Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGES2OU)

• DOT Name: Dynein axonemal heavy chain 8 (DNAH8)
• Synonyms: Axonemal beta dynein heavy chain 8; Ciliary dynein heavy chain 8
• Gene Name: DNAH8
• Related Disease:
  Coeliac disease
  Type-1 diabetes
  Advanced cancer
  Arteriosclerosis
  Atherosclerosis
  Bipolar disorder
  Breast neoplasm
  Cardiac disease
  Cardiac failure
  Cardiomyopathy
  Cocaine addiction
  Cytomegalovirus infection
  Depression
  Dilated cardiomyopathy 1A
  Drug dependence
  Duchenne muscular dystrophy
  Epilepsy
  Epithelial ovarian cancer
  Fatty liver disease
  Melanoma
  Myopathy
  Narcolepsy
  Neuralgia
  Non-small-cell lung cancer
  Obesity
  Ovarian cancer
  Ovarian neoplasm
  Pulmonary fibrosis
  Spermatogenic failure 46
  Substance abuse
  Substance dependence
  Plasmodium falciparum malaria
  Spermatogenic failure 5
  Type-1/2 diabetes
  Breast cancer
  Breast carcinoma
  Primary ciliary dyskinesia
  Alzheimer disease
  Congestive heart failure
  Corpus callosum, agenesis of
  Hepatocellular carcinoma
  Neoplasm
  Neuroblastoma
  Renal fibrosis
  Rheumatoid arthritis
  Temporal lobe epilepsy
• UniProt ID: DYH8_HUMAN
• Pfam ID: PF12774 ; PF12775 ; PF12780 ; PF12781 ; PF17857 ; PF18198 ; PF08385 ; PF08393 ; PF17852 ; PF18199 ; PF03028 ; PF12777
• Sequence:
  MMKLYIDNAAPDKLKGLCIFFVRCRNDVAINVKTIQEEALFTVLDASKGLLNGIRDMLAN
  IFLPAVLATNNWGALNQSKQGESEKHIFTETINRYLSFLDGARISIEGTVKLKTIDNVNF
  SKLHTFEEVTAAASNSETVHQLEEVLMVWYKQIEQVLIESEQMRKEAGDSGPLTELEHWK
  RMSAKFNYIIEQIKGPSCKAVINVLNVAHSKLLKNWRDLDARITDTANESKDNVRYLYTL
  EKVCQPLYNHDLVSMAHGIQNLINAIRMIHGVSRYYNTSERMTSLFIKVTNQMVTACKAY
  ITDGGLNHVWDQETPVVLKKIQDCIFLFKEYQASFHKTRKLISESSGEKSFEVSEMYIFG
  KFEAFCKRLEKITEMITVVQTYSTLSNSTIEGIDIMAIKFRNIYQGVKKKQYDILDPRRT
  EFDTDFLDFMTKINGLEVQIQAFMNSSFGKILSSQQALQLLQRFQKLNIPCLGLEINHTI
  ERILQYYVAELDATKKLYHSQKDDPPLARNMPPIAGKILWVRQLYRRISEPINYFFKNSD
  ILSSPDGKAVIRQYNKISYVLVEFEVVYHTAWIREISQLHYALQATLFVRHPETGKLLVN
  FDPKILEVVRETKCMIKMKLDVPEQAKRLLKLESKLKADKLYLQGLLQYYDELCQEVPSV
  FVNLMTPKMKKVESVLRQGLTVLTWSSLTLESFFQEVELVLDMFNQLLKKISDLCEMHID
  TVLKEIAKTVLISLPESGATKVEDMLTLNETYTKEWADILNHKSKHVEEAVRELISIFEQ
  IYEVKYTGKVGKQSEQRKHVVFGSETGEGENNDYEANIVNEFDTHDKEDEFKKECKEVFA
  FFSHQLLDSLQKATRLSLDTMKRRIFVASLYGRKQSEDIISFIKSEVHLAIPNVVMIPSL
  DDIQQAINRMIQLTLEVSRGVAHWGQQQIRPIKSVIPSPTTTDVTHQNTGKLLKKEERSF
  EEAIPARKLKNFYPGVAEHKDISKLVLLLSSSVNSLRKAAHEALQDFQKYKTLWTEDRDV
  KVKEFLANNPSLTEIRSEILHYATFEQEIDELKPIIVVGALELHTEPMKLALSIEAKAWK
  MLLCRYLNEEYKKKMSYMIAFINEYLKKLSRPIRDLDDVRFAMEALSCIRDNEIQMDMTL
  GPIEEAYAILNRFEVEVTKEESEAVDTLRYSFNKLQSKAVSVQEDLVQVQPKFKSNLLES
  VEVFREDVINFAEAYELEGPMVPNIPPQEASNRLQIFQASFDDLWRKFVTYSSGEQLFGL
  PVTDYEVLHKTRKELNLLQKLYGLYDTVMSSISGYYEILWGDVDIEKINAELLEFQNRCR
  KLPKGLKDWQAFLDLKKRIDDFSESCPLLEMMTNKAMKQRHWDRISELTGTPFDVESDSF
  CLRNIMEAPLLKHKDDIEDICISAIKEKDIEAKLTQVIENWTNQNLSFAAFKGKGELLLK
  GTESGEIITLMEDSLMVLGSLLSNRYNAPFKKNIQNWVYKLSTSSDIIEEWLVVQNLWVY
  LEAVFVGGDIAKQLPQEAKRFQNIDKSWIKIMQRAHENPNVINCCVGDETMGQLLPHLHE
  QLEVCQKSLTGYLEKKRLLFPRFFFVSDPVLLEILGQASDSHTIQPHLPAVSDNINEVTF
  HAKDYDRIMAVISREGEKIVLDNSVMAKGPVEIWLLDLLKMQMSSLHNIIRSAFYQISDS
  GFQLLPFLSHFPAQVGLLGIQMLWTHDSEEALRNAKDDRKIMQVTNQKFLDILNTLISQT
  THDLSKFDRVKFETLITIHVHQRDIFDDLVKMHIKSPTDFEWLKQSRFYFKEDLDQTVVS
  ITDVDFIYQNEFLGCTDRLVITPLTDRCYITLAQALGMNMGGAPAGPAGTGKTETTKDMG
  RCLGKYVVVFNCSDQMDFRGLGRIFKGLAQSGSWGCFDEFNRIELPVLSVAAQQIYIVLT
  ARKERKKQFIFSDGDCVDLNPEFGIFLTMNPGYAGRQELPENLKIQFRTVAMMVPDRQII
  MRVKLASCGFLENVILAQKFYVLYKLCEEQLTKQVHYDFGLRNILSVLRTLGSQKRARPE
  DSELSIVMRGLRDMNLSKLVDEDEPLFLSLINDLFPGLQLDSNTYAELQNAVAHQVQIEG
  LINHPPWNLKLVQLYETSLVRHGLMTLGPSGSGKTTVITILMKAQTECGRPHREMRMNPK
  AITAPQMFGRLDTATNDWTDGIFSTLWRKTLKAKKGENIFLILDGPVDAIWIENLNSVLD
  DNKTLTLANGDRIPMAPSCKLLFEVHNIENASPATVSRMGMVYISSSALSWRPILQAWLK
  KRTAQEAAVFLTLYEKVFEDTYTYMKLNLNPKMQLLECNYIVQSLNLLEGLIPSKEEGGV
  SCVEHLHKLFVFGLMWSLGALLELESREKLEAFLRQHESKLDLPEIPKGSNQTMYEFYVT
  DYGDWEHWNKKLQPYYYPTDSIPEYSSILVPNVDNIRTNFLIDTIAKQHKAVLLTGEQGT
  AKTVMVKAYLKKYDPEVQLSKSLNFSSATEPMMFQRTIESYVDKRIGSTYGPPGGRKMTV
  FIDDINMPVINEWGDQITNEIVRQMMEMEGMYSLDKPGDFTTIVDVQLIAAMIHPGGGRN
  DIPQRLKRQFTVFNCTLPSNASIDKIFGIIGCGYFDPCRSFKPQICEMIVNLVSVGRVLW
  QWTKVKMLPTPSKFHYIFNLRDLSRIWQGMLTIKAEECASIPTLLSLFKHECSRVIADRF
  ITPEDEQWFNAHLTRAVEENIGSDAASCILPEPYFVDFLREMPEPTGDEPEDSVFEVPKI
  YELMPSFDFLAEKLQFYQRQFNEIIRGTSLDLVFFKDAMTHLIKISRIIRTSCGNALLVG
  VGGSGKQSLSRLASFIAGYQIFQITLTRSYNVTNLTDDLKALYKVAGADGKGITFIFTDS
  EIKDEAFLEYLNNLLSSGEISNLFARDEMDEITQGLISVMKRELPRHPPTFDNLYEYFIS
  RSRKNLHVVLCFSPVGEKFRARSLKFPGLISGCTMDWFSRWPREALIAVASYFLSDYNIV
  CSSEIKRQVVETMGLFHDMVSESCESYFQRYRRRAHVTPKSYLSFINGYKNIYAEKVKFI
  NEQAERMNIGLDKLMEASESVAKLSQDLAVKEKELAVASIKADEVLAEVTVSAQASAKIK
  NEVQEVKDKAQKIVDEIDSEKVKAESKLEAAKPALEEAEAALNTIKPNDIATVRKLAKPP
  HLIMRIMDCVLLLFQKKIDPVTMDPEKSCCKPSWGESLKLMSATGFLWSLQQFPKDTINE
  ETVELLQPYFNMDDYTFESAKKVCGNVAGLLSWTLAMAIFYGINREVLPLKANLAKQEGR
  LAVANAELGKAQALLDEKQAELDKVQAKFDAAMNEKMDLLNDADTCRKKMQAASTLIDGL
  SGEKIRWTQQSKEFKAQINRLVGDILLCTGFLSYLGPFNQIFRNYLLKDQWEMELRARKI
  PFTENLNLISMLVDPPTIGEWGLQGLPGDDLSIQNGIIVTKATRYPLLIDPQTQGKTWIK
  SKEKENDLQVTSLNHKYFRTHLEDSLSLGRPLLIEDIHEELDPALDNVLEKNFIKSGTTF
  KVKVGDKECDIMDTFKLYITTKLPNPAFTPEINAKTSVIDFTVTMKGLENQLLRRVILTE
  KQELEAERVKLLEDVTFNKRKMKELEDNLLYKLSATKGSLVDDESLIGVLRTTKQTAAEV
  SEKLHVAAETEIKINAAQEEFRPAATRGSILYFLITEMSMVNIMYQTSLAQFLKLFDQSM
  ARSEKSPLPQKRITNIIEYLTYEVFTYSVRGLYENHKFLFVLLMTLKIDLQRGTVKHREF
  QALIKGGAALDLKACPPKPYRWILDMTWLNLVELSKLPQFAEIMNQISRNEKGWKSWFDK
  DAPEEEIIPDGYNDSLDTCHKLLLIRSWCPDRTVFQARKYIADSLEEKYTEPVILNLEKT
  WEESDTRTPLICFLSMGSDPTNQIDALAKKLKLECRTISMGQGQEVHARKLIQMSMQQGG
  WVLLQNCHLGLEFMEELLETLITTEASDDSFRVWITTEPHDRFPITLLQTSLKFTNEPPQ
  GVRAGLKRTFAGINQDLLDISNLPMWKPMLYTVAFLHSTVQERRKFGPLGWNIPYEFNSA
  DFSASVQFIQNHLDECDIKKGVSWNTVRYMIGEVQYGGRVTDDFDKRLLNCFARVWFSEK
  MFEPSFCFYTGYKIPLCKTLDQYFEYIQSLPSLDNPEVFGLHPNADITYQSNTASAVLET
  ITNIQPKESGGGVGETREAIVYRLSEDMLSKLPPDYIPHEVKSRLIKMGHLNSMNIFLRQ
  EIDRMQRVISILRSSLSDLKLAIEGTIIMSENLRDALDNMYDARIPQLWKRVSWDSSTLG
  FWFTELLERNAQFSTWIFEGRPNVFWMTGFFNPQGFLTAMRQEVTRAHKGWALDTVTIHN
  EVLRQTKEEITSPPGEGVYIYGLYMDGAAWDRRNGKLMESTPKVLFTQLPVLHIFAINST
  APKDPKLYVCPIYKKPRRTDLTFITVVYLRTVLSPDHWILRGVALLCDIK
• Function: Force generating protein component of the outer dynein arms (ODAs) in the sperm flagellum. Produces force towards the minus ends of microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Involved in sperm motility; implicated in sperm flagellar assembly.
• Tissue Specificity: Expressed in spermatozoa (at protein level). Not detected in airway epithelial cells (at protein level).
• KEGG Pathway:
  Motor proteins (hsa04814)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Pathways of neurodegeneration - multiple diseases (hsa05022)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Coeliac disease	DISIY60C	Definitive	Biomarker	[1]
Type-1 diabetes	DIS7HLUB	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[3]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[3]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[4]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[5]
Cardiac disease	DISVO1I5	Strong	Biomarker	[6]
Cardiac failure	DISDC067	Strong	Biomarker	[7]
Cardiomyopathy	DISUPZRG	Strong	Biomarker	[8]
Cocaine addiction	DISHTRXG	Strong	Biomarker	[9]
Cytomegalovirus infection	DISCEMGC	Strong	Altered Expression	[10]
Depression	DIS3XJ69	Strong	Genetic Variation	[11]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Altered Expression	[12]
Drug dependence	DIS9IXRC	Strong	Biomarker	[13]
Duchenne muscular dystrophy	DISRQ3NV	Strong	Biomarker	[14]
Epilepsy	DISBB28L	Strong	Genetic Variation	[15]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[16]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[3]
Melanoma	DIS1RRCY	Strong	Altered Expression	[17]
Myopathy	DISOWG27	Strong	Genetic Variation	[18]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[19]
Neuralgia	DISWO58J	Strong	Biomarker	[20]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[21]
Obesity	DIS47Y1K	Strong	Biomarker	[22]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[16]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[16]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[23]
Spermatogenic failure 46	DISU4WQ1	Strong	Autosomal recessive	[24]
Substance abuse	DIS327VW	Strong	Biomarker	[13]
Substance dependence	DISDRAAR	Strong	Biomarker	[13]
Plasmodium falciparum malaria	DIS3Q9KF	moderate	Genetic Variation	[25]
Spermatogenic failure 5	DIS2U2A0	Moderate	Autosomal recessive	[26]
Type-1/2 diabetes	DISIUHAP	moderate	Biomarker	[27]
Breast cancer	DIS7DPX1	Disputed	Altered Expression	[28]
Breast carcinoma	DIS2UE88	Disputed	Altered Expression	[28]
Primary ciliary dyskinesia	DISOBC7V	Disputed	Autosomal recessive	[24]
Alzheimer disease	DISF8S70	Limited	Biomarker	[4]
Congestive heart failure	DIS32MEA	Limited	Genetic Variation	[29]
Corpus callosum, agenesis of	DISO9P40	Limited	Biomarker	[30]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[31]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[5]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[32]
Renal fibrosis	DISMHI3I	Limited	Biomarker	[33]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[34]
Temporal lobe epilepsy	DISNOPXX	Limited	Biomarker	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cocaine	DMSOX7I	Approved	Dynein axonemal heavy chain 8 (DNAH8) affects the response to substance of Cocaine.	[9]

4 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 Dynein axonemal heavy chain 8 (DNAH8).	[36]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Dynein axonemal heavy chain 8 (DNAH8).	[37]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Dynein axonemal heavy chain 8 (DNAH8).	[38]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Dynein axonemal heavy chain 8 (DNAH8).	[39]

References

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• [35] Lack of association between temporal lobe epilepsy and a novel polymorphism in the alpha 2 subunit gene (ATP1A2) of the sodium potassium transporting ATPase.Am J Med Genet. 2000 Feb 7;96(1):79-83.
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• [40] Substance dependence low-density whole genome association study in two distinct American populations. Hum Genet. 2008 Jun;123(5):495-506. doi: 10.1007/s00439-008-0501-0. Epub 2008 Apr 26.