YTHDF3

Summary

YTHDF3 (YTH N6-methyladenosine RNA binding protein F3, HGNC:26465) is a protein-coding gene on chromosome 8q12.3, encoding YTH domain-containing family protein 3 (Q7Z739). Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, and regulates their stability.

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.

Source: NCBI Gene 253943 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 13 total — 1 likely-pathogenic
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_152758

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26465
Approved symbol	YTHDF3
Name	YTH N6-methyladenosine RNA binding protein F3
Location	8q12.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ31657
Ensembl gene	ENSG00000185728
Ensembl biotype	protein_coding
OMIM	618669
Entrez	253943

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 13 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000517371, ENST00000518373, ENST00000519428, ENST00000522282, ENST00000539294, ENST00000612880, ENST00000613853, ENST00000615676, ENST00000617200, ENST00000617952, ENST00000619337, ENST00000621413, ENST00000621820, ENST00000621890, ENST00000621957, ENST00000623280, ENST00000934586

RefSeq mRNA: 7 — MANE Select: NM_152758 NM_001277813, NM_001277814, NM_001277815, NM_001277816, NM_001277817, NM_001277818, NM_152758

CCDS: CCDS75747, CCDS75748, CCDS75749

Canonical transcript exons

ENST00000539294 — 5 exons

Exon	Start	End
ENSE00001389273	63186147	63187745
ENSE00002305093	63209683	63212786
ENSE00003570601	63168621	63168901
ENSE00003578391	63169387	63169411
ENSE00003665304	63175331	63175416

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 98.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 49.8819 / max 684.8592, expressed in 1823 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89103	45.4949	1823
89102	1.5363	1052
89106	0.9515	555
89107	0.7834	401
89104	0.3816	135
89101	0.2390	65
89109	0.2245	46
89105	0.1549	44
89108	0.1157	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	98.91	gold quality
germinal epithelium of ovary	UBERON:0001304	98.58	gold quality
choroid plexus epithelium	UBERON:0003911	98.56	gold quality
tibia	UBERON:0000979	97.74	gold quality
parietal pleura	UBERON:0002400	97.48	gold quality
superficial temporal artery	UBERON:0001614	97.47	gold quality
visceral pleura	UBERON:0002401	97.36	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.36	gold quality
pleura	UBERON:0000977	97.16	gold quality
biceps brachii	UBERON:0001507	97.07	gold quality
epithelium of nasopharynx	UBERON:0001951	97.06	gold quality
palpebral conjunctiva	UBERON:0001812	96.95	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.95	gold quality
cauda epididymis	UBERON:0004360	96.81	gold quality
heart right ventricle	UBERON:0002080	96.77	gold quality
jejunum	UBERON:0002115	96.65	gold quality
gingival epithelium	UBERON:0001949	96.57	gold quality
jejunal mucosa	UBERON:0000399	96.52	gold quality
skin of hip	UBERON:0001554	96.43	gold quality
esophagus squamous epithelium	UBERON:0006920	96.32	gold quality
mammary duct	UBERON:0001765	96.24	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.15	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.10	gold quality
blood vessel layer	UBERON:0004797	96.09	gold quality
gingiva	UBERON:0001828	95.95	gold quality
upper leg skin	UBERON:0004262	95.93	gold quality
epithelium of mammary gland	UBERON:0003244	95.90	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.90	gold quality
penis	UBERON:0000989	95.88	gold quality
colonic mucosa	UBERON:0000317	95.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP63

miRNA regulators (miRDB)

283 targeting YTHDF3, 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-3646	100.00	73.56	5283
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 23)

• Includes a multi-species analysis of YTHDF family members. (PMID:20463905)
• 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)
• These results indicate that together with YTHDF1 and YTHDF2, YTHDF3 plays critical roles to accelerate metabolism of N(6)-methyladenosine -modified mRNAs in the cytoplasm. (PMID:28106072)
• Abundance of N-6-methyladenosine and expression of VIRMA/YTHDF3 were different among testicular germ cell tumors subtypes, with higher levels in seminomas (SEs), suggesting a contribution to SE phenotype maintenance. (PMID:30866959)
• m(6)A-binding YTHDF proteins promote stress granule formation. (PMID:32451507)
• YTHDF2/3 Are Required for Somatic Reprogramming through Different RNA Deadenylation Pathways. (PMID:32905781)
• YTHDF3 Induces the Translation of m(6)A-Enriched Gene Transcripts to Promote Breast Cancer Brain Metastasis. (PMID:33125861)
• Enterovirus 2A(pro) Cleavage of the YTHDF m(6)A Readers Implicates YTHDF3 as a Mediator of Type I Interferon-Driven JAK/STAT Signaling. (PMID:33849973)
• Development and validation of m6A regulators’ prognostic significance for endometrial cancer. (PMID:34190193)
• Comprehensive Analysis of YTH Domain Family in Lung Adenocarcinoma: Expression Profile, Association with Prognostic Value, and Immune Infiltration. (PMID:34497675)
• Mono-allelic loss of YTHDF3 and neurodevelopmental disorder: clinical features of four individuals with 8q12.3 deletions. (PMID:34708403)
• N6-methyladenosine reader YTH N6-methyladenosine RNA binding protein 3 or insulin like growth factor 2 mRNA binding protein 2 knockdown protects human bronchial epithelial cells from hypoxia/reoxygenation injury by inactivating p38 MAPK, AKT, ERK1/2, and NF-kappaB pathways. (PMID:34709120)
• The m[6]A reading protein YTHDF3 potentiates tumorigenicity of cancer stem-like cells in ocular melanoma through facilitating CTNNB1 translation. (PMID:35110680)
• YTHDF3 Facilitates eIF2AK2 and eIF3A Recruitment on mRNAs to Regulate Translational Processes in Oxaliplatin-Resistant Colorectal Cancer. (PMID:35708211)
• N[6]-methyladenosine reader YTHDF3 contributes to the aerobic glycolysis of osteosarcoma through stabilizing PGK1 stability. (PMID:36171455)
• YTHDF3 mediates HNF1alpha regulation of cervical cancer radio-resistance by promoting RAD51D translation in an m6A-dependent manner. (PMID:36380687)
• m[6]A reader YTHDF3 is associated with clinical prognosis, related RNA signatures and immunosuppression in gastric cancer. (PMID:37149073)
• m[6] A reader YTHDF3 triggers the progression of hepatocellular carcinoma through the YTHDF3/m[6] A-EGFR/STAT3 axis and EMT. (PMID:37449789)
• YTHDF3 Modulates EGFR/ATK/ERK/p21 Signaling Axis to Promote Cancer Progression and Osimertinib Resistance of Glioblastoma Cells. (PMID:38030188)
• The inhibition of YTHDF3/m[6]A/LRP6 reprograms fatty acid metabolism and suppresses lymph node metastasis in cervical cancer. (PMID:38250152)
• ZDHHC20-mediated S-palmitoylation of YTHDF3 stabilizes MYC mRNA to promote pancreatic cancer progression. (PMID:38821916)
• Knockdown of YAP1 Reduces YTHDF3 to Stabilize SMAD7 and thus Inhibit Bladder Cancer Stem Cell Stemness. (PMID:39054719)
• YTHDF3 Regulates the Degradation and Stability of m6A-Enriched Transcripts to Facilitate the Progression of Castration-Resistant Prostate Cancer. (PMID:39143673)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ythdf3	ENSDARG00000057939
mus_musculus	Ythdf3	ENSMUSG00000047213
rattus_norvegicus	Ythdf3	ENSRNOG00000010084
drosophila_melanogaster	Ythdf	FBGN0039261

Paralogs (3): YTHDC1 (ENSG00000083896), YTHDF1 (ENSG00000149658), YTHDF2 (ENSG00000198492)

Protein

Protein identifiers

YTH domain-containing family protein 3 — Q7Z739 (reviewed: Q7Z739)

All UniProt accessions (10): A0A024R7W5, A0A087WU40, A0A087WU63, A0A087WWB0, A0A087WY31, A0A087X0C3, A0A087X0Q1, A0A087X0U5, Q7Z739, S4R373

UniProt curated annotations — full annotation on UniProt →

Function. Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, 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 or PAN3. The YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3) share m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation. Acts as a negative regulator of type I interferon response by down-regulating interferon-stimulated genes (ISGs) expression: acts by binding to FOXO3 mRNAs. Binds to FOXO3 mRNAs independently of METTL3-mediated m6A modification. Can also act as a regulator of mRNA stability in cooperation with YTHDF2 by binding to m6A-containing mRNA and promoting their degradation. Recognizes and binds m6A-containing circular RNAs (circRNAs); circRNAs are generated through back-splicing of pre-mRNAs, a non-canonical splicing process promoted by dsRNA structures across circularizing exons. 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. May also recognize and bind N1-methyladenosine (m1A)-containing mRNAs: inhibits trophoblast invasion by binding to m1A-methylated transcripts of IGF1R, promoting their degradation. Has some antiviral activity against HIV-1 virus: incorporated into HIV-1 particles in a nucleocapsid-dependent manner and reduces viral infectivity in the next cycle of infection. May interfere with this early step of the viral life cycle by binding to N6-methyladenosine (m6A) modified sites on the HIV-1 RNA genome.

Subunit / interactions. Interacts with CNOT1; promoting recruitment of the CCR4-NOT complex. Interacts with YTHDF1. Interacts with YTHDF2. Interacts with PAN3.

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

Post-translational modifications. (Microbial infection) Proteolytically cleaved by HIV-1 protease when incorporated into HIV-1 particles in a nucleocapsid-dependent-manner. Cleavage by HIV-1 protease probably ensures optimal infectivity of the mature virion.

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.

Induction. Following heat shock stress.

Similarity. Belongs to the YTHDF family. YTHDF3 subfamily.

RefSeq proteins (7): NP_001264742, NP_001264743, NP_001264744, NP_001264745, NP_001264746, NP_001264747, NP_689971* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007275	YTH_domain	Domain
IPR045168	YTH_prot	Family

Pfam: PF04146

UniProt features (39 total): helix 8, binding site 6, strand 6, site 3, sequence conflict 3, region of interest 3, compositionally biased region 3, modified residue 2, turn 2, initiator methionine 1, chain 1, domain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8BS6	X-RAY DIFFRACTION	1.2
8BS5	X-RAY DIFFRACTION	2.49
6ZOT	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z739-F1	61.63	0.31

Functional residue map

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

Catalytic / active sites (3): 157–158 ((microbial infection) cleavage; by hiv-1 protease); 538–539 ((microbial infection) cleavage; by hiv-1 protease); 570–571 ((microbial infection) cleavage; by hiv-1 protease)

Ligand- & substrate-binding residues (6): 428; 438–439; 468; 492; 497; 422–424

Post-translational modifications (2): 2, 23

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 299 (showing top): GGGACCA_MIR133A_MIR133B, TGGTGCT_MIR29A_MIR29B_MIR29C, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_RESPONSE_TO_PEPTIDE, AAGCCAT_MIR135A_MIR135B, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_INNATE_IMMUNE_RESPONSE, GCAAGGA_MIR502, TATTATA_MIR374, GOBP_TRANSLATIONAL_INITIATION, TGACCTY_ERR1_Q2, FOXO1_01

GO Biological Process (8): stress granule assembly (GO:0034063), regulation of mRNA stability (GO:0043488), positive regulation of translation (GO:0045727), positive regulation of translational initiation (GO:0045948), negative regulation of type I interferon-mediated signaling pathway (GO:0060339), mRNA destabilization (GO:0061157), organelle assembly (GO:0070925), regulation of trophoblast cell migration (GO:1901163)

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 (4): P-body (GO:0000932), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoplasmic stress granule (GO:0010494)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA binding	2
cytoplasmic ribonucleoprotein granule	2
cellular anatomical structure	2
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 cytokine-mediated signaling pathway	1
negative regulation of innate immune response	1
type I interferon-mediated signaling pathway	1
regulation of type I interferon-mediated signaling pathway	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 cell migration	1
trophoblast cell migration	1
nucleic acid binding	1
ribonucleoprotein complex binding	1
protein-RNA adaptor activity	1
binding	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1746 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
YTHDF3	EIF4G2	P78344	994
YTHDF3	METTL3	Q86U44	988
YTHDF3	YTHDF2	Q9Y5A9	971
YTHDF3	VIRMA	Q69YN4	924
YTHDF3	YTHDF1	Q9BYJ9	921
YTHDF3	METTL14	Q9HCE5	912
YTHDF3	WTAP	Q15007	903
YTHDF3	ALKBH5	Q6P6C2	900
YTHDF3	FTO	Q9C0B1	881
YTHDF3	HNRNPC	P07910	859
YTHDF3	HNRNPA2B1	P22626	854
YTHDF3	RBMX	P38159	854
YTHDF3	IGF2BP1	Q9NZI8	851
YTHDF3	IGF2BP3	O00425	850
YTHDF3	IGF2BP2	Q9Y6M1	848

IntAct

91 interactions, top by confidence:

A	B	Type	Score
MAPK6	HERC2	psi-mi:“MI:0914”(association)	0.840
N	EIF2AK2	psi-mi:“MI:0914”(association)	0.820
YTHDF3	YTHDF1	psi-mi:“MI:0915”(physical association)	0.720
YTHDF1	YTHDF3	psi-mi:“MI:0914”(association)	0.720
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
YTHDF3	FAF1	psi-mi:“MI:0915”(physical association)	0.560
CSF1R	EPHB2	psi-mi:“MI:0914”(association)	0.500
gag	YTHDF3	psi-mi:“MI:0915”(physical association)	0.500
KIF1C	KIF1B	psi-mi:“MI:2364”(proximity)	0.480
N	YTHDF3	psi-mi:“MI:0403”(colocalization)	0.430
RAB11A	LANCL1	psi-mi:“MI:2364”(proximity)	0.420
TGOLN2	PGRMC1	psi-mi:“MI:0914”(association)	0.420
TNFAIP3	LRRIQ3	psi-mi:“MI:0914”(association)	0.420
TNFAIP3	LRRIQ3	psi-mi:“MI:2364”(proximity)	0.420
	AGPS	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
ZDHHC17	YTHDF3	psi-mi:“MI:0915”(physical association)	0.370
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
RPL10	RPS6	psi-mi:“MI:0914”(association)	0.350
Rrbp1	PIPSL	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
PTPRO	PLXNB2	psi-mi:“MI:0914”(association)	0.350
ORF10	NUP42	psi-mi:“MI:0914”(association)	0.350
CDK7	SEC16A	psi-mi:“MI:0914”(association)	0.350

BioGRID (370): YTHDF3 (Two-hybrid), YTHDF3 (Affinity Capture-MS), YTHDF3 (Affinity Capture-MS), YTHDF3 (Proximity Label-MS), YTHDF3 (Proximity Label-MS), YTHDF3 (Proximity Label-MS), YTHDF3 (Proximity Label-MS), YTHDF3 (Affinity Capture-MS), YTHDF3 (Affinity Capture-MS), YTHDF3 (Affinity Capture-MS), YTHDF3 (Affinity Capture-MS), YTHDF3 (Affinity Capture-MS), YTHDF3 (Affinity Capture-MS), YTHDF1 (Affinity Capture-MS), YTHDF3 (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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	0
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2506105	NC_000008.10:g.(?64081111)(64125347_?)del	Likely pathogenic

SpliceAI

1256 predictions. Top by Δscore:

Variant	Effect	Δscore
8:63169361:A:AG	acceptor_gain	1.0000
8:63169361:ACC:A	acceptor_gain	1.0000
8:63169362:C:G	acceptor_gain	1.0000
8:63169363:C:A	acceptor_gain	1.0000
8:63169372:C:A	acceptor_gain	1.0000
8:63169410:AGGT:A	donor_loss	1.0000
8:63169412:G:GG	donor_gain	1.0000
8:63175329:A:AG	acceptor_gain	1.0000
8:63175330:G:GT	acceptor_gain	1.0000
8:63175416:GGTAA:G	donor_loss	1.0000
8:63175417:G:GC	donor_loss	1.0000
8:63175418:T:TC	donor_loss	1.0000
8:63209681:A:AG	acceptor_gain	1.0000
8:63209682:G:GG	acceptor_gain	1.0000
8:63209682:GGAGA:G	acceptor_gain	1.0000
8:63168812:GCT:G	donor_gain	0.9900
8:63168815:G:GG	donor_gain	0.9900
8:63169366:A:AG	acceptor_gain	0.9900
8:63169367:T:G	acceptor_gain	0.9900
8:63169377:T:A	acceptor_gain	0.9900
8:63169380:A:AG	acceptor_gain	0.9900
8:63169381:A:AG	acceptor_gain	0.9900
8:63169383:A:AG	acceptor_gain	0.9900
8:63169383:ACAG:A	acceptor_loss	0.9900
8:63169384:C:G	acceptor_gain	0.9900
8:63169385:AGAG:A	acceptor_loss	0.9900
8:63169386:G:GA	acceptor_gain	0.9900
8:63169386:GA:G	acceptor_gain	0.9900
8:63169386:GAGA:G	acceptor_gain	0.9900
8:63169386:GAGAC:G	acceptor_gain	0.9900

AlphaMissense

3877 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:63186237:T:A	W76R	1.000
8:63186237:T:C	W76R	1.000
8:63186723:T:A	W238R	1.000
8:63186723:T:C	W238R	1.000
8:63186725:G:C	W238C	1.000
8:63186725:G:T	W238C	1.000
8:63186736:C:A	A242D	1.000
8:63187204:T:C	L398P	1.000
8:63187221:T:G	Y404D	1.000
8:63187226:T:A	N405K	1.000
8:63187226:T:G	N405K	1.000
8:63187261:G:C	R417P	1.000
8:63187264:T:A	V418E	1.000
8:63187266:T:A	F419I	1.000
8:63187266:T:C	F419L	1.000
8:63187267:T:C	F419S	1.000
8:63187268:T:A	F419L	1.000
8:63187268:T:G	F419L	1.000
8:63187270:T:A	I420K	1.000
8:63187270:T:G	I420R	1.000
8:63187272:A:T	I421F	1.000
8:63187273:T:A	I421N	1.000
8:63187273:T:C	I421T	1.000
8:63187273:T:G	I421S	1.000
8:63187275:A:C	K422Q	1.000
8:63187275:A:G	K422E	1.000
8:63187276:A:C	K422T	1.000
8:63187276:A:T	K422I	1.000
8:63187277:A:C	K422N	1.000
8:63187277:A:T	K422N	1.000

dbSNP variants (sampled 300 via entrez): RS1000031766 (8:63195754 G>A), RS1000104947 (8:63195997 T>C), RS1000145216 (8:63196087 C>T), RS1000148366 (8:63206773 G>A), RS1000213374 (8:63173093 T>G), RS1000233381 (8:63184882 G>C), RS1000331056 (8:63183472 T>C), RS1000338313 (8:63189527 T>C), RS1000415196 (8:63207005 A>T), RS1000642355 (8:63173356 T>TA), RS1000721666 (8:63191284 G>A), RS1000752194 (8:63197364 T>A,G), RS1000905932 (8:63174871 C>A,G,T), RS1000941996 (8:63188472 A>G), RS1000954872 (8:63197053 C>T)

Disease associations

OMIM: gene MIM:618669 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST003471_5	Myocardial infarction	7.000000e-09
GCST006628_14	Systolic blood pressure	2.000000e-15
GCST007576_185	Chronotype	4.000000e-08
GCST008555_6	Breakfast cereal skipping frequency	4.000000e-08
GCST008556_6	Breakfast skipping	4.000000e-08
GCST008809_5	Smoking behaviour (cigarettes smoked per day)	4.000000e-09
GCST010242_437	HDL cholesterol levels	2.000000e-11
GCST010244_433	Triglyceride levels	1.000000e-09
GCST010988_298	Adult body size	2.000000e-09
GCST010989_142	Body size at age 10	2.000000e-17
GCST011769_16	Schizophrenia	2.000000e-08

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0008328	chronotype measurement
EFO:0010129	breakfast skipping measurement
EFO:0006525	cigarettes per day measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0009819	comparative body size at age 10, self-reported

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5169172 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases activity, increases expression	3
bisphenol A	decreases expression	2
Tobacco Smoke Pollution	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	decreases phosphorylation	1
2,4,6-tribromophenol	increases expression	1
uranyl acetate	affects expression	1
cadmium sulfate	increases expression	1
bicalutamide	increases expression	1
fumonisin B1	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Zoledronic Acid	increases expression	1
Crizotinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases expression	1
Cadmium	increases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Demecolcine	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5149949	Binding	Binding affinity to GST-tagged YTHDF3 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

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8AJ	Abcam Raji YTHDF3 KO	Cancer cell line	Male
CVCL_C0BE	Abcam THP-1 YTHDF3 KO	Cancer cell line	Male
CVCL_C7D1	Abcam PC-3 YTHDF3 KO	Cancer cell line	Male
CVCL_E2PE	HAP1 YTHDF3 (-) 2	Cancer cell line	Male
CVCL_XV21	HAP1 YTHDF3 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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