene expression;Gene expression (Transcription)
(Consensus)
Recessive Scores
- pRec
- 0.109
Intolerance Scores
- loftool
- 0.247
- rvis_EVS
- 0.4
- rvis_percentile_EVS
- 76.32
Haploinsufficiency Scores
- pHI
- 0.676
- hipred
- N
- hipred_score
- 0.233
- ghis
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.194
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | Medium | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |
Mouse Genome Informatics
- Gene name
- Tet1
- Phenotype
- embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; 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); reproductive system phenotype; hematopoietic system phenotype; neoplasm; pigmentation 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); vision/eye phenotype; immune system phenotype; skeleton phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- inner cell mass cell differentiation;5-methylcytosine catabolic process;chromatin organization;protein O-linked glycosylation;positive regulation of cell population proliferation;stem cell population maintenance;positive regulation of histone methylation;positive regulation of transcription by RNA polymerase II;oxidation-reduction process;oxidative demethylation;DNA demethylation;negative regulation of methylation-dependent chromatin silencing
- Cellular component
- nucleus
- Molecular function
- DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;iron ion binding;zinc ion binding;methylcytosine dioxygenase activity