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. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

168

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.09

LOEUF· LoF intol.

LOF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in YTHDC1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

709 rare PASS variants

Rare truncating (LoF)

1 in 4,500

34 rare PASS variants

Rare synonymous (reference)

1 in 170

312 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for YTHDC1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 6,100
South Asian	~43k	1 in 130	1 in 8,500
Remaining (unassigned)	~30k	1 in 100	1 in 3,000
European (Finnish)	~27k	1 in 220	1 in 490
Admixed American	~22k	1 in 120	≈ 1 in 5,600
African / African American	~21k	1 in 93	none seen
East Asian	~20k	1 in 140	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 300	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 140	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 17 coding exons well covered in gnomAD exomes and genomes.? see exons ↓