Details of Drug Off-Target (DOT)

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

• DOT Name: ATP-binding cassette sub-family A member 13 (ABCA13)
• Synonyms: EC 7.6.2.-
• Gene Name: ABCA13
• Related Disease:
  Asthma
  Colorectal carcinoma
  Colorectal neoplasm
  Autism
  Autism spectrum disorder
  Bipolar disorder
  Chromosomal disorder
  Clear cell renal carcinoma
  Depression
  Major depressive disorder
  Mental disorder
  Ovarian serous adenocarcinoma
  Pervasive developmental disorder
  Renal cell carcinoma
  Glioblastoma multiforme
  Nervous system disease
  Schizophrenia
• UniProt ID: ABCAD_HUMAN
• EC Number: 7.6.2.-
• Pfam ID: PF12698 ; PF00005
• Sequence:
  MGHAGCQFKALLWKNWLCRLRNPVLFLAEFFWPCILFVILTVLRFQEPPRYRDICYLQPR
  DLPSCGVIPFVQSLLCNTGSRCRNFSYEGSMEHHFRLSRFQTAADPKKVNNLAFLKEIQD
  LAEEIHGMMDKAKNLKRLWVERSNTPDSSYGSSFFTMDLNKTEEVILKLESLHQQPHIWD
  FLLLLPRLHTSHDHVEDGMDVAVNLLQTILNSLISLEDLDWLPLNQTFSQVSELVLNVTI
  STLTFLQQHGVAVTEPVYHLSMQNIVWDPQKVQYDLKSQFGFDDLHTEQILNSSAELKEI
  PTDTSLEKMVCSVLSSTSEDEAEKWGHVGGCHPKWSEAKNYLVHAVSWLRVYQQVFVQWQ
  QGSLLQKTLTGMGHSLEALRNQFEEESKPWKVVEALHTALLLLNDSLSADGPKDNHTFPK
  ILQHLWKLQSLLQNLPQWPALKRFLQLDGALRNAIAQNLHFVQEVLICLETSANDFKWFE
  LNQLKLEKDVFFWELKQMLAKNAVCPNGRFSEKEVFLPPGNSSIWGGLQGLLCYCNSSET
  SVLNKLLGSVEDADRILQEVITWHKNMSVLIPEEYLDWQELEMQLSEASLSCTRLFLLLG
  ADPSPENDVFSSDCKHQLVSTVIFHTLEKTQFFLEQAYYWKAFKKFIRKTCEVAQYVNMQ
  ESFQNRLLAFPEESPCFEENMDWKMISDNYFQFLNNLLKSPTASISRALNFTKHLLMMEK
  KLHTLEDEQMNFLLSFVEFFEKLLLPNLFDSSIVPSFHSLPSLTEDILNISSLWTNHLKS
  LKRDPSATDAQKLLEFGNEVIWKMQTLGSHWIRKEPKNLLRFIELILFEINPKLLELWAY
  GISKGKRAKLENFFTLLNFSVPENEILSTSFNFSQLFHSDWPKSPAMNIDFVRLSEAIIT
  SLHEFGFLEQEQISEALNTVYAIRNASDLFSALSEPQKQEVDKILTHIHLNVFQDKDSAL
  LLQIYSSFYRYIYELLNIQSRGSSLTFLTQISKHILDIIKQFNFQNISKAFAFLFKTAEV
  LGGISNVSYCQQLLSIFNFLELQAQSFMSTEGQELEVIHTTLTGLKQLLIIDEDFRISLF
  QYMSQFFNSSVEDLLDNKCLISDNKHISSVNYSTSEESSFVFPLAQIFSNLSANVSVFNK
  FMSIHCTVSWLQMWTEIWETISQLFKFDMNVFTSLHHGFTQLLDELEDDVKVSKSCQGIL
  PTHNVARLILNLFKNVTQANDFHNWEDFLDLRDFLVALGNALVSVKKLNLEQVEKSLFTM
  EAALHQLKTFPFNESTSREFLNSLLEVFIEFSSTSEYIVRNLDSINDFLSNNLTNYGEKF
  ENIITELREAIVFLRNVSHDRDLFSCADIFQNVTECILEDGFLYVNTSQRMLRILDTLNS
