TET3

Chr 2

tet methylcytosine dioxygenase 3

Also known as: BEFAHRS, hCG_40738

NCBI Gene: 200424 ENSG00000187605 UniProt: O43151

TET3 encodes a dioxygenase that catalyzes the conversion of 5-methylcytosine to 5-hydroxymethylcytosine and plays a key role in DNA demethylation and epigenetic chromatin reprogramming, particularly in the paternal pronucleus following fertilization. Mutations cause Beck-Fahrner syndrome with both autosomal dominant and autosomal recessive inheritance patterns reported. The gene is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.086), indicating that complete loss of function is likely not tolerated.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

Enables RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; methyl-CpG binding activity; and zinc ion binding activity. Involved in positive regulation of transcription by RNA polymerase II and protein O-linked glycosylation. Predicted to be located in cytoplasm and male pronucleus. Predicted to be active in nucleus. Biomarker of esophagus squamous cell carcinoma. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtBeck-Fahrner syndrome

Clinical highlights

Gene-disease validity (ClinGen)

Beck-Fahrner syndrome · ADDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.09

LOEUF· LoF intol.

LOF

Mechanism· G2P

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