YTHDF2

YTH N6-methyladenosine RNA binding protein F2, the group of YTH domain containing N6-methyladenosine readers

Basic information

Region (hg38): 1:28736620-28769775

Links

ENSG00000198492

∙ NCBI:51441 ∙ OMIM:610640 ∙ HGNC:31675 ∙ Uniprot:Q9Y5A9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the YTHDF2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the YTHDF2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			14 clinvar			14
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	14	0	0

Variants in YTHDF2

This is a list of pathogenic ClinVar variants found in the YTHDF2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Phenotype	Significance	ClinVar
1-28742479-T-C	not specified	Uncertain significance (Jul 11, 2023)	2610291
1-28742524-A-T	not specified	Uncertain significance (Dec 14, 2022)	2382017
1-28742709-T-C	not specified	Uncertain significance (Dec 17, 2021)	2399844
1-28742788-A-G	not specified	Likely benign (Mar 18, 2024)	3333751
1-28742823-A-G	not specified	Uncertain significance (Jun 11, 2021)	2232656
1-28742859-A-G	not specified	Uncertain significance (Jun 23, 2023)	2595701
1-28742904-G-C	not specified	Uncertain significance (Dec 13, 2021)	2266540
1-28742919-A-G	not specified	Uncertain significance (Dec 13, 2022)	2364582
1-28743124-C-G	not specified	Uncertain significance (Dec 28, 2022)	2402615
1-28743217-C-T	not specified	Uncertain significance (Jun 24, 2022)	2296675
1-28743447-C-T	not specified	Uncertain significance (Jun 09, 2022)	2294765
1-28743514-T-C	not specified	Uncertain significance (May 21, 2024)	3333753
1-28743633-G-A	not specified	Uncertain significance (Jun 27, 2023)	2602736
1-28743756-G-A	not specified	Uncertain significance (Jan 23, 2023)	2477251
1-28743907-G-C	not specified	Uncertain significance (Mar 30, 2024)	3333752
1-28743910-A-G	not specified	Uncertain significance (Nov 10, 2022)	2325841
1-28743913-A-G	not specified	Uncertain significance (Nov 19, 2022)	2353752
1-28768933-G-A	not specified	Uncertain significance (Jun 05, 2024)	3333754

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
YTHDF2	protein_coding	protein_coding	ENST00000373812	5	33155

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000568	124713	0	1	124714	0.00000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.27	207	321	0.644	0.0000171	3812
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000884	0.00000884
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

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

Haploinsufficiency Scores

pHI: 0.548
hipred: Y
hipred_score: 0.728
ghis: 0.589

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.980

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Ythdf2
Phenotype: cellular phenotype; reproductive system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);

Zebrafish Information Network

Gene name: ythdf2
Affected structure: whole organism
Phenotype tag: abnormal
Phenotype quality: increased amount

Gene ontology

Biological process: oocyte maturation;humoral immune response;regulation of mRNA stability;negative regulation of Notch signaling pathway;embryonic morphogenesis;mRNA destabilization;endothelial to hematopoietic transition;regulation of hematopoietic stem cell differentiation;regulation of meiotic cell cycle process involved in oocyte maturation;positive regulation of cap-independent translational initiation
Cellular component: P-body;nucleus;microtubule organizing center;cytosol;cytoplasmic ribonucleoprotein granule
Molecular function: RNA binding;protein binding;N6-methyladenosine-containing RNA binding