YTHDF1

Summary

YTHDF1 (YTH N6-methyladenosine RNA binding protein F1, HGNC:15867) is a protein-coding gene on chromosome 20q13.33, encoding YTH domain-containing family protein 1 (Q9BYJ9). Specifically recognizes and binds N6-methyladenosine (m6A)-containing mRNAs, and regulates their stability.

Enables N6-methyladenosine-containing RNA reader activity and ribosome binding activity. Involved in mRNA destabilization; positive regulation of translational initiation; and stress granule assembly. Located in P-body and cytoplasmic stress granule. Implicated in colorectal cancer.

Source: NCBI Gene 54915 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 90 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_017798

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15867
Approved symbol	YTHDF1
Name	YTH N6-methyladenosine RNA binding protein F1
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20391
Ensembl gene	ENSG00000149658
Ensembl biotype	protein_coding
OMIM	616529
Entrez	54915

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000370334, ENST00000370339, ENST00000960125

RefSeq mRNA: 1 — MANE Select: NM_017798 NM_017798

CCDS: CCDS13511

Canonical transcript exons

ENST00000370339 — 5 exons

Exon	Start	End
ENSE00001044223	63195429	63196734
ENSE00001174126	63213864	63213943
ENSE00001316509	63215577	63215601
ENSE00001868463	63215866	63216131
ENSE00003570097	63202287	63203807

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.3494 / max 221.2218, expressed in 1821 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188326	43.3059	1819
188327	1.0234	447
188324	0.5203	267
188325	0.4996	248

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.41	gold quality
oocyte	CL:0000023	97.76	gold quality
tendon of biceps brachii	UBERON:0008188	96.82	gold quality
middle temporal gyrus	UBERON:0002771	96.19	gold quality
medial globus pallidus	UBERON:0002477	96.10	gold quality
esophagus squamous epithelium	UBERON:0006920	95.98	gold quality
cerebellar vermis	UBERON:0004720	95.95	gold quality
globus pallidus	UBERON:0001875	95.29	gold quality
tibia	UBERON:0000979	94.69	gold quality
epithelial cell of pancreas	CL:0000083	94.51	gold quality
tibialis anterior	UBERON:0001385	94.33	gold quality
epithelium of esophagus	UBERON:0001976	94.17	gold quality
type B pancreatic cell	CL:0000169	93.96	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.95	gold quality
buccal mucosa cell	CL:0002336	93.87	gold quality
thymus	UBERON:0002370	93.87	gold quality
nipple	UBERON:0002030	93.86	gold quality
pancreatic ductal cell	CL:0002079	93.74	gold quality
deltoid	UBERON:0001476	93.74	gold quality
body of tongue	UBERON:0011876	93.46	gold quality
squamous epithelium	UBERON:0006914	93.43	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	93.29	gold quality
quadriceps femoris	UBERON:0001377	93.28	gold quality
vastus lateralis	UBERON:0001379	93.21	gold quality
trachea	UBERON:0003126	93.19	gold quality
adult organism	UBERON:0007023	93.14	gold quality
visceral pleura	UBERON:0002401	93.09	gold quality
pleura	UBERON:0000977	93.08	gold quality
parietal pleura	UBERON:0002400	92.99	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.86	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

117 targeting YTHDF1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-374A-5P	99.90	71.34	2923

Literature-anchored findings (GeneRIF, showing 40)

• binding affinities of the YTH domains of three human proteins and yeast YTH domain protein Pho92 (PMID:26318451)
• The authors found that the overexpression of YTHDF proteins in cells inhibited HIV-1 infection mainly by decreasing HIV-1 reverse transcription, while knockdown of YTHDF1-3 in cells had the opposite effects. Moreover, silencing the N(6)-methyladenosine writers decreased HIV-1 Gag protein expression in virus-producing cells, while silencing the N(6)-methyladenosine erasers increased Gag expression. (PMID:27371828)
• YTHDF1 played an important role in regulating hepatocellular carcinoma cell cycle progression and metabolism (PMID:29439311)
• Anti-tumour immunity controlled through mRNA m(6)A methylation and YTHDF1 in dendritic cells (PMID:30728504)
• Findings highlight the critical role of YTHDF1 in both hypoxia adaptation and pathogenesis of non-small cell lung cancer. (PMID:31653849)
• YTHDF1 augments the translation of EIF3C in an m6A-dependent manner by binding to m6A-modified EIF3C mRNA and concomitantly promotes the overall translational output, thereby facilitating tumorigenesis and metastasis of ovarian cancer. (PMID:31996915)
• Prognostic values of YTHDF1 regulated negatively by mir-3436 in Glioma. (PMID:32449290)
• m(6)A-binding YTHDF proteins promote stress granule formation. (PMID:32451507)
• YTHDF1 Promotes Gastric Carcinogenesis by Controlling Translation of FZD7. (PMID:32788173)
• m6A-YTHDF1-mediated TRIM29 upregulation facilitates the stem cell-like phenotype of cisplatin-resistant ovarian cancer cells. (PMID:33011193)
• N(6)-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1/HK2 modification. (PMID:33099572)
• YTHDF1-enhanced iron metabolism depends on TFRC m(6)A methylation. (PMID:33204330)
• Loading MicroRNA-376c in Extracellular Vesicles Inhibits Properties of Non-Small Cell Lung Cancer Cells by Targeting YTHDF1. (PMID:33280517)
• ALKBH5 regulates cardiomyocyte proliferation and heart regeneration by demethylating the mRNA of YTHDF1. (PMID:33456585)
• HIF-1alpha-induced expression of m6A reader YTHDF1 drives hypoxia-induced autophagy and malignancy of hepatocellular carcinoma by promoting ATG2A and ATG14 translation. (PMID:33619246)
• YTHDF1 promotes NLRP3 translation to induce intestinal epithelial cell inflammatory injury during endotoxic shock. (PMID:33825148)
• YTHDF1-regulated expression of TEAD1 contributes to the maintenance of intestinal stem cells. (PMID:33862464)
• The N6-methyladenosine RNA-binding protein YTHDF1 modulates the translation of TRAF6 to mediate the intestinal immune response. (PMID:33999206)
• Impact of YTHDF1 gene polymorphisms on Wilms tumor susceptibility: A five-center case-control study. (PMID:34151473)
• YTHDF1 Promotes Cyclin B1 Translation through m(6)A Modulation and Contributes to the Poor Prognosis of Lung Adenocarcinoma with KRAS/TP53 Co-Mutation. (PMID:34359836)
• YTHDF1 and YTHDF2 are associated with better patient survival and an inflamed tumor-immune microenvironment in non-small-cell lung cancer. (PMID:34408926)
• Comprehensive Analysis of YTH Domain Family in Lung Adenocarcinoma: Expression Profile, Association with Prognostic Value, and Immune Infiltration. (PMID:34497675)
• YTHDF1 promotes the proliferation, migration, and invasion of prostate cancer cells by regulating TRIM44. (PMID:34677810)
• YTHDF1 promotes mRNA degradation via YTHDF1-AGO2 interaction and phase separation. (PMID:34821414)
• N6-Methyladenosine Reader YTHDF1 Promotes ARHGEF2 Translation and RhoA Signaling in Colorectal Cancer. (PMID:34968454)
• Involvement of YTHDF1 in renal fibrosis progression via up-regulating YAP. (PMID:34990050)
• Methylation recognition protein YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) regulates the proliferation, migration and invasion of osteosarcoma by regulating m6A level of CCR4-NOT transcription complex subunit 7 (CNOT7). (PMID:35156522)
• YTHDF1 promotes intrahepatic cholangiocarcinoma progression via regulating EGFR mRNA translation. (PMID:35233828)
• YTHDF1 promotes breast cancer cell growth, DNA damage repair and chemoresistance. (PMID:35279688)
• YTHDF1 amplification is correlated with worse outcome and lower immune cell infiltrations in breast cancer. (PMID:35342079)
• Infralimbic YTHDF1 is necessary for the beneficial effects of acute mild exercise on auditory fear extinction retention. (PMID:35511705)
• Mettl3 regulates hypertrophic differentiation of chondrocytes through modulating Dmp1 mRNA via Ythdf1-mediated m(6)A modification. (PMID:35981698)
• METTL3 promotes non-small cell lung cancer (NSCLC) cell proliferation and colony formation in a m6A-YTHDF1 dependent way. (PMID:36008805)
• METTL3 promotes m6A hypermethylation of RBM14 via YTHDF1 leading to the progression of hepatocellular carcinoma. (PMID:36087219)
• N(6)-Methyladenine Modification of Hepatitis Delta Virus Regulates Its Virion Assembly by Recruiting YTHDF1. (PMID:36102650)
• YTHDF1 regulates endoplasmic reticulum stress, NF-kappaB, MAPK and PI3K-AKT signaling pathways in inflammatory osteoclastogenesis. (PMID:36368367)
• The RNA m6A Reader YTHDF1 Is Required for Acute Myeloid Leukemia Progression. (PMID:36634204)
• The mechanism underlying redundant functions of the YTHDF proteins. (PMID:36694229)
• Inhibition of YTHDF1 prevents hypoxia-induced pulmonary artery smooth muscle cell proliferation by regulating Foxm1 translation in an m6A-dependent manner. (PMID:36736607)
• A novel MYCN-YTHDF1 cascade contributes to retinoblastoma tumor growth by eliciting m[6]A -dependent activation of multiple oncogenes. (PMID:36949231)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ythdf1	ENSDARG00000016447
mus_musculus	Ythdf1	ENSMUSG00000038848
rattus_norvegicus	Ythdf1	ENSRNOG00000027015
drosophila_melanogaster	Ythdf	FBGN0039261

Paralogs (3): YTHDC1 (ENSG00000083896), YTHDF3 (ENSG00000185728), YTHDF2 (ENSG00000198492)

Protein

Protein identifiers

YTH domain-containing family protein 1 — Q9BYJ9 (reviewed: Q9BYJ9)

Alternative names: Dermatomyositis associated with cancer putative autoantigen 1

All UniProt accessions (2): Q9BYJ9, Q5JXC6

UniProt curated annotations — full annotation on UniProt →

Function. Specifically recognizes and binds N6-methyladenosine (m6A)-containing mRNAs, and regulates their stability. M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in mRNA stability and processing. Acts as a regulator of mRNA stability by promoting degradation of m6A-containing mRNAs via interaction with the CCR4-NOT complex. The YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3) shares m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation. Required to facilitate learning and memory formation in the hippocampus by binding to m6A-containing neuronal mRNAs. Acts as a regulator of axon guidance by binding to m6A-containing ROBO3 transcripts. Acts as a negative regulator of antigen cross-presentation in myeloid dendritic cells. In the context of tumorigenesis, negative regulation of antigen cross-presentation limits the anti-tumor response by reducing efficiency of tumor-antigen cross-presentation. Promotes formation of phase-separated membraneless compartments, such as P-bodies or stress granules, by undergoing liquid-liquid phase separation upon binding to mRNAs containing multiple m6A-modified residues: polymethylated mRNAs act as a multivalent scaffold for the binding of YTHDF proteins, juxtaposing their disordered regions and thereby leading to phase separation. The resulting mRNA-YTHDF complexes then partition into different endogenous phase-separated membraneless compartments, such as P-bodies, stress granules or neuronal RNA granules.

Subunit / interactions. Interacts with CNOT1; promoting recruitment of the CCR4-NOT complex. Interacts with ribosomes. Interacts with eIF3 (EIF3A or EIF3B). Interacts with YTHDF3.

Subcellular location. Cytoplasm. P-body. Stress granule.

Post-translational modifications. Ubiquitinated by the CUL7-FBXW8 E3 ligase complex leading to degradation. Deubiquitinated and stabilized by USP5 by removing ‘Lys-11’-linked polyubiquitination.

Domain organisation. The disordered regions have the ability to interact with each other and to ‘phase separate’ into liquid droplets within the cytosol following binding to mRNAs containing multiple m6A-modified residues. This leads to the partition of m6A-containing mRNAs into membraneless compartments, where mRNAs may be stored, degraded or used to transport mRNAs to dendritic arbors in neurons.

Similarity. Belongs to the YTHDF family. YTHDF1 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BYJ9-1	1	yes
Q9BYJ9-2	2

RefSeq proteins (1): NP_060268* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007275	YTH_domain	Domain
IPR045168	YTH_prot	Family

Pfam: PF04146

UniProt features (45 total): helix 9, strand 7, binding site 6, mutagenesis site 6, compositionally biased region 4, splice variant 3, modified residue 2, sequence conflict 2, region of interest 2, initiator methionine 1, chain 1, domain 1, turn 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
4RCJ	X-RAY DIFFRACTION	1.6
4RCI	X-RAY DIFFRACTION	1.97
7YYE	X-RAY DIFFRACTION	2
7YYJ	X-RAY DIFFRACTION	2.1
8BS4	X-RAY DIFFRACTION	2.1
7QKN	X-RAY DIFFRACTION	2.15
7QL7	X-RAY DIFFRACTION	2.3
7YYF	X-RAY DIFFRACTION	2.3
7YZ8	X-RAY DIFFRACTION	2.5
7PCU	X-RAY DIFFRACTION	2.65

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYJ9-F1	62.83	0.32

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (6): 401; 411–412; 441; 465; 470; 395–397

Post-translational modifications (2): 2, 182

Mutagenesis-validated functional residues (6):

Position	Phenotype
397	strongly reduced binding to n6-methyladenosine (m6a)-containing rnas.
401	increased binding to n6-methyladenosine (m6a)-containing rnas.
411	abolished binding to n6-methyladenosine (m6a)-containing rnas.
465	abolished binding to n6-methyladenosine (m6a)-containing rnas.
470	abolished binding to n6-methyladenosine (m6a)-containing rnas.
506	reduced binding to n6-methyladenosine (m6a)-containing rnas.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 196 (showing top): GOBP_MEMORY, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_TRANSLATIONAL_INITIATION, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_AXON_GUIDANCE, GOBP_CELL_CELL_SIGNALING, GOBP_TRANSLATION, GOBP_POSITIVE_REGULATION_OF_TRANSLATIONAL_INITIATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_TAXIS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_REGULATION_OF_SYNAPTIC_PLASTICITY

GO Biological Process (12): immune system process (GO:0002376), regulation of antigen processing and presentation (GO:0002577), learning (GO:0007612), memory (GO:0007613), stress granule assembly (GO:0034063), regulation of mRNA stability (GO:0043488), positive regulation of translation (GO:0045727), positive regulation of translational initiation (GO:0045948), mRNA destabilization (GO:0061157), organelle assembly (GO:0070925), regulation of long-term synaptic potentiation (GO:1900271), regulation of axon guidance (GO:1902667)

GO Molecular Function (5): RNA binding (GO:0003723), mRNA binding (GO:0003729), ribosome binding (GO:0043022), N6-methyladenosine-containing RNA reader activity (GO:1990247), protein binding (GO:0005515)