  TFSSENTISSLKGCIVWLDVINHLYLLSNSSFSQGHLQNILGNFRDIENKMNSILKIVTW
  VLNIKKPLCSSNGSHINCVNIYLKDVTDFLNIVLTTVFEKEKKPKFEILLALLNDSTKQV
  RMSINNLTTDFDFASQSNWRYFTELILRPIEMSDEIPNQFQNIWLHLITLGKEFQKLVKG
  IYFNILENNSSSKTENLLNIFATSPKEKDVNSVGNSIYHLASYLAFSLSHDLQNSPKIII
  SPEIMKATGLGIQLIRDVFNSLMPVVHHTSPQNAGYMQALKKVTSVMRTLKKADIDLLVD
  QLEQVSVNLMDFFKNISSVGTGNLVVNLLVGLMEKFADSSHSWNVNHLLQLSRLFPKDVV
  DAVIDVYYVLPHAVRLLQGVPGKNITEGLKDVYSFTLLHGITISNITKEDFAIVIKILLD
  TIELVSDKPDIISEALACFPVVWCWNHTNSGFRQNSKIDPCNVHGLMSSSFYGKVASILD
  HFHLSPQGEDSPCSNESSRMEITRKVVCIIHELVDWNSILLELSEVFHVNISLVKTVQKF
  WHKILPFVPPSINQTRDSISELCPSGSIKQVALQIIEKLKNVNFTKVTSGENILDKLSSL
  NKILNINEDTETSVQNIISSNLERTVQLISEDWSLEKSTHNLLSLFMMLQNANVTGSSLE
  ALSSFIEKSETPYNFEELWPKFQQIMKDLTQDFRIRHLLSEMNKGIKSINSMALQKITLQ
  FAHFLEILDSPSLKTLEIIEDFLLVTKNWLQEYANEDYSRMIETLFIPVTNESSTEDIAL
  LAKAIATFWGSLKNISRAGNFDVAFLTHLLNQEQLTNFSVVQLLFENILINLINNLAGNS
  QEAAWNLNDTDLQIMNFINLILNHMQSETSRKTVLSLRSIVDFTEQFLKTFFSLFLKEDS
  ENKISLLLKYFHKDVIAEMSFVPKDKILEILKLDQFLTLMIQDRLMNIFSSLKETIYHLM
  KSSFILDNGEFYFDTHQGLKFMQDLFNALLRETSMKNKTENNIDFFTVVSQLFFHVNKSE
  DLFKLNQDLGSALHLVRECSTEMARLLDTILHSPNKDFYALYPTLQEVILANLTDLLFFI
  NNSFPLRNRATLEITKRLVGAISRASEESHVLKPLLEMSGTLVMLLNDSADLRDLATSMD
  SIVKLLKLVKKVSGKMSTVFKTHFISNTKDSVKFFDTLYSIMQQSVQNLVKEIATLKKID
  HFTFEKINDLLVPFLDLAFEMIGVEPYISSNSDIFSMSPSILSYMNQSKDFSDILEEIAE
  FLTSVKMNLEDMRSLAVAFNNETQTFSMDSVNLREEILGCLVPINNITNQMDFLYPNPIS
  THSGPQDIKWEIIHEVIPFLDKILSQNSTEIGSFLKMVICLTLEALWKNLKKDNWNVSNV
  LMTFTQHPNNLLKTIETVLEASSGIKSDYEGDLNKSLYFDTPLSQNITHHQLEKAIHNVL
  SRIALWRKGLLFNNSEWITSTRTLFQPLFEIFIKATTGKNVTSEKEERTKKEMIDFPYSF
  KPFFCLEKYLGGLFVLTKYWQQIPLTDQSVVEICEVFQQTVKPSEAMEMLQKVKMMVVRV
  LTIVAENPSWTKDILCATLSCKQNGIRHLILSAIQGVTLAQDHFQEIEKIWSSPNQLNCE
  SLSKNLSSTLESFKSSLENATGQDCTSQPRLETVQQHLYMLAKSLEETWSSGNPIMTFLS
  NFTVTEDVKIKDLMKNITKLTEELRSSIQISNETIHSILEANISHSKVLFSALTVALSGK
  CDQEILHLLLTFPKGEKSWIAAEELCSLPGSKVYSLIVLLSRNLDVRAFIYKTLMPSEAN
  GLLNSLLDIVSSLSALLAKAQHVFEYLPEFLHTFKITALLETLDFQQVSQNVQARSSAFG
  SFQFVMKMVCKDQASFLSDSNMFINLPRVKELLEDDKEKFNIPEDSTPFCLKLYQEILQL
  PNGALVWTFLKPILHGKILYTPNTPEINKVIQKANYTFYIVDKLKTLSETLLEMSSLFQR
