YTHDC2
protein-codingYTH N6-methyladenosine RNA binding protein C2, the group of YTH domain containing N6-methyladenosine readers
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~81.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to YTHDC2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_022828.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 7 | 9 | 19 | ||
| missense | 161 | 5 | 4 | 170 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 171 | 12 | 13 | 196 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_073739.3 | 29 | MANE Select | |
| Ensembl | ENSP00000161863.4 | 29 | MANE Select | |
| RefSeq | NP_001332904.1 | 26 | Standard | |
| RefSeq | NP_001332905.1 | 24 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- spermatid development
- response to tumor necrosis factor
- positive regulation by host of viral genome replication
- oocyte development
- meiotic cell cycle
Molecular Function
- RNA binding
- protein binding
- ATP binding
- RNA-dependent ATPase activity
- 3'-5' RNA helicase activity
Cellular Component
- nucleus
- cytoplasm
- endoplasmic reticulum
- ribonucleoprotein granule
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000161863
- Coding exons
- 29
- Length
- 81603
- Individuals with no LoFs
- 125731
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 16
- Defined
- 125747
- p
- 0.0000636
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.325 | 712 | 737 | 0.966 | 0.0000370 | 9361 |
| Missense (PolyPhen) | 122 | 180.01 | 0.67775 | 2360 | ||
| Synonymous | -2.27 | 291 | 246 | 1.18 | 0.0000117 | 2728 |
| Loss of Function | 7.78 | 5 | 80.1 | 0.0624 | 0.00000494 | 905 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000097 | 0.000097 | rare |
| South Asian | 0.000034 | 0.000033 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: 3'-5' RNA helicase that plays a key role in the male and female germline by promoting transition from mitotic to meiotic divisions in stem cells (PubMed:26318451, PubMed:29033321). Specifically recognizes and binds N6-methyladenosine (m6A)- containing RNAs, a modification present at internal sites of mRNAs and some non-coding RNAs that plays a role in the efficiency of RNA processing and stability (PubMed:26318451, PubMed:29033321). Essential for ensuring a successful progression of the meiotic program in the germline by regulating the level of m6A-containing RNAs (By similarity). Acts by binding and promoting degradation of m6A-containing mRNAs: the 3'-5' RNA helicase activity is required for this process and RNA degradation may be mediated by XRN1 exoribonuclease (PubMed:29033321). Required for both spermatogenesis and oogenesis (By similarity). {ECO:0000250|UniProtKB:B2RR83, ECO:0000269|PubMed:26318451, ECO:0000269|PubMed:29033321}.;
Recessive Scores
- pRec
- 0.0970
Intolerance Scores
- LoFtool
- 0.400
- RVIS EVS
- -0.28
- RVIS percentile EVS
- 33.59
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.829
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |