TET3

Chr 2ADAR

tet methylcytosine dioxygenase 3

Also known as: BEFAHRS, hCG_40738

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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 0.091 OMIM phenotype
Clinical SummaryTET3
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Gene-Disease Validity (ClinGen)
Beck-Fahrner syndrome · ARLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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GeneReview available — TET3
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.09LOEUF
pLI 1.000
Z-score 6.75
OE 0.02 (0.010.09)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
2.88Z-score
OE missense 0.74 (0.700.79)
732 obs / 986.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.02 (0.010.09)
00.351.4
Missense OE0.74 (0.700.79)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 1 / 55.1Missense obs/exp: 732 / 986.4Syn Z: -1.04
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongTET3-related DNA demethylation disorderLOFAD
strongTET3-related DNA demethylation disorderLOFAR
DN
0.15100th %ile
GOF
0.1699th %ile
LOF
0.88top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.09

Literature Evidence

LOFTET3 is a methylcytosine dioxygenase that initiates DNA demethylation during early zygote formation, embryogenesis, and neuronal differentiation and is intolerant to haploinsufficiency in mice and humans.PMID:31928709

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TET3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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