YTHDF3
protein-codingYTH N6-methyladenosine RNA binding protein F3, the group of YTH domain containing N6-methyladenosine readers
Gene summary
This gene encodes a member of the YTH (YT521-B homology) domain protein family. The YTH domain is common in eukaryotes, is often found in the middle of the protein sequence, and may function in binding to RNA. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~44.2 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 YTHDF3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_152758.6. 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 | 0 | |||||
| missense | 3 | 1 | 4 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 5 | 1 | 0 | 6 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_689971.4 | 5 | MANE Select | |
| Ensembl | ENSP00000473496.2 | 5 | MANE Select | |
| RefSeq | NP_001264742.1 | 4 | Standard | |
| RefSeq | NP_001264743.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- positive regulation of translation
- positive regulation of translational initiation
- mRNA destabilization
Molecular Function
- RNA binding
- protein binding
- ribosome binding
- N6-methyladenosine-containing RNA binding
Cellular Component
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000539294
- Coding exons
- 5
- Length
- 44235
- Individuals with no LoFs
- 124706
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 124709
- p
- 0.0000120
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.66 | 180 | 312 | 0.576 | 0.0000156 | 3848 |
| Missense (PolyPhen) | 29 | 79.434 | 0.36508 | 1033 | ||
| Synonymous | -0.353 | 114 | 109 | 1.04 | 0.00000543 | 1137 |
| Loss of Function | 4.10 | 1 | 21.5 | 0.0465 | 9.19e-7 | 263 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000069 | 0.000065 | rare |
| 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) | 0.000036 | 0.000018 | 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 promotes RNA translation efficiency (PubMed:28106072, PubMed:28106076, PubMed:28281539). M6A is a modification present at internal sites of mRNAs and some non- coding RNAs and plays a role in the efficiency of mRNA splicing, processing and stability (PubMed:22575960, PubMed:24284625, PubMed:28106072, PubMed:28106076, PubMed:28281539). Shares m6A- containing mRNAs targets with YTHDF1 and YTHDF2, and regulates different processes depending on the context (PubMed:28106072, PubMed:28106076). Facilitates the translation of targeted mRNAs in cooperation with YTHDF1 by binding to m6A-containing mRNAs and interacting with 40S and 60S ribosome subunits (PubMed:28106072, PubMed:28106076). Can also act as a regulator of mRNA stability in cooperation with YTHDF2 by binding to m6A-containing mRNA and promoting their degradation (PubMed:28106072). Recognizes and binds m6A-containing circular RNAs (circRNAs) and promotes their translation (PubMed:28281539). circRNAs are generated through back-splicing of pre-mRNAs, a non-canonical splicing process promoted by dsRNA structures across circularizing exons (PubMed:28281539). {ECO:0000269|PubMed:22575960, ECO:0000269|PubMed:24284625, ECO:0000269|PubMed:28106072, ECO:0000269|PubMed:28106076, ECO:0000269|PubMed:28281539}.;
Essentials
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.352
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |