YTHDF2 Gene

Name	YTH N(6)-methyladenosine RNA binding protein 2
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nYTHDF2 is a critical N⁶‐methyladenosine (m⁶A) “reader” protein that selectively binds m⁶A‐modified RNAs and promotes their degradation. Early work demonstrated that the carboxy‐terminal domain of YTHDF2 directly interacts with m⁶A sites (with a conserved G(m⁶A)C motif) and, via its amino‐terminal region, shuttles bound mRNAs from the translatable pool to cytoplasmic decay sites (processing bodies). In parallel, YTHDF2 was shown to mediate mRNA deadenylation by recruiting the CCR4–NOT deadenylase complex, and also to direct an alternative endoribonucleolytic decay pathway with the help of HRSP12 and RNase P/MRP complexes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn hematologic malignancies, YTHDF2 plays a pivotal role in acute myeloid leukemia (AML) by being overexpressed and required for both disease initiation and propagation; by accelerating the decay of various m⁶A‐modified transcripts (e.g. those involved in leukemic stem cell function), its activity can influence cell survival and differentiation. In liver cancer, context‐dependent roles have been reported: on one hand, YTHDF2 can destabilize transcripts such as the EGFR mRNA to suppress hepatocellular carcinoma (HCC) proliferation, while in other settings, it modulates m⁶A levels in the 5′‐UTR of OCT4 mRNA thereby promoting a cancer stem cell phenotype and metastasis. Moreover, microRNA‐mediated regulation (e.g. via miR‑145) has been implicated in controlling YTHDF2 levels in HCC."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond liver and blood cancers, YTHDF2 has emerged as a key regulator in several solid tumors. In glioblastoma, its expression is upregulated via the EGFR/SRC/ERK pathway, with phosphorylation events enhancing its stability and facilitating m⁶A‐mediated decay of mRNAs involved in cholesterol homeostasis. In prostate and pancreatic cancers, YTHDF2 contributes to tumor cell proliferation—with pancreatic cancer studies highlighting its role in orchestrating migration–proliferation dichotomy and epithelial–mesenchymal transition via pathways including YAP signaling. In breast cancer models, particularly in MYC‐driven triple‑negative subtypes, YTHDF2 loss leads to accumulation of MAPK pathway transcripts and triggers apoptosis. Similar oncogenic functions have been reported in multiple myeloma, where YTHDF2 promotes growth by targeting STAT5A mRNA, and in urothelial bladder carcinoma, where it degrades DDX58 (encoding RIG‑I) to facilitate immune evasion. In lung adenocarcinoma, aberrant YTHDF2 activity (including m⁶A‑modified circular RNA cleavage, as seen with circASK1) has been linked to drug resistance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nYTHDF2 is also central to the regulation of cellular identity and development. It is highly expressed in induced pluripotent stem cells (iPSCs), where it helps clear lineage‑specific transcripts to maintain pluripotency; during reprogramming, a cooperative action of YTHDF2 (and its paralog YTHDF3) ensures the degradation of somatic mRNAs, thereby facilitating acquisition of a pluripotent state."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to modulating differentiation, YTHDF2 influences the cell cycle and immune microenvironments. It promotes cell cycle progression by targeting m⁶A‐modified transcripts such as WEE1, an inhibitor of mitotic entry, thereby forming a feedforward loop with cyclin‑dependent kinase 1. In t(8;21) AML, YTHDF2 functions downstream of an AML1/ETO–HIF1α regulatory circuit to control the decay of transcripts (e.g. TNFRSF1b) pivotal for leukemic proliferation. Moreover, in the context of radiotherapy, YTHDF2 induction in myeloid cells contributes to immunosuppressive myeloid-derived suppressor cell expansion through an NF‑κB feedback loop."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "20", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPost-transcriptional and post-translational regulation further modulate YTHDF2 activity. Its interaction with microRNAs (for example, in colorectal cancer where m⁶A modifications on target transcripts such as YPEL5 require YTHDF2 for decay) and its regulation by post-translational modifications such as SUMOylation and O‑GlcNAcylation (which enhance its binding affinity and stability, respectively) fine-tune its function in cancer cells. Altered YTHDF2 expression has also been noted in non‐oncologic pathology; reduced YTHDF2 levels in autoimmune contexts such as systemic lupus erythematosus have been associated with deleterious immunological features, and genetic variations in YTHDF2 have been linked to human longevity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "27"}, {"type": "fg_f", "ref": "23"}, {"type": "fg_fs", "start_ref": "28", "end_ref": "30"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xiao Wang, Zhike Lu, Adrian Gomez, et al. 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Synonyms	HGRG8, NY-REN-2, CAHL
Proteins	YTHD2_HUMAN
NCBI Gene ID	51441
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

YTHDF2 has 8,040 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 110 datasets.

Click the + buttons to view associations for YTHDF2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

YTHDF2 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of YTHDF2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of YTHDF2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of YTHDF2 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of YTHDF2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of YTHDF2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of YTHDF2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of YTHDF2 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of YTHDF2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of YTHDF2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of YTHDF2 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of YTHDF2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with YTHDF2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with YTHDF2 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of YTHDF2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of YTHDF2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of YTHDF2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of YTHDF2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing YTHDF2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing YTHDF2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with YTHDF2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with YTHDF2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with YTHDF2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with YTHDF2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with YTHDF2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by YTHDF2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with YTHDF2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with YTHDF2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with YTHDF2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with YTHDF2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with YTHDF2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at YTHDF2 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of YTHDF2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of YTHDF2 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing YTHDF2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of YTHDF2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with YTHDF2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing YTHDF2 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of YTHDF2 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of YTHDF2 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Kinase Perturbations	kinase perturbations changing expression of YTHDF2 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.