Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6IYFVV)

• DOT Name: Dynein axonemal heavy chain 11 (DNAH11)
• Synonyms: Axonemal beta dynein heavy chain 11; Ciliary dynein heavy chain 11
• Gene Name: DNAH11
• Related Disease:
  Primary ciliary dyskinesia 7
  Asthma
  Breast carcinoma
  Bronchiectasis
  Congenital heart disease
  Cystic fibrosis
  Esophageal squamous cell carcinoma
  Lung carcinoma
  Plasma cell myeloma
  Respiratory disease
  Sarcoidosis
  Squamous cell carcinoma
  Stomach cancer
  Visceral heterotaxy
  Situs inversus
  Primary ciliary dyskinesia
  Al amyloidosis
• UniProt ID: DYH11_HUMAN
• Pfam ID: PF12774 ; PF12775 ; PF12780 ; PF12781 ; PF17857 ; PF18198 ; PF08385 ; PF08393 ; PF17852 ; PF18199 ; PF03028 ; PF12777
• Sequence:
  MAAQVAAREARDFREAPTLRLTSGAGLEAVGAVELEEEEENEEEAAARRARSFAQDARVR
  FLGGRLAMMLGFTEEKWSQYLESEDNRQVLGEFLESTSPACLVFSFAASGRLAASQEIPR
  DANHKLVFISKKITESIGVNDFSQVVLFGELPALSLGHVSAFLDEILVPVLSNKNNHKSW
  SCFTSQDMEYHIEVMKKKMYIFRGKMSRRTLLPIPTVAGKMDLDQNCSENKPPSNERIIL
  HAIESVVIEWSHQIQEIIERDSVQRLLNGLHLSPQAELDFWMMRRENLSCIYDQLQAPVV
  LKMVKILTTKQSSYFPTLKDIFLAVENALLEAQDVELYLRPLRRHIQCLQETEFPQTRIL
  IAPLFHTICLIWSHSKFYNTPARVIVLLQEFCNLFINQATAYLSPEDLLRGEIEESLEKV
  QVAVNILKTFKNSFFNYRKKLASYFMGRKLRPWDFQSHLVFCRFDKFLDRLIKIEDIFAT
  TLEFEKLERLEFGGTKGAILNGQVHEMSEELMELCKLFKQSTYDPSDCTNMEFESDYVAF
  KSKTLEFDRRLGTIICEAFFNCNGLEAAFKLLTIFGNFLEKPVVMEIFSLHYSTLVHMFN
  TELDVCKQLYNEHMKQIECGHVVLNKNMPFTSGNMKWAQQVLQRLQMFWSNFASLRYLFL
  GNPDHALVYQKYVEMTTLLDQFESRIYNEWKSNVDEICEFNLNQPLVKFSAINGLLCVNF
  DPKLVAVLREVKYLLMLKKQDIPDSALAIFKKRNTILKYIGNLDLLVQGYNKLKQTLLEV
  EYPLIEDELRAIDEQLTAATTWLTWQDDCWGYIERVRAATSELEHRVERTQKNVKVIQQT
  MRGWARCVLPPRREHRREAAFTLEDKGDLFTKKYKLIQGDGCKIHNLVEENRKLFKANPS
  LDTWKIYVEFIDDIVVEGFFQAIMHDLDFFLKNTEKQLKPAPFFQAQMILLPPEIVFKPS
  LDREAGDGFYDLVEEMLCNSFRMSAQMNRIATHLEIKNYQNDMDNMLGLAEVRQEIMNRV
  VNVINKVLDFRNTLETHTYLWVDDRAEFMKHFLLYGHAVSSDEMDAHANEEIPEQPPTLE
  QFKEQIDIYEALYVQMSKFEDFRVFDSWFKVDMKPFKVSLLTIIKKWSWMFQEHLLRFVI
  DSLNELQEFIKETDSGLQRELNEGDHDGLVDIMVHLLAVRSRQRATDELFEPLKETITLL
  ESYGQKMPEQVYIQLEELPERWETTKKIAATVRHEVSPLHNAEVTLIRKKCILFDAKQAE
  FRERFRHYAPLGFNAENPYTALDKANEELEALEEEMLQMQESTRLFEVALPEYKQMKQCR
  KEIKLLKGLWDVIIYVRRSIDNWTKTQWRQIHVEQMDVELRRFAKEIWSLNKEVRVWDAY
  TGLEGTVKDMTASLRAITELQSPALRDRHWHQLMKAIGVKFLINEATTLADLLALRLHRV
  EDDVRRIVDKAVKELGTEKVITEISQTWATMKFSYEVHYRTGIPLLKSDEQLFETLEHNQ
  VQLQTLLQSKYVEYFIEQVLSWQNKLNIADLVIFTWMEVQRTWSHLESIFVCSEDIRIQL
  VKDARRFDGVDAEFKELMFKTAKVENVLEATCRPNLYEKLKDLQSRLSLCEKALAEYLET
  KRIAFPRFYFVSSADLLDILSKGAQPKQVTCHLAKLFDSIADLQFEDNQDVSAHRAVGMY
  SKEKEYVPFQAECECVGHVETWLLQLEQTMQETVRHSITEAIVAYEEKPRELWIFDFPAQ
  VALTSSQIWWTTDVGIAFSRLEEGYETALKDFHKKQISQLNTLITLLLGELPPGDRQKIM
  TICTIDVHARDVVAKLISQKVVSPQAFTWLSQLRHRWEDTQKHCFVNICDAQFQYFYEYL
  GNSPRLVITPLTDRCYITLTQSLHLTMSGAPAGPAGTGKTETTKDLGRALGMMVYVFNCS
  EQMDYKSIGNIYKGLVQTGAWGCFDEFNRISVEVLSVVAVQVKMIHDAIRNRKKRFVFLG
  EAITLKPSVGIFITMNPGYAGRTELPENLKALFRPCAMVAPDIELICEILLVAEGFVDAR
  ALARKFITLYTLCKELLSKQDHYDWGLRAIKSVLVVAGSLKRGDKNRPEDQVLMRALRDF
  NMPKIVTDDIPVFLGLVGDLFPALDVPRRRKLHFEQMVRQSTLELRLQPEESFILKVVQL
  EELLAVRHSVFVVGNAGTGKSKILRTLNRTYVNMKQKPVWNDLNPKAVTTDELFGFIHHA
  TREWKDGKIVYSYFIGLFSSILREQANLKHDGPKWIVLDGDIDPMWIESLNTVMDDNKVL
  TLASNERIALTPFMRLLFEIHHLRSATPATVSRAGILYVNPQDLGWNPYVASWIDRRRHQ
  SEKANLTILFDKYVPACLDKLRTSFKTITSIPESSLVQTLCVLLECLLTPENVPSDSPKE
  VYEVYFVFACIWAFGGTLLQDQISDYQADFSRWWQKEMKAVKFPSQGTIFDYYVDHKTKK
  LLPWADKIAQFTMDPDVPLQTVLVHTTETARLRYFMELLLEKGKPLMLVGNAGVGKTVFV
  GDTLASLSEDYIVSRVPFNYYTTSTALQKILEKPLEKKAGHNYGPGGNKKLIYFIDDMNM
  PEVDLYGTVQPHTLIRQHIDYGHWYDRQKVMLKEIHNCQYVACMNPMVGSFTINPRLQRH
  FTVFAFNFPSLDALNTIYGQIFSFHFQQQAFAPSILRSGPTLIQATIAFHQTMMCNFLPT
  AIKFHYIFNLRDLSNVFQGILFASPECLKGPLDLIHLWLHESARVYGDKLIDKKDCDLFQ
  RRMLETAYKYFEGIDSHMLLQQPLIYCHFADRGKDPHYMPVKDWEVLKTILTETLDNYNE
  LNAAMHLVLFEDAMQHVCRISRILRTPQGCALLVGVGGSGKQSLSRLAAYLRGLEVFQIT
  LTEGYGIQELRVDLANLYIRTGAKNMPTVFLLTDAQVLDESFLVLINDLLASGEIPDLFS
  DEDVDKIISGIHNEVHALGMVDSRENCWKFFMARVRLQLKIILCFSPVGRTLRVRARKFP
  AIVNCTAIDWFHAWPQEALVSVSRRFIEETKGIEPVHKDSISLFMAHVHTTVNEMSTRYY
  QNERRHNYTTPKSFLEQISLFKNLLKKKQNEVSEKKERLVNGIQKLKTTASQVGDLKARL
  ASQEAELQLRNHDAEALITKIGLQTEKVSREKTIADAEERKVTAIQTEVFQKQRECEADL
  LKAEPALVAATAALNTLNRVNLSELKAFPNPPIAVTNVTAAVMVLLAPRGRVPKDRSWKA
  AKVFMGKVDDFLQALINYDKEHIPENCLKVVNEHYLKDPEFNPNLIRTKSFAAAGLCAWV
  INIIKFYEVYCDVEPKRQALAQANLELAAATEKLEAIRKKLVDLDRNLSRLTASFEKATA
  EKVRCQEEVNQTNKTIKLANRLVKELEAKKIRWGQSIKSFEAQEKTLCGDVLLTAAFVSY
  VGPFTRQYRQELVHCKWVPFLQQKVSIPLTEGLDLISMLTDDATIAAWNNEGLPSDRMST
  ENAAILTHCERWPLVIDPQQQGIKWIKNKYGMDLKVTHLGQKGFLNAIETALAFGDVILI
  ENLEETIDPVLDPLLGRNTIKKGKYIRIGDKECEFNKNFRLILHTKLANPHYKPELQAQT
  TLLNFTVTEDGLEAQLLAEVVSIERPDLEKLKLVLTKHQNDFKIELKYLEDDLLLRLSAA
  EGSFLDDTKLVERLEATKTTVAEIEHKVIEAKENERKINEARECYRPVAARASLLYFVIN
  DLQKINPLYQFSLKAFNVLFHRAIEQADKVEDMQGRISILMESITHAVFLYTSQALFEKD
  KLTFLSQMAFQILLRKKEIDPLELDFLLRFTVEHTHLSPVDFLTSQSWSAIKAIAVMEEF
  RGIDRDVEGSAKQWRKWVESECPEKEKLPQEWKKKSLIQKLILLRAMRPDRMTYALRNFV
  EEKLGAKYVERTRLDLVKAFEESSPATPIFFILSPGVDALKDLEILGKRLGFTIDSGKFH
  NVSLGQGQETVAEVALEKASKGGHWVILQNVHLVAKWLGTLEKLLERFSQGSHRDYRVFM
  SAESAPTPDEHIIPQGLLENSIKITNEPPTGMLANLHAALYNFDQDTLEICSKEQEFKSI
  LFSLCYFHACVAGRLRFGPQGWSRSYPFNPGDLTICASVLYNYLEANSKVPWEDLRYLFG
  EIMYGGHITDDWDRKLCRVYLEEFMNPSLTEDELMLAPGFAAPPYLDYAGYHQYIEEMLP
  PESPALYGLHPNAEIEFLTVTSNTLFRTLLEMQPRNALSGDELGQSTEEKVKNVLDDILE
  KLPEEFNMAEIMQKNSNRSPYVLVCFQECERMNILIREIRISLEQLDLSLKGELALSPAV
  EAQQFALSYDTVPDTWSKLAYPSTYGLAQWFNDLLLRCRELDTWTQDLTLPAVVWLSGFF
  NPQSFLTAIMQTMARKNEWPLDKTRLTADVTKKTKEDYGHPPREGAYLHGLFMEGARWDT
  QAGTIVEARLKELACPMPVIFAKATPVDRQETKQTYECPVYRTKLRGPSYIWTFRLKSEE
  KTAKWVLAGVALLLEA
• Function: Force generating protein of respiratory cilia. 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.
• Tissue Specificity: Expressed in airway ciliated epithelial cells (at protein level) . Not detected in spermatozoa (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

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Primary ciliary dyskinesia 7	DIS39GX2	Definitive	Autosomal recessive	[1]
Asthma	DISW9QNS	Strong	Genetic Variation	[2]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[3]
Bronchiectasis	DIS5MYEE	Strong	Biomarker	[4]
Congenital heart disease	DISQBA23	Strong	Genetic Variation	[5]
Cystic fibrosis	DIS2OK1Q	Strong	Genetic Variation	[2]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Genetic Variation	[6]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[7]
Plasma cell myeloma	DIS0DFZ0	Strong	Genetic Variation	[8]
Respiratory disease	DISGGAGJ	Strong	Biomarker	[4]
Sarcoidosis	DISE5B8Z	Strong	Biomarker	[9]
Squamous cell carcinoma	DISQVIFL	Strong	Genetic Variation	[7]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[7]
Visceral heterotaxy	DIS1DV90	Strong	Genetic Variation	[5]
Situs inversus	DISFA7AJ	moderate	Genetic Variation	[10]
Primary ciliary dyskinesia	DISOBC7V	Supportive	Autosomal dominant	[11]
Al amyloidosis	DISMHVSL	Limited	Genetic Variation	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Dynein axonemal heavy chain 11 (DNAH11).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Dynein axonemal heavy chain 11 (DNAH11).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Dynein axonemal heavy chain 11 (DNAH11).	[14]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia.Ann Am Thorac Soc. 2013 Dec;10(6):574-81. doi: 10.1513/AnnalsATS.201305-110OC.
• [3] Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
• [4] Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure.Thorax. 2012 May;67(5):433-41. doi: 10.1136/thoraxjnl-2011-200301. Epub 2011 Dec 18.
• [5] DNAH11 variants and its association with congenital heart disease and heterotaxy syndrome.Sci Rep. 2019 Apr 30;9(1):6683. doi: 10.1038/s41598-019-43109-6.
• [6] Intronic polymorphisms in genes LRFN2 (rs2494938) and DNAH11 (rs2285947) are prognostic indicators of esophageal squamous cell carcinoma.BMC Med Genet. 2019 May 3;20(1):72. doi: 10.1186/s12881-019-0796-9.
• [7] Genetic variants at 6p21.1 and 7p15.3 are associated with risk of multiple cancers in Han Chinese.Am J Hum Genet. 2012 Nov 2;91(5):928-34. doi: 10.1016/j.ajhg.2012.09.009. Epub 2012 Oct 25.
• [8] Variants in ELL2 influencing immunoglobulin levels associate with multiple myeloma.Nat Commun. 2015 May 26;6:7213. doi: 10.1038/ncomms8213.
• [9] Whole exome sequencing in three families segregating a pediatric case of sarcoidosis.BMC Med Genomics. 2018 Mar 6;11(1):23. doi: 10.1186/s12920-018-0338-x.
• [10] Mutations in the DNAH11 (axonemal heavy chain dynein type 11) gene cause one form of situs inversus totalis and most likely primary ciliary dyskinesia. Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10282-6. doi: 10.1073/pnas.152337699. Epub 2002 Jul 25.
• [11] Primary Ciliary Dyskinesia. 2007 Jan 24 [updated 2019 Dec 5]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [12] Genome-wide association study of immunoglobulin light chain amyloidosis in three patient cohorts: comparison with myeloma.Leukemia. 2017 Aug;31(8):1735-1742. doi: 10.1038/leu.2016.387. Epub 2016 Dec 27.
• [13] Chronic ethanol exposure increases goosecoid (GSC) expression in human embryonic carcinoma cell differentiation. J Appl Toxicol. 2014 Jan;34(1):66-75.
• [14] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [15] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.