YTHDF1

Chr 20

YTH N6-methyladenosine RNA binding protein F1

YTHDF1 encodes a protein that specifically recognizes and binds N6-methyladenosine (m6A)-containing mRNAs and regulates their stability and translation, playing essential roles in learning, memory formation, and axon guidance in the nervous system. The gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.24), suggesting that mutations would likely cause severe developmental consequences, though specific disease associations have not yet been established in patients. Given its critical function in neuronal mRNA regulation and memory formation, pathogenic variants would be expected to cause neurodevelopmental disorders.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.24
Clinical SummaryYTHDF1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.24LOEUF
pLI 0.994
Z-score 3.91
OE 0.05 (0.020.24)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.60Z-score
OE missense 0.76 (0.690.84)
263 obs / 346.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.05 (0.020.24)
00.351.4
Missense OE0.76 (0.690.84)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 1 / 19.7Missense obs/exp: 263 / 346.8Syn Z: -1.09
DN
0.3594th %ile
GOF
0.3887th %ile
LOF
0.78top 5%

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

LOFprediction above median · LOEUF 0.24

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

YTHDF1 · 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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