  SGSGQMFNQLQEALRNKFVRNFVENQLHIDVDKLTEKLQTYGGLLDEMFNHAGAGRFRFL
  GSILVNLSSCVALNRFQALQSVDILETKAHELLQQNSFLASIIFSNSLFDKNFRSESVKL
  PPHVSYTIRTNVLYSVRTDVVKNPSWKFHPQNLPADGFKYNYVFAPLQDMIERAIILVQT
  GQEALEPAAQTQAAPYPCHTSDLFLNNVGFFFPLIMMLTWMVSVASMVRKLVYEQEIQIE
  EYMRMMGVHPVIHFLAWFLENMAVLTISSATLAIVLKTSGIFAHSNTFIVFLFLLDFGMS
  VVMLSYLLSAFFSQANTAALCTSLVYMISFLPYIVLLVLHNQLSFVNQTFLCLLSTTAFG
  QGVFFITFLEGQETGIQWNNMYQALEQGGMTFGWVCWMILFDSSLYFLCGWYLSNLIPGT
  FGLRKPWYFPFTASYWKSVGFLVEKRQYFLSSSLFFFNENFDNKGSSLQNREGELEGSAP
  GVTLVSVTKEYEGHKAVVQDLSLTFYRDQITALLGTNGAGKTTIISMLTGLHPPTSGTII
  INGKNLQTDLSRVRMELGVCPQQDILLDNLTVREHLLLFASIKAPQWTKKELHQQVNQTL
  QDVDLTQHQHKQTRALSGGLKRKLSLGIAFMGMSRTVVLDEPTSGVDPCSRHSLWDILLK
  YREGRTIIFTTHHLDEAEALSDRVAVLQHGRLRCCGPPFCLKEAYGQGLRLTLTRQPSVL
  EAHDLKDMACVTSLIKIYIPQAFLKDSSGSELTYTIPKDTDKACLKGLFQALDENLHQLH
  LTGYGISDTTLEEVFLMLLQDSNKKSHIALGTESELQNHRPTGHLSGYCGSLARPATVQG
  VQLLRAQVAAILARRLRRTLRAGKSTLADLLLPVLFVALAMGLFMVRPLATEYPPLRLTP
  GHYQRAETYFFSSGGDNLDLTRVLLRKFRDQDLPCADLNPRQKNSSCWRTDPFSHPEFQD
  SCGCLKCPNRSASAPYLTNHLGHTLLNLSGFNMEEYLLAPSEKPRLGGWSFGLKIPSEAG
  GANGNISKPPTLAKVWYNQKGFHSLPSYLNHLNNLILWQHLPPTVDWRQYGITLYSHPYG
  GALLNKDKILESIRQCGVALCIVLGFSILSASIGSSVVRDRVIGAKRLQHISGLGYRMYW
  FTNFLYDMLFYLVSVCLCVAVIVAFQLTAFTFRKNLAATALLLSLFGYATLPWMYLMSRI
  FSSSDVAFISYVSLNFIFGLCTMLITIMPRLLAIISKAKNLQNIYDVLKWVFTIFPQFCL
  GQGLVELCYNQIKYDLTHNFGIDSYVSPFEMNFLGWIFVQLASQGTVLLLLRVLLHWDLL
  RWPRGHSTLQGTVKSSKDTDVEKEEKRVFEGRTNGDILVLYNLSKHYRRFFQNIIAVQDI
  SLGIPKGECFGLLGVNGAGKSTTFKMLNGEVSLTSGHAIIRTPMGDAVDLSSAGTAGVLI
  GYCPQQDALDELLTGWEHLYYYCSLRGIPRQCIPEVAGDLIRRLHLEAHADKPVATYSGG
  TKRKLSTALALVGKPDILLLDEPSSGMDPCSKRYLWQTIMKEVREGCAAVLTSHSMEECE
  ALCTRLAIMVNGSFKCLGSPQHIKNRFGDGYTVKVWLCKEANQHCTVSDHLKLYFPGIQF
  KGQHLNLLEYHVPKRWGCLADLFKVIENNKTFLNIKHYSINQTTLEQVFINFASEQQQTL
  QSTLDPSTDSHHTHHLPI
• Function: May mediate the cholesterol and gangliosides transport from the plasma membrane to intracellular vesicles in an ATP hydrolysis dependent manner, thus playing a role in their internalization by endocytic retrograde transport and may also participate in the endocytosis of synaptic vesicle in cortical neurons.
