Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMMAZQX)

• DOT Name: Histone-lysine N-methyltransferase 2B (KMT2B)
• Synonyms: Lysine N-methyltransferase 2B; EC 2.1.1.364; Myeloid/lymphoid or mixed-lineage leukemia protein 4; Trithorax homolog 2; WW domain-binding protein 7; WBP-7
• Gene Name: KMT2B
• Related Disease:
  Complex neurodevelopmental disorder with motor features
  Dystonia 28, childhood-onset
  Hepatitis B virus infection
  Intellectual disability
  Acute lymphocytic leukaemia
  Acute myelogenous leukaemia
  Adenocarcinoma
  Adult glioblastoma
  Arteriosclerosis
  Atherosclerosis
  B-cell lymphoma
  B-cell neoplasm
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Cardiac failure
  Cervical cancer
  Cervical carcinoma
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Congestive heart failure
  Dilated cardiomyopathy 1A
  Dystonia
  Esophageal squamous cell carcinoma
  Follicular lymphoma
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  Medulloblastoma
  Movement disorder
  Neoplasm
  Non-small-cell lung cancer
  Paroxysmal dystonia
  Renal cell carcinoma
  Squamous cell carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Fatty liver disease
  Gastric cancer
  Obesity
  Prostate cancer
  Stomach cancer
  Melanoma
  Advanced cancer
  Intellectual developmental disorder, autosomal dominant 68
  Kabuki syndrome
  leukaemia
  Leukemia
• UniProt ID: KMT2B_HUMAN
• PDB ID: 3UVM; 4ERZ; 4PZI; 7BRE
• EC Number: 2.1.1.364
• Pfam ID: PF05965 ; PF05964 ; PF00628 ; PF00856 ; PF02008 ; PF13771
• Sequence:
  MAAAAGGGSCPGPGSARGRFPGRPRGAGGGGGRGGRGNGAERVRVALRRGGGATGPGGAE
  PGEDTALLRLLGLRRGLRRLRRLWAGPRVQRGRGRGRGRGWGPSRGCVPEEESSDGESDE
  EEFQGFHSDEDVAPSSLRSALRSQRGRAPRGRGRKHKTTPLPPPRLADVAPTPPKTPARK
  RGEEGTERMVQALTELLRRAQAPQAPRSRACEPSTPRRSRGRPPGRPAGPCRRKQQAVVV
  AEAAVTIPKPEPPPPVVPVKHQTGSWKCKEGPGPGPGTPRRGGQSSRGGRGGRGRGRGGG
  LPFVIKFVSRAKKVKMGQLSLGLESGQGQGQHEESWQDVPQRRVGSGQGGSPCWKKQEQK
  LDDEEEEKKEEEEKDKEGEEKEERAVAEEMMPAAEKEEAKLPPPPLTPPAPSPPPPLPPP
  STSPPPPLCPPPPPPVSPPPLPSPPPPPAQEEQEESPPPVVPATCSRKRGRPPLTPSQRA
  EREAARAGPEGTSPPTPTPSTATGGPPEDSPTVAPKSTTFLKNIRQFIMPVVSARSSRVI
  KTPRRFMDEDPPKPPKVEVSPVLRPPITTSPPVPQEPAPVPSPPRAPTPPSTPVPLPEKR
  RSILREPTFRWTSLTRELPPPPPAPPPPPAPSPPPAPATSSRRPLLLRAPQFTPSEAHLK
  IYESVLTPPPLGAPEAPEPEPPPADDSPAEPEPRAVGRTNHLSLPRFAPVVTTPVKAEVS
  PHGAPALSNGPQTQAQLLQPLQALQTQLLPQALPPPQPQLQPPPSPQQMPPLEKARIAGV
  GSLPLSGVEEKMFSLLKRAKVQLFKIDQQQQQKVAASMPLSPGGQMEEVAGAVKQISDRG
  PVRSEDESVEAKRERPSGPESPVQGPRIKHVCRHAAVALGQARAMVPEDVPRLSALPLRD
  RQDLATEDTSSASETESVPSRSRRGKVEAAGPGGESEPTGSGGTLAHTPRRSLPSHHGKK
  MRMARCGHCRGCLRVQDCGSCVNCLDKPKFGGPNTKKQCCVYRKCDKIEARKMERLAKKG
  RTIVKTLLPWDSDESPEASPGPPGPRRGAGAGGPREEVVAHPGPEEQDSLLQRKSARRCV
  KQRPSYDIFEDSDDSEPGGPPAPRRRTPRENELPLPEPEEQSRPRKPTLQPVLQLKARRR
  LDKDALAPGPFASFPNGWTGKQKSPDGVHRVRVDFKEDCDLENVWLMGGLSVLTSVPGGP
  PMVCLLCASKGLHELVFCQVCCDPFHPFCLEEAERPLPQHHDTWCCRRCKFCHVCGRKGR
  GSKHLLECERCRHAYHPACLGPSYPTRATRKRRHWICSACVRCKSCGATPGKNWDVEWSG
  DYSLCPRCTQLYEKGNYCPICTRCYEDNDYESKMMQCAQCDHWVHAKCEGLSDEDYEILS
  GLPDSVLYTCGPCAGAAQPRWREALSGALQGGLRQVLQGLLSSKVVGPLLLCTQCGPDGK
  QLHPGPCGLQAVSQRFEDGHYKSVHSFMEDMVGILMRHSEEGETPDRRAGGQMKGLLLKL
  LESAFGWFDAHDPKYWRRSTRLPNGVLPNAVLPPSLDHVYAQWRQQEPETPESGQPPGDP
  SAAFQGKDPAAFSHLEDPRQCALCLKYGDADSKEAGRLLYIGQNEWTHVNCAIWSAEVFE
  ENDGSLKNVHAAVARGRQMRCELCLKPGATVGCCLSSCLSNFHFMCARASYCIFQDDKKV
  FCQKHTDLLDGKEIVNPDGFDVLRRVYVDFEGINFKRKFLTGLEPDAINVLIGSIRIDSL
  GTLSDLSDCEGRLFPIGYQCSRLYWSTVDARRRCWYRCRILEYRPWGPREEPAHLEAAEE
  NQTIVHSPAPSSEPPGGEDPPLDTDVLVPGAPERHSPIQNLDPPLRPDSGSAPPPAPRSF
  SGARIKVPNYSPSRRPLGGVSFGPLPSPGSPSSLTHHIPTVGDPDFPAPPRRSRRPSPLA
  PRPPPSRWASPPLKTSPQLRVPPPTSVVTALTPTSGELAPPGPAPSPPPPEDLGPDFEDM
  EVVSGLSAADLDFAASLLGTEPFQEEIVAAGAMGSSHGGPGDSSEEESSPTSRYIHFPVT
  VVSAPGLAPSATPGAPRIEQLDGVDDGTDSEAEAVQQPRGQGTPPSGPGVVRAGVLGAAG
  DRARPPEDLPSEIVDFVLKNLGGPGDGGAGPREESLPPAPPLANGSQPSQGLTASPADPT
  RTFAWLPGAPGVRVLSLGPAPEPPKPATSKIILVNKLGQVFVKMAGEGEPVPPPVKQPPL
  PPTISPTAPTSWTLPPGPLLGVLPVVGVVRPAPPPPPPPLTLVLSSGPASPPRQAIRVKR
  VSTFSGRSPPAPPPYKAPRLDEDGEASEDTPQVPGLGSGGFSRVRMKTPTVRGVLDLDRP
  GEPAGEESPGPLQERSPLLPLPEDGPPQVPDGPPDLLLESQWHHYSGEASSSEEEPPSPD
  DKENQAPKRTGPHLRFEISSEDGFSVEAESLEGAWRTLIEKVQEARGHARLRHLSFSGMS
  GARLLGIHHDAVIFLAEQLPGAQRCQHYKFRYHQQGEGQEEPPLNPHGAARAEVYLRKCT
  FDMFNFLASQHRVLPEGATCDEEEDEVQLRSTRRATSLELPMAMRFRHLKKTSKEAVGVY
  RSAIHGRGLFCKRNIDAGEMVIEYSGIVIRSVLTDKREKFYDGKGIGCYMFRMDDFDVVD
  ATMHGNAARFINHSCEPNCFSRVIHVEGQKHIVIFALRRILRGEELTYDYKFPIEDASNK
  LPCNCGAKRCRRFLN
• 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.
• 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.
• KEGG Pathway:
  Lysine degradation (hsa00310)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function (R-HSA-8936459)
  Formation of WDR5-containing histone-modifying complexes (R-HSA-9772755)
  PKMTs methylate histone lysines (R-HSA-3214841)
• BioCyc Pathway: MetaCyc:HS02784-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Complex neurodevelopmental disorder with motor features	DIS09FBL	Definitive	Autosomal dominant	[1]
Dystonia 28, childhood-onset	DISHWWOS	Definitive	Autosomal dominant	[2]
Hepatitis B virus infection	DISLQ2XY	Definitive	Biomarker	[3]
Intellectual disability	DISMBNXP	Definitive	Genetic Variation	[4]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[5]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[6]
Adenocarcinoma	DIS3IHTY	Strong	Genetic Variation	[7]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[8]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[9]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[9]
B-cell lymphoma	DISIH1YQ	Strong	Genetic Variation	[10]
B-cell neoplasm	DISVY326	Strong	Genetic Variation	[11]
Bladder cancer	DISUHNM0	Strong	Biomarker	[12]
Breast cancer	DIS7DPX1	Strong	Biomarker	[13]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[13]
Cardiac failure	DISDC067	Strong	Biomarker	[14]
Cervical cancer	DISFSHPF	Strong	Genetic Variation	[15]
Cervical carcinoma	DIST4S00	Strong	Genetic Variation	[15]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[16]
Colon cancer	DISVC52G	Strong	Altered Expression	[17]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[17]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[14]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[14]
Dystonia	DISJLFGW	Strong	Biomarker	[18]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[19]
Follicular lymphoma	DISVEUR6	Strong	Genetic Variation	[11]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[20]
Glioma	DIS5RPEH	Strong	Altered Expression	[21]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[22]
Medulloblastoma	DISZD2ZL	Strong	Altered Expression	[23]
Movement disorder	DISOJJ2D	Strong	CausalMutation	[24]
Neoplasm	DISZKGEW	Strong	Altered Expression	[25]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[26]
Paroxysmal dystonia	DISV0MSQ	Strong	Biomarker	[24]
Renal cell carcinoma	DISQZ2X8	Strong	Genetic Variation	[27]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[25]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[12]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[12]
Fatty liver disease	DIS485QZ	moderate	Biomarker	[28]
Gastric cancer	DISXGOUK	moderate	Biomarker	[29]
Obesity	DIS47Y1K	moderate	Biomarker	[28]
Prostate cancer	DISF190Y	moderate	Genetic Variation	[30]
Stomach cancer	DISKIJSX	moderate	Biomarker	[29]
Melanoma	DIS1RRCY	Disputed	Biomarker	[31]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[19]
Intellectual developmental disorder, autosomal dominant 68	DISRHNIN	Limited	Unknown	[32]
Kabuki syndrome	DISZN97H	Limited	Genetic Variation	[33]
leukaemia	DISS7D1V	Limited	Altered Expression	[34]
Leukemia	DISNAKFL	Limited	Altered Expression	[34]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Histone-lysine N-methyltransferase 2B (KMT2B) increases the Leukaemias ADR of Etoposide.	[44]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Histone-lysine N-methyltransferase 2B (KMT2B).	[35]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Histone-lysine N-methyltransferase 2B (KMT2B).	[42]

9 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of Histone-lysine N-methyltransferase 2B (KMT2B).	[36]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Histone-lysine N-methyltransferase 2B (KMT2B).	[37]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of Histone-lysine N-methyltransferase 2B (KMT2B).	[38]
Selenium	DM25CGV	Approved	Selenium increases the expression of Histone-lysine N-methyltransferase 2B (KMT2B).	[39]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Histone-lysine N-methyltransferase 2B (KMT2B).	[40]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Histone-lysine N-methyltransferase 2B (KMT2B).	[36]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Histone-lysine N-methyltransferase 2B (KMT2B).	[39]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Histone-lysine N-methyltransferase 2B (KMT2B).	[41]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Histone-lysine N-methyltransferase 2B (KMT2B).	[43]

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