L3MBTL1

Summary

L3MBTL1 (L3MBTL histone methyl-lysine binding protein 1, HGNC:15905) is a protein-coding gene on chromosome 20q13.12, encoding Lethal(3)malignant brain tumor-like protein 1 (Q9Y468). Polycomb group (PcG) protein that specifically recognizes and binds mono- and dimethyllysine residues on target proteins, thereby acting as a ‘reader’ of a network of post-translational modifications.

This gene represents a polycomb group gene. The encoded protein functions to regulate gene activity, likely via chromatin modification. The encoded protein may also be necessary for mitosis. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 26013 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 154 total — 1 likely-pathogenic
• Druggable target: yes — 42 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001377303

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15905
Approved symbol	L3MBTL1
Name	L3MBTL histone methyl-lysine binding protein 1
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	ZC2HC3, dJ138B7.3, DKFZp586P1522, KIAA0681
Ensembl gene	ENSG00000185513
Ensembl biotype	protein_coding
OMIM	608802
Entrez	26013

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 11 retained_intron, 10 protein_coding, 10 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000373133, ENST00000373134, ENST00000373135, ENST00000418998, ENST00000422861, ENST00000427442, ENST00000430781, ENST00000434666, ENST00000439769, ENST00000445228, ENST00000457824, ENST00000468336, ENST00000471977, ENST00000473289, ENST00000473981, ENST00000485334, ENST00000494117, ENST00000497347, ENST00000647827, ENST00000647860, ENST00000648421, ENST00000648570, ENST00000648715, ENST00000648774, ENST00000648786, ENST00000649084, ENST00000649501, ENST00000649698, ENST00000649917, ENST00000650071, ENST00000650349, ENST00000650484, ENST00000704961

RefSeq mRNA: 9 — MANE Select: NM_001377303 NM_001377303, NM_001377306, NM_001377307, NM_001377308, NM_001377309, NM_001377310, NM_001377311, NM_015478, NM_032107

CCDS: CCDS13319, CCDS46602, CCDS93043, CCDS93044, CCDS93045, CCDS93046, CCDS93047

Canonical transcript exons

ENST00000418998 — 22 exons

Exon	Start	End
ENSE00001655380	43513476	43513639
ENSE00001664154	43529264	43529368
ENSE00001735831	43530284	43530419
ENSE00001751978	43540934	43541895
ENSE00003506953	43513838	43514061
ENSE00003540227	43514635	43514776
ENSE00003558755	43515009	43515159
ENSE00003569427	43515292	43515415
ENSE00003605744	43516093	43516177
ENSE00003617573	43528657	43528745
ENSE00003832084	43507697	43507744
ENSE00003990797	43536409	43536458
ENSE00003990799	43533342	43533418
ENSE00003990800	43540753	43540815
ENSE00003990801	43530798	43530889
ENSE00003990802	43540151	43540308
ENSE00003990803	43534828	43534942
ENSE00003990804	43536097	43536294
ENSE00003990805	43534284	43534394
ENSE00003990806	43535837	43535936
ENSE00003990807	43534008	43534093
ENSE00003990808	43532773	43532924

Expression profiles

Bgee: expression breadth ubiquitous, 206 present calls, max score 96.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.1576 / max 77.9198, expressed in 1206 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184661	1.7337	794
184660	1.2233	486
184662	1.0428	587
209114	0.1578	77

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	96.59	silver quality
olfactory bulb	UBERON:0002264	95.51	gold quality
parotid gland	UBERON:0001831	91.83	gold quality
vena cava	UBERON:0004087	91.53	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.72	gold quality
heart right ventricle	UBERON:0002080	89.42	gold quality
pituitary gland	UBERON:0000007	89.05	gold quality
diaphragm	UBERON:0001103	89.02	gold quality
body of tongue	UBERON:0011876	88.99	gold quality
cerebellar hemisphere	UBERON:0002245	88.97	gold quality
cerebellar cortex	UBERON:0002129	88.85	gold quality
adenohypophysis	UBERON:0002196	88.74	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	88.59	gold quality
subthalamic nucleus	UBERON:0001906	88.21	silver quality
pancreatic ductal cell	CL:0002079	88.02	silver quality
right uterine tube	UBERON:0001302	87.89	gold quality
cerebellum	UBERON:0002037	87.71	gold quality
tongue	UBERON:0001723	87.54	silver quality
substantia nigra pars compacta	UBERON:0001965	87.47	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	87.40	gold quality
cervix squamous epithelium	UBERON:0006922	87.34	gold quality
nasal cavity epithelium	UBERON:0005384	87.28	gold quality
myocardium	UBERON:0002349	87.20	gold quality
cardia of stomach	UBERON:0001162	87.15	gold quality
substantia nigra pars reticulata	UBERON:0001966	87.08	gold quality
pylorus	UBERON:0001166	86.93	gold quality
pharyngeal mucosa	UBERON:0000355	86.76	gold quality
right frontal lobe	UBERON:0002810	86.67	gold quality
superior surface of tongue	UBERON:0007371	86.30	gold quality
pericardium	UBERON:0002407	86.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.78

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
CCNE1
MYC	Unknown
RUNX1	Repression

miRNA regulators (miRDB)

45 targeting L3MBTL1, 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-4262	100.00	73.26	3931
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-6797-3P	99.17	66.94	668
HSA-MIR-4464	98.95	67.73	820
HSA-MIR-4748	98.95	67.53	810
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-942-3P	98.81	69.04	876
HSA-MIR-6076	98.61	65.69	637

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 17)

• The ability of TEL to repress TEL-responsive promoters is enhanced by the presence of H-L(3)MBT, an effect dependent on the H-L(3)MBT and the TEL interacting domains, which are mapped to their respective SPM/SAM domains. (PMID:12588862)
• represents a previously undescribed imprinted locus, a vertebrate Polycomb group gene shown to be regulated by this mechanism, and has implications for the pathogenesis of myeloid malignancies associated with 20q deletions (PMID:15123827)
• L3MBTL may have a role in myeloid leukemia (PMID:15334543)
• The MBT domain is related to protein domains that directly bind methylated histone residues and study found that L3MBTL1 MBT domains compact nucleosomal arrays dependent on mono- and dimethylation of histone H4 lysine 20 and of histone H1b lysine 26. (PMID:17540172)
• An unexpected mode of peptide-mediated dimerization suggests a possible mechanism for chromatin compaction by L3MBTL1 (PMID:18026117)
• The structural and binding studies of the two modules provide insights into the molecular principles governing the decoding of lysine methylation states, thereby highlighting a methylation state-specific layer of histone mark readout. (PMID:18042461)
• H4K20 monomethylation and PR-SET7 are important for L3MBTL1 function (PMID:18408754)
• haploinsufficiency of L3MBTL1 contributes to some (20q-) myeloproliferative neoplasms, especially polycythemia vera, by promoting erythroid differentiation (PMID:20585043)
• SET8-mediated methylation of p53 at Lys-382 promotes the interaction between L3MBTL1 and p53 in cells. (PMID:20870725)
• Data suggest that the loss of L3MBTL1 contributes to the development of 20q(-) hematopoietic malignancies by inducing replicative stress, DNA damage, and genomic instability. (PMID:21149733)
• depletion of L3MBTL1 does not affect hESC self-renewal, rather it enhances differentiation toward extra-embryonic trophoblast tissues (PMID:21341991)
• High expression of L3MBTL1 was associated with low grade and hormone receptor-positive tumors, as well as low risk of disease recurrence and breast cancer death. (PMID:21837478)
• Data indicate that germline genes, some of which drive oncogenesis in Drosophila melanogaster, are similarly ectopically activated in a wide range of human cancers. (PMID:24243547)
• The polycomb group protein L3MBTL1 represses a SMAD5-mediated hematopoietic transcriptional program in human pluripotent stem cells. (PMID:25754204)
• Loss of the paternally derived allele of the imprinted L3MBTL1 gene is associated with Shwachman-Diamond syndrome. (PMID:27553422)
• results revealed that the three RNAs-based biomarker network (long non-coding intergenic RNA-[lncRNA RP11-909B2.1], Homo sapiens microRNA-595 [hsa-miRNA-595], and L3MBTL1 mRNA), had high sensitivity and specificity for discriminating CRC from healthy controls and also from benign colorectal neoplasm. (PMID:29737552)
• Expression and DNA Methylation Status of the Imprinted Genes PEG10 and L3MBTL1 in the Umbilical Cord Blood and Placenta of the Offspring of Assisted Reproductive Technology. (PMID:33515207)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	l3mbtl1a	ENSDARG00000014828
mus_musculus	L3mbtl1	ENSMUSG00000035576
rattus_norvegicus	L3mbtl1	ENSRNOG00000007044
drosophila_melanogaster	l(3)mbt	FBGN0002441
drosophila_melanogaster	Sfmbt	FBGN0032475
caenorhabditis_elegans	lin-61	WBGENE00003041
caenorhabditis_elegans	mbtr-1	WBGENE00021661

Paralogs (18): SCMH1 (ENSG00000010803), MBTD1 (ENSG00000011258), SCML1 (ENSG00000047634), L3MBTL2 (ENSG00000100395), SCML2 (ENSG00000102098), PHC1 (ENSG00000111752), THAP10 (ENSG00000129028), PHC2 (ENSG00000134686), SAMD1 (ENSG00000141858), SCML4 (ENSG00000146285), L3MBTL4 (ENSG00000154655), SFMBT1 (ENSG00000163935), PHC3 (ENSG00000173889), SAMD7 (ENSG00000187033), SAMD11 (ENSG00000187634), SFMBT2 (ENSG00000198879), L3MBTL3 (ENSG00000198945), SAMD13 (ENSG00000203943)

Protein

Protein identifiers

Lethal(3)malignant brain tumor-like protein 1 — Q9Y468 (reviewed: Q9Y468)

Alternative names: L(3)mbt protein homolog, L3MBTL1

All UniProt accessions (16): A0A0A0MRR4, A0A3B3IS65, A0A3B3ISB7, A0A3B3ISK5, A0A3B3ISP5, A0A3B3ISS0, A0A3B3ISV7, A0A3B3IT75, A0A3B3ITG5, A0A3B3IUA3, A0A3F2YNZ1, A0A994J4Z1, B0QYN4, B0QYN5, Q9Y468, H0Y7I2

UniProt curated annotations — full annotation on UniProt →

Function. Polycomb group (PcG) protein that specifically recognizes and binds mono- and dimethyllysine residues on target proteins, thereby acting as a ‘reader’ of a network of post-translational modifications. PcG proteins maintain the transcriptionally repressive state of genes: acts as a chromatin compaction factor by recognizing and binding mono- and dimethylated histone H1b/H1-4 at ‘Lys-26’ (H1bK26me1 and H1bK26me2) and histone H4 at ‘Lys-20’ (H4K20me1 and H4K20me2), leading to condense chromatin and repress transcription. Recognizes and binds p53/TP53 monomethylated at ‘Lys-382’, leading to repress p53/TP53-target genes. Also recognizes and binds RB1/RB monomethylated at ‘Lys-860’. Participates in the ETV6-mediated repression. Probably plays a role in cell proliferation. Overexpression induces multinucleated cells, suggesting that it is required to accomplish normal mitosis.

Subunit / interactions. Homodimer. Interacts with RB1/RB (when monomethylated at ‘Lys-860’). Interacts with p53/TP53 (when monomethylated at ‘Lys-382’). Interacts with CBX3, ETV6, KMT5A and VCP/p97.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed. Expression is reduced in colorectal cancer cell line SW480 and promyelocytic leukemia cell line HL-60.

Post-translational modifications. Ubiquitinated in a VCP/p97-dependent way following DNA damage, leading to its removal from DNA damage sites, promoting accessibility of H4K20me2 mark for DNA repair protein TP53BP1, which is then recruited to DNA damage sites.

Domain organisation. The MBT repeat 2 specifically recognizes and binds monomethylated and dimethylated proteins. In contrast, it does not bind trimethylated proteins. The MBT repeat 1 does not bind methylated peptides but inserts a proline ring in a Pro-Ser-Ser/Thr sequence context.

Miscellaneous. The L3MBTL1 locus is imprinted. Paternal inherited gene is expressed, while the maternal inherited gene is silenced.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9Y468-5	5	yes
Q9Y468-1	1, mbt-I
Q9Y468-2	2, mbt-II
Q9Y468-3	3
Q9Y468-4	4

RefSeq proteins (9): NP_001364232, NP_001364235, NP_001364236, NP_001364237, NP_001364238, NP_001364239, NP_001364240, NP_056293, NP_115479 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002515	Znf_C2H2C	Repeat
IPR004092	Mbt	Domain
IPR036060	Znf_C2H2C_sf	Homologous_superfamily
IPR047361	MBT_L3MBTL1_rpt1	Repeat
IPR047362	MBT_L3MBTL1_rpt3	Repeat
IPR050548	PcG_chromatin_remod_factors	Family

Pfam: PF01530, PF02820

UniProt features (76 total): helix 15, strand 14, mutagenesis site 12, sequence conflict 6, compositionally biased region 5, binding site 4, splice variant 4, region of interest 4, repeat 3, sequence variant 3, site 2, chain 1, modified residue 1, zinc finger region 1, turn 1

Structure

Experimental structures (PDB)

20 structures.

PDB	Method	Resolution (Å)
1OZ2	X-RAY DIFFRACTION	1.55
2RJD	X-RAY DIFFRACTION	1.65
2RHI	X-RAY DIFFRACTION	1.66
6BYB	X-RAY DIFFRACTION	1.74
1OYX	X-RAY DIFFRACTION	1.85
1OZ3	X-RAY DIFFRACTION	1.85
2RJE	X-RAY DIFFRACTION	1.86
2RHU	X-RAY DIFFRACTION	1.9
2RHY	X-RAY DIFFRACTION	1.9
2PQW	X-RAY DIFFRACTION	2
2RI3	X-RAY DIFFRACTION	2
2RI5	X-RAY DIFFRACTION	2
2RJC	X-RAY DIFFRACTION	2
2RJF	X-RAY DIFFRACTION	2.05
2RHX	X-RAY DIFFRACTION	2.1
3UWN	X-RAY DIFFRACTION	2.15
2RHZ	X-RAY DIFFRACTION	2.2
2RI2	X-RAY DIFFRACTION	2.2
3OQ5	X-RAY DIFFRACTION	2.5
3P8H	X-RAY DIFFRACTION	2.55

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y468-F1	64.90	0.39

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 (2): 423 (mediates recognition of monomethylated and dimethylated peptides); 426 (positioned at the entrance of mbt 2 and is required for recognition of monomethylated and dimethylated peptides)

Ligand- & substrate-binding residues (4): 622; 627; 640; 646

Post-translational modifications (1): 117

Mutagenesis-validated functional residues (12):

Position	Phenotype
316	does not affect binding to monomethylated and dimethylated peptides.
340	does not affect binding to monomethylated and dimethylated peptides.
423	abolishes binding to monomethylated and dimethylated peptides.
423	strongly impairs binding to monomethylated and dimethylated peptides. abolishes binding to p53/tp53 monomethylated at ’l
426	abolishes binding to monomethylated and dimethylated peptides.
426	strongly impairs binding to monomethylated and dimethylated peptides. abolishes binding to p53/tp53 monomethylated at ’l
431	strongly impairs binding to monomethylated and dimethylated peptides.
447	abolishes binding to monomethylated and dimethylated peptides. abolishes binding to p53/tp53 monomethylated at ’lys-382’
450	abolishes binding to p53/tp53 monomethylated at ’lys-382’.
454	abolishes binding to p53/tp53 monomethylated at ’lys-382’.
527	does not affect binding to monomethylated and dimethylated peptides.
551	does not affect binding to monomethylated and dimethylated peptides.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-6804760	Regulation of TP53 Activity through Methylation
R-HSA-212436	Generic Transcription Pathway
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-5633007	Regulation of TP53 Activity
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 104 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_NUCLEAR_DIVISION, MODULE_493, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A5, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_REGULATION_OF_HEMOPOIESIS, GOBP_ORGANELLE_FISSION, GOBP_REGULATION_OF_MEGAKARYOCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_MITOTIC_NUCLEAR_DIVISION, GOBP_MITOTIC_CELL_CYCLE, GOBP_MEGAKARYOCYTE_DIFFERENTIATION, HAN_SATB1_TARGETS_DN, GOBP_CHROMATIN_REMODELING, GOBP_HETEROCHROMATIN_ORGANIZATION

GO Biological Process (12): chromatin organization (GO:0006325), regulation of mitotic nuclear division (GO:0007088), hemopoiesis (GO:0030097), heterochromatin formation (GO:0031507), regulation of megakaryocyte differentiation (GO:0045652), negative regulation of DNA-templated transcription (GO:0045892), regulation of cell cycle (GO:0051726), constitutive heterochromatin formation (GO:0140719), regulation of DNA-templated transcription (GO:0006355), regulation of macromolecule metabolic process (GO:0060255), regulation of primary metabolic process (GO:0080090), regulation of ubiquitin-dependent protein catabolic process (GO:2000058)

GO Molecular Function (12): chromatin binding (GO:0003682), zinc ion binding (GO:0008270), nucleosome binding (GO:0031491), SAM domain binding (GO:0032093), histone binding (GO:0042393), identical protein binding (GO:0042802), histone H4K20me2 reader activity (GO:0140005), histone H1 reader activity (GO:0140128), histone H1K26me1 reader activity (GO:0160267), histone H1K26me2 reader activity (GO:0160268), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): chromatin (GO:0000785), condensed chromosome (GO:0000793), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromatin lock complex (GO:0061793)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Regulation of TP53 Activity	1
RNA Polymerase II Transcription	1
Generic Transcription Pathway	1
Transcriptional Regulation by TP53	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	2
regulation of metabolic process	2
binding	2
protein binding	2
histone H1 reader activity	2
chromosome	2
cellular anatomical structure	2
cellular component organization	1
regulation of mitotic cell cycle	1
regulation of cell cycle process	1
regulation of nuclear division	1
mitotic nuclear division	1
cell development	1
cellular component assembly	1
heterochromatin boundary formation	1
negative regulation of gene expression, epigenetic	1
heterochromatin organization	1
megakaryocyte differentiation	1
regulation of myeloid cell differentiation	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
cell cycle	1
regulation of cellular process	1
heterochromatin formation	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
macromolecule metabolic process	1
primary metabolic process	1
ubiquitin-dependent protein catabolic process	1
regulation of protein catabolic process	1
transition metal ion binding	1
chromatin binding	1
protein-containing complex binding	1
protein domain specific binding	1
histone H4 reader activity	1
histone reader activity	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
chromatin silencing complex	1

Protein interactions and networks

STRING

1174 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
L3MBTL1	CBX3	Q13185	939
L3MBTL1	KMT5A	Q9NQR1	925
L3MBTL1	TP53	P04637	891
L3MBTL1	MRPL3	P09001	813
L3MBTL1	CBX4	O00257	805
L3MBTL1	H1-5	P16401	728
L3MBTL1	H4C7	Q99525	707
L3MBTL1	H4C16	P02304	705
L3MBTL1	PIWIL4	Q7Z3Z4	692
L3MBTL1	PIWIL1	Q96J94	682
L3MBTL1	H1-4	P10412	675
L3MBTL1	RNF8	O76064	636
L3MBTL1	OTUB2	Q96DC9	631
L3MBTL1	RNF2	Q99496	629
L3MBTL1	E2F4	Q16254	624

IntAct

32 interactions, top by confidence:

A	B	Type	Score
L3MBTL1	H4C16	psi-mi:“MI:0407”(direct interaction)	0.670
L3MBTL1	MCM2	psi-mi:“MI:0915”(physical association)	0.620
L3MBTL1	H1-4	psi-mi:“MI:0914”(association)	0.590
L3MBTL1	H1-4	psi-mi:“MI:0915”(physical association)	0.590
L3MBTL1	H1-4	psi-mi:“MI:0407”(direct interaction)	0.590
L3MBTL1		psi-mi:“MI:0407”(direct interaction)	0.560
CFAP337	ARHGAP17	psi-mi:“MI:0914”(association)	0.560
L3MBTL1	H3C1	psi-mi:“MI:0407”(direct interaction)	0.560
L3MBTL1	DNAJB6	psi-mi:“MI:0914”(association)	0.530
L3MBTL1	MCM5	psi-mi:“MI:0915”(physical association)	0.500
L3MBTL1		psi-mi:“MI:0407”(direct interaction)	0.440
L3MBTL1	VCP	psi-mi:“MI:0915”(physical association)	0.400
L3MBTL1		psi-mi:“MI:0915”(physical association)	0.400
L3MBTL1	FXR2	psi-mi:“MI:0915”(physical association)	0.370
L3MBTL1	RB1	psi-mi:“MI:0914”(association)	0.350
H4C16	H1-4	psi-mi:“MI:0914”(association)	0.350
KDM5C	NCOR1	psi-mi:“MI:0914”(association)	0.350
L3MBTL1	CDC45	psi-mi:“MI:0914”(association)	0.350
L3MBTL4	GAPDHS	psi-mi:“MI:0914”(association)	0.350
L3MBTL1	ZNF195	psi-mi:“MI:0914”(association)	0.350
L3MBTL1	L3MBTL2	psi-mi:“MI:0914”(association)	0.350

BioGRID (148): ZNF644 (Affinity Capture-MS), SATB2 (Affinity Capture-MS), SAMD11 (Affinity Capture-MS), FAM208B (Affinity Capture-MS), WIZ (Affinity Capture-MS), EHMT2 (Affinity Capture-MS), ZNF195 (Affinity Capture-MS), ANAPC1 (Affinity Capture-MS), EHMT1 (Affinity Capture-MS), CBX2 (Affinity Capture-MS), PPHLN1 (Affinity Capture-MS), ANAPC5 (Affinity Capture-MS), ZBTB34 (Affinity Capture-MS), BCOR (Affinity Capture-MS), ZNF281 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M9QN10, A1BPI0, A2ARM1, A2CI97, A2CI98, A2CJ06, C9JE40, O15055, O43147, O54943, O70173, O70303, O70361, O95238, P0C2N6, P0C6P5, P56645, P59025, P59729, P97433, Q0P4K8, Q3TD16, Q5EB20, Q5PQS0, Q5SSZ5, Q5VUB5, Q6IRN0, Q6P4K6, Q76I79, Q7TSI1, Q80TQ5, Q80UW3, Q810F8, Q8C8C1, Q8CCC3, Q8CJE2, Q8N1W1, Q8ND61, Q8TB24, Q8WWF5

Diamond homologs: A2A5N8, B1B1A0, D3YUG0, D3YXK1, D3ZWK4, E1C2V1, O02274, O60284, O95251, P39769, P59178, P70047, P70475, P78364, P97500, Q01538, Q05BQ5, Q1JQD9, Q1RNF8, Q29L50, Q32N90, Q3MIF2, Q4V7W5, Q5DTW2, Q5R737, Q5SVQ0, Q5VUG0, Q5VXD3, Q64028, Q6DIN3, Q6P5G3, Q6SPE9, Q6SPF0, Q7Z3H4, Q80TY4, Q810T5, Q8BLB7, Q8C8Y5, Q8CFC2, Q8CHP6

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
L3MBTL1	“down-regulates activity”	TP53BP1	binding
SVIP	“down-regulates activity”	L3MBTL1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	116
Likely benign	13
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
986171	NM_001377303.1(L3MBTL1):c.2041G>T (p.Glu681Ter)	Likely pathogenic

SpliceAI

4161 predictions. Top by Δscore:

Variant	Effect	Δscore
20:43514707:G:GT	donor_gain	1.0000
20:43530276:G:A	acceptor_gain	1.0000
20:43532905:G:GT	donor_gain	1.0000
20:43532905:G:T	donor_gain	1.0000
20:43532925:GTA:G	donor_gain	1.0000
20:43534371:G:GT	donor_gain	1.0000
20:43534388:GA:G	donor_gain	1.0000
20:43534419:G:T	donor_gain	1.0000
20:43534919:G:GT	donor_gain	1.0000
20:43536095:A:AG	acceptor_gain	1.0000
20:43536096:G:GG	acceptor_gain	1.0000
20:43536096:GGAA:G	acceptor_gain	1.0000
20:43536271:G:GT	donor_gain	1.0000
20:43536291:GCCG:G	donor_gain	1.0000
20:43536292:CCGGT:C	donor_loss	1.0000
20:43536295:G:GA	donor_loss	1.0000
20:43536295:G:GG	donor_gain	1.0000
20:43536296:T:G	donor_loss	1.0000
20:43536309:G:T	donor_gain	1.0000
20:43536457:GA:G	donor_gain	1.0000
20:43536459:G:GG	donor_gain	1.0000
20:43540307:AGGTG:A	donor_loss	1.0000
20:43540308:GGTGA:G	donor_loss	1.0000
20:43540309:G:GC	donor_loss	1.0000
20:43540310:T:G	donor_loss	1.0000
20:43514708:A:T	donor_gain	0.9900
20:43514725:G:GT	donor_gain	0.9900
20:43514773:GCGG:G	donor_gain	0.9900
20:43515291:GGTCA:G	acceptor_gain	0.9900
20:43515412:CATGG:C	donor_loss	0.9900

AlphaMissense

5670 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:43532810:T:C	L419P	1.000
20:43532815:G:C	A421P	1.000
20:43532852:C:A	A433D	1.000
20:43532893:T:C	F447L	1.000
20:43532895:T:A	F447L	1.000
20:43532895:T:G	F447L	1.000
20:43534034:T:A	W492R	1.000
20:43534034:T:C	W492R	1.000
20:43534036:G:C	W492C	1.000
20:43534036:G:T	W492C	1.000
20:43529318:G:C	G314R	0.999
20:43529355:T:C	L326P	0.999
20:43530306:T:C	L338P	0.999
20:43530341:T:A	W350R	0.999
20:43530341:T:C	W350R	0.999
20:43530821:T:A	W384R	0.999
20:43530821:T:C	W384R	0.999
20:43532816:C:A	A421D	0.999
20:43532822:A:C	D423A	0.999
20:43532822:A:G	D423G	0.999
20:43532822:A:T	D423V	0.999
20:43532840:T:C	L429P	0.999
20:43532845:T:C	C431R	0.999
20:43532846:G:A	C431Y	0.999
20:43532847:C:G	C431W	0.999
20:43532851:G:C	A433P	0.999
20:43532858:T:A	V435E	0.999
20:43532885:T:C	L444P	0.999
20:43532888:T:A	V445E	0.999
20:43532894:T:C	F447S	0.999

dbSNP variants (sampled 300 via entrez): RS1000122837 (20:43520352 A>G), RS1000128782 (20:43524810 A>G), RS1000198318 (20:43544275 A>C), RS1000375826 (20:43515479 C>A,G,T), RS1000384666 (20:43520693 C>A,T), RS1000491880 (20:43514212 C>T), RS1000531223 (20:43545475 C>T), RS1000586557 (20:43545793 A>G), RS1000592188 (20:43538301 T>A), RS1000678760 (20:43526686 G>A), RS1000727817 (20:43526379 C>T), RS1000742853 (20:43532208 C>T), RS1000832357 (20:43527249 T>C), RS1000871557 (20:43550813 C>A), RS1000919546 (20:43538567 T>A)

Disease associations

OMIM: gene MIM:608802 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002804_2	Antibody level in response to infection	5.000000e-08
GCST003518_11	Daytime sleep phenotypes	5.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007034	seropositivity measurement
EFO:0007035	Chlamydia pneumoniae seropositivity
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1287622 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

42 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 386,528 (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
CHEMBL1010	CEFOTAXIME SODIUM	4	4,928
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1200398	BUTOCONAZOLE NITRATE	4	2,443
CHEMBL1200493	NAFTIFINE HYDROCHLORIDE	4	1,499
CHEMBL1200725	SERTACONAZOLE NITRATE	4	1,396
CHEMBL1201043	CEPHAPIRIN SODIUM	4	3,301
CHEMBL1201154	PROCHLORPERAZINE EDISYLATE	4	1,206
CHEMBL1417019	MITOXANTRONE HYDROCHLORIDE	4	69,932
CHEMBL1434513	NOREPINEPHRINE BITARTRATE	4	737
CHEMBL1525	PERMETHRIN	4	47,289
CHEMBL1541	CEFIXIME	4	27,787
CHEMBL1668	RESCINNAMINE	4	3,124
CHEMBL1670	MITOTANE	4	83,856
CHEMBL2146123	METHACYCLINE HYDROCHLORIDE	4	2,985
CHEMBL261772	MECLOCYCLINE SULFOSALICYLATE	4	826
CHEMBL282052	METHAQUALONE	4	14,678
CHEMBL3187985	APOMORPHINE HYDROCHLORIDE	4	5,278
CHEMBL4303232	CEFOTIAM HYDROCHLORIDE	4	2,052
CHEMBL46516	FLUSPIRILENE	4	41,239
CHEMBL474579	CEFOTETAN	4	15,647
CHEMBL505	CHLORPHENIRAMINE	4
CHEMBL506247	TANNIC ACID	4
CHEMBL689	MANNITOL	4
CHEMBL772	RESERPINE	4
CHEMBL786	TAMOXIFEN CITRATE	4
CHEMBL857	BIOTIN	4
CHEMBL11608	TYRAMINE	3
CHEMBL248095	SINOMENINE	3
CHEMBL33864	LIPOIC ACID, ALPHA	3
CHEMBL464982	GAMOLENIC ACID	3

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

ChEMBL bioactivities

5469 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.96	Potency	1.1	nM	CHEMBL1383055
8.96	Potency	1.1	nM	CHEMBL1366206
8.89	Potency	1.3	nM	CHEMBL1459193
8.70	Potency	2	nM	CHEMBL1464826
8.70	Potency	2	nM	CHEMBL1348716
8.60	Potency	2.5	nM	CHEMBL1573631
8.60	Potency	2.5	nM	CHEMBL1386435
8.49	Potency	3.2	nM	CHEMBL1438556
8.49	Potency	3.2	nM	CHEMBL1474221
8.46	Potency	3.5	nM	CHEMBL1598177
8.30	Potency	5	nM	CHEMBL1398109
8.30	Potency	5	nM	CHEMBL1469237
8.30	Potency	5	nM	CHEMBL1492129
8.30	Potency	5	nM	CHEMBL1502347
8.25	Potency	5.6	nM	CHEMBL1434495
8.20	Potency	6.3	nM	CHEMBL1405256
8.20	Potency	6.3	nM	CHEMBL1364547
8.15	Potency	7.1	nM	CHEMBL1513210
8.15	Potency	7.1	nM	CHEMBL1353247
8.15	Potency	7.1	nM	CHEMBL1511600
8.10	Potency	7.9	nM	CHEMBL1497180
8.10	Potency	7.9	nM	CHEMBL1548993
8.05	Potency	8.9	nM	CHEMBL1349662
8.05	Potency	8.9	nM	CHEMBL1429803
8.05	Potency	8.9	nM	CHEMBL3192714
8.05	Potency	8.9	nM	CHEMBL1303448
8.05	Potency	8.9	nM	CHEMBL1360930
8.05	Potency	8.9	nM	CHEMBL1522086
8.00	Potency	10	nM	CHEMBL1458027
8.00	Potency	10	nM	CHEMBL1383792
7.95	Potency	11.2	nM	CHEMBL1314718
7.95	Potency	11.2	nM	CHEMBL1331365
7.95	Potency	11.2	nM	CHEMBL1551746
7.90	Potency	12.6	nM	CHEMBL1367140
7.90	Potency	12.6	nM	CHEMBL1423117
7.90	Potency	12.6	nM	CHEMBL1301812
7.85	Potency	14.1	nM	CHEMBL1378797
7.80	Potency	15.8	nM	CHEMBL1300025
7.80	Potency	15.8	nM	CHEMBL1420204
7.80	Potency	15.8	nM	CHEMBL1342722
7.75	Potency	17.8	nM	CHEMBL1467330
7.70	Potency	20	nM	CHEMBL1576043
7.70	Potency	20	nM	CHEMBL1386639
7.65	Potency	22.4	nM	CHEMBL1343476
7.65	Potency	22.4	nM	CHEMBL1320399
7.60	Potency	25.1	nM	CHEMBL1429308
7.60	Potency	25.1	nM	CHEMBL1485390
7.60	Potency	25.1	nM	CHEMBL1549439
7.60	Potency	25.1	nM	CHEMBL1432803
7.60	Potency	25.1	nM	CHEMBL1499434

PubChem BioAssay actives

62 with measured affinity, of 183 total; 50 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
(6R,7R)-3-[(4-carbamoylpyridin-1-ium-1-yl)methyl]-8-oxo-7-[[(2R)-2-phenyl-2-sulfoacetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate	1506809: Inhibition of L3MBTL1 (unknown origin) by AlphaScreen assay	ic50	0.0980	uM
(E)-2-(3,4-dihydroxybenzoyl)-3-(4-hydroxy-3-iodo-5-methoxyphenyl)prop-2-enenitrile	1506809: Inhibition of L3MBTL1 (unknown origin) by AlphaScreen assay	ic50	0.2820	uM
[3-(benzylamino)-4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	0.7400	uM
[2,5-dimethyl-4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	1.2000	uM
(4-pyrrolidin-1-ylpiperidin-1-yl)-[4-(4-pyrrolidin-1-ylpiperidin-1-yl)phenyl]methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	1.5000	uM
[3-benzyl-4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	1.7000	uM
[3-anilino-4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	2189737: Inhibition of MBT domain containing L3MBTL1 (unknown origin) using H4K20me2 peptide by Alpha-Screen methylated histone peptide competition assay	ic50	2.0000	uM
[3-phenyl-4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	2.0000	uM
[3,4-bis(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	2.2000	uM
[5-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)furan-2-yl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	2.3000	uM
[3-bromo-4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	2.5000	uM
[3-nitro-4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	2.7000	uM
[3-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	2.8000	uM
[4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	2.9000	uM
(4-pyrrolidin-1-ylpiperidin-1-yl)-[2,3,5,6-tetrafluoro-4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	2.9000	uM
[3-phenoxy-4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	3.0000	uM
[2-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	3.0000	uM
[4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)naphthalen-1-yl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	3.1000	uM
(4-pyrrolidin-1-ylpiperidin-1-yl)-[4-(4-pyrrolidin-1-ylpiperidin-1-yl)sulfonylphenyl]methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	3.3000	uM
[4-[4-(1-methylpiperidin-4-yl)piperazine-1-carbonyl]phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	3.3000	uM
1-[4-(2-piperidin-1-ylethyl)phenyl]-4-pyrrolidin-1-ylpiperidine	1077868: Binding affinity to L3MBTL1 (unknown origin) by isothermal titration calorimetric analysis	kd	3.3000	uM
(4-piperidin-4-ylpiperidin-1-yl)-[4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	3.5000	uM
[5-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)thiophen-2-yl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	3.7000	uM
(4-pyrrolidin-1-ylpiperidin-1-yl)-[4-[(4-pyrrolidin-1-ylpiperidin-1-yl)methyl]phenyl]methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	3.8000	uM
N-(2-ethyl-1,3-dihydroisoindol-5-yl)-4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)benzamide	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	4.0000	uM
(5-bromo-3-pyridinyl)-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	4.2000	uM
[4-(azepan-1-yl)piperidin-1-yl]-[4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	4.2000	uM
[4-[1-(4-methylpiperazin-1-yl)ethyl]piperidin-1-yl]-[4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	4.4000	uM
[6-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)-3-pyridinyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	4.5000	uM
(3-bromophenyl)-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	4.7000	uM
[6-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)naphthalen-2-yl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	5.0000	uM
[4-(2,8-diazaspiro[4.5]decane-8-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	5.0000	uM
[4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]-(4-pyrrolidin-2-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	5.2000	uM
4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)-N-(3-pyrrolidin-1-ylpropyl)benzamide	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	5.5000	uM
[4-(2,7-diazaspiro[3.4]octane-2-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	5.6000	uM
(4-pyrrolidin-1-ylazepan-1-yl)-[4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	5.9000	uM
(4-pyrrolidin-1-ylpiperidin-1-yl)-[4-(3-pyrrolidin-1-ylpyrrolidine-1-carbonyl)phenyl]methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	6.5000	uM
2-anilino-N-(2-ethyl-1,3-dihydroisoindol-5-yl)-4-(4-pyrrolidin-2-ylpiperidine-1-carbonyl)benzamide	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	6.6000	uM
[4-(8-pyrrolidin-1-yl-3-azabicyclo[3.2.1]octane-3-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	6.6000	uM
(4-piperidin-1-ylpiperidin-1-yl)-[4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	6.8000	uM
[3-amino-4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	6.8000	uM
N-(2-ethyl-1,3-dihydroisoindol-5-yl)-4-(8-pyrrolidin-1-yl-3-azabicyclo[3.2.1]octane-3-carbonyl)benzamide	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	6.8000	uM
[4-(2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrole-5-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	6.9000	uM
[4-(4-morpholin-4-ylpiperidine-1-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	7.1000	uM
[4-(2,7-diazaspiro[4.4]nonane-2-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	7.1000	uM
[4-[4-(dimethylamino)piperidine-1-carbonyl]phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	7.2000	uM
[4-[4-(1-methylpyrrolidin-1-ium-1-yl)piperidine-1-carbonyl]phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	7.5000	uM
[4-(4-cyclopentylpiperazine-1-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	7.6000	uM
[4-(4-pyrrolidin-1-ylazepane-1-carbonyl)phenyl]-(4-pyrrolidin-1-ylazepan-1-yl)methanone	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	8.1000	uM
N-(2-methyl-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-7-yl)-4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)benzamide	771619: Inhibition of L3MBTL1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	8.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, decreases expression	5
trichostatin A	affects cotreatment, decreases expression	2
sodium arsenite	increases abundance, increases expression	2
Nickel	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Aflatoxin B1	increases expression, increases methylation	2
GSK-J4	decreases expression	1
bisphenol F	affects cotreatment, decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
beta-lapachone	decreases expression	1
aflatoxin B2	decreases methylation	1
avobenzone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
entinostat	increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
clothianidin	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation, decreases methylation	1
Acetaminophen	increases expression	1
Amiodarone	increases expression	1
Arsenic	increases abundance, increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1

ChEMBL screening assays

28 unique, capped per target: 26 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1286362	Binding	Activity at L3MBTL1 at 100 uM	Identification of non-peptide malignant brain tumor (MBT) repeat antagonists by virtual screening of commercially available compounds. — J Med Chem
CHEMBL1614280	Functional	PUBCHEM_BIOASSAY: qHTS Assay for the Inhibitors of L3MBTL1. (Class of assay: confirmatory) [Related pubchem assays: 485292 (Probe Development Summary for Inhibitors of L3MBTL1)]	PubChem BioAssay data set

Clinical trials (associated diseases)

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