YTHDC2

Chr 5

YTH N6-methyladenosine RNA binding protein C2

Also known as: CAHL, hYTHDC2

This gene encodes a member of the DEAH (Asp-Glu-Ala-His) subfamily of proteins, part of the DEAD (Asp-Glu-Ala-Asp) box family of RNA helicases. The encoded protein binds to N6-methyladenosine, a common modified RNA nucleotide that is enriched in the stop codons and 3' UTRs of eukaryotic messenger RNAs. Binding of proteins to this modified nucleotide may regulate mRNA translation and stability. This gene may be associated with susceptibility to pancreatic cancer in human patients, and knockdown of this gene resulted in reduced proliferation in a human liver cancer cell line. [provided by RefSeq, Sep 2016]

ResearchGenerating clinical summary…
LOFmechanismLOEUF 0.13
Clinical SummaryYTHDC2
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.
📋
ClinVar Variants
156 VUS of 241 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint?
0.13LOEUF
pLI 1.000
Z-score 7.78
OE 0.06 (0.030.13)
Highly constrained

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

Missense Constraint?
0.33Z-score
OE missense 0.97 (0.911.03)
712 obs / 736.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.06 (0.030.13)
00.351.4
Missense OE?0.97 (0.911.03)
00.61.4
Synonymous OE?1.18
01.21.6
LoF obs/exp: 5 / 80.1Missense obs/exp: 712 / 736.8Syn Z: -2.27

This gene — mechanism propensity

DN
0.3693th %ile
GOF
0.3888th %ile
LOF
0.69top 10%

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

LOFprediction above median · LOEUF 0.13

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

241 submitted variants in ClinVar

Classification Summary

VUS156
Likely Benign22
Benign29
156
VUS
22
Likely Benign
29
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
156
0
0
156
Likely Benign
0
5
10
7
22
Benign
0
8
7
14
29
Total01691721207

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

View in ClinVar →

28 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap YTHDC2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

YTHDC2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →