KMT2B

Summary

KMT2B (lysine methyltransferase 2B, HGNC:15840) is a protein-coding gene on chromosome 19q13.12, encoding Histone-lysine N-methyltransferase 2B (Q9UMN6). Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4) via a non-processive mechanism. It is a selective cancer dependency (DepMap: 11.8% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a protein which contains multiple domains including a CXXC zinc finger, three PHD zinc fingers, two FY-rich domains, and a SET (suppressor of variegation, enhancer of zeste, and trithorax) domain. The SET domain is a conserved C-terminal domain that characterizes proteins of the MLL (mixed-lineage leukemia) family. This gene is ubiquitously expressed in adult tissues. It is also amplified in solid tumor cell lines, and may be involved in human cancer. Two alternatively spliced transcript variants encoding distinct isoforms have been reported for this gene, however, the full length nature of the shorter transcript is not known.

Source: NCBI Gene 9757 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder with motor features (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 2,633 total — 84 pathogenic, 51 likely-pathogenic
• Phenotypes (HPO): 79
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types
• Cancer dependency (DepMap): dependent in 11.8% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 15 downstream targets (CollecTRI)
• MANE Select transcript: NM_014727

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15840
Approved symbol	KMT2B
Name	lysine methyltransferase 2B
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0304, MLL2, TRX2, HRX2, WBP7, MLL1B, MLL4, CXXC10
Ensembl gene	ENSG00000272333
Ensembl biotype	protein_coding
OMIM	606834
Entrez	9757

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 12 protein_coding, 11 nonsense_mediated_decay, 5 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000420124, ENST00000585476, ENST00000586308, ENST00000592092, ENST00000606995, ENST00000673918, ENST00000673946, ENST00000674101, ENST00000674114, ENST00000684977, ENST00000685062, ENST00000685168, ENST00000685609, ENST00000686920, ENST00000687718, ENST00000689139, ENST00000689544, ENST00000689864, ENST00000689929, ENST00000690290, ENST00000690487, ENST00000691421, ENST00000691855, ENST00000691968, ENST00000692961, ENST00000693161, ENST00000693175, ENST00000693540, ENST00000693677

RefSeq mRNA: 1 — MANE Select: NM_014727 NM_014727

CCDS: CCDS46055

Canonical transcript exons

ENST00000420124 — 37 exons

Exon	Start	End
ENSE00000000209	35718003	35718381
ENSE00000699648	35733597	35733686
ENSE00000699650	35732215	35733508
ENSE00000699674	35731908	35732135
ENSE00000699675	35730707	35730867
ENSE00000699676	35730538	35730616
ENSE00000699677	35730342	35730462
ENSE00000699679	35729967	35730125
ENSE00000699681	35729159	35729296
ENSE00000699682	35728985	35729076
ENSE00000699684	35728774	35728889
ENSE00000699686	35728098	35728171
ENSE00000699687	35727881	35727985
ENSE00000699689	35727156	35727269
ENSE00000699690	35726236	35726353
ENSE00000699692	35725723	35725818
ENSE00000699693	35725479	35725625
ENSE00000699694	35725220	35725333
ENSE00000699695	35724989	35725087
ENSE00000699696	35724637	35724731
ENSE00000699701	35722995	35723274
ENSE00000699703	35722568	35722718
ENSE00000699705	35722359	35722472
ENSE00000699758	35719469	35719541
ENSE00000862809	35727438	35727622
ENSE00000862810	35727698	35727787
ENSE00001388562	35719784	35721804
ENSE00001765686	35723732	35724007
ENSE00001803626	35723447	35723502
ENSE00003463796	35737086	35737263
ENSE00003470980	35737859	35737942
ENSE00003498481	35738062	35738191
ENSE00003510252	35736690	35736827
ENSE00003513102	35733763	35733872
ENSE00003545828	35737636	35737743
ENSE00003547961	35736912	35736986
ENSE00003902269	35738282	35738878

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 96.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.0537 / max 713.9909, expressed in 1783 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175374	13.0537	1783

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	96.44	gold quality
left testis	UBERON:0004533	96.24	gold quality
lower esophagus mucosa	UBERON:0035834	96.04	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.07	gold quality
adenohypophysis	UBERON:0002196	94.02	gold quality
granulocyte	CL:0000094	93.82	gold quality
skin of leg	UBERON:0001511	93.60	gold quality
testis	UBERON:0000473	93.46	gold quality
right lobe of thyroid gland	UBERON:0001119	93.21	gold quality
cerebellar hemisphere	UBERON:0002245	93.18	gold quality
skin of abdomen	UBERON:0001416	93.17	gold quality
pituitary gland	UBERON:0000007	93.08	gold quality
left lobe of thyroid gland	UBERON:0001120	93.05	gold quality
mucosa of stomach	UBERON:0001199	92.97	gold quality
cerebellar cortex	UBERON:0002129	92.96	gold quality
spleen	UBERON:0002106	92.94	gold quality
right ovary	UBERON:0002118	92.94	gold quality
left ovary	UBERON:0002119	92.88	gold quality
left uterine tube	UBERON:0001303	92.83	gold quality
metanephros cortex	UBERON:0010533	92.82	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.65	gold quality
mucosa of transverse colon	UBERON:0004991	92.56	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.54	gold quality
body of pancreas	UBERON:0001150	92.39	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.31	gold quality
sural nerve	UBERON:0015488	92.30	gold quality
body of stomach	UBERON:0001161	92.27	gold quality
oocyte	CL:0000023	92.24	gold quality
right lobe of liver	UBERON:0001114	92.24	gold quality
lower esophagus	UBERON:0013473	92.23	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	11.35
E-ANND-3	no	4.11

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

15 targets.

Target	Regulation
GHRHR
HHAT
HOXC10
HOXC13
HOXC6
HRH4
KMT2D
ME2
MMP9
NFKBIA
PCNA
PRMT5
PRMT7
SCARB1
TXN2

Upstream regulators (CollecTRI, top): KMT2A

miRNA regulators (miRDB)

60 targeting KMT2B, 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-5692A	100.00	74.40	6850
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-143-3P	99.49	69.05	1457

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 11.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• data suggest that the translocation breakpoint of MLL4 gene is one of the preferential targets for HBV DNA integration into the MLL4 gene and the HBV DNA integration may be involved in liver oncogenesis (PMID:18320596)
• Alterations of the CxxC domain preclude oncogenic activation of mixed-lineage leukemia 2 (PMID:19060922)
• knockdown of MLL4 severely affects cell-cycle progression and induces apoptotic cell death in cultured tumour cells. (PMID:22713656)
• the second PHD finger (PHD2) of MLL1 is an E3 ubiquitin ligase in the presence of the E2-conjugating enzyme CDC34. This activity is conserved in the second PHD finger of MLL4, the closest homolog to MLL1 but not in MLL2 or MLL3. (PMID:23129768)
• KMT2B transgene mediates hippocampal histone 3 lysine 4 di- and trimethylation and is a critical player for memory formation. (PMID:23426673)
• Chromosomal translocation in a pediatric undifferentiated spindle cell sarcoma have characterized this alteration to show rearrangement of the MLL4 and GPS2 genes, resulting in fusion gene MLL4-GPS2, the expression of which promotes independent growth. (PMID:25139254)
• HBV-MLL4 integration occurred frequently in Chinese HCC patients, representing a unique molecular segment for HCC with HBV infection (PMID:25901726)
• We propose that MLL3 and MLL4 are broadly required for controlling MAFA and MAFB transactivation during development and postnatally. (PMID:26180087)
• The Aven RGG/RG motif bound G4 structures within the coding regions of the MLL1 and MLL4 mRNAs increasing their polysomal association and translation, resulting in the induction of transcription of leukemic genes. (PMID:26267306)
• The results explain how the MLL SET domains of MLL1 and MLL4 are able to add multiple methyl groups to the target histone H3 lysine. (PMID:26320581)
• we describe a method to seamlessly modify a putative CDK2 phosphorylation site on MLL2 to restrict its phosphorylation and activation. Specifically, by utilizing dimeric CRISPR RNA-guided nucleases, RFNs (commercially known as the NextGENtrade mark CRISPR), in combination with an excision-only piggyBactrade mark transposase, we demonstrate how to generate a point mutation of threonine-542, a predicted site to prevent M… (PMID:27075976)
• In the univariate analyses, TP53, PPP1R3A, and KMT2B were significantly more frequently mutated in interval cancers than in screen-detected cancers. (PMID:27587435)
• Results show that KMT2B interacts with ERalpha to bind the ERalpha-binding sites of IL-20 and other ERalpha target genes with H3K4 modifications suggesting an important role for KMT2B in the epigenetic transcriptional regulation of cytokine IL-20, and other ERalpha-responsive genes, in breast cancer cells. (PMID:27806114)
• findings thus establish generalized dystonia as the human phenotype associated with haploinsufficiency of KMT2B; moreover, we provide evidence for a causative role of disordered histone modification, chromatin states, and transcriptional deregulation in dystonia pathogenesis (PMID:27839873)
• The crucial role of KMT2B in the physiological control of voluntary movement. (PMID:27992417)
• MLL4 mutation along with BRCA1 mutation confers chemoresistance in breast cancer. (PMID:28124401)
• Rare missense variation in KMT2B represents an additional cause of generalized dystonia. (PMID:28520167)
• Gene silencing experiments of MLL4 and the subunits PA1 and PTIP confirm TGF-beta-specific genes to be regulated by the MLL4 complex, which links TGF-beta signaling to transcription regulation by the MLL4 methyltransferase complex. (PMID:28976802)
• Summary of variants in KMT2B associated with dystonia, as well as the clinical phenotype (review) (PMID:29289525)
• KMT2B frameshift variants in sporadic cases with combined generalized dystonia; phenotypic variability, including myoclonus, chorea, dysphonia and hypotonia. (PMID:29653907)
• the role of KMT2A and KMT2B, two histone H3 lysine 4 methylases with cardinal roles in development, through individual and combined inactivation, were investigated. (PMID:30355503)
• Study identifies a binding mode of the extended PHD domain of MLL3/4 for the histone H4 N-terminal fragment and provides insights into a trans-histone regulatory mechanism of MLL3/4-mediated H3K4 methylation. (PMID:30604749)
• Childhood-onset progressive dystonia with orofacial involvement is one of the main clinical manifestations of KMT2B mutations. In all, 26% (18/69) of the reported cases have T2 signal alterations of the globus pallidus internus, mostly at a younger age. Anticholinergic medication and GPi-DBS are promising treatment options and shall be considered early (PMID:31165786)
• KMT2B mutations are frequent in childhood-onset dystonia and cause a complex neurodevelopmental syndrome (PMID:31216378)
• Histone methyltransferase MLL4 controls myofiber identity and muscle performance through MEF2 interaction. (PMID:32544095)
• Clinical phenotypes, genotypes and treatment in Chinese dystonia patients with KMT2B variants. (PMID:32634684)
• Histone 3 lysine-27 demethylase KDM6A coordinates with KMT2B to play an oncogenic role in NSCLC by regulating H3K4me3. (PMID:32879445)
• KMT2B-related disorders: expansion of the phenotypic spectrum and long-term efficacy of deep brain stimulation. (PMID:33150406)
• Identification of a novel de novo KMT2B variant in a Greek dystonia patient via exome sequencing genotype-phenotype correlations of all published cases. (PMID:33300088)
• Childhood-onset dystonia-causing KMT2B variants result in a distinctive genomic hypermethylation profile. (PMID:34380541)
• Novel KMT2B mutation causes cerebellar ataxia: Expanding the clinical phenotype. (PMID:34477219)
• Blood DNA methylation provides an accurate biomarker of KMT2B-related dystonia and predicts onset. (PMID:34590685)
• KMT2B promotes SHPRH expression to regulate (131)I sensitivity in thyroid carcinoma cells by affecting FYN protein stability. (PMID:34606908)
• A New Pathologic KMT2B Variant Associated with Childhood Onset Dystonia Presenting as Variable Phenotypes among Family Members. (PMID:35415007)
• Comparison of methylation episignatures in KMT2B- and KMT2D-related human disorders. (PMID:35506254)
• Kabuki syndrome stem cell models reveal locus specificity of histone methyltransferase 2D (KMT2D/MLL4). (PMID:35640156)
• Histone Methyltransferase KMT2B Promotes Metastasis and Angiogenesis of Cervical Cancer by Upregulating EGF Expression. (PMID:36594087)
• Histone H4K16ac Binding Function of the Triple PHD Finger Cassette of MLL4. (PMID:37481158)
• LncRNA SEMA3B-AS1 suppresses the tumor-initiating characteristics of triple negative breast cancer via engaging in MLL4-mediated H3K4 trimethylation. (PMID:37975495)
• MLL4 binds TET3. (PMID:38579707)

Cross-species orthologs

22 orthologs

Organism	Symbol	Gene ID
mus_musculus	Kmt2b	ENSMUSG00000006307
rattus_norvegicus	Kmt2b	ENSRNOG00000055525
drosophila_melanogaster	ash1	FBGN0005386
drosophila_melanogaster	trr	FBGN0023518
drosophila_melanogaster	Set2	FBGN0030486
drosophila_melanogaster	CG4565	FBGN0037841
drosophila_melanogaster	Set1	FBGN0040022
drosophila_melanogaster	G9a	FBGN0040372
drosophila_melanogaster	egg	FBGN0086908
caenorhabditis_elegans		WBGENE00004782
caenorhabditis_elegans	set-32	WBGENE00008062
caenorhabditis_elegans		WBGENE00008206
caenorhabditis_elegans		WBGENE00008527
caenorhabditis_elegans		WBGENE00011729
caenorhabditis_elegans	met-1	WBGENE00016603
caenorhabditis_elegans		WBGENE00018023
caenorhabditis_elegans		WBGENE00019584
caenorhabditis_elegans		WBGENE00019690
caenorhabditis_elegans		WBGENE00019883
caenorhabditis_elegans		WBGENE00020006
caenorhabditis_elegans		WBGENE00020919
caenorhabditis_elegans		WBGENE00021282

Paralogs (19): KMT2C (ENSG00000055609), SETD1A (ENSG00000099381), SUV39H1 (ENSG00000101945), EZH2 (ENSG00000106462), EZH1 (ENSG00000108799), NSD2 (ENSG00000109685), ASH1L (ENSG00000116539), KMT2A (ENSG00000118058), SETDB2 (ENSG00000136169), SETD1B (ENSG00000139718), SETDB1 (ENSG00000143379), NSD3 (ENSG00000147548), SETBP1 (ENSG00000152217), SUV39H2 (ENSG00000152455), NSD1 (ENSG00000165671), KMT2D (ENSG00000167548), EHMT1 (ENSG00000181090), SETD2 (ENSG00000181555), EHMT2 (ENSG00000204371)

Protein

Protein identifiers

Histone-lysine N-methyltransferase 2B — Q9UMN6 (reviewed: Q9UMN6)

Alternative names: Myeloid/lymphoid or mixed-lineage leukemia protein 4, Trithorax homolog 2, WW domain-binding protein 7

All UniProt accessions (23): A0A669KAX8, A0A669KB23, A0A669KBD5, A0A669KBI7, A0A8I5KPK0, A0A8I5KR41, A0A8I5KRR3, A0A8I5KTD0, A0A8I5KU66, A0A8I5KUC7, A0A8I5KUL1, A0A8I5KVT4, A0A8I5KWL4, A0A8I5KWP7, A0A8I5KWS6, A0A8I5KX30, A0A8I5KX31, A0A8I5KXU7, A0A8I5KY89, A0A8I5KZ64, A0A8I5QJW0, A0A8I5QL11, Q9UMN6

UniProt curated annotations — full annotation on UniProt →

Function. Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4) via a non-processive mechanism. Part of chromatin remodeling machinery predominantly forms H3K4me1 and H3K4me2 methylation marks at active chromatin sites where transcription and DNA repair take place. Likely plays a redundant role with KMT2C in enriching H3K4me1 marks on primed and active enhancer elements. Plays a central role in beta-globin locus transcription regulation by being recruited by NFE2. Plays an important role in controlling bulk H3K4me during oocyte growth and preimplantation development. Required during the transcriptionally active period of oocyte growth for the establishment and/or maintenance of bulk H3K4 trimethylation (H3K4me3), global transcriptional silencing that preceeds resumption of meiosis, oocyte survival and normal zygotic genome activation.

Subunit / interactions. Component of the menin-associated histone methyltransferase complex, at least composed of KMT2B/MLL4, ASH2L, RBBP5, WDR5, DPY30, MEN1; the complex interacts with POLR2A and POLR2B via MEN1. Interacts with NFE2. Interacts with KDM6B. Interacts (via WIN motif) with WDR5. Interacts (via MBM motif) with MEN1. Forms a core complex with the evolutionary conserved subcomplex WRAD composed of WDR5, RBBP5, ASH2L/ASH2 and DPY30 subunits; WRAD differentially stimulates the methyltransferase activity.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed. Highest levels in testis. Also found in brain with higher expression in the cerebellum than in any other region, bone marrow, heart, muscle, kidney, placenta, spleen, thymus, prostate, ovary, intestine, colon, peripheral blood lymphocytes and pancreas. Often amplified in pancreatic carcinomas.

Disease relevance. Dystonia 28, childhood-onset (DYT28) [MIM:617284] A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT28 is an autosomal dominant, progressive form characterized by onset in the first decade of life and variable severity. Dystonia begins focally in the lower limbs, resulting in gait difficulties, with later progression to other body regions, including the upper limbs, neck, and orofacial region. The disease is caused by variants affecting the gene represented in this entry. Intellectual developmental disorder, autosomal dominant 68 (MRD68) [MIM:619934] An autosomal dominant disorder characterized by developmental delay, intellectual disability, microcephaly, poor growth, feeding difficulties, and dysmorphic features. Some patients may have autism spectrum disorder or attention deficit-hyperactivity disorder. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The CXXC zinc finger mediates binding to DNA containing unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides.

Similarity. Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. TRX/MLL subfamily.

RefSeq proteins (1): NP_055542* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001214	SET_dom	Domain
IPR001965	Znf_PHD	Domain
IPR002857	Znf_CXXC	Domain
IPR003616	Post-SET_dom	Domain
IPR003888	FYrich_N	Conserved_site
IPR003889	FYrich_C	Conserved_site
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR016569	MeTrfase_trithorax	Family
IPR019787	Znf_PHD-finger	Domain
IPR034732	EPHD	Domain
IPR036427	Bromodomain-like_sf	Homologous_superfamily
IPR041959	KMT2B_ePHD	Domain
IPR046341	SET_dom_sf	Homologous_superfamily
IPR047219	KMT2A_2B_SET	Domain

Pfam: PF00628, PF00856, PF02008, PF05964, PF05965, PF13771

Catalyzed reactions (Rhea), 2 shown:

• L-lysyl(4)-[histone H3] + S-adenosyl-L-methionine = N(6)-methyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-homocysteine + H(+) (RHEA:60264)
• N(6)-methyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-methionine = N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-homocysteine + H(+) (RHEA:60268)

UniProt features (149 total): compositionally biased region 26, sequence variant 24, modified residue 19, binding site 17, region of interest 13, helix 11, strand 11, sequence conflict 7, zinc finger region 6, domain 5, DNA-binding region 3, short sequence motif 2, cross-link 2, initiator methionine 1, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
3UVM	X-RAY DIFFRACTION	1.57
4ERZ	X-RAY DIFFRACTION	1.75
4PZI	X-RAY DIFFRACTION	2.15
7BRE	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

No AlphaFold model available for Q9UMN6 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

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

Ligand- & substrate-binding residues (17): 966; 969; 972; 978; 981; 984; 1000; 1005; 2585; 2587; 2629; 2652–2653 …

Post-translational modifications (21): 2, 113, 114, 118, 351, 821, 844, 861, 936, 1032, 1035, 1092, 1095, 1930, 1936, 2068, 2083, 2288, 2348, 805 …

Mutagenesis-validated functional residues (1):

Position	Phenotype
2652	abolishes interaction with s-adenosyl-l-methionine.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-201722	Formation of the beta-catenin:TCF transactivating complex
R-HSA-3214841	PKMTs methylate histone lysines
R-HSA-3769402	Deactivation of the beta-catenin transactivating complex
R-HSA-8936459	RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function
R-HSA-9772755	Formation of WDR5-containing histone-modifying complexes
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-212436	Generic Transcription Pathway
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878171	Transcriptional regulation by RUNX1
R-HSA-9917777	Epigenetic regulation by WDR5-containing histone modifying complexes

MSigDB gene sets: 247 (showing top): HOFFMANN_SMALL_PRE_BII_TO_IMMATURE_B_LYMPHOCYTE_DN, BROWNE_HCMV_INFECTION_24HR_UP, LEE_CALORIE_RESTRICTION_NEOCORTEX_UP, GOBP_CHROMATIN_REMODELING, GOBP_METHYLATION, SCHLOSSER_SERUM_RESPONSE_UP, GOCC_TRANSFERASE_COMPLEX, GOCC_HISTONE_METHYLTRANSFERASE_COMPLEX, GOCC_MLL1_2_COMPLEX, GOCC_METHYLTRANSFERASE_COMPLEX, GOMF_N_METHYLTRANSFERASE_ACTIVITY, COLDREN_GEFITINIB_RESISTANCE_UP, GOMF_PROTEIN_METHYLTRANSFERASE_ACTIVITY, GOMF_S_ADENOSYLMETHIONINE_DEPENDENT_METHYLTRANSFERASE_ACTIVITY, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_ONE_CARBON_GROUPS

GO Biological Process (5): methylation (GO:0032259), positive regulation of DNA-templated transcription (GO:0045893), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (10): zinc ion binding (GO:0008270), histone H3K4 methyltransferase activity (GO:0042800), unmethylated CpG binding (GO:0045322), histone H3K4 monomethyltransferase activity (GO:0140945), DNA binding (GO:0003677), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740), metal ion binding (GO:0046872), histone H3K4 trimethyltransferase activity (GO:0140999)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), histone methyltransferase complex (GO:0035097), MLL1/2 complex (GO:0044665)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
TCF dependent signaling in response to WNT	2
Gene expression (Transcription)	2
Chromatin modifying enzymes	1
Transcriptional regulation by RUNX1	1
Epigenetic regulation by WDR5-containing histone modifying complexes	1
RNA Polymerase II Transcription	1
Chromatin organization	1
Generic Transcription Pathway	1
Epigenetic regulation of gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	2
histone H3K4 methyltransferase activity	2
metabolic process	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
cellular component organization	1
chromatin organization	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transition metal ion binding	1
protein-lysine N-methyltransferase activity	1
histone H3 methyltransferase activity	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nucleoplasm	1
methyltransferase complex	1
nuclear protein-containing complex	1
histone methyltransferase complex	1

Protein interactions and networks

STRING

2364 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KMT2B	KMT2C	Q8NEZ4	941
KMT2B	KMT2A	Q03164	876
KMT2B	KMT2D	O14686	850
KMT2B	SETD1B	Q9UPS6	842
KMT2B	WDR5	P61964	795
KMT2B	CBX8	Q9HC52	766
KMT2B	MEN1	O00255	661
KMT2B	RBBP5	Q15291	640
KMT2B	ASH2L	Q9UBL3	610
KMT2B	PAXIP1	Q6ZW49	605
KMT2B	DPY30	Q9C005	580
KMT2B	THAP1	Q9NVV9	578
KMT2B	TERT	O14746	554
KMT2B	PAX7	P23759	499
KMT2B	AFF1	P51825	482

IntAct

97 interactions, top by confidence:

A	B	Type	Score
WDR5	KANSL1	psi-mi:“MI:0915”(physical association)	0.950
KMT2B	WDR5	psi-mi:“MI:0407”(direct interaction)	0.940
WDR5	KMT2D	psi-mi:“MI:0914”(association)	0.910
ASH2L	KMT2D	psi-mi:“MI:0914”(association)	0.890
RBBP5	KMT2D	psi-mi:“MI:0914”(association)	0.840
KMT2B	NCOA6	psi-mi:“MI:0915”(physical association)	0.760
WDR5	MEN1	psi-mi:“MI:0914”(association)	0.710
P4HA3	FAM171A2	psi-mi:“MI:0914”(association)	0.640
CSNK2B	RPS6KA4	psi-mi:“MI:0914”(association)	0.640
DPY30	AKAP8	psi-mi:“MI:0914”(association)	0.610
ASH2L	RBBP5	psi-mi:“MI:0914”(association)	0.600
CSNK2A1	SURF6	psi-mi:“MI:0914”(association)	0.590
AKAP8	WDR5	psi-mi:“MI:0915”(physical association)	0.580
NCOA6	UTY	psi-mi:“MI:0914”(association)	0.530
HCFC2	SETD1A	psi-mi:“MI:0914”(association)	0.530
KMT2B	TP53BP1	psi-mi:“MI:0915”(physical association)	0.520
ASH2L	KMT2B	psi-mi:“MI:0915”(physical association)	0.500
KMT2B	MEN1	psi-mi:“MI:0914”(association)	0.460
MEN1	KMT2B	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (178): HIST1H3A (Biochemical Activity), KMT2B (Affinity Capture-MS), KMT2B (Two-hybrid), KMT2B (Affinity Capture-MS), KMT2B (Affinity Capture-MS), KMT2B (Affinity Capture-MS), KMT2B (Reconstituted Complex), KMT2B (Affinity Capture-MS), KMT2B (Affinity Capture-MS), KMT2B (Affinity Capture-MS), KMT2B (Affinity Capture-MS), WDR5 (Reconstituted Complex), RBBP5 (Reconstituted Complex), ASH2L (Reconstituted Complex), KMT2B (Affinity Capture-MS)

ESM2 similar proteins: A6H619, A6NFR6, A8MZF0, B1B0V2, H3BKT1, O08550, O08664, O15054, P08393, P0C674, P0DOD9, P0DPQ3, P14379, P18346, P28284, Q00587, Q0VBZ8, Q17QW1, Q32PF7, Q5NCY0, Q5U2Y8, Q5U4C3, Q5VV67, Q63003, Q63624, Q63625, Q66648, Q66HC8, Q6NZN1, Q6ZRT6, Q80U35, Q80WJ1, Q86UU5, Q86X51, Q8C1R3, Q8V7G4, Q8V7J2, Q8WUZ0, Q914N2, Q91W92

Diamond homologs: A4IGY9, A8XI75, C6KTD2, E9Q5F9, F4K1J4, J9VWH9, O08550, O22781, O43463, O54864, O60016, O64827, O82175, O88974, P20659, P38827, P45975, P55200, Q03164, Q06ZW3, Q08BR4, Q08D57, Q0VD24, Q18221, Q1DR06, Q1DU03, Q1L8U8, Q1LY77, Q24742, Q28CQ7, Q28Z18, Q294B9, Q2GWF3, Q2H988, Q2LAE1, Q2NL30, Q2UMH3, Q2UTN6, Q32KD2, Q32PH7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 91 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of WDR5-containing histone-modifying complexes	12	48.3×	4e-15
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	8	23.9×	2e-07
Deactivation of the beta-catenin transactivating complex	6	21.2×	2e-05
Epigenetic regulation by WDR5-containing histone modifying complexes	8	18.7×	7e-07
PKMTs methylate histone lysines	7	17.1×	1e-05
Formation of the beta-catenin:TCF transactivating complex	9	16.4×	4e-07
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	5	16.3×	4e-04
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	8	14.6×	5e-06

GO biological processes:

GO term	Partners	Fold	FDR
transcription initiation-coupled chromatin remodeling	5	21.8×	5e-04
DNA damage response	13	7.9×	3e-06

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 2 cancer types — HCC, VULVA.

Clinical variants and AI predictions

ClinVar

2633 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	84
Likely pathogenic	51
Uncertain significance	975
Likely benign	886
Benign	309

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1172540	NM_014727.3(KMT2B):c.7614del (p.Thr2539fs)	Pathogenic
1207914	NM_014727.3(KMT2B):c.1656dup (p.Lys553fs)	Pathogenic
1297015	NM_014727.3(KMT2B):c.6413dup (p.Ala2139fs)	Pathogenic
1351418	NM_014727.3(KMT2B):c.3199C>T (p.Gln1067Ter)	Pathogenic
1374033	NM_014727.3(KMT2B):c.6210_6213del (p.Ser2070fs)	Pathogenic
1395227	NM_014727.3(KMT2B):c.1656del (p.Lys553fs)	Pathogenic
1437671	NM_014727.3(KMT2B):c.3386dup (p.Gln1130fs)	Pathogenic
1452284	NM_014727.3(KMT2B):c.5572dup (p.Arg1858fs)	Pathogenic
1453167	NM_014727.3(KMT2B):c.12_24del (p.Ala5fs)	Pathogenic
1454823	NM_014727.3(KMT2B):c.6710del (p.Gly2237fs)	Pathogenic
1525972	NM_014727.3(KMT2B):c.5073C>T (p.Gly1691=)	Pathogenic
1678828	NM_014727.3(KMT2B):c.6895dup (p.Arg2299fs)	Pathogenic
1685914	NM_014727.3(KMT2B):c.683del (p.Ala228fs)	Pathogenic
1687549	NM_014727.3(KMT2B):c.5230_5233del (p.Ser1744fs)	Pathogenic
1708481	NM_014727.3(KMT2B):c.5741_5748dup (p.Ser1917fs)	Pathogenic
1803994	NM_014727.3(KMT2B):c.7012del (p.Asp2338fs)	Pathogenic
1975543	NM_014727.3(KMT2B):c.7501dup (p.Glu2501fs)	Pathogenic
1995855	NM_014727.3(KMT2B):c.17_23dup (p.Ser9fs)	Pathogenic
2027897	NM_014727.3(KMT2B):c.1723del (p.Gln575fs)	Pathogenic
2052813	NM_014727.3(KMT2B):c.6733_6757del (p.Val2245fs)	Pathogenic
2065920	NM_014727.3(KMT2B):c.1886dup (p.Ala630fs)	Pathogenic
2069005	NM_014727.3(KMT2B):c.5730del (p.Arg1911fs)	Pathogenic
2099156	NM_014727.3(KMT2B):c.6866del (p.Pro2289fs)	Pathogenic
2104038	NM_014727.3(KMT2B):c.7265A>G (p.Asp2422Gly)	Pathogenic
2120147	NM_014727.3(KMT2B):c.4480_4481insGGGCGCCACGGCTCTAGTCTGGGCCTTCTCAGTACTTGCCCAAAATAGAAACGCTTTCTGAAAACTAATAACNNNNNNNNNNTCTGGGCCACAAGACCCAACACCTTAAACCAGATGTCAAAGAAAGAAGCCACGGGAAGTAAACACTTTGCTTATGA (p.Lys1494delinsArgAlaProArgLeuTer)	Pathogenic
2127890	NM_014727.3(KMT2B):c.4171_4207dup (p.Glu1403fs)	Pathogenic
2132480	NM_014727.3(KMT2B):c.2200_2201del (p.Gln734fs)	Pathogenic
2134599	NM_014727.3(KMT2B):c.4053_4063del (p.Glu1351fs)	Pathogenic
2227434	NM_014727.3(KMT2B):c.7513_7514del (p.Asn2505fs)	Pathogenic
2284068	NM_014727.3(KMT2B):c.6552dup (p.Lys2185fs)	Pathogenic

SpliceAI

6582 predictions. Top by Δscore:

Variant	Effect	Δscore
19:35718378:GGAG:G	donor_gain	1.0000
19:35718379:GAGG:G	donor_gain	1.0000
19:35718380:AG:A	donor_loss	1.0000
19:35718382:G:GA	donor_loss	1.0000
19:35719449:ACCCC:A	acceptor_gain	1.0000
19:35719453:C:A	acceptor_gain	1.0000
19:35722453:C:G	donor_gain	1.0000
19:35722473:G:GG	donor_gain	1.0000
19:35722487:G:GT	donor_gain	1.0000
19:35722566:A:AG	acceptor_gain	1.0000
19:35722566:AG:A	acceptor_gain	1.0000
19:35722567:G:A	acceptor_gain	1.0000
19:35722567:G:GG	acceptor_gain	1.0000
19:35722715:GAGG:G	donor_gain	1.0000
19:35722717:GG:G	donor_gain	1.0000
19:35722718:GG:G	donor_gain	1.0000
19:35722719:G:GG	donor_gain	1.0000
19:35722719:G:T	donor_gain	1.0000
19:35722719:GT:G	donor_loss	1.0000
19:35722720:T:G	donor_loss	1.0000
19:35723500:AAGG:A	donor_loss	1.0000
19:35723501:AGGTG:A	donor_loss	1.0000
19:35723502:GG:G	donor_loss	1.0000
19:35723503:G:C	donor_loss	1.0000
19:35724005:ATGGT:A	donor_loss	1.0000
19:35724006:TGG:T	donor_loss	1.0000
19:35724008:G:GC	donor_loss	1.0000
19:35724008:G:GG	donor_gain	1.0000
19:35724009:T:A	donor_loss	1.0000
19:35724630:T:A	acceptor_gain	1.0000

AlphaMissense

17323 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:35720926:T:C	F527L	1.000
19:35720927:T:C	F527S	1.000
19:35720928:T:A	F527L	1.000
19:35720928:T:G	F527L	1.000
19:35721172:T:C	F609L	1.000
19:35721174:T:A	F609L	1.000
19:35721174:T:G	F609L	1.000
19:35721178:T:A	W611R	1.000
19:35721178:T:C	W611R	1.000
19:35721180:G:C	W611C	1.000
19:35721180:G:T	W611C	1.000
19:35721734:T:C	L796P	1.000
19:35721755:T:C	L803P	1.000
19:35722589:G:C	G865R	1.000
19:35722595:C:A	R867S	1.000
19:35722599:T:A	I868N	1.000
19:35722599:T:C	I868T	1.000
19:35722599:T:G	I868S	1.000
19:35722601:A:G	K869E	1.000
19:35722602:A:T	K869I	1.000
19:35722603:A:C	K869N	1.000
19:35722603:A:T	K869N	1.000
19:35722604:C:A	H870N	1.000
19:35722604:C:G	H870D	1.000
19:35722605:A:G	H870R	1.000
19:35722606:T:A	H870Q	1.000
19:35722606:T:G	H870Q	1.000
19:35722608:T:A	V871D	1.000
19:35722610:T:A	C872S	1.000
19:35722610:T:C	C872R	1.000

dbSNP variants (sampled 300 via entrez): RS1000006092 (19:35718479 C>G,T), RS1000386224 (19:35717542 G>A), RS1000387112 (19:35722130 G>A), RS1000544799 (19:35728150 G>A), RS1000617920 (19:35723579 T>C,G), RS1000754649 (19:35737493 G>A), RS1000816894 (19:35722254 C>G,T), RS1000932098 (19:35722724 T>G), RS1001157040 (19:35731640 C>G), RS1001174696 (19:35718535 CG>C), RS1001467005 (19:35736331 C>T), RS1001725763 (19:35726565 C>T), RS1001821773 (19:35720905 T>G), RS1001886314 (19:35727606 T>C), RS1001976793 (19:35731705 C>G,T)

Disease associations

OMIM: gene MIM:606834 | disease phenotypes: MIM:617284, MIM:619934, MIM:619681, MIM:611934, MIM:147920, MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
dystonia 28, childhood-onset	Definitive	Autosomal dominant
intellectual developmental disorder, autosomal dominant 68	Limited	Unknown

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
complex neurodevelopmental disorder with motor features	Definitive	AD

Mondo (13): dystonia 28, childhood-onset (MONDO:0015004), dystonic disorder (MONDO:0003441), intellectual developmental disorder, autosomal dominant 68 (MONDO:0030969), dystonia, early-onset, and/or spastic paraplegia (MONDO:0859215), autism spectrum disorder (MONDO:0005258), complex neurodevelopmental disorder with motor features (MONDO:0100516), intellectual disability (MONDO:0001071), epilepsy, idiopathic generalized, susceptibility to, 5 (MONDO:0012760), Kabuki syndrome 1 (MONDO:0007843), generalized dystonia (MONDO:0000476), Castleman-Kojima disease (MONDO:0018702), specific learning disability (MONDO:0016225), autism (MONDO:0005260)

Orphanet (8): Dystonia 28 (Orphanet:589618), Kabuki syndrome (Orphanet:2322), Generalized isolated dystonia (Orphanet:376724), TAFRO syndrome (Orphanet:457077), Specific learning disability (Orphanet:211047), Rare genetic intellectual disability (Orphanet:183757), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

79 total (30 of 79 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000020	Urinary incontinence
HP:0000154	Wide mouth
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000276	Long face
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000358	Posteriorly rotated ears
HP:0000387	Absent earlobe
HP:0000414	Bulbous nose
HP:0000473	Torticollis
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000496	Abnormality of eye movement
HP:0000508	Ptosis
HP:0000540	Hypermetropia
HP:0000629	Periorbital fullness
HP:0000639	Nystagmus
HP:0000716	Depression
HP:0000729	Autistic behavior
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000821	Hypothyroidism
HP:0000826	Precocious puberty
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002942_6	Percentage gas trapping	8.000000e-08
GCST004139_23	Bipolar disorder	6.000000e-08
GCST008103_109	Bipolar disorder	4.000000e-06
GCST010002_54	Refractive error	1.000000e-10
GCST010703_277	Brain morphology (MOSTest)	2.000000e-15
GCST90002382_462	Eosinophil percentage of white cells	7.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007628	gas trapping measurement
EFO:0004346	neuroimaging measurement
EFO:0007991	eosinophil percentage of leukocytes

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D004422	Dystonia Musculorum Deformans	C10.228.140.079.357; C10.228.662.300.200; C10.574.500.393; C16.320.400.330
D020821	Dystonic Disorders	C10.228.662.300
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D000067559	Specific Learning Disorder	C10.597.606.150.550.700; C23.888.592.604.150.550.700; F03.625.374.188.700; F03.625.562.700

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2189112 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 2.1.1.43 Histone methyltransferases (HMTs)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	affects expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
beta-methylcholine	affects expression	1
tamibarotene	affects expression	1
di-n-butylphosphoric acid	affects expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	increases expression	1
abrine	increases expression	1
bisphenol AF	affects binding, decreases reaction	1
Sunitinib	increases expression	1
Ethanol	decreases expression	1
Benzene	increases expression	1
Caffeine	affects phosphorylation	1
Doxorubicin	affects expression	1
Estradiol	affects binding, increases reaction	1
Formaldehyde	increases expression	1
Ivermectin	increases expression	1
Mercury	increases expression	1
Methapyrilene	increases methylation	1
Ozone	affects expression, increases abundance	1
Selenium	affects cotreatment, increases expression	1
Smoke	decreases expression	1

ChEMBL screening assays

15 unique, capped per target: 15 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2209111	Binding	Inhibition of MLL4 using core histone as substrate preincubated for 10 mins followed by addition of [3H]SAM and incubated for 60 mins	Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2. — ACS Med Chem Lett

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E3GB	HCI-EC-23	Cancer cell line	Female
CVCL_SU99	HAP1 KMT2B (-) 1	Cancer cell line	Male
CVCL_SV00	HAP1 KMT2B (-) 2	Cancer cell line	Male
CVCL_SV01	HAP1 KMT2B (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00142259	PHASE4	UNKNOWN	Efficacy and Safety of DBS of the GPi in Patients With Primary Generalized and Segmental Dystonia
NCT00950196	PHASE4	COMPLETED	Amantadine for Improving Neurologic Symptoms in Ataxia-Telangiectasia
NCT00998660	PHASE4	COMPLETED	RECHARGE Sub-Study to the Implantable Systems Performance Registry (ISPR)
NCT02263417	PHASE4	COMPLETED	A Randomized Controlled Trail Comparing Subthalamic and Pallidal Deep Brain Stimulation for Dystonia
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
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NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
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NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00169403	PHASE3	UNKNOWN	Pallidal Stimulation in Patients With Idiopathic Generalised Dystonia
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NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
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NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
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