YTHDF2
protein-codingYTH N6-methyladenosine RNA binding protein F2, the group of YTH domain containing N6-methyladenosine readers
Gene summary
This gene encodes a member of the YTH (YT521-B homology) superfamily containing YTH domain. The YTH domain is typical for the eukaryotes and is particularly abundant in plants. The YTH domain is usually located in the middle of the protein sequence and may function in binding to RNA. In addition to a YTH domain, this protein has a proline rich region which may be involved in signal transduction. An Alu-rich domain has been identified in one of the introns of this gene, which is thought to be associated with human longevity. In addition, reciprocal translocations between this gene and the Runx1 (AML1) gene on chromosome 21 has been observed in patients with acute myeloid leukemia. This gene was initially mapped to chromosome 14, which was later turned out to be a pseudogene. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene. [provided by RefSeq, Oct 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~33.2 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 YTHDF2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016258.3. 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 | 1 | 1 | ||||
| missense | 47 | 1 | 48 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 53 | 1 | 0 | 54 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057342.2 | 5 | MANE Select | |
| Ensembl | ENSP00000362918.3 | 5 | MANE Select | |
| RefSeq | NP_001166299.1 | 2 | Standard | |
| RefSeq | NP_001166599.1 | 5 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ythdf2 | Danio rerio | Structure: whole organism Quality: increased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- oocyte maturation
- humoral immune response
- regulation of mRNA stability
- negative regulation of Notch signaling pathway
- embryonic morphogenesis
Molecular Function
- RNA binding
- protein binding
- N6-methyladenosine-containing RNA binding
Cellular Component
- P-body
- nucleus
- microtubule organizing center
- cytosol
- cytoplasmic ribonucleoprotein granule
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000373812
- Coding exons
- 5
- Length
- 33155
- Individuals with no LoFs
- 124713
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 124714
- p
- 0.00000401
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.27 | 207 | 321 | 0.644 | 0.0000171 | 3812 |
| Missense (PolyPhen) | 26 | 97.407 | 0.26692 | 1192 | ||
| Synonymous | -0.0831 | 119 | 118 | 1.01 | 0.00000657 | 1142 |
| Loss of Function | 4.30 | 0 | 21.5 | 0.00 | 0.00000101 | 254 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, and regulates mRNA stability (PubMed:24284625, PubMed:26046440, PubMed:26318451). M6A is a modification present at internal sites of mRNAs and some non- coding RNAs and plays a role in mRNA stability and processing (PubMed:22575960, PubMed:24284625, PubMed:25412658, PubMed:25412661). Acts as a regulator of mRNA stability: binding to m6A-containing mRNAs results in the localization to mRNA decay sites, such as processing bodies (P-bodies), leading to mRNA degradation (PubMed:24284625, PubMed:26046440). Required maternally to regulate oocyte maturation: probably acts by binding to m6A-containing mRNAs, thereby regulating maternal transcript dosage during oocyte maturation, which is essential for the competence of oocytes to sustain early zygotic development (By similarity). Also involved in haematopoietic stem cells specification: acts by binding to m6A-containing mRNAs, leading to decrease Notch dignaling and promote endothelial to haematopoietic transition (By similarity). Also acts as a promoter of cap- independent mRNA translation following heat shock stress: upon stress, relocalizes to the nucleus and specifically binds mRNAs with some m6A methylation mark at their 5'-UTR, protecting demethylation of mRNAs by FTO, thereby promoting cap-independent mRNA translation (PubMed:26458103). May inhibit replication of kaposis sarcoma-associated herpesvirus (KSHV); its role is however unclear and additional evidences are needed to confirm such results (PubMed:29109479). {ECO:0000250|UniProtKB:E7F1H9, ECO:0000250|UniProtKB:Q91YT7, ECO:0000269|PubMed:22575960, ECO:0000269|PubMed:24284625, ECO:0000269|PubMed:25412658, ECO:0000269|PubMed:25412661, ECO:0000269|PubMed:26046440, ECO:0000269|PubMed:26318451, ECO:0000269|PubMed:26458103, ECO:0000269|PubMed:29109479}.; FUNCTION: (Microbial infection) Promotes viral gene expression and virion production of kaposis sarcoma-associated herpesvirus (KSHV) at some stage of the KSHV life cycle (in iSLK.219 and iSLK.BAC16 cells) (PubMed:29659627). Acts by binding to N6-methyladenosine (m6A)-containing viral RNAs (PubMed:29659627). {ECO:0000269|PubMed:29659627}.;
Recessive Scores
- pRec
- 0.156
Intolerance Scores
- LoFtool
- 0.0668
- RVIS EVS
- -0.01
- RVIS percentile EVS
- 53.51
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.980
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |