YTHDC1

Chr 4

YTH N6-methyladenosine RNA binding protein C1

Also known as: YT521, YT521-B

NCBI Gene: 91746 ENSG00000083896 UniProt: Q96MU7 OMIM: 617283

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables N6-methyladenosine-containing RNA reader activity and RNA binding activity. Involved in gene expression and regulation of gene expression. Located in nuclear speck and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.09

Clinical Summary— YTHDC1

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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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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.09LOEUF

pLI 1.000

Z-score 6.46

OE 0.02 (0.01–0.09)

Highly constrained

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

Missense Constraint?

2.48Z-score

OE missense 0.66 (0.59–0.72)

269 obs / 410.2 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.02 (0.01–0.09)

0≤0.351.4

Missense OE?0.66 (0.59–0.72)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 1 / 50.5Missense obs/exp: 269 / 410.2Syn Z: -0.35

This gene — mechanism propensity

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.