• Tissue Specificity: Significantly expressed in the bone marrow, trachea, testis, thyroid and lung as well as in skin fibroblasts.
• KEGG Pathway: ABC transporters (hsa02010)
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Definitive	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Definitive	Biomarker	[2]
Colorectal neoplasm	DISR1UCN	Definitive	Biomarker	[2]
Autism	DISV4V1Z	Strong	Genetic Variation	[3]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[4]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[5]
Chromosomal disorder	DISM5BB5	Strong	Genetic Variation	[5]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[6]
Depression	DIS3XJ69	Strong	Genetic Variation	[5]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[7]
Mental disorder	DIS3J5R8	Strong	Genetic Variation	[7]
Ovarian serous adenocarcinoma	DISSU72Z	Strong	Biomarker	[8]
Pervasive developmental disorder	DIS51975	Strong	Genetic Variation	[3]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[6]
Glioblastoma multiforme	DISK8246	Limited	Altered Expression	[9]
Nervous system disease	DISJ7GGT	Limited	Genetic Variation	[10]
Schizophrenia	DISSRV2N	Limited	Unknown	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Colchicine	DM2POTE	Approved	ATP-binding cassette sub-family A member 13 (ABCA13) affects the response to substance of Colchicine.	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of ATP-binding cassette sub-family A member 13 (ABCA13).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of ATP-binding cassette sub-family A member 13 (ABCA13).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of ATP-binding cassette sub-family A member 13 (ABCA13).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of ATP-binding cassette sub-family A member 13 (ABCA13).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of ATP-binding cassette sub-family A member 13 (ABCA13).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of ATP-binding cassette sub-family A member 13 (ABCA13).	[16]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of ATP-binding cassette sub-family A member 13 (ABCA13).	[17]

References

• [1] The impact of cigarette smoke exposure, COPD, or asthma status on ABC transporter gene expression in human airway epithelial cells.Sci Rep. 2019 Jan 17;9(1):153. doi: 10.1038/s41598-018-36248-9.
• [2] The role of ABC transporters in progression and clinical outcome of colorectal cancer.Mutagenesis. 2012 Mar;27(2):187-96. doi: 10.1093/mutage/ger075.
• [3] The neuropathological investigation of the brain in a monkey model of autism spectrum disorder with ABCA13 deletion.Int J Dev Neurosci. 2018 Dec;71:130-139. doi: 10.1016/j.ijdevneu.2018.09.002. Epub 2018 Sep 7.
• [4] Novel Drosophila model for psychiatric disorders including autism spectrum disorder by targeting of ATP-binding cassette protein A.Exp Neurol. 2018 Feb;300:51-59. doi: 10.1016/j.expneurol.2017.10.027. Epub 2017 Oct 29.
• [5] A cytogenetic abnormality and rare coding variants identify ABCA13 as a candidate gene in schizophrenia, bipolar disorder, and depression. Am J Hum Genet. 2009 Dec;85(6):833-46. doi: 10.1016/j.ajhg.2009.11.003.
• [6] The network of DAB2IP-miR-138 in regulating drug resistance of renal cell carcinoma associated with stem-like phenotypes.Oncotarget. 2017 May 9;8(40):66975-66986. doi: 10.18632/oncotarget.17756. eCollection 2017 Sep 15.
• [7] Association between the variability of the ABCA13 gene and the risk of major depressive disorder and schizophrenia in the Han Chinese population.World J Biol Psychiatry. 2017 Oct;18(7):550-556. doi: 10.1080/15622975.2016.1245442. Epub 2016 Nov 16.
• [8] CIAPIN1 and ABCA13 are markers of poor survival in metastatic ovarian serous carcinoma.Mol Cancer. 2015 Feb 18;14:44. doi: 10.1186/s12943-015-0317-1.
• [9] ATP binding cassette (ABC) transporters: expression and clinical value in glioblastoma.J Neurooncol. 2018 Jul;138(3):479-486. doi: 10.1007/s11060-018-2819-3. Epub 2018 Mar 8.
• [10] The effects of neurological disorder-related codon variations of ABCA13 on the function of the ABC protein.Biosci Biotechnol Biochem. 2012;76(12):2289-93. doi: 10.1271/bbb.120563. Epub 2012 Dec 7.
• [11] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [12] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [13] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [14] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [15] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [16] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [17] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
• [18] Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study. Environ Health Perspect. 2015 May;123(5):458-66. doi: 10.1289/ehp.1408775. Epub 2015 Jan 13.