METTL14

gene
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Also known as KIAA1627

Summary

METTL14 (methyltransferase 14, N6-adenosine-methyltransferase non-catalytic subunit, HGNC:29330) is a protein-coding gene on chromosome 4q26, encoding N(6)-adenosine-methyltransferase non-catalytic subunit METTL14 (Q9HCE5). The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N(6) position of some mRNAs and regulates the circadian clock, differentiation of embryonic stem cells and cortical neurogenesis. It is a selective cancer dependency (DepMap: 78.8% of cell lines).

Enables mRNA binding activity and mRNA m(6)A methyltransferase activity. Involved in mRNA modification; mRNA splicing, via spliceosome; and mRNA stabilization. Located in nucleoplasm. Is active in RNA N6-methyladenosine methyltransferase complex.

Source: NCBI Gene 57721 — RefSeq curated summary.

At a glance

  • Clinical variants (ClinVar): 37 total
  • Druggable target: yes — 4 molecules with ChEMBL bioactivity
  • Cancer dependency (DepMap): dependent in 78.8% of screened cell lines
  • MANE Select transcript: NM_020961

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:29330
Approved symbolMETTL14
Namemethyltransferase 14, N6-adenosine-methyltransferase non-catalytic subunit
Location4q26
Locus typegene with protein product
StatusApproved
AliasesKIAA1627
Ensembl geneENSG00000145388
Ensembl biotypeprotein_coding
OMIM616504
Entrez57721

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000388822, ENST00000502564, ENST00000506780, ENST00000508801, ENST00000626212, ENST00000628452, ENST00000900246, ENST00000900247, ENST00000900248, ENST00000900250, ENST00000949682

RefSeq mRNA: 1 — MANE Select: NM_020961 NM_020961

CCDS: CCDS34053

Canonical transcript exons

ENST00000388822 — 11 exons

ExonStartEnd
ENSE00000935079118691981118692068
ENSE00001016825118705611118705821
ENSE00001016833118703935118704051
ENSE00001161537118691532118691612
ENSE00001226176118709998118715430
ENSE00001504043118689370118689457
ENSE00002045472118685392118685600
ENSE00003579246118687923118688011
ENSE00003637889118694436118694526
ENSE00003658931118700550118700642
ENSE00003659042118697182118697323

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 95.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.1406 / max 617.2054, expressed in 1788 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
4942522.79971788
494260.3409126

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
calcaneal tendonUBERON:000370195.46gold quality
secondary oocyteCL:000065593.03gold quality
cauda epididymisUBERON:000436091.23gold quality
islet of LangerhansUBERON:000000691.10gold quality
caput epididymisUBERON:000435890.50gold quality
corpus epididymisUBERON:000435990.42gold quality
ventricular zoneUBERON:000305389.54gold quality
colonic epitheliumUBERON:000039789.41gold quality
tendonUBERON:000004389.27gold quality
thymusUBERON:000237089.14gold quality
epithelial cell of pancreasCL:000008389.07silver quality
right testisUBERON:000453488.82gold quality
adrenal tissueUBERON:001830388.78gold quality
left testisUBERON:000453388.66gold quality
smooth muscle tissueUBERON:000113588.36gold quality
bone marrowUBERON:000237188.32gold quality
ganglionic eminenceUBERON:000402388.24gold quality
amniotic fluidUBERON:000017388.00gold quality
testisUBERON:000047388.00gold quality
spermCL:000001987.99gold quality
trabecular bone tissueUBERON:000248387.86gold quality
sural nerveUBERON:001548887.73gold quality
kidney epitheliumUBERON:000481987.63silver quality
cortical plateUBERON:000534387.26gold quality
nippleUBERON:000203087.15gold quality
corpus callosumUBERON:000233687.00gold quality
endothelial cellCL:000011586.93gold quality
upper arm skinUBERON:000426386.86silver quality
skeletal muscle tissue of biceps brachiiUBERON:000450286.86gold quality
endometriumUBERON:000129586.69gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes6.70

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SPI1

miRNA regulators (miRDB)

94 targeting METTL14, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-3163100.0077.238605
HSA-MIR-4682100.0068.891258
HSA-MIR-4668-3P100.0068.742635
HSA-MIR-450A-1-3P100.0069.331837
HSA-MIR-6867-5P100.0082.213464
HSA-MIR-9-5P100.0072.282361
HSA-MIR-428299.9975.366408
HSA-MIR-371B-5P99.9975.344759
HSA-MIR-196A-1-3P99.9972.152772
HSA-MIR-548P99.9872.253784
HSA-MIR-569699.9872.364487
HSA-MIR-373-5P99.9875.364753
HSA-MIR-616-5P99.9875.584775
HSA-MIR-548AN99.9770.912817
HSA-MIR-1468-3P99.9672.743797
HSA-MIR-3605-5P99.9667.12932
HSA-MIR-548AT-5P99.9670.832666
HSA-MIR-545-3P99.9570.742783
HSA-MIR-971899.9468.91918
HSA-MIR-335-3P99.9373.364958
HSA-MIR-6835-3P99.9370.492904
HSA-MIR-391999.8769.452489
HSA-MIR-548D-3P99.8770.674362
HSA-MIR-5582-3P99.8672.484221
HSA-MIR-579-3P99.8671.663628
HSA-MIR-548BB-3P99.8670.584354
HSA-MIR-664B-3P99.8471.653590
HSA-MIR-548AC99.8470.774351
HSA-MIR-548H-3P99.8470.804349
HSA-MIR-548Z99.8470.804349

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 78.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

  • methyltransferase-like protein 14 in a complex with METTL3 mediates nuclear RNA methylation (PMID:24316715)
  • Structure of the METTL3-METTL14 complex (PMID:27281194)
  • The structure reveals the heterodimeric architecture of the complex and donor substrate binding by METTL3. Structure-guided mutagenesis indicates that METTL3 is the catalytic subunit of the complex, whereas METTL14 has a degenerate active site and plays non-catalytic roles in maintaining complex integrity and substrate RNA binding. (PMID:27627798)
  • methylation at m6A by METTL3/METTL14 facilitates the methylation of m5C by NSUN2, and vice versa. NSUN2-mediated m5C and METTL3/METTL14-mediated m6A methylation synergistically enhance p21 expression at the translational level (PMID:28247949)
  • The critical roles of METTL14 and N(6)-methyladenosine modification in normal and malignant hematopoiesis, are reported. (PMID:29290617)
  • METTL3 is soluble and inactive while the catalytic center of METTL14 is degenerated and thus also inactive. In addition, the C-terminal RGG repeats of METTL14 are required for METTL3/14 activity by contributing to RNA substrate binding. (PMID:29348140)
  • The Mettl3-Mettl14-mediated m6A was found to promote the development of acute myeloid leukemia and maintain leukemia-initiating cells. (PMID:30006613)
  • METTL14 and ALKBH5 determine the N6-methyladenosine of target genes by controlling each other’s expression and by inhibiting YTHDF3.METTL14 role in the cancer growth and progression. (PMID:30306128)
  • This demonstrated that EBV hijacks METTL14 to drive EBV-mediated tumorigenesis. METTL14 is now a new target for development of therapeutics for treatment of EBV-associated cancers. (PMID:31226160)
  • The N6-methyladenosine mRNA methylase METTL14 promotes renal ischemic reperfusion injury via suppressing YAP1. (PMID:31318098)
  • A Mass Spectrometric Assay of METTL3/METTL14 Methyltransferase Activity. (PMID:31585521)
  • our results demonstrated the functional importance of METTL14-dependent vascular m6A methylome in vascular functions during calcification and provided a novel mechanistic insight to the therapeutic mechanisms of METTL14 (PMID:31697949)
  • This work reveals a novel role of Mettl14 and N(6)-methyladenosine in bladder tumorigenesis and bladder TICs, adding new layers for bladder TIC regulation and N(6)-methyladenosine function. (PMID:31760940)
  • Bioinformatics analysis demonstrated that downregulated METTL14 mRNA expression has a significantly negative correlation with the kidney renal clear cell carcinoma (KIRC) stages and a positive correlation with overall survival of KIRC patients. Furthermore, circRNAs may regulate METTL14 mRNA as miRNAs sponge to affect the progression of KIRC. (PMID:31976022)
  • Downregulation of METTL14 increases apoptosis and autophagy induced by cisplatin in pancreatic cancer cells. (PMID:32097728)
  • METTL14 suppresses proliferation and metastasis of colorectal cancer by down-regulating oncogenic long non-coding RNA XIST. (PMID:32111213)
  • METTL14 promotes the migration and invasion of breast cancer cells by modulating N6methyladenosine and hsamiR146a5p expression. (PMID:32323801)
  • m6A RNA methylation regulators correlate with malignant progression and have potential predictive values in clear cell renal cell carcinoma. (PMID:32333907)
  • METTL14-mediated N6-methyladenosine modification of SOX4 mRNA inhibits tumor metastasis in colorectal cancer. (PMID:32552762)
  • LNC942 promoting METTL14-mediated m(6)A methylation in breast cancer cell proliferation and progression. (PMID:32576970)
  • The study of METTL14, ALKBH5, and YTHDF2 in peripheral blood mononuclear cells from systemic lupus erythematosus. (PMID:32583611)
  • METTL14 regulates M6A methylation-modified primary miR-19a to promote cardiovascular endothelial cell proliferation and invasion. (PMID:32633395)
  • Lamin A safeguards the m(6) A methylase METTL14 nuclear speckle reservoir to prevent cellular senescence. (PMID:32813328)
  • Upregulation of METTL14 mediates the elevation of PERP mRNA N(6) adenosine methylation promoting the growth and metastasis of pancreatic cancer. (PMID:32843065)
  • m(6) A RNA methyltransferases METTL3/14 regulate immune responses to anti-PD-1 therapy. (PMID:32964498)
  • Downregulated METTL14 Expression Correlates with Breast Cancer Tumor Grade and Molecular Classification. (PMID:33134390)
  • Analysis of METTL3 and METTL14 in hepatocellular carcinoma. (PMID:33159022)
  • The m6A methyltransferase METTL14 inhibits the proliferation, migration, and invasion of gastric cancer by regulating the PI3K/AKT/mTOR signaling pathway. (PMID:33314339)
  • METTL14-regulated PI3K/Akt signaling pathway via PTEN affects HDAC5-mediated epithelial-mesenchymal transition of renal tubular cells in diabetic kidney disease. (PMID:33414476)
  • RNA secondary structure dependence in METTL3-METTL14 mRNA methylation is modulated by the N-terminal domain of METTL3. (PMID:33544495)
  • Downregulated METTL14 accumulates BPTF that reinforces super-enhancers and distal lung metastasis via glycolytic reprogramming in renal cell carcinoma. (PMID:33664855)
  • CLK1/SRSF5 pathway induces aberrant exon skipping of METTL14 and Cyclin L2 and promotes growth and metastasis of pancreatic cancer. (PMID:33849617)
  • USP48 Is Upregulated by Mettl14 to Attenuate Hepatocellular Carcinoma via Regulating SIRT6 Stabilization. (PMID:33903120)
  • Methyl CpG binding protein 2 promotes colorectal cancer metastasis by regulating N(6) -methyladenosine methylation through methyltransferase-like 14. (PMID:34097350)
  • METTL14 promotes tumorigenesis by regulating lncRNA OIP5-AS1/miR-98/ADAMTS8 signaling in papillary thyroid cancer. (PMID:34131102)
  • Isorhapontigenin (ISO) inhibits EMT through FOXO3A/METTL14/VIMENTIN pathway in bladder cancer cells. (PMID:34332039)
  • Human umbilical cord mesenchymal stem cells deliver exogenous miR-26a-5p via exosomes to inhibit nucleus pulposus cell pyroptosis through METTL14/NLRP3. (PMID:34412584)
  • METTL14 promotes glomerular endothelial cell injury and diabetic nephropathy via m6A modification of alpha-klotho. (PMID:34503454)
  • METTL14-Mediated miR-30c-1-3p Maturation Represses the Progression of Lung Cancer via Regulation of MARCKSL1 Expression. (PMID:34586620)
  • A methyltransferase-like 14/miR-99a-5p/tribble 2 positive feedback circuit promotes cancer stem cell persistence and radioresistance via histone deacetylase 2-mediated epigenetic modulation in esophageal squamous cell carcinoma. (PMID:34586732)

Cross-species orthologs

4 orthologs

OrganismSymbolGene ID
danio_reriomettl14ENSDARG00000070278
mus_musculusMettl14ENSMUSG00000028114
rattus_norvegicusMettl14ENSRNOG00000015250
drosophila_melanogasterMettl14FBGN0032016

Protein

Protein identifiers

N(6)-adenosine-methyltransferase non-catalytic subunit METTL14Q9HCE5 (reviewed: Q9HCE5)

Alternative names: Methyltransferase-like protein 14

All UniProt accessions (5): A0A0D9SF88, A0A0D9SFW0, D6RBL4, D6RD73, Q9HCE5

UniProt curated annotations — full annotation on UniProt →

Function. The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N(6) position of some mRNAs and regulates the circadian clock, differentiation of embryonic stem cells and cortical neurogenesis. In the heterodimer formed with METTL3, METTL14 constitutes the RNA-binding scaffold that recognizes the substrate rather than the catalytic core. N6-methyladenosine (m6A), which takes place at the 5’-[AG]GAC-3’ consensus sites of some mRNAs, plays a role in mRNA stability and processing. M6A acts as a key regulator of mRNA stability by promoting mRNA destabilization and degradation. In embryonic stem cells (ESCs), m6A methylation of mRNAs encoding key naive pluripotency-promoting transcripts results in transcript destabilization. M6A regulates spermatogonial differentiation and meiosis and is essential for male fertility and spermatogenesis. M6A also regulates cortical neurogenesis: m6A methylation of transcripts related to transcription factors, neural stem cells, the cell cycle and neuronal differentiation during brain development promotes their destabilization and decay, promoting differentiation of radial glial cells.

Subunit / interactions. Heterodimer; heterodimerizes with METTL3 to form an antiparallel heterodimer that constitutes an active methyltransferase. Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM. The MAC subcomplex is composed of METTL3 and METTL14. The MACOM subcomplex is composed of WTAP, ZC3H13, CBLL1/HAKAI, VIRMA, and, in some cases of RBM15 (RBM15 or RBM15B).

Subcellular location. Nucleus.

Similarity. Belongs to the MT-A70-like family.

RefSeq proteins (1): NP_066012* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR007757MT-A70-likeFamily
IPR029063SAM-dependent_MTases_sfHomologous_superfamily
IPR045123METTL14-likeFamily

Pfam: PF05063

Enzyme classification (BRENDA):

  • EC 2.1.1.348 — mRNA m6A methyltransferase (BRENDA: 11 organisms, 24 substrates, 64 inhibitors, 6 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
ADENINE IN DOUBLE-STRANDED DNA CONTAINING A CYCL0.0006–0.00072
ADENINE IN MRNA0.0002–0.0232
ADENINE IN SINGLE-STRANDED DNA0.0032–0.00772

UniProt features (60 total): mutagenesis site 13, helix 12, strand 12, region of interest 9, site 5, turn 4, compositionally biased region 3, chain 1, modified residue 1

Structure

Experimental structures (PDB)

76 structures, top 30 by resolution.

PDBMethodResolution (Å)
5IL2X-RAY DIFFRACTION1.61
7RX7X-RAY DIFFRACTION1.65
5K7MX-RAY DIFFRACTION1.65
5K7WX-RAY DIFFRACTION1.65
5K7UX-RAY DIFFRACTION1.7
5IL1X-RAY DIFFRACTION1.71
9RS1X-RAY DIFFRACTION1.73
9Q8GX-RAY DIFFRACTION1.75
5TEYX-RAY DIFFRACTION1.8
7O09X-RAY DIFFRACTION1.8
7RX6X-RAY DIFFRACTION1.8
7NHIX-RAY DIFFRACTION1.85
7RX8X-RAY DIFFRACTION1.85
9G4WX-RAY DIFFRACTION1.85
9IH5X-RAY DIFFRACTION1.85
5L6DX-RAY DIFFRACTION1.85
7OELX-RAY DIFFRACTION1.86
5IL0X-RAY DIFFRACTION1.88
6Y4GX-RAY DIFFRACTION1.9
7O0LX-RAY DIFFRACTION1.9
7OEKX-RAY DIFFRACTION1.9
5L6EX-RAY DIFFRACTION1.9
7NHVX-RAY DIFFRACTION1.91
9RRYX-RAY DIFFRACTION1.91
9G4SX-RAY DIFFRACTION1.95
9Q89X-RAY DIFFRACTION1.95
9Q8AX-RAY DIFFRACTION1.95
6TTPX-RAY DIFFRACTION2
6TTXX-RAY DIFFRACTION2
7O08X-RAY DIFFRACTION2

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9HCE5-F179.880.58

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 (5): 146 (interaction with mettl3); 242 (interaction with mettl3); 245 (interaction with mettl3); 298 (interaction with mettl3); 399 (interaction with mettl3)

Post-translational modifications (1): 399

Mutagenesis-validated functional residues (13):

PositionPhenotype
63–65does not affect nuclear localization.
173little or no effect on s-adenosyl-l-methionine-binding or methyltransferase activity; when associated with a-192.
192little or no effect on methyltransferase activity. little or no effect on s-adenosyl-l-methionine-binding or methyltrans
198does not affect methyltransferase activity of the heterodimer complex formed with mettl3.
245reduced rna-binding. reduced rna-binding; when associated with e-255.
254–255strongly reduced methyltransferase activity of the heterodimer complex formed with mettl3.
255reduced rna-binding; when associated with e-245.
297–298reduced rna-binding.
298strongly decreased methyltransferase activity of the heterodimer complex formed with mettl3, probably due to reduced rna
312decreased methyltransferase activity of the heterodimer complex formed with mettl3.
338does not affect methyltransferase activity of the heterodimer complex formed with mettl3.
362–363little or no effect on methyltransferase activity of the heterodimer complex formed with mettl3.
399does not affect interaction with mettl3.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

IDPathway
R-HSA-72203Processing of Capped Intron-Containing Pre-mRNA
R-HSA-8953854Metabolism of RNA

MSigDB gene sets: 154 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, LU_IL4_SIGNALING, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEUROGENESIS, GOBP_MALE_GAMETE_GENERATION, GOBP_RNA_METHYLATION, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_MRNA_MODIFICATION, GOBP_FOREBRAIN_GENERATION_OF_NEURONS, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_LEUKOCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_HEMOPOIESIS

GO Biological Process (16): mRNA splicing, via spliceosome (GO:0000398), RNA methylation (GO:0001510), mRNA processing (GO:0006397), spermatogenesis (GO:0007283), mRNA modification (GO:0016556), stem cell population maintenance (GO:0019827), forebrain radial glial cell differentiation (GO:0021861), response to nutrient levels (GO:0031667), gliogenesis (GO:0042063), regulation of neuron differentiation (GO:0045664), positive regulation of translation (GO:0045727), mRNA stabilization (GO:0048255), mRNA destabilization (GO:0061157), negative regulation of hematopoietic progenitor cell differentiation (GO:1901533), mRNA export from nucleus (GO:0006406), cell differentiation (GO:0030154)

GO Molecular Function (6): mRNA m(6)A methyltransferase activity (GO:0001734), mRNA binding (GO:0003729), RNA binding (GO:0003723), protein binding (GO:0005515), S-adenosylmethionine-dependent methyltransferase activity (GO:0008757), catalytic activity, acting on a nucleic acid (GO:0140640)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), RNA N6-methyladenosine methyltransferase complex (GO:0036396)

Reactome top-level categories

Rollup of top-1 pathways:

CategoryPathways
Metabolism of RNA1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
RNA modification2
mRNA metabolic process2
regulation of mRNA stability2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile1
mRNA processing1
macromolecule methylation1
RNA processing1
developmental process involved in reproduction1
male gamete generation1
multicellular organismal process1
maintenance of cell number1
forebrain generation of neurons1
radial glial cell differentiation1
response to stimulus1
neurogenesis1
neuron differentiation1
regulation of cell differentiation1
translation1
regulation of translation1
positive regulation of gene expression1
positive regulation of protein metabolic process1
RNA stabilization1
negative regulation of mRNA catabolic process1
negative regulation of gene expression1
RNA destabilization1
positive regulation of mRNA catabolic process1
hematopoietic progenitor cell differentiation1
negative regulation of cell differentiation1
regulation of hematopoietic progenitor cell differentiation1
RNA export from nucleus1
gene expression1
mRNA transport1
cellular developmental process1
mRNA methyltransferase activity1
RNA binding1
nucleic acid binding1
binding1
methyltransferase activity1
catalytic activity1
intracellular membrane-bounded organelle1

Protein interactions and networks

STRING

3086 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
METTL14VIRMAQ69YN4999
METTL14WTAPQ15007999
METTL14ZC3H13Q5T200998
METTL14RBM15Q96T37998
METTL14RBM15BQ8NDT2998
METTL14CBLL1Q75N03997
METTL14METTL16Q86W50995
METTL14METTL3Q86U44993
METTL14METTL4Q8N3J2992
METTL14DGCR8Q8WYQ5989
METTL14SMAD2Q15796975
METTL14ALKBH5Q6P6C2952
METTL14YTHDF1Q9BYJ9950
METTL14YTHDC1Q96MU7949
METTL14YTHDF2Q9Y5A9945

IntAct

47 interactions, top by confidence:

ABTypeScore
METTL14METTL3psi-mi:“MI:0915”(physical association)0.940
METTL14METTL3psi-mi:“MI:0407”(direct interaction)0.940
METTL3METTL14psi-mi:“MI:0407”(direct interaction)0.940
METTL3METTL14psi-mi:“MI:0914”(association)0.940
METTL3METTL14psi-mi:“MI:0407”(direct interaction)0.780
METTL14METTL3psi-mi:“MI:0915”(physical association)0.780
METTL14WTAPpsi-mi:“MI:0915”(physical association)0.580
METTL14WTAPpsi-mi:“MI:0914”(association)0.580
WTAPMETTL14psi-mi:“MI:0915”(physical association)0.580
METTL3EIF3Hpsi-mi:“MI:0914”(association)0.560
METTL3WTAPpsi-mi:“MI:0914”(association)0.530
METTL14WTAPpsi-mi:“MI:0914”(association)0.530
METTL14psi-mi:“MI:0213”(methylation reaction)0.440

BioGRID (618): DDI2 (Co-fractionation), METTL3 (Co-fractionation), METTL14 (Affinity Capture-MS), METTL14 (Affinity Capture-MS), METTL14 (Affinity Capture-MS), SMAD2 (Affinity Capture-Western), SMAD3 (Affinity Capture-Western), METTL3 (Affinity Capture-Western), METTL14 (Affinity Capture-Western), METTL14 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), KRT1 (Affinity Capture-MS), KRT2 (Affinity Capture-MS), HSPA1A (Affinity Capture-MS), KRT10 (Affinity Capture-MS)

ESM2 similar proteins: A2QVS9, A3LS77, A4IFD8, A5E7T4, A8WRG3, A8XYX2, C8V3W5, F4JRS4, F4KAF2, J9VI03, O45380, O60306, O82486, O89042, O94268, P0CO28, P0CO29, P13382, P25583, P32335, P33294, P97496, Q04089, Q2HVD6, Q3UIK4, Q5ADX5, Q5K2C1, Q5K2C4, Q5R5N4, Q5ZK35, Q62847, Q66KJ9, Q6FKD6, Q6FPQ3, Q6FWI7, Q6NU56, Q6NZ22, Q756E1, Q7SB74, Q7YZT6

Diamond homologs: A4IFD8, F1R777, O82486, Q3UIK4, Q5R5N4, Q5ZK35, Q66KJ9, Q6EU10, Q6NU56, Q6NZ22, Q86U44, Q8C3P7, Q94AI4, Q9HCE5, Q9VCE6, Q9VLP7, P41833, Q2HVD6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance27
Likely benign1
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2009 predictions. Top by Δscore:

VariantEffectΔscore
4:118685597:GCAG:Gdonor_gain1.0000
4:118685600:GGT:Gdonor_loss1.0000
4:118685601:G:Cdonor_loss1.0000
4:118687921:A:AGacceptor_gain1.0000
4:118687921:AGTT:Aacceptor_gain1.0000
4:118687921:AGTTG:Aacceptor_gain1.0000
4:118687922:G:GGacceptor_gain1.0000
4:118687922:GT:Gacceptor_gain1.0000
4:118687922:GTT:Gacceptor_gain1.0000
4:118687922:GTTG:Gacceptor_gain1.0000
4:118687922:GTTGG:Gacceptor_gain1.0000
4:118688009:CAGGT:Cdonor_loss1.0000
4:118688010:AGG:Adonor_loss1.0000
4:118688012:G:GCdonor_loss1.0000
4:118688013:T:Adonor_loss1.0000
4:118689361:A:AGacceptor_gain1.0000
4:118689362:T:Gacceptor_gain1.0000
4:118689364:TTTCA:Tacceptor_loss1.0000
4:118689367:CAG:Cacceptor_loss1.0000
4:118689368:A:AGacceptor_gain1.0000
4:118689368:AG:Aacceptor_gain1.0000
4:118689368:AGG:Aacceptor_gain1.0000
4:118689369:G:Aacceptor_gain1.0000
4:118689369:G:GTacceptor_gain1.0000
4:118689369:GGG:Gacceptor_gain1.0000
4:118689369:GGGC:Gacceptor_gain1.0000
4:118689369:GGGCT:Gacceptor_gain1.0000
4:118691520:AT:Aacceptor_gain1.0000
4:118691521:T:Gacceptor_gain1.0000
4:118691521:T:TAacceptor_gain1.0000

AlphaMissense

2992 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
4:118691604:T:CF106L1.000
4:118691605:T:GF106C1.000
4:118691606:T:AF106L1.000
4:118691606:T:GF106L1.000
4:118691608:T:CL107P1.000
4:118691981:G:AG109R1.000
4:118691981:G:CG109R1.000
4:118691982:G:AG109E1.000
4:118691990:A:CS112R1.000
4:118691992:C:AS112R1.000
4:118691992:C:GS112R1.000
4:118692002:C:GH116D1.000
4:118692005:A:GN117D1.000
4:118692007:T:AN117K1.000
4:118692007:T:GN117K1.000
4:118692008:G:CD118H1.000
4:118692008:G:TD118Y1.000
4:118692009:A:CD118A1.000
4:118692009:A:GD118G1.000
4:118692009:A:TD118V1.000
4:118692010:T:AD118E1.000
4:118692010:T:GD118E1.000
4:118692011:T:CY119H1.000
4:118692011:T:GY119D1.000
4:118692014:T:CC120R1.000
4:118692015:G:AC120Y1.000
4:118692016:C:GC120W1.000
4:118692018:A:CQ121P1.000
4:118692019:A:CQ121H1.000
4:118692019:A:TQ121H1.000

dbSNP variants (sampled 300 via entrez): RS1000171053 (4:118686395 G>A), RS10002843 (4:118687821 G>A), RS1000351122 (4:118684947 C>T), RS1000354689 (4:118709549 A>G), RS1000385956 (4:118698908 C>G,T), RS1000535510 (4:118691146 G>A), RS1000559837 (4:118687734 C>T), RS1000726918 (4:118704551 T>G), RS1000779691 (4:118704764 A>C), RS1000909806 (4:118687999 G>A), RS1000959954 (4:118711555 C>T), RS10011169 (4:118702971 A>C,G), RS1001255771 (4:118713844 C>G), RS1001480097 (4:118706756 C>T), RS1001529565 (4:118684493 G>A,T)

Disease associations

OMIM: gene MIM:616504 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4106140 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 100,849 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL461101ELTROMBOPAG4602
CHEMBL50QUERCETIN374,559
CHEMBL1214186SINEFUNGIN22,165
CHEMBL151LUTEOLIN223,523

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

PharmGKB variants

1 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs62328061METTL140.000

Binding affinities (BindingDB)

135 measured of 135 human assays (135 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
US20250214997, Compound E-57IC500.1 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
5-[1-[[2-[(4,4-dimethylpiperidin-1-yl)methyl]-1H-indol-6-yl]methyl]triazol-4-yl]-N,N-dimethylpyridin-3-amineIC500.12 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
N-[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methyl]-1-[2-[[4-[5-(3-fluoropyrrolidin-1-yl)-3-pyridinyl]triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methanamineIC500.16 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
N-[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methyl]-1-[2-[[4-(5-pyrrolidin-1-yl-3-pyridinyl)triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methanamineIC500.16 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
US20250214997, Compound E-140IC500.17 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
US20250214997, Compound E-87IC500.19 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
US20250214997, Compound E-121IC500.2 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
US20250214997, Compound E-84IC500.24 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
US20250214997, Compound E-111IC500.24 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
US20250214997, Compound E-51IC500.25 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
US20250214997, Compound E-101IC500.25 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
US20250214997, Compound E-50IC500.29 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
US20250214997, Compound E-105IC500.29 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
US20250214997, Compound E-119IC500.29 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
8-bromo-2-[(1-methylpiperidin-4-yl)amino]-4-(4-phenylmethoxyanilino)-6H-pyrido[4,3-d]pyrimidin-5-one;hydrochlorideIC500.3 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
N-[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methyl]-1-[2-[[4-(5-pyrrol-1-yl-3-pyridinyl)triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methanamineIC500.31 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
US20250214997, Compound E-56IC500.32 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
N-[[6-[[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methylamino]methyl]imidazo[1,2-a]pyridin-2-yl]methyl]-5-pyrrolidin-1-ylpyridine-3-carboxamideIC500.33 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
2-[[4-[5-(2,5-dihydropyrrol-1-yl)-3-pyridinyl]triazol-1-yl]methyl]-6-[(4,4-dimethylpiperidin-1-yl)methyl]imidazo[1,2-a]pyridineIC500.36 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
US20250214997, Compound E-49IC500.37 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
6-(aziridin-1-yl)-4-[1-[[2-[(4,4-dimethylpiperidin-1-yl)methyl]-1H-indol-6-yl]methyl]triazol-4-yl]-1H-indazoleIC500.4 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
6-[(4,4-dimethylpiperidin-1-yl)methyl]-2-[[4-(5-pyrrolidin-1-yl-3-pyridinyl)triazol-1-yl]methyl]imidazo[1,2-a]pyridineIC500.4 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
1-[2-[[4-[5-(3,3-difluoropyrrolidin-1-yl)-3-pyridinyl]triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]-N-[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methyl]methanamineIC500.41 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
US20250214997, Compound E-106IC500.48 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
6-[[4-[5-(azetidin-1-yl)-3-pyridinyl]triazol-1-yl]methyl]-2-[(4,4-dimethylpiperidin-1-yl)methyl]-1H-indoleIC500.5 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
US20250214997, Compound E-79IC500.54 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
8-bromo-4-(4-phenoxyanilino)-2-[[1-(2,2,2-trifluoroethyl)piperidin-4-yl]amino]-6H-pyrido[4,3-d]pyrimidin-5-oneIC500.56 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
US20250214997, Compound E-59IC500.59 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
8-bromo-4-(3-methyl-4-phenoxyanilino)-2-[(1-methylpiperidin-4-yl)amino]-6H-pyrido[4,3-d]pyrimidin-5-one;hydrochlorideIC500.61 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
8-bromo-4-[4-(3,5-difluorophenoxy)anilino]-2-[(1-methylpiperidin-4-yl)amino]-6H-pyrido[4,3-d]pyrimidin-5-one;hydrochlorideIC500.69 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
1-cyclobutyl-N-[[2-[[4-[5-(2,5-dihydropyrrol-1-yl)-3-pyridinyl]triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methyl]methanamineIC500.74 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
8-bromo-2-[(1-methylpiperidin-4-yl)amino]-4-(4-phenylmethoxyanilino)-6H-pyrido[4,3-d]pyrimidin-5-oneIC500.75 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
US20250214997, Compound E-39IC500.75 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
US20250214997, Compound E-143IC500.77 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
8-bromo-4-[3-fluoro-4-(3-fluorophenoxy)anilino]-2-[(1-methylpiperidin-4-yl)amino]-6H-pyrido[4,3-d]pyrimidin-5-one;hydrochlorideIC500.8 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
8-chloro-4-(4-cyclohexyloxyanilino)-2-[(1-methylpiperidin-4-yl)amino]-6H-pyrido[4,3-d]pyrimidin-5-oneIC500.9 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
1-cyclobutyl-N-[[2-[[4-(5-pyrrolidin-1-yl-3-pyridinyl)triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methyl]methanamineIC501.02 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
5-[1-[[6-[(4,4-dimethylpiperidin-1-yl)methyl]imidazo[1,2-a]pyridin-2-yl]methyl]triazol-4-yl]-N,N-dimethylpyridin-3-amineIC501.06 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
5-(dimethylamino)-N-[[2-[(4,4-dimethylpiperidin-1-yl)methyl]-1H-indol-6-yl]methyl]pyridine-3-carboxamideIC501.09 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
2-[[(3S)-pyrrolidin-3-yl]amino]-4-[4-(trifluoromethyl)anilino]-6H-pyrido[4,3-d]pyrimidin-5-oneIC501.17 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
US20250214997, Compound E-58IC501.18 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
8-bromo-4-[4-(4-chlorophenoxy)anilino]-2-[(1-methylpiperidin-4-yl)amino]-6H-pyrido[4,3-d]pyrimidin-5-one;hydrochlorideIC501.21 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
4-[1-[[2-(6-azaspiro[3.4]octan-6-ylmethyl)-1H-indol-6-yl]methyl]triazol-4-yl]-6-methylsulfanyl-1H-indazoleIC501.23 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
1-cyclobutyl-N-[[2-[[4-(6-iodo-1H-indazol-4-yl)triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methyl]methanamineIC501.24 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
US20250214997, Compound E-112IC501.25 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
4-[1-[[2-(6-azaspiro[3.4]octan-6-ylmethyl)-1H-indol-6-yl]methyl]triazol-4-yl]-6-bromo-1H-indazoleIC501.37 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
8-bromo-4-[4-(4-methylphenoxy)anilino]-2-[(1-methylpiperidin-4-yl)amino]-6H-pyrido[4,3-d]pyrimidin-5-oneIC501.38 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
US20250214997, Compound E-60IC501.39 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
8-bromo-4-[4-(3-fluorophenoxy)-3-methylanilino]-2-[(1-methylpiperidin-4-yl)amino]-6H-pyrido[4,3-d]pyrimidin-5-one;hydrochlorideIC501.4 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
US20250214997, Compound E-43IC501.4 nMUS-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF

ChEMBL bioactivities

271 potent at pChembl≥5 of 282 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
9.00IC501nMCHEMBL6171683
9.00IC501nMCHEMBL6161197
9.00IC501nMCHEMBL6174416
9.00IC501nMCHEMBL6162072
8.85Kd1.4nMCHEMBL5291234
8.70IC502nMCHEMBL6149057
8.70IC502nMCHEMBL6169196
8.70IC502nMCHEMBL6164629
8.70IC502nMCHEMBL6145109
8.70IC502nMCHEMBL6167143
8.70IC502nMCHEMBL6162084
8.70IC502nMCHEMBL6170438
8.70IC502nMCHEMBL6174400
8.70IC502nMCHEMBL6175655
8.70IC502nMCHEMBL6173476
8.70IC502nMCHEMBL6161072
8.52IC503nMCHEMBL6167275
8.52IC503nMCHEMBL6169100
8.52IC503nMCHEMBL6147720
8.52IC503nMCHEMBL6148888
8.52IC503nMCHEMBL6163833
8.52IC503nMCHEMBL6161072
8.44IC503.63nMCHEMBL5396973
8.42IC503.84nMCHEMBL5076382
8.41IC503.85nMCHEMBL5077332
8.40IC504nMCHEMBL6171694
8.40IC504nMCHEMBL6143768
8.40IC504nMCHEMBL6170155
8.40IC504nMCHEMBL6165737
8.40IC504nMCHEMBL6165967
8.40IC504nMCHEMBL5075067
8.36IC504.35nMCHEMBL5405105
8.30IC505nMCHEMBL6152127
8.30IC505nMCHEMBL6166439
8.30IC505nMCHEMBL6161960
8.30IC505nMCHEMBL6161072
8.22IC506nMCHEMBL6162091
8.22IC506nMCHEMBL6147934
8.22IC506nMCHEMBL6151936
8.22IC506nMCHEMBL6146295
8.22IC506nMCHEMBL6161072
8.21IC506.1nMCHEMBL5075067
8.21IC506.1nMCHEMBL5090558
8.21IC506.1nMCHEMBL5094327
8.21IC506.1nMCHEMBL5078682
8.21IC506.1nMCHEMBL5088632
8.21IC506.1nMCHEMBL5082086
8.21IC506.1nMCHEMBL5082807
8.21IC506.1nMCHEMBL5088101
8.21IC506.1nMCHEMBL5084043

PubChem BioAssay actives

67 with measured affinity, of 128 total; 46 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
N-[[6-[(cyclohexylmethylamino)methyl]imidazo[1,2-a]pyridin-2-yl]methyl]-4-oxopyrido[1,2-a]pyrimidine-2-carboxamide1986901: Binding affinity to full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system assessed as dissociation constant using SAM as substrate by SPR assaykd0.0014uM
1-cyclobutyl-N-[[2-[[4-(6-methoxy-1H-indazol-4-yl)triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methyl]methanamine1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysisic500.0036uM
N-[[2-[[4-(6-chloro-1H-indazol-4-yl)triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methyl]-1-cyclobutylmethanamine1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysisic500.0043uM
(1R,2S,3R,5R)-3-(4-amino-5-bromopyrrolo[2,3-d]pyrimidin-7-yl)-5-[2-[[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methylamino]methyl]-1H-indol-6-yl]cyclopentane-1,2-diol1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysisic500.0060uM
N-[(1-methoxycyclobutyl)methyl]-1-[2-[[4-(6-methoxy-1H-indazol-4-yl)triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methanamine1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysisic500.0061uM
N-[[6-[[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methylamino]methyl]imidazo[1,2-a]pyridin-2-yl]methyl]-4-oxopyrido[1,2-a]pyrimidine-2-carboxamide1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysisic500.0061uM
1-cyclobutyl-N-[[2-[[4-(5-methoxy-1H-indazol-4-yl)triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methyl]methanamine1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysisic500.0061uM
N-[[2-[[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methylamino]methyl]-1H-indol-6-yl]methyl]-5-oxo-[1,3]thiazolo[3,2-a]pyrimidine-7-carboxamide1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysisic500.0061uM
N-[[2-[(cyclobutylmethylamino)methyl]-1H-indol-6-yl]methyl]-4-oxopyrido[1,2-a]pyrimidine-2-carboxamide1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysisic500.0061uM
N-[[2-[(cyclobutylmethylamino)methyl]-5-fluoro-1H-indol-6-yl]methyl]-4-oxopyrido[1,2-a]pyrimidine-2-carboxamide1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysisic500.0061uM
N-[[2-[[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methylamino]methyl]-1H-indol-6-yl]methyl]-4-oxopyrido[1,2-a]pyrimidine-2-carboxamide1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysisic500.0061uM
N-[[2-[(3,3-diethylazetidin-1-yl)methyl]-1H-indol-6-yl]methyl]-4-oxopyrido[1,2-a]pyrimidine-2-carboxamide1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysisic500.0061uM
N-[[2-[[1-(3-fluoro-1-bicyclo[1.1.1]pentanyl)ethylamino]methyl]-1H-indol-6-yl]methyl]-4-oxopyrido[1,2-a]pyrimidine-2-carboxamide1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysisic500.0061uM
N-(1-bicyclo[1.1.1]pentanylmethyl)-1-[2-[[4-(6-methoxyimidazo[1,5-a]pyridin-8-yl)triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methanamine1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysisic500.0061uM
1-cyclobutyl-N-[[2-[[4-(6-methoxyimidazo[1,5-a]pyridin-8-yl)triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methyl]methanamine1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysisic500.0061uM
N-[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methyl]-1-[2-[[4-(6-methoxyimidazo[1,5-a]pyridin-8-yl)triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methanamine1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysisic500.0061uM
(1R,2S,3R,5R)-3-(4-amino-5-bromopyrrolo[2,3-d]pyrimidin-7-yl)-5-[2-(6-azaspiro[3.4]octan-6-ylmethyl)-1H-indol-6-yl]cyclopentane-1,2-diol1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysisic500.0061uM
(1R,2S,3R,5R)-3-(4-amino-5-chloropyrrolo[2,3-d]pyrimidin-7-yl)-5-[2-[[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methylamino]methyl]-1H-indol-6-yl]cyclopentane-1,2-diol1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysisic500.0061uM
(1R,2S,3R,5R)-3-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-[2-(6-azaspiro[3.4]octan-6-ylmethyl)-1H-indol-6-yl]cyclopentane-1,2-diol1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysisic500.0062uM
2-[[4-(6-bromo-1H-indazol-4-yl)triazol-1-yl]methyl]-6-[(4,4-dimethylpiperidin-1-yl)methyl]imidazo[1,2-a]pyridine1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysisic500.0079uM
7-[2-[5-[4-amino-5-(1-methylpyrazol-3-yl)pyrrolo[2,3-d]pyrimidin-7-yl]-3-pyridinyl]ethyl]-N-methylquinolin-2-amine1986933: Inhibition of METTL3/METTL14 (unknown origin) using biotinylated RNA (UCUGGACUAAA-biotin) and 3H-SAM as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by scintillation counter analysisic500.0100uM
7-[2-[5-[4-amino-5-(1-methylpyrazol-3-yl)pyrrolo[2,3-d]pyrimidin-7-yl]-3-pyridinyl]ethyl]-2-ethyl-N-(2-methoxyethyl)-N-methylquinolin-4-amine1986933: Inhibition of METTL3/METTL14 (unknown origin) using biotinylated RNA (UCUGGACUAAA-biotin) and 3H-SAM as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by scintillation counter analysisic500.0100uM
7-[2-[5-[4-amino-5-(1-methylpyrazol-3-yl)pyrrolo[2,3-d]pyrimidin-7-yl]-3-pyridinyl]ethyl]-2-ethyl-N-(2-methoxyethyl)quinolin-4-amine1986933: Inhibition of METTL3/METTL14 (unknown origin) using biotinylated RNA (UCUGGACUAAA-biotin) and 3H-SAM as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by scintillation counter analysisic500.0100uM
7-[[5-[4-amino-5-[(2S)-oxolan-2-yl]pyrrolo[2,3-d]pyrimidin-7-yl]-3-pyridinyl]methoxy]-N-methylquinolin-2-amine1986933: Inhibition of METTL3/METTL14 (unknown origin) using biotinylated RNA (UCUGGACUAAA-biotin) and 3H-SAM as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by scintillation counter analysisic500.0100uM
(2R,3R,4S,5R)-5-[4-amino-5-(1-methylpyrazol-3-yl)pyrrolo[2,3-d]pyrimidin-7-yl]-2-[[2-(azetidin-1-yl)quinolin-7-yl]oxymethyl]-4-fluorooxolan-3-ol1986933: Inhibition of METTL3/METTL14 (unknown origin) using biotinylated RNA (UCUGGACUAAA-biotin) and 3H-SAM as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by scintillation counter analysisic500.0100uM
(2R,3S,5R)-5-[4-amino-5-(1-methylpyrazol-3-yl)pyrrolo[2,3-d]pyrimidin-7-yl]-2-[[2-(azetidin-1-yl)quinolin-7-yl]oxymethyl]oxolan-3-ol1986933: Inhibition of METTL3/METTL14 (unknown origin) using biotinylated RNA (UCUGGACUAAA-biotin) and 3H-SAM as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by scintillation counter analysisic500.0100uM
(2R,3R,4S,5R)-5-(4-amino-5-pyrazol-1-ylpyrrolo[2,3-d]pyrimidin-7-yl)-2-[[2-(azetidin-1-yl)quinolin-7-yl]oxymethyl]-4-fluorooxolan-3-ol1986933: Inhibition of METTL3/METTL14 (unknown origin) using biotinylated RNA (UCUGGACUAAA-biotin) and 3H-SAM as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by scintillation counter analysisic500.0100uM
(2R,3R,4S,5R)-5-[4-amino-5-(4-methyl-1,3-oxazol-2-yl)pyrrolo[2,3-d]pyrimidin-7-yl]-2-[[2-(azetidin-1-yl)quinolin-7-yl]oxymethyl]-4-fluorooxolan-3-ol1986933: Inhibition of METTL3/METTL14 (unknown origin) using biotinylated RNA (UCUGGACUAAA-biotin) and 3H-SAM as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by scintillation counter analysisic500.0100uM
(2R,3R,4S,5R)-5-[4-amino-5-(1-methylpyrazol-3-yl)pyrrolo[2,3-d]pyrimidin-7-yl]-2-[[2-(cyclobutylamino)quinolin-7-yl]oxymethyl]-4-fluorooxolan-3-ol1986933: Inhibition of METTL3/METTL14 (unknown origin) using biotinylated RNA (UCUGGACUAAA-biotin) and 3H-SAM as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by scintillation counter analysisic500.0100uM
(2R,3S,5R)-5-(4-amino-5-pyrazol-1-ylpyrrolo[2,3-d]pyrimidin-7-yl)-2-[[2-(azetidin-1-yl)quinolin-7-yl]oxymethyl]oxolan-3-ol1986933: Inhibition of METTL3/METTL14 (unknown origin) using biotinylated RNA (UCUGGACUAAA-biotin) and 3H-SAM as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by scintillation counter analysisic500.0100uM
(2R,3R,4S,5R)-5-[4-amino-5-[(2S)-oxolan-2-yl]pyrrolo[2,3-d]pyrimidin-7-yl]-4-fluoro-2-[[2-(methylamino)quinolin-7-yl]oxymethyl]oxolan-3-ol1986933: Inhibition of METTL3/METTL14 (unknown origin) using biotinylated RNA (UCUGGACUAAA-biotin) and 3H-SAM as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by scintillation counter analysisic500.0100uM
(2S,3R,4S,5R)-5-[4-amino-5-(1-methylpyrazol-3-yl)pyrrolo[2,3-d]pyrimidin-7-yl]-N-[2-(azetidin-1-yl)quinolin-7-yl]-4-fluoro-3-hydroxyoxolane-2-carboxamide1986933: Inhibition of METTL3/METTL14 (unknown origin) using biotinylated RNA (UCUGGACUAAA-biotin) and 3H-SAM as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by scintillation counter analysisic500.0100uM
N-[[(3R)-1-[6-(benzylamino)pyrimidin-4-yl]-3-hydroxypiperidin-3-yl]methyl]-4-[(4,4-dimethylpiperidin-1-yl)methyl]-2-hydroxybenzamide1986898: Inhibition of recombinant METTL3 (354 to 580 residues)/METTL14 (106 to 396 residues) (unknown origin) using m6A oligonucleotide as substrate by HTRF assayic500.2800uM
(2S)-2-amino-4-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methylsulfanyl]butanoic acid2119490: Inhibition of METTL3/METTL14 (unknown origin)ic500.5200uM
(2S,5S)-2,5-diamino-6-[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]hexanoic acid2119490: Inhibition of METTL3/METTL14 (unknown origin)ic501.3000uM
Quercetin2119492: Inhibition of full length His-tagged METTL3 co-expressed with full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using (5’P-UACACUCGAUCUGGACUAAAGCUGCUC-3’) as substrate pre-treated for 60 mins followed by substrate addition and measured for 1 hr by RapidFire mass spectrometry analysisic502.7000uM
2-[2-[5-(4-fluorophenyl)-1-(3-phenylphenyl)indol-3-yl]ethoxy]benzoic acid1986910: Inhibition of METTL3/METTL14 (unknown origin)ic502.7400uM
2-[2-[1-[4-(2,6-dichlorophenyl)phenyl]-5-(4-fluorophenyl)indol-3-yl]ethoxy]benzoic acid1986910: Inhibition of METTL3/METTL14 (unknown origin)ic502.8100uM
2-[2-[5-(4-fluorophenyl)-1-(4-phenylphenyl)indol-3-yl]ethoxy]benzoic acid1986910: Inhibition of METTL3/METTL14 (unknown origin)ic502.9500uM
2-[2-[1-[4-(4-chlorophenyl)phenyl]-5-(4-fluorophenyl)indol-3-yl]ethoxy]benzoic acid1986910: Inhibition of METTL3/METTL14 (unknown origin)ic503.1300uM
3-[3-[[2-(3,4-dimethylphenyl)-5-methyl-3-oxo-1H-pyrazol-4-yl]diazenyl]-2-hydroxyphenyl]benzoic acid1986923: Inhibition of METTL3/METTL14 (unknown origin) by bioluminescence assayic503.6500uM
5,7,17,19-tetraoxa-13-azoniahexacyclo[11.11.0.02,10.04,8.015,23.016,20]tetracosa-1(13),2,4(8),9,14,16(20),21,23-octaene chloride2127402: Inhibition of METTL3/METTL14 (unknown origin) by FRET assayic505.4900uM
2-[2-[1-benzhydryl-5-(4-fluorophenyl)indol-3-yl]ethoxy]benzoic acid1986910: Inhibition of METTL3/METTL14 (unknown origin)ic506.0000uM
2-(3,4-dihydroxyphenyl)-5,7-dihydroxychromen-4-one2119492: Inhibition of full length His-tagged METTL3 co-expressed with full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using (5’P-UACACUCGAUCUGGACUAAAGCUGCUC-3’) as substrate pre-treated for 60 mins followed by substrate addition and measured for 1 hr by RapidFire mass spectrometry analysisic506.2000uM
2-[2-(1-benzhydryl-5-phenylindol-3-yl)ethoxy]benzoic acid1986910: Inhibition of METTL3/METTL14 (unknown origin)ic508.6300uM
(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxy-N-(4-pyrrolidin-1-ylbutyl)oxolane-2-carboxamide1986897: Competive inhibition of full length human METTL3/METTL14 expressed in Sf9 cells using single strand RNA 5’-AAGAACCGGACUAAGCU-3’ and SAM as substrate incubated for 40 mins by HTRF assayic508.7000uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
sodium arseniteaffects expression, decreases expression, decreases reaction, increases expression5
Valproic Aciddecreases methylation, decreases expression2
aristolochic acid Idecreases expression, increases expression1
TAK-243increases sumoylation1
dicrotophosdecreases expression1
triphenyl phosphateaffects expression1
bisphenol Adecreases expression1
deoxynivalenolincreases expression1
beta-lapachonedecreases expression1
arseniteaffects binding, increases reaction1
3-deazaadenosinedecreases reaction, increases expression1
thallium acetatedecreases reaction, increases expression, affects reaction1
cupric oxideincreases expression1
cadmium sulfateincreases expression1
fumonisin B1increases expression1
di-n-butylphosphoric acidaffects expression1
Docetaxelincreases expression, affects binding, increases reaction, increases methylation, increases response to substance (+2 more)1
Resveratrolaffects cotreatment, increases expression1
Decitabinedecreases reaction, decreases response to substance, increases expression, affects binding, increases reaction1
Arsenic Trioxideaffects binding, increases reaction, decreases reaction, increases phosphorylation, increases expression (+2 more)1
Acetylcysteinedecreases reaction, increases expression1
Arsenicincreases expression1
Benzo(a)pyreneincreases methylation1
Doxorubicinincreases expression, increases abundance, increases reaction, increases methylation, increases stability (+1 more)1
Ethyl Methanesulfonateincreases expression1
Ivermectindecreases expression1
Lipid Peroxidesincreases abundance, increases reaction1
Lipopolysaccharidesaffects reaction, increases expression1
Methyl Methanesulfonateincreases expression1
Plant Extractsaffects cotreatment, increases expression1

ChEMBL screening assays

45 unique, capped per target: 45 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL4005637BindingInhibition of METTL3-14 (unknown origin) at 10 uM using biotin-labeled peptide as substrate and [3H]-SAM measured after 1 hr by scintillation proximity assayDiscovery of Potent and Selective Inhibitors for G9a-Like Protein (GLP) Lysine Methyltransferase. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

CellosaurusNameCategorySex
CVCL_SX93HAP1 METTL14 (-)Cancer cell lineMale

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.