TET1

tet methylcytosine dioxygenase 1, the group of Zinc fingers CXXC-type|Tet methylcytosine dioxygenase family

Basic information

Region (hg38): 10:68560336-68694487

Previous symbols: [ "CXXC6" ]

Links

ENSG00000138336 ∙ NCBI:80312 ∙ OMIM:607790 ∙ HGNC:29484 ∙ Uniprot:Q8NFU7 ∙ 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 TET1 gene.

• Inborn genetic diseases (62 variants)
• not provided (21 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.

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				2	7	9
missense			60	6	7	73
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	60	8	14

Variants in TET1

This is a list of pathogenic ClinVar variants found in the TET1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-68572376-T-C		not specified	Uncertain significance (Feb 07, 2023)
10-68572441-A-G		not specified	Uncertain significance (Mar 12, 2024)
10-68572514-A-G		not specified	Uncertain significance (Aug 02, 2022)
10-68572580-G-C		not specified	Uncertain significance (Sep 01, 2021)
10-68572591-G-A		not specified	Uncertain significance (Aug 15, 2023)
10-68572598-C-G		TET1-related disorder	Likely benign (Feb 03, 2022)
10-68572702-G-A		not specified	Likely benign (Dec 14, 2023)
10-68572756-T-C		not specified	Uncertain significance (Aug 02, 2023)
10-68572757-G-A		not specified	Uncertain significance (Jan 18, 2023)
10-68572808-C-T		not specified	Uncertain significance (Sep 14, 2021)
10-68572834-C-T		TET1-related disorder	Benign (Jun 12, 2019)
10-68572854-A-C		TET1-related disorder	Benign/Likely benign (Feb 04, 2020)
10-68572967-C-T		not specified	Uncertain significance (Feb 17, 2024)
10-68573002-C-T		not specified	Likely benign (Jun 11, 2021)
10-68573024-C-T		not specified	Uncertain significance (Oct 22, 2021)
10-68573033-C-T		not specified	Uncertain significance (Jul 12, 2022)
10-68573070-T-C		TET1-related disorder	Likely benign (Aug 12, 2019)
10-68573113-A-G			Uncertain significance (Nov 01, 2023)
10-68573116-G-A		not specified	Uncertain significance (Oct 14, 2023)
10-68573126-A-G		not specified	Uncertain significance (Jul 12, 2022)
10-68573168-T-C		not specified	Uncertain significance (Mar 24, 2023)
10-68573360-C-T		not specified	Uncertain significance (Oct 26, 2021)
10-68573381-C-G		not specified	Uncertain significance (Sep 22, 2023)
10-68573488-G-T		not specified	Uncertain significance (Dec 19, 2022)
10-68573615-T-C		not specified	Likely benign (Apr 13, 2022)

GnomAD

Source: gnomAD

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: dbNSFP

• 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

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