GO Cellular Component (3): P-body (GO:0000932), cytoplasm (GO:0005737), cytoplasmic stress granule (GO:0010494)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
learning or memory	2
RNA binding	2
cytoplasmic ribonucleoprotein granule	2
biological_process	1
regulation of immune system process	1
antigen processing and presentation	1
membraneless organelle assembly	1
regulation of RNA stability	1
regulation of mRNA catabolic process	1
translation	1
regulation of translation	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
translational initiation	1
regulation of translational initiation	1
positive regulation of translation	1
negative regulation of gene expression	1
regulation of mRNA stability	1
RNA destabilization	1
positive regulation of mRNA catabolic process	1
organelle organization	1
cellular component assembly	1
regulation of synaptic plasticity	1
long-term synaptic potentiation	1
axon guidance	1
regulation of neuron projection development	1
regulation of chemotaxis	1
nucleic acid binding	1
ribonucleoprotein complex binding	1
protein-RNA adaptor activity	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1872 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
YTHDF1	EEF2	P13639	966
YTHDF1	ALKBH5	Q6P6C2	954
YTHDF1	METTL14	Q9HCE5	950
YTHDF1	HNRNPC	P07910	941
YTHDF1	METTL3	Q86U44	939
YTHDF1	IGF2BP1	Q9NZI8	932
YTHDF1	EIF3B	P55884	928
YTHDF1	HNRNPA2B1	P22626	922
YTHDF1	WTAP	Q15007	922
YTHDF1	YTHDF3	Q7Z739	921
YTHDF1	YTHDC1	Q96MU7	912
YTHDF1	IGF2BP3	O00425	906
YTHDF1	FTO	Q9C0B1	897
YTHDF1	VIRMA	Q69YN4	896
YTHDF1	ZC3H13	Q5T200	885

IntAct

207 interactions, top by confidence:

A	B	Type	Score
CEP97	CCP110	psi-mi:“MI:2364”(proximity)	0.950
YTHDF3	YTHDF1	psi-mi:“MI:0915”(physical association)	0.720
YTHDF1	YTHDF3	psi-mi:“MI:0914”(association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
TNFSF14	TMEM11	psi-mi:“MI:0914”(association)	0.670
ZNF76	FHL2	psi-mi:“MI:0914”(association)	0.670
FAM136A	RBFOX3	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
YTHDF1	FAM168A	psi-mi:“MI:0915”(physical association)	0.560
YTHDF1	KRTAP8-1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP26-1	YTHDF1	psi-mi:“MI:0915”(physical association)	0.560
YTHDF1	HSF4	psi-mi:“MI:0915”(physical association)	0.560
PRR32	YTHDF1	psi-mi:“MI:0915”(physical association)	0.560
YTHDF1	MAGED1	psi-mi:“MI:0915”(physical association)	0.560
	YTHDF1	psi-mi:“MI:0915”(physical association)	0.560
TLE5	YTHDF1	psi-mi:“MI:0915”(physical association)	0.560
BATF2	YTHDF1	psi-mi:“MI:0915”(physical association)	0.560
ABHD11	YTHDF1	psi-mi:“MI:0915”(physical association)	0.560
MSX2	YTHDF1	psi-mi:“MI:0915”(physical association)	0.560
OIP5	YTHDF1	psi-mi:“MI:0915”(physical association)	0.560
C6orf15	YTHDF1	psi-mi:“MI:0915”(physical association)	0.560
VPS37C	YTHDF1	psi-mi:“MI:0915”(physical association)	0.560
YTHDF1	HEY1	psi-mi:“MI:0915”(physical association)	0.560
LASP1	YTHDF1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (598): YTHDF1 (Affinity Capture-RNA), YTHDF1 (Affinity Capture-MS), YTHDF1 (Affinity Capture-MS), YTHDF1 (Affinity Capture-MS), YTHDF1 (Affinity Capture-MS), YTHDF1 (Affinity Capture-MS), YTHDF1 (Affinity Capture-MS), YTHDF1 (Affinity Capture-MS), YTHDF1 (Affinity Capture-MS), YTHDF1 (Affinity Capture-MS), YTHDF1 (Affinity Capture-MS), YTHDF1 (Affinity Capture-MS), YTHDF1 (Affinity Capture-MS), YTHDF1 (Affinity Capture-MS), YTHDF1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0A2J9B3, A0A0K0QSV4, A0A9P4XWM4, A1CT57, A1DMG9, A7E8B6, A8JPF9, A8NYG2, A9LNK9, E5AD52, E7F1H9, G4MRQ6, G4NF05, M2SQ20, N1PJ97, O42632, P0C5H8, P0DPB0, P38093, P59326, P87253, Q05534, Q0U086, Q15459, Q1K6U0, Q2UNX4, Q2UPS5, Q4R1B9, Q4WN42, Q4WVG0, Q4WXX4, Q4X228, Q5B3I8, Q5RFL8, Q6DDU9, Q6L612, Q7RZQ3, Q7Z739, Q8BYK6, Q8K4Z5

Diamond homologs: A0A1P8AS03, E7F1H9, E9Q5K9, F4K1Z0, G4MRQ6, P59326, Q06390, Q0VCZ3, Q3MK94, Q4R5D9, Q5RFL8, Q7Z739, Q8BYK6, Q91YT7, Q96MU7, Q9BYJ9, Q9LJE5, Q9QY02, Q9VBZ5, Q9VZQ1, Q9Y5A9, A0A9P4XWM4, A9LNK9, B2RR83, Q5R746, Q9H6S0, A3KMI0, B4LX81, D4A2Z8, F4HYJ7, F4I9Q5, F4IDQ6, F4ILR7, F4IM84, F4INY4, O17438, O22243, O70133, P0C7L7, P24785

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 221 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SARS-CoV-1 modulates host translation machinery	7	15.7×	1e-04
Eukaryotic Translation Initiation	6	13.4×	2e-04
Cap-dependent Translation Initiation	6	13.4×	2e-04
Eukaryotic Translation Elongation	6	12.1×	3e-04
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	6	11.8×	3e-04
Influenza Viral RNA Transcription and Replication	7	10.9×	2e-04
SARS-CoV-1-host interactions	8	10.2×	2e-04
Nonsense-Mediated Decay (NMD)	6	10.1×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	10	9.4×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

90 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	75
Likely benign	5
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

800 predictions. Top by Δscore:

Variant	Effect	Δscore
20:63213859:CTCA:C	donor_loss	1.0000
20:63213860:TCACC:T	donor_loss	1.0000
20:63213861:CA:C	donor_loss	1.0000
20:63213862:A:AC	donor_gain	1.0000
20:63213862:A:T	donor_loss	1.0000
20:63213863:C:CC	donor_gain	1.0000
20:63213863:C:CG	donor_loss	1.0000
20:63213863:CCTG:C	donor_gain	1.0000
20:63213939:TTGTA:T	acceptor_gain	1.0000
20:63213940:TGTA:T	acceptor_gain	1.0000
20:63213941:GTA:G	acceptor_gain	1.0000
20:63213942:TA:T	acceptor_gain	1.0000
20:63213943:AC:A	acceptor_loss	1.0000
20:63213944:C:CC	acceptor_gain	1.0000
20:63213944:C:CG	acceptor_loss	1.0000
20:63215641:C:CT	acceptor_gain	1.0000
20:63215641:C:T	acceptor_gain	1.0000
20:63215642:G:T	acceptor_gain	1.0000
20:63196733:TCC:T	acceptor_loss	0.9900
20:63196734:CCTGT:C	acceptor_loss	0.9900
20:63196735:C:CA	acceptor_loss	0.9900
20:63196736:T:A	acceptor_loss	0.9900
20:63202300:T:TA	donor_gain	0.9900
20:63203806:CT:C	acceptor_gain	0.9900
20:63213863:CCT:C	donor_gain	0.9900
20:63213950:C:CT	acceptor_gain	0.9900
20:63213951:A:T	acceptor_gain	0.9900
20:63215573:TCACC:T	donor_loss	0.9900
20:63215574:CACC:C	donor_loss	0.9900
20:63215575:ACC:A	donor_loss	0.9900

AlphaMissense

3728 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:63202325:A:C	Y539D	1.000
20:63202325:A:G	Y539H	1.000
20:63202332:A:C	F536L	1.000
20:63202332:A:T	F536L	1.000
20:63202333:A:G	F536S	1.000
20:63202334:A:G	F536L	1.000
20:63202336:T:A	D535V	1.000
20:63202336:T:C	D535G	1.000
20:63202336:T:G	D535A	1.000
20:63202345:A:T	I532N	1.000
20:63202349:A:G	S531P	1.000
20:63202408:A:T	V511E	1.000
20:63202414:T:G	Q509P	1.000
20:63202419:G:C	D507E	1.000
20:63202419:G:T	D507E	1.000
20:63202420:T:A	D507V	1.000
20:63202420:T:C	D507G	1.000
20:63202420:T:G	D507A	1.000
20:63202421:C:A	D507Y	1.000
20:63202421:C:G	D507H	1.000
20:63202421:C:T	D507N	1.000
20:63202423:C:A	R506L	1.000
20:63202423:C:G	R506P	1.000
20:63202424:G:C	R506G	1.000
20:63202426:G:A	S505F	1.000
20:63202426:G:T	S505Y	1.000
20:63202427:A:G	S505P	1.000
20:63202432:G:T	T503K	1.000
20:63202435:A:T	V502D	1.000
20:63202440:T:A	K500N	1.000

dbSNP variants (sampled 300 via entrez): RS1000055964 (20:63212007 A>T), RS1000129100 (20:63213061 T>A,C), RS1000232959 (20:63217792 T>C), RS1000487122 (20:63194986 T>C), RS1000570267 (20:63216527 G>A,C,T), RS1000580107 (20:63216350 T>C), RS1000832221 (20:63196324 C>T), RS1000897521 (20:63215479 G>A,T), RS1001010858 (20:63209764 T>A,C), RS1001032235 (20:63201705 A>T), RS1001033824 (20:63216142 A>G,T), RS1001096543 (20:63195989 C>T), RS1001276658 (20:63204151 C>A,T), RS1001504226 (20:63210018 C>T), RS1001702089 (20:63211917 C>A)

Disease associations

OMIM: gene MIM:616529 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002345_14	Response to cytadine analogues (cytosine arabinoside)	2.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5169192 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 13,237 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL51085	EBSELEN	3	13,237

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

1 potent at pChembl≥5 of 3 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.44	IC50	3600	nM	EBSELEN

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-phenyl-1,2-benzoselenazol-3-one	2119520: Inhibition of YTHDF1 (unknown origin) by AlphaScreen assay	ic50	3.6000	uM

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects reaction, increases activity, increases phosphorylation, affects binding, increases reaction (+1 more)	3
bisphenol A	affects expression, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	increases expression	1
ethylbenzene	affects cotreatment, decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance	1
potassium chromate(VI)	affects cotreatment, increases expression	1
coumarin	decreases phosphorylation	1
cadmium sulfate	increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
fumonisin B1	increases expression	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Arsenic	increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Dactinomycin	affects reaction, decreases stability	1
Diethylhexyl Phthalate	decreases methylation, increases abundance	1
Hydralazine	affects cotreatment, increases expression	1
Plant Oils	increases expression	1
Ribonucleotides	affects binding	1
Rotenone	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Toluene	affects cotreatment, decreases expression	1
Urethane	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5149948	Binding	Binding affinity to GST-tagged YTHDF1 m6A-reader domain (unknown origin) using RRACH-containing methylated oligoRNA incubated for 3 hrs by HTRF assay	Fragment Ligands of the m6A-RNA Reader YTHDF2. — ACS Med Chem Lett

Cellosaurus cell lines

7 cell lines: 7 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B5L7	HAP1 YTHDF1 (-) 2	Cancer cell line	Male
CVCL_B5L8	HAP1 YTHDF1 (-) 3	Cancer cell line	Male
CVCL_B8AI	Abcam Raji YTHDF1 KO	Cancer cell line	Male
CVCL_C0BD	Abcam THP-1 YTHDF1 KO	Cancer cell line	Male
CVCL_C7D0	Abcam PC-3 YTHDF1 KO	Cancer cell line	Male
CVCL_D8DG	Ubigene A-549 YTHDF1 KO	Cancer cell line	Male
CVCL_XV19	HAP1 YTHDF1 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.