YTHDC1

Chr 4

YTH N6-methyladenosine RNA binding protein C1

The YTHDC1 protein recognizes and binds N6-methyladenosine (m6A)-modified RNAs to regulate alternative splicing by controlling recruitment of splicing factors and facilitating nuclear export of modified mRNAs. Mutations cause autosomal dominant intellectual disability with variable features that may include developmental delay and other neurodevelopmental phenotypes. This gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.094), indicating that complete loss of function is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.09
Clinical SummaryYTHDC1
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.09LOEUF
pLI 1.000
Z-score 6.46
OE 0.02 (0.010.09)
Highly constrained

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

Missense Constraint
2.48Z-score
OE missense 0.66 (0.590.72)
269 obs / 410.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.02 (0.010.09)
00.351.4
Missense OE0.66 (0.590.72)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 1 / 50.5Missense obs/exp: 269 / 410.2Syn Z: -0.35
DN
0.19100th %ile
GOF
0.1899th %ile
LOF
0.86top 5%

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

LOFprediction above median · LOEUF 0.09

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

YTHDC1 · 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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