Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW9IBRI)

• DOT Name: NBAS subunit of NRZ tethering complex (NBAS)
• Synonyms: Neuroblastoma-amplified gene protein; Neuroblastoma-amplified sequence
• Gene Name: NBAS
• Related Disease:
  Infantile liver failure syndrome 2
  Osteogenesis imperfecta
  Short stature-optic atrophy-Pelger-HuC+t anomaly syndrome
  Type-1/2 diabetes
  Adenocarcinoma
  Adenoma
  Adrenocortical carcinoma
  Aplasia cutis congenita
  Appendicitis
  Burkitt lymphoma
  Cardiac failure
  Chronic kidney disease
  Congestive heart failure
  Corpus callosum, agenesis of
  Dentatorubral-pallidoluysian atrophy
  Focal segmental glomerulosclerosis
  Gastric neoplasm
  Glomerulosclerosis
  Hepatitis
  Hepatitis A virus infection
  Hereditary diffuse gastric adenocarcinoma
  Immunodeficiency
  Inborn error of immunity
  Liver cirrhosis
  Liver failure
  Major depressive disorder
  Neoplasm
  Nephropathy
  Neuroblastoma
  Oculocerebrorenal syndrome
  Panic disorder
  Pelger-Huet anomaly
  Polyp
  Psoriasis
  Stomach cancer
  Urolithiasis
  Plasma cell myeloma
  Arteriosclerosis
  Atherosclerosis
  Non-insulin dependent diabetes
  Acute liver failure
  Chronic hepatitis B virus infection
  Cystitis
  Gastric cancer
  Malignant pleural mesothelioma
  Vibrio cholerae infection
• UniProt ID: NBAS_HUMAN
• Pfam ID: PF15492 ; PF08314
• Sequence:
  MAAPESGPALSPGTAEGEEETILYDLLVNTEWPPETEVQPRGNQKHGASFIITKAIRDRL
  LFLRQYIWYSPAPFLLPDGLVRLVNKQINWHLVLASNGKLLAAVQDQCVEIRSAKDDFTS
  IIGKCQVPKDPKPQWRRVAWSYDCTLLAYAESTGTVRVFDLMGSELFVISPASSFIGDLS
  YAIAGLIFLEYKASAQWSAELLVINYRGELRSYLVSVGTNQSYQESHCFSFSSHYPHGIN
  TAIYHPGHRLLLVGGCETAEVGMSKASSCGLSAWRVLSGSPYYKQVTNGGDGVTAVPKTL
  GLLRMLSVKFYSRQGQEQDGIFKMSLSPDGMLLAAIHFSGKLSIWAIPSLKQQGEWGQNE
  QPGYDDLNPDWRLSTEKRKKIKDKESFYPLIDVNWWADSAVTLARCSGALTVSSVKTLKN
  LLGKSCEWFEPSPQVTATHDGGFLSLECEIKLAPKRSRLETRAGEEDEGEEDSDSDYEIS
  AKARYFGYIKQGLYLVTEMERFAPPRKRPRTITKNYRLVSLRSTTPEELYQRKIESEEYE
  EALSLAHTYGLDTDLVYQRQWRKSAVNVASIQNYLSKIKKRSWVLHECLERVPENVDAAK
  ELLQYGLKGTDLEALLAIGKGADDGRFTLPGEIDIDSISYEELSPPDEEPAKNKKEKELK
  KRQELLKLVNFSKLTLEQKELCRCRRKLLTYLDRLATYEEILGVPHASEQRYDAEFFKKF
  RNQNIVLSARTYAQESNVQALEILFTYHGSDLLPHRLAILSNFPETTSPHEYSVLLPEAC
  FNGDSLMIIPWHEHKHRAKDWCEELACRMVVEPNLQDESEFLYAAQPELLRFRMTQLTVE
  KVMDWYQTRAEEIEHYARQVDCALSLIRLGMERNIPGLLVLCDNLVTLETLVYEARCDVT
  LTLKELQQMKDIEKLRLLMNSCSEDKYVTSAYQWMVPFLHRCEKQSPGVANELLKEYLVT
  LAKGDLKFPLKIFQHSKPDLQQKIIPDQDQLMAIALECIYTCERNDQLCLCYDLLECLPE
  RGYGDKTEATTKLHDMVDQLEQILSVSELLEKHGLEKPISFVKNTQSSSEEARKLMