Details of Drug Off-Target (DOT)

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

• DOT Name: Histone-lysine N-methyltransferase 2D (KMT2D)
• Synonyms: Lysine N-methyltransferase 2D; EC 2.1.1.364; ALL1-related protein; Myeloid/lymphoid or mixed-lineage leukemia protein 2
• Gene Name: KMT2D
• Related Disease:
  Hepatitis B virus infection
  Kabuki syndrome 1
  Adult glioblastoma
  Adult lymphoma
  Bladder cancer
  Branchial arch abnormalities, choanal atresia, athelia, hearing loss, and hypothyroidism syndrome
  Breast neoplasm
  Diabetic retinopathy
  Follicular lymphoma
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Intellectual disability
  Isolated cleft palate
  Lymphoma
  Male infertility
  Medulloblastoma
  Microphthalmia
  Neoplasm
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Obesity
  Pediatric lymphoma
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Sensorineural hearing loss disorder
  Sezary syndrome
  Squamous cell carcinoma
  T-cell lymphoma
  Type-1/2 diabetes
  Ventricular septal defect
  B-cell lymphoma
  Bipolar disorder
  Choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome
  Gastric cancer
  Movement disorder
  Stomach cancer
  Kabuki syndrome
  Advanced cancer
  B-cell neoplasm
  Breast cancer
  Breast carcinoma
  Esophageal squamous cell carcinoma
  Heart septal defect
  Hereditary pheochromocytoma-paraganglioma
  leukaemia
  Leukemia
  Plasma cell myeloma
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: KMT2D_HUMAN
• PDB ID: 3UVK; 4ERQ; 4Z4P; 6O7G
• EC Number: 2.1.1.364
• Pfam ID: PF05965 ; PF05964 ; PF00628 ; PF00856 ; PF13771 ; PF13832
• Sequence:
  MDSQKLAGEDKDSEPAADGPAASEDPSATESDLPNPHVGEVSVLSSGSPRLQETPQDCSG
  GPVRRCALCNCGEPSLHGQRELRRFELPFDWPRCPVVSPGGSPGPNEAVLPSEDLSQIGF
  PEGLTPAHLGEPGGSCWAHHWCAAWSAGVWGQEGPELCGVDKAIFSGISQRCSHCTRLGA
  SIPCRSPGCPRLYHFPCATASGSFLSMKTLQLLCPEHSEGAAYLEEARCAVCEGPGELCD
  LFFCTSCGHHYHGACLDTALTARKRAGWQCPECKVCQACRKPGNDSKMLVCETCDKGYHT
  FCLKPPMEELPAHSWKCKACRVCRACGAGSAELNPNSEWFENYSLCHRCHKAQGGQTIRS
  VAEQHTPVCSRFSPPEPGDTPTDEPDALYVACQGQPKGGHVTSMQPKEPGPLQCEAKPLG
  KAGVQLEPQLEAPLNEEMPLLPPPEESPLSPPPEESPTSPPPEASRLSPPPEELPASPLP
  EALHLSRPLEESPLSPPPEESPLSPPPESSPFSPLEESPLSPPEESPPSPALETPLSPPP
  EASPLSPPFEESPLSPPPEELPTSPPPEASRLSPPPEESPMSPPPEESPMSPPPEASRLF
  PPFEESPLSPPPEESPLSPPPEASRLSPPPEDSPMSPPPEESPMSPPPEVSRLSPLPVVS
  RLSPPPEESPLSPPPEESPTSPPPEASRLSPPPEDSPTSPPPEDSPASPPPEDSLMSLPL
  EESPLLPLPEEPQLCPRSEGPHLSPRPEEPHLSPRPEEPHLSPQAEEPHLSPQPEEPCLC
  AVPEEPHLSPQAEGPHLSPQPEELHLSPQTEEPHLSPVPEEPCLSPQPEESHLSPQSEEP
  CLSPRPEESHLSPELEKPPLSPRPEKPPEEPGQCPAPEELPLFPPPGEPSLSPLLGEPAL
  SEPGEPPLSPLPEELPLSPSGEPSLSPQLMPPDPLPPPLSPIITAAAPPALSPLGELEYP
  FGAKGDSDPESPLAAPILETPISPPPEANCTDPEPVPPMILPPSPGSPVGPASPILMEPL
  PPQCSPLLQHSLVPQNSPPSQCSPPALPLSVPSPLSPIGKVVGVSDEAELHEMETEKVSE
  PECPALEPSATSPLPSPMGDLSCPAPSPAPALDDFSGLGEDTAPLDGIDAPGSQPEPGQT
  PGSLASELKGSPVLLDPEELAPVTPMEVYPECKQTAGQGSPCEEQEEPRAPVAPTPPTLI
  KSDIVNEISNLSQGDASASFPGSEPLLGSPDPEGGGSLSMELGVSTDVSPARDEGSLRLC
  TDSLPETDDSLLCDAGTAISGGKAEGEKGRRRSSPARSRIKQGRSSSFPGRRRPRGGAHG
  GRGRGRARLKSTASSIETLVVADIDSSPSKEEEEEDDDTMQNTVVLFSNTDKFVLMQDMC
  VVCGSFGRGAEGHLLACSQCSQCYHPYCVNSKITKVMLLKGWRCVECIVCEVCGQASDPS
  RLLLCDDCDISYHTYCLDPPLLTVPKGGWKCKWCVSCMQCGAASPGFHCEWQNSYTHCGP
  CASLVTCPICHAPYVEEDLLIQCRHCERWMHAGCESLFTEDDVEQAADEGFDCVSCQPYV
  VKPVAPVAPPELVPMKVKEPEPQYFRFEGVWLTETGMALLRNLTMSPLHKRRQRRGRLGL
  PGEAGLEGSEPSDALGPDDKKDGDLDTDELLKGEGGVEHMECEIKLEGPVSPDVEPGKEE
  TEESKKRKRKPYRPGIGGFMVRQRKSHTRTKKGPAAQAEVLSGDGQPDEVIPADLPAEGA
  VEQSLAEGDEKKKQQRRGRKKSKLEDMFPAYLQEAFFGKELLDLSRKALFAVGVGRPSFG
  LGTPKAKGDGGSERKELPTSQKGDDGPDIADEESRGLEGKADTPGPEDGGVKASPVPSDP
  EKPGTPGEGMLSSDLDRISTEELPKMESKDLQQLFKDVLGSEREQHLGCGTPGLEGSRTP
  LQRPFLQGGLPLGNLPSSSPMDSYPGLCQSPFLDSRERGGFFSPEPGEPDSPWTGSGGTT
  PSTPTTPTTEGEGDGLSYNQRSLQRWEKDEELGQLSTISPVLYANINFPNLKQDYPDWSS
  RCKQIMKLWRKVPAADKAPYLQKAKDNRAAHRINKVQKQAESQINKQTKVGDIARKTDRP
  ALHLRIPPQPGALGSPPPAAAPTIFIGSPTTPAGLSTSADGFLKPPAGSVPGPDSPGELF
  LKLPPQVPAQVPSQDPFGLAPAYPLEPRFPTAPPTYPPYPSPTGAPAQPPMLGASSRPGA
  GQPGEFHTTPPGTPRHQPSTPDPFLKPRCPSLDNLAVPESPGVGGGKASEPLLSPPPFGE
  SRKALEVKKEELGASSPSYGPPNLGFVDSPSSGTHLGGLELKTPDVFKAPLTPRASQVEP
  QSPGLGLRPQEPPPAQALAPSPPSHPDIFRPGSYTDPYAQPPLTPRPQPPPPESCCALPP
  RSLPSDPFSRVPASPQSQSSSQSPLTPRPLSAEAFCPSPVTPRFQSPDPYSRPPSRPQSR
  DPFAPLHKPPRPQPPEVAFKAGSLAHTSLGAGGFPAALPAGPAGELHAKVPSGQPPNFVR
  SPGTGAFVGTPSPMRFTFPQAVGEPSLKPPVPQPGLPPPHGINSHFGPGPTLGKPQSTNY
  TVATGNFHPSGSPLGPSSGSTGESYGLSPLRPPSVLPPPAPDGSLPYLSHGASQRSGITS
  PVEKREDPGTGMGSSLATAELPGTQDPGMSGLSQTELEKQRQRQRLRELLIRQQIQRNTL
  RQEKETAAAAAGAVGPPGSWGAEPSSPAFEQLSRGQTPFAGTQDKSSLVGLPPSKLSGPI
  LGPGSFPSDDRLSRPPPPATPSSMDVNSRQLVGGSQAFYQRAPYPGSLPLQQQQQQLWQQ
  QQATAATSMRFAMSARFPSTPGPELGRQALGSPLAGISTRLPGPGEPVPGPAGPAQFIEL
  RHNVQKGLGPGGTPFPGQGPPQRPRFYPVSEDPHRLAPEGLRGLAVSGLPPQKPSAPPAP
  ELNNSLHPTPHTKGPTLPTGLELVNRPPSSTELGRPNPLALEAGKLPCEDPELDDDFDAH
  KALEDDEELAHLGLGVDVAKGDDELGTLENLETNDPHLDDLLNGDEFDLLAYTDPELDTG
  DKKDIFNEHLRLVESANEKAEREALLRGVEPGPLGPEERPPPAADASEPRLASVLPEVKP
  KVEEGGRHPSPCQFTIATPKVEPAPAANSLGLGLKPGQSMMGSRDTRMGTGPFSSSGHTA
  EKASFGATGGPPAHLLTPSPLSGPGGSSLLEKFELESGALTLPGGPAASGDELDKMESSL
  VASELPLLIEDLLEHEKKELQKKQQLSAQLQPAQQQQQQQQQHSLLSAPGPAQAMSLPHE
  GSSPSLAGSQQQLSLGLAGARQPGLPQPLMPTQPPAHALQQRLAPSMAMVSNQGHMLSGQ
  HGGQAGLVPQQSSQPVLSQKPMGTMPPSMCMKPQQLAMQQQLANSFFPDTDLDKFAAEDI
  IDPIAKAKMVALKGIKKVMAQGSIGVAPGMNRQQVSLLAQRLSGGPSSDLQNHVAAGSGQ
  ERSAGDPSQPRPNPPTFAQGVINEADQRQYEEWLFHTQQLLQMQLKVLEEQIGVHRKSRK
  ALCAKQRTAKKAGREFPEADAEKLKLVTEQQSKIQKQLDQVRKQQKEHTNLMAEYRNKQQ
  QQQQQQQQQQQQHSAVLALSPSQSPRLLTKLPGQLLPGHGLQPPQGPPGGQAGGLRLTPG
  GMALPGQPGGPFLNTALAQQQQQQHSGGAGSLAGPSGGFFPGNLALRSLGPDSRLLQERQ
  LQLQQQRMQLAQKLQQQQQQQQQQQHLLGQVAIQQQQQQGPGVQTNQALGPKPQGLMPPS
  SHQGLLVQQLSPQPPQGPQGMLGPAQVAVLQQQHPGALGPQGPHRQVLMTQSRVLSSPQL
  AQQGQGLMGHRLVTAQQQQQQQQHQQQGSMAGLSHLQQSLMSHSGQPKLSAQPMGSLQQL
  QQQQQLQQQQQLQQQQQQQLQQQQQLQQQQLQQQQQQQQLQQQQQQQLQQQQQQLQQQQQ
  QQQQQFQQQQQQQQMGLLNQSRTLLSPQQQQQQQVALGPGMPAKPLQHFSSPGALGPTLL
  LTGKEQNTVDPAVSSEATEGPSTHQGGPLAIGTTPESMATEPGEVKPSLSGDSQLLLVQP
  QPQPQPSSLQLQPPLRLPGQQQQQVSLLHTAGGGSHGQLGSGSSSEASSVPHLLAQPSVS
  LGDQPGSMTQNLLGPQQPMLERPMQNNTGPQPPKPGPVLQSGQGLPGVGIMPTVGQLRAQ
  LQGVLAKNPQLRHLSPQQQQQLQALLMQRQLQQSQAVRQTPPYQEPGTQTSPLQGLLGCQ
  PQLGGFPGPQTGPLQELGAGPRPQGPPRLPAPPGALSTGPVLGPVHPTPPPSSPQEPKRP
  SQLPSPSSQLPTEAQLPPTHPGTPKPQGPTLEPPPGRVSPAAAQLADTLFSKGLGPWDPP
  DNLAETQKPEQSSLVPGHLDQVNGQVVPEASQLSIKQEPREEPCALGAQSVKREANGEPI
  GAPGTSNHLLLAGPRSEAGHLLLQKLLRAKNVQLSTGRGSEGLRAEINGHIDSKLAGLEQ
  KLQGTPSNKEDAAARKPLTPKPKRVQKASDRLVSSRKKLRKEDGVRASEALLKQLKQELS
  LLPLTEPAITANFSLFAPFGSGCPVNGQSQLRGAFGSGALPTGPDYYSQLLTKNNLSNPP
  TPPSSLPPTPPPSVQQKMVNGVTPSEELGEHPKDAASARDSERALRDTSEVKSLDLLAAL
  PTPPHNQTEDVRMESDEDSDSPDSIVPASSPESILGEEAPRFPHLGSGRWEQEDRALSPV
  IPLIPRASIPVFPDTKPYGALGLEVPGKLPVTTWEKGKGSEVSVMLTVSAAAAKNLNGVM
  VAVAELLSMKIPNSYEVLFPESPARAGTEPKKGEAEGPGGKEKGLEGKSPDTGPDWLKQF
  DAVLPGYTLKSQLDILSLLKQESPAPEPPTQHSYTYNVSNLDVRQLSAPPPEEPSPPPSP
  LAPSPASPPTEPLVELPTEPLAEPPVPSPLPLASSPESARPKPRARPPEEGEDSRPPRLK
  KWKGVRWKRLRLLLTIQKGSGRQEDEREVAEFMEQLGTALRPDKVPRDMRRCCFCHEEGD
  GATDGPARLLNLDLDLWVHLNCALWSTEVYETQGGALMNVEVALHRGLLTKCSLCQRTGA
  TSSCNRMRCPNVYHFACAIRAKCMFFKDKTMLCPMHKIKGPCEQELSSFAVFRRVYIERD
  EVKQIASIIQRGERLHMFRVGGLVFHAIGQLLPHQMADFHSATALYPVGYEATRIYWSLR
  TNNRRCCYRCSIGENNGRPEFVIKVIEQGLEDLVFTDASPQAVWNRIIEPVAAMRKEADM
  LRLFPEYLKGEELFGLTVHAVLRIAESLPGVESCQNYLFRYGRHPLMELPLMINPTGCAR
  SEPKILTHYKRPHTLNSTSMSKAYQSTFTGETNTPYSKQFVHSKSSQYRRLRTEWKNNVY
  LARSRIQGLGLYAAKDLEKHTMVIEYIGTIIRNEVANRREKIYEEQNRGIYMFRINNEHV
  IDATLTGGPARYINHSCAPNCVAEVVTFDKEDKIIIISSRRIPKGEELTYDYQFDFEDDQ
  HKIPCHCGAWNCRKWMN
• 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). Part of chromatin remodeling machinery predominantly forms H3K4me1 methylation marks at active chromatin sites where transcription and DNA repair take place. Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription.
• Tissue Specificity: Expressed in most adult tissues, including a variety of hematoipoietic cells, with the exception of the liver.
• KEGG Pathway:
  Lysine degradation (hsa00310)
  Metabolic pathways (hsa01100)
  Cushing syndrome (hsa04934)
• Reactome Pathway:
  PKMTs methylate histone lysines (R-HSA-3214841)
  Deactivation of the beta-catenin transactivating complex (R-HSA-3769402)
  Activation of anterior HOX genes in hindbrain development during early embryogenesis (R-HSA-5617472)
  RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function (R-HSA-8936459)
  Formation of WDR5-containing histone-modifying complexes (R-HSA-9772755)
  Formation of the beta-catenin (R-HSA-201722)
• BioCyc Pathway: MetaCyc:HS09574-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis B virus infection	DISLQ2XY	Definitive	Biomarker	[1]
Kabuki syndrome 1	DIS1Y6X7	Definitive	Autosomal dominant	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[3]
Adult lymphoma	DISK8IZR	Strong	Altered Expression	[4]
Bladder cancer	DISUHNM0	Strong	Genetic Variation	[5]
Branchial arch abnormalities, choanal atresia, athelia, hearing loss, and hypothyroidism syndrome	DISB0I2J	Strong	Autosomal dominant	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Diabetic retinopathy	DISHGUJM	Strong	Genetic Variation	[8]
Follicular lymphoma	DISVEUR6	Strong	Genetic Variation	[9]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[11]
Isolated cleft palate	DISV80CD	Strong	CausalMutation	[12]
Lymphoma	DISN6V4S	Strong	Altered Expression	[4]
Male infertility	DISY3YZZ	Strong	Biomarker	[13]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[14]
Microphthalmia	DISGEBES	Strong	Biomarker	[15]
Neoplasm	DISZKGEW	Strong	Altered Expression	[16]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[17]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[18]
Obesity	DIS47Y1K	Strong	Biomarker	[19]
Pediatric lymphoma	DIS51BK2	Strong	Altered Expression	[4]
Prostate cancer	DISF190Y	Strong	Biomarker	[20]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[20]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[21]
Sensorineural hearing loss disorder	DISJV45Z	Strong	CausalMutation	[12]
Sezary syndrome	DISFMTC7	Strong	Biomarker	[22]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[16]
T-cell lymphoma	DISSXRTQ	Strong	Biomarker	[23]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[17]
Ventricular septal defect	DISICO41	Strong	CausalMutation	[12]
B-cell lymphoma	DISIH1YQ	moderate	Altered Expression	[24]
Bipolar disorder	DISAM7J2	moderate	Genetic Variation	[25]
Choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome	DISZOS19	Moderate	Autosomal dominant	[6]
Gastric cancer	DISXGOUK	moderate	Biomarker	[26]
Movement disorder	DISOJJ2D	moderate	CausalMutation	[27]
Stomach cancer	DISKIJSX	moderate	Biomarker	[26]
Kabuki syndrome	DISZN97H	Supportive	Autosomal dominant	[28]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[29]
B-cell neoplasm	DISVY326	Limited	Altered Expression	[30]
Breast cancer	DIS7DPX1	Limited	Posttranslational Modification	[31]
Breast carcinoma	DIS2UE88	Limited	Posttranslational Modification	[31]
Esophageal squamous cell carcinoma	DIS5N2GV	Limited	Altered Expression	[29]
Heart septal defect	DISQ5C5J	Limited	Genetic Variation	[32]
Hereditary pheochromocytoma-paraganglioma	DISP9K7L	Limited	Biomarker	[33]
leukaemia	DISS7D1V	Limited	Altered Expression	[34]
Leukemia	DISNAKFL	Limited	Altered Expression	[34]
Plasma cell myeloma	DIS0DFZ0	Limited	Biomarker	[35]
Urinary bladder cancer	DISDV4T7	Limited	Genetic Variation	[5]
Urinary bladder neoplasm	DIS7HACE	Limited	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Histone-lysine N-methyltransferase 2D (KMT2D).	[36]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Histone-lysine N-methyltransferase 2D (KMT2D).	[37]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Histone-lysine N-methyltransferase 2D (KMT2D).	[38]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of Histone-lysine N-methyltransferase 2D (KMT2D).	[40]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Histone-lysine N-methyltransferase 2D (KMT2D).	[44]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Histone-lysine N-methyltransferase 2D (KMT2D).	[45]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Histone-lysine N-methyltransferase 2D (KMT2D).	[46]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Histone-lysine N-methyltransferase 2D (KMT2D).	[39]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Histone-lysine N-methyltransferase 2D (KMT2D).	[41]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Histone-lysine N-methyltransferase 2D (KMT2D).	[42]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Histone-lysine N-methyltransferase 2D (KMT2D).	[39]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Histone-lysine N-methyltransferase 2D (KMT2D).	[43]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Histone-lysine N-methyltransferase 2D (KMT2D).	[39]

References

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