YTHDF1

Chr 20

YTH N6-methyladenosine RNA binding protein F1

Also known as: C20orf21, DF1

NCBI Gene: 54915 ENSG00000149658 UniProt: Q9BYJ9 OMIM: 616529

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables N6-methyladenosine-containing RNA reader activity and ribosome binding activity. Involved in mRNA destabilization; positive regulation of translational initiation; and stress granule assembly. Located in P-body and cytoplasmic stress granule. Implicated in colorectal cancer. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.24

Clinical Summary— YTHDF1

⚡

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.

📋

ClinVar Variants

75 VUS of 90 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.24LOEUF

pLI 0.994

Z-score 3.91

OE 0.05 (0.02–0.24)

Highly constrained

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

Missense Constraint?

1.60Z-score

OE missense 0.76 (0.69–0.84)

263 obs / 346.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.05 (0.02–0.24)

0≤0.351.4

Missense OE?0.76 (0.69–0.84)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 1 / 19.7Missense obs/exp: 263 / 346.8Syn Z: -1.09

This gene — mechanism propensity

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

90 submitted variants in ClinVar

ClinVar

Classification Summary

VUS75

Likely Benign5

Benign7

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	75	0	75
Likely Benign	2	3	5
Benign	1	6	7
Total	78	9	87

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

47 pathogenic / likely-pathogenic (of 69) ClinVar copy-number / structural variants overlap YTHDF1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →