YTHDC2

Chr 5

YTH N6-methyladenosine RNA binding protein C2

Also known as: CAHL, hYTHDC2

NCBI Gene: 64848ENSG00000047188UniProt: Q9H6S0

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]

239
ClinVar variants
26
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— YTHDC2
⚡
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
26 Pathogenic / Likely Pathogenic· 161 VUS of 239 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.13LOEUF
pLI 1.000
Z-score 7.78
OE 0.06 (0.03–0.13)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.33Z-score
OE missense 0.97 (0.91–1.03)
712 obs / 736.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.06 (0.03–0.13)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.91–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.18
0≤1.21.6
LoF obs/exp: 5 / 80.1Missense obs/exp: 712 / 736.8Syn Z: -2.27

ClinVar Variant Classifications

239 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
VUS161
Likely Benign23
Benign29
26
Pathogenic
161
VUS
23
Likely Benign
29
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
26
0
26
Likely Pathogenic
0
0
0
0
0
VUS
0
156
5
0
161
Likely Benign
0
5
11
7
23
Benign
0
8
7
14
29
Total01694921239

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

View in ClinVar →

Protein Context — Lollipop Plot

YTHDC2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
lncRNA ZNRD1-AS1 promotes malignant lung cell proliferation, migration, and angiogenesis via the miR-942/TNS1 axis and is positively regulated by the m(6)A reader YTHDC2.
Wang J et al.·Mol Cancer
2022
Targeting Zfp36 to combat cardiac hypertrophy: Insights into ferroptosis pathways.
Zhang M et al.·Clin Transl Med
2025
YTHDC2 inhibits the resistance of lung cancer to EGFR-TKI through cuproptosis.
Luo J et al.·Oncogene
2026
Uncovering the molecular networks of ferroptosis in the pathogenesis of type 2 diabetes and its complications: a multi-omics investigation.
Dong C et al.·Mol Med
2024
Epigenetics of glaucoma in the trabecular meshwork.
Liu Z et al.·Clin Epigenetics
2025Review
METTL16 inhibits pancreatic cancer proliferation and metastasis by promoting MROH8 RNA stability and inhibiting CAPN2 expression - experimental studies.
Yi T et al.·Int J Surg
2024
Pathogenic variants in the human m6A reader YTHDC2 are associated with primary ovarian insufficiency.
McGlacken-Byrne SM et al.·JCI Insight
2022
Construction and clinical evaluation of N6-methyladenosine risk signature of YTHDC2, IGF2BP2, and HNRNPC in head and neck squamous cell carcinoma.
Yue Q et al.·Hua Xi Kou Qiang Yi Xue Za Zhi
2022
Overexpression of YTHDC2 contributes to the progression of prostate cancer and predicts poor outcomes in patients with prostate cancer.
Song J et al.·J Biochem Mol Toxicol
2023Cohort
An association study of m6A methylation with major depressive disorder.
Li Y et al.·BMC Psychiatry
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools