TET3

tet methylcytosine dioxygenase 3, the group of Zinc fingers CXXC-type|Tet methylcytosine dioxygenase family

Basic information

Region (hg38): 2:73984910-74108177

Links

ENSG00000187605 ∙ NCBI:200424 ∙ OMIM:613555 ∙ HGNC:28313 ∙ Uniprot:O43151 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Beck-Fahrner syndrome (Moderate), mode of inheritance: Semidominant
• Beck-Fahrner syndrome (Moderate), mode of inheritance: Semidominant
• Beck-Fahrner syndrome (Strong), mode of inheritance: AR
• Beck-Fahrner syndrome (Limited), mode of inheritance: AR
• Beck-Fahrner syndrome (Definitive), mode of inheritance: AD
• Beck-Fahrner syndrome (Strong), mode of inheritance: AR
• Beck-Fahrner syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Beck-Fahrner syndrome	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	31928709

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TET3 gene.

• not_provided (247 variants)
• Beck-Fahrner_syndrome (102 variants)
• TET3-related_disorder (56 variants)
• Inborn_genetic_diseases (34 variants)
• TET3_deficiency (10 variants)
• not_specified (7 variants)
• Neurodevelopmental_disorder (3 variants)
• Schizophrenia (1 variants)
• Intellectual_disability (1 variants)
• See_cases (1 variants)
• Multiple_myeloma (1 variants)
• Neurodevelopmental-craniofacial_syndrome_with_variable_renal_and_cardiac_abnormalities (1 variants)
• Developmental_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TET3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001287491.2. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	51	9	63
missense	2	17	245	22	1	287
nonsense	2	11	2			15
start loss						0
frameshift	3	15	6			24
splice donor/acceptor (+/-2bp)		1	2			3
Total	7	44	258	73	10

Highest pathogenic variant AF is 0.000019721754

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TET3	protein_coding	protein_coding	ENST00000409262	9	105464

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.04e-8	124619	0	4	124623	0.0000160

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.88	732	986	0.742	0.0000607	10594
Missense in Polyphen		172	376.76	0.45653		4067
Synonymous	-1.04	460	432	1.06	0.0000294	3541
Loss of Function	6.75	1	55.1	0.0181	0.00000271	636

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000556	0.0000556
Finnish	0.00	0.00
European (Non-Finnish)	0.0000270	0.0000266
Middle Eastern	0.0000556	0.0000556
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 epigenetic chromatin reprogramming in the zygote following fertilization. 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 (By similarity). Selectively binds to the promoter region of target genes and contributes to regulate the expression of numerous developmental genes (PubMed:23217707). In zygotes, DNA demethylation occurs selectively in the paternal pronucleus before the first cell division, while the adjacent maternal pronucleus and certain paternally-imprinted loci are protected from this process. Participates in DNA demethylation in the paternal pronucleus by mediating conversion of 5mC into 5hmC, 5fC and 5caC. Does not mediate DNA demethylation of maternal pronucleus because of the presence of DPPA3/PGC7 on maternal chromatin that prevents TET3- binding to chromatin (By similarity). In addition to its role in DNA demethylation, also 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 (PubMed:23353889). {ECO:0000250|UniProtKB:Q8BG87, ECO:0000269|PubMed:23217707, ECO:0000269|PubMed:23353889}.
• 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: 0.103

Intolerance Scores

• loftool: 0.129
• rvis_EVS: -1.51
• rvis_percentile_EVS: 3.48

Haploinsufficiency Scores

• pHI: 0.858
• hipred: Y
• hipred_score: 0.662
• ghis: 0.577

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0980

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tet3
• Phenotype: reproductive system phenotype; cellular phenotype

Gene ontology

• Biological process: 5-methylcytosine catabolic process;protein O-linked glycosylation;DNA demethylation of male pronucleus;positive regulation of transcription by RNA polymerase II;oxidation-reduction process;oxidative demethylation;DNA demethylation;histone H3-K4 trimethylation
• Cellular component: female pronucleus;male pronucleus;nucleus;chromosome;cytoplasm
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;iron ion binding;protein binding;methylcytosine dioxygenase activity