Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ3IRBP)

• DOT Name: Ankyrin-3 (ANK3)
• Synonyms: ANK-3; Ankyrin-G
• Gene Name: ANK3
• Related Disease:
  Alzheimer disease
  Anxiety
  Anxiety disorder
  Attention deficit hyperactivity disorder
  Autism
  Autism spectrum disorder
  Bipolar depression
  Cognitive impairment
  Focal segmental glomerulosclerosis
  Hutchinson-Gilford progeria syndrome
  Intellectual disability-hypotonia-spasticity-sleep disorder syndrome
  Lung cancer
  Lung neoplasm
  Major depressive disorder
  Mental disorder
  Neurodevelopmental disorder
  Neuroma
  Pervasive developmental disorder
  Post-traumatic stress disorder
  Psychotic disorder
  Substance abuse
  Acute myelogenous leukaemia
  Chronic graft versus host disease
  Intellectual disability
  Mood disorder
  Prion disease
  Status epilepticus seizure
  Advanced cancer
  Amyotrophic lateral sclerosis type 1
  Breast cancer
  Breast carcinoma
  Nervous system disease
  Tourette syndrome
• UniProt ID: ANK3_HUMAN
• PDB ID: 4O6X
• Pfam ID: PF00023 ; PF12796 ; PF13637 ; PF00531 ; PF17809 ; PF00791
• Sequence:
  MAHAASQLKKNRDLEINAEEEPEKKRKHRKRSRDRKKKSDANASYLRAARAGHLEKALDY
  IKNGVDINICNQNGLNALHLASKEGHVEVVSELLQREANVDAATKKGNTALHIASLAGQA
  EVVKVLVTNGANVNAQSQNGFTPLYMAAQENHLEVVKFLLDNGASQSLATEDGFTPLAVA
  LQQGHDQVVSLLLENDTKGKVRLPALHIAARKDDTKAAALLLQNDNNADVESKSGFTPLH
  IAAHYGNINVATLLLNRAAAVDFTARNDITPLHVASKRGNANMVKLLLDRGAKIDAKTRD
  GLTPLHCGARSGHEQVVEMLLDRAAPILSKTKNGLSPLHMATQGDHLNCVQLLLQHNVPV
  DDVTNDYLTALHVAAHCGHYKVAKVLLDKKANPNAKALNGFTPLHIACKKNRIKVMELLL
  KHGASIQAVTESGLTPIHVAAFMGHVNIVSQLMHHGASPNTTNVRGETALHMAARSGQAE
  VVRYLVQDGAQVEAKAKDDQTPLHISARLGKADIVQQLLQQGASPNAATTSGYTPLHLSA
  REGHEDVAAFLLDHGASLSITTKKGFTPLHVAAKYGKLEVANLLLQKSASPDAAGKSGLT
  PLHVAAHYDNQKVALLLLDQGASPHAAAKNGYTPLHIAAKKNQMDIATTLLEYGADANAV
  TRQGIASVHLAAQEGHVDMVSLLLGRNANVNLSNKSGLTPLHLAAQEDRVNVAEVLVNQG
  AHVDAQTKMGYTPLHVGCHYGNIKIVNFLLQHSAKVNAKTKNGYTPLHQAAQQGHTHIIN
  VLLQNNASPNELTVNGNTALGIARRLGYISVVDTLKIVTEETMTTTTVTEKHKMNVPETM
  NEVLDMSDDEVRKANAPEMLSDGEYISDVEEGEDAMTGDTDKYLGPQDLKELGDDSLPAE
  GYMGFSLGARSASLRSFSSDRSYTLNRSSYARDSMMIEELLVPSKEQHLTFTREFDSDSL
  RHYSWAADTLDNVNLVSSPIHSGFLVSFMVDARGGSMRGSRHHGMRIIIPPRKCTAPTRI
  TCRLVKRHKLANPPPMVEGEGLASRLVEMGPAGAQFLGPVIVEIPHFGSMRGKERELIVL
  RSENGETWKEHQFDSKNEDLTELLNGMDEELDSPEELGKKRICRIITKDFPQYFAVVSRI
  KQESNQIGPEGGILSSTTVPLVQASFPEGALTKRIRVGLQAQPVPDEIVKKILGNKATFS
  PIVTVEPRRRKFHKPITMTIPVPPPSGEGVSNGYKGDTTPNLRLLCSITGGTSPAQWEDI
  TGTTPLTFIKDCVSFTTNVSARFWLADCHQVLETVGLATQLYRELICVPYMAKFVVFAKM
  NDPVESSLRCFCMTDDKVDKTLEQQENFEEVARSKDIEVLEGKPIYVDCYGNLAPLTKGG
  QQLVFNFYSFKENRLPFSIKIRDTSQEPCGRLSFLKEPKTTKGLPQTAVCNLNITLPAHK
  KETESDQDDEIEKTDRRQSFASLALRKRYSYLTEPGMIERSTGATRSLPTTYSYKPFFST
  RPYQSWTTAPITVPGPAKSGFTSLSSSSSNTPSASPLKSIWSVSTPSPIKSTLGASTTSS
  VKSISDVASPIRSFRTMSSPIKTVVSQSPYNIQVSSGTLARAPAVTEATPLKGLASNSTF
  SSRTSPVTTAGSLLERSSITMTPPASPKSNINMYSSSLPFKSIITSAAPLISSPLKSVVS
  PVKSAVDVISSAKITMASSLSSPVKQMPGHAEVALVNGSISPLKYPSSSTLINGCKATAT
  LQEKISSATNSVSSVVSAATDTVEKVFSTTTAMPFSPLRSYVSAAPSAFQSLRTPSASAL
  YTSLGSSISATTSSVTSSIITVPVYSVVNVLPEPALKKLPDSNSFTKSAAALLSPIKTLT
  TETHPQPHFSRTSSPVKSSLFLAPSALKLSTPSSLSSSQEILKDVAEMKEDLMRMTAILQ
  TDVPEEKPFQPELPKEGRIDDEEPFKIVEKVKEDLVKVSEILKKDVCVDNKGSPKSPKSD
  KGHSPEDDWIEFSSEEIREARQQAAASQSPSLPERVQVKAKAASEKDYNLTKVIDYLTND
  IGSSSLTNLKYKFEDAKKDGEERQKRVLKPAIALQEHKLKMPPASMRTSTSEKELCKMAD
  SFFGTDTILESPDDFSQHDQDKSPLSDSGFETRSEKTPSAPQSAESTGPKPLFHEVPIPP
  VITETRTEVVHVIRSYDPSAGDVPQTQPEEPVSPKPSPTFMELEPKPTTSSIKEKVKAFQ
  MKASSEEDDHNRVLSKGMRVKEETHITTTTRMVYHSPPGGEGASERIEETMSVHDIMKAF
  QSGRDPSKELAGLFEHKSAVSPDVHKSAAETSAQHAEKDNQMKPKLERIIEVHIEKGNQA
  EPTEVIIRETKKHPEKEMYVYQKDLSRGDINLKDFLPEKHDAFPCSEEQGQQEEEELTAE
  ESLPSYLESSRVNTPVSQEEDSRPSSAQLISDDSYKTLKLLSQHSIEYHDDELSELRGES
  YRFAEKMLLSEKLDVSHSDTEESVTDHAGPPSSELQGSDKRSREKIATAPKKEILSKIYK
  DVSENGVGKVSKDEHFDKVTVLHYSGNVSSPKHAMWMRFTEDRLDRGREKLIYEDRVDRT
  VKEAEEKLTEVSQFFRDKTEKLNDELQSPEKKARPKNGKEYSSQSPTSSSPEKVLLTELL
  ASNDEWVKARQHGPDGQGFPKAEEKAPSLPSSPEKMVLSQQTEDSKSTVEAKGSISQSKA
  PDGPQSGFQLKQSKLSSIRLKFEQGTHAKSKDMSQEDRKSDGQSRIPVKKIQESKLPVYQ
  VFAREKQQKAIDLPDESVSVQKDFMVLKTKDEHAQSNEIVVNDSGSDNVKKQRTEMSSKA
  MPDSFSEQQAKDLACHITSDLATRGPWDKKVFRTWESSGATNNKSQKEKLSHVLVHDVRE
  NHIGHPESKSVDQKNEFMSVTERERKLLTNGSLSEIKEMTVKSPSKKVLYREYVVKEGDH
  PGGLLDQPSRRSESSAVSHIPVRVADERRMLSSNIPDGFCEQSAFPKHELSQKLSQSSMS
  KETVETQHFNSIEDEKVTYSEISKVSKHQSYVGLCPPLEETETSPTKSPDSLEFSPGKES
  PSSDVFDHSPIDGLEKLAPLAQTEGGKEIKTLPVYVSFVQVGKQYEKEIQQGGVKKIISQ
  ECKTVQETRGTFYTTRQQKQPPSPQGSPEDDTLEQVSFLDSSGKSPLTPETPSSEEVSYE
  FTSKTPDSLIAYIPGKPSPIPEVSEESEEEEQAKSTSLKQTTVEETAVEREMPNDVSKDS
  NQRPKNNRVAYIEFPPPPPLDADQIESDKKHHYLPEKEVDMIEVNLQDEHDKYQLAEPVI
  RVQPPSPVPPGADVSDSSDDESIYQPVPVKKYTFKLKEVDDEQKEKPKASAEKASNQKEL
  ESNGSGKDNEFGLGLDSPQNEIAQNGNNDQSITECSIATTAEFSHDTDATEIDSLDGYDL
  QDEDDGLTESDSKLPIQAMEIKKDIWNTEGILKPADRSFSQSKLEVIEEEGKVGPDEDKP
  PSKSSSSEKTPDKTDQKSGAQFFTLEGRHPDRSVFPDTYFSYKVDEEFATPFKTVATKGL
  DFDPWSNNRGDDEVFDSKSREDETKPFGLAVEDRSPATTPDTTPARTPTDESTPTSEPNP
  FPFHEGKMFEMTRSGAIDMSKRDFVEERLQFFQIGEHTSEGKSGDQGEGDKSMVTATPQP
  QSGDTTVETNLERNVETPTVEPNPSIPTSGECQEGTSSSGSLEKSAAATNTSKVDPKLRT
  PIKMGISASTMTMKKEGPGEITDKIEAVMTSCQGLENETITMISNTANSQMGVRPHEKHD
  FQKDNFNNNNNLDSSTIQTDNIMSNIVLTEHSAPTCTTEKDNPVKVSSGKKTGVLQGHCV
  RDKQKVLGEQQKTKELIGIRQKSKLPIKATSPKDTFPPNHMSNTKASKMKQVSQSEKTKA
  LTTSSCVDVKSRIPVKNTHRDNIIAVRKACATQKQGQPEKGKAKQLPSKLPVKVRSTCVT
  TTTTTATTTTTTTTTTTTSCTVKVRKSQLKEVCKHSIEYFKGISGETLKLVDRLSEEEKK
  MQSELSDEEESTSRNTSLSETSRGGQPSVTTKSARDKKTEAAPLKSKSEKAGSEKRSSRR
  TGPQSPCERTDIRMAIVADHLGLSWTELARELNFSVDEINQIRVENPNSLISQSFMLLKK
  WVTRDGKNATTDALTSVLTKINRIDIVTLLEGPIFDYGNISGTRSFADENNVFHDPVDGW
  QNETSSGNLESCAQARRVTGGLLDRLDDSPDQCRDSITSYLKGEAGKFEANGSHTEITPE
  AKTKSYFPESQNDVGKQSTKETLKPKIHGSGHVEEPASPLAAYQKSLEETSKLIIEETKP
  CVPVSMKKMSRTSPADGKPRLSLHEEEGSSGSEQKQGEGFKVKTKKEIRHVEKKSHS
• Function: Membrane-cytoskeleton linker. May participate in the maintenance/targeting of ion channels and cell adhesion molecules at the nodes of Ranvier and axonal initial segments. In skeletal muscle, required for costamere localization of DMD and betaDAG1. Regulates KCNA1 channel activity in function of dietary Mg(2+) levels, and thereby contributes to the regulation of renal Mg(2+) reabsorption. Required for intracellular adhesion and junctional conductance in myocytes, potentially via stabilization of GJA1/CX43 protein abundance and promotion of PKP2, GJA1/CX43, and SCN5A/Nav1.5 localization to cell-cell junctions; [Isoform 5]: May be part of a Golgi-specific membrane cytoskeleton in association with beta-spectrin.
• Tissue Specificity: Expressed in brain, neurons, muscles and other tissues.
• KEGG Pathway:
  Cytoskeleton in muscle cells (hsa04820)
  Proteoglycans in cancer (hsa05205)
• Reactome Pathway:
  COPI-mediated anterograde transport (R-HSA-6807878)
  Interaction between L1 and Ankyrins (R-HSA-445095)

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Anxiety	DISIJDBA	Strong	Biomarker	[2]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[2]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[3]
Autism	DISV4V1Z	Strong	Biomarker	[4]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[5]
Bipolar depression	DISA75FU	Strong	Biomarker	[6]
Cognitive impairment	DISH2ERD	Strong	Genetic Variation	[7]
Focal segmental glomerulosclerosis	DISJNHH0	Strong	Genetic Variation	[8]
Hutchinson-Gilford progeria syndrome	DISY55BU	Strong	Biomarker	[9]
Intellectual disability-hypotonia-spasticity-sleep disorder syndrome	DISY35HR	Strong	Autosomal recessive	[7]
Lung cancer	DISCM4YA	Strong	Biomarker	[10]
Lung neoplasm	DISVARNB	Strong	Biomarker	[10]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[11]
Mental disorder	DIS3J5R8	Strong	Biomarker	[12]
Neurodevelopmental disorder	DIS372XH	Strong	Genetic Variation	[13]
Neuroma	DISIENZM	Strong	Biomarker	[14]
Pervasive developmental disorder	DIS51975	Strong	Genetic Variation	[15]
Post-traumatic stress disorder	DISHL1EY	Strong	Biomarker	[16]
Psychotic disorder	DIS4UQOT	Strong	Altered Expression	[17]
Substance abuse	DIS327VW	Strong	Biomarker	[16]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[18]
Chronic graft versus host disease	DIS1MM9J	moderate	Biomarker	[19]
Intellectual disability	DISMBNXP	Moderate	Autosomal recessive	[20]
Mood disorder	DISLVMWO	moderate	Genetic Variation	[21]
Prion disease	DISOUMB0	moderate	Genetic Variation	[22]
Status epilepticus seizure	DISY3BIC	Disputed	Biomarker	[23]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[24]
Amyotrophic lateral sclerosis type 1	DIS5A2M0	Limited	Genetic Variation	[25]
Breast cancer	DIS7DPX1	Limited	Biomarker	[26]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[26]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[27]
Tourette syndrome	DISX9D54	Limited	Unknown	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ethanol	DMDRQZU	Approved	Ankyrin-3 (ANK3) affects the response to substance of Ethanol.	[50]

21 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 Ankyrin-3 (ANK3).	[29]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ankyrin-3 (ANK3).	[30]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ankyrin-3 (ANK3).	[31]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ankyrin-3 (ANK3).	[32]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Ankyrin-3 (ANK3).	[33]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ankyrin-3 (ANK3).	[34]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Ankyrin-3 (ANK3).	[35]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Ankyrin-3 (ANK3).	[36]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Ankyrin-3 (ANK3).	[37]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Ankyrin-3 (ANK3).	[38]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Ankyrin-3 (ANK3).	[40]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Ankyrin-3 (ANK3).	[41]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Ankyrin-3 (ANK3).	[42]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Ankyrin-3 (ANK3).	[43]
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of Ankyrin-3 (ANK3).	[44]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Ankyrin-3 (ANK3).	[45]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Ankyrin-3 (ANK3).	[46]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ankyrin-3 (ANK3).	[30]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ankyrin-3 (ANK3).	[47]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Ankyrin-3 (ANK3).	[48]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ankyrin-3 (ANK3).	[49]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Ankyrin-3 (ANK3).	[39]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Ankyrin-3 (ANK3).	[39]

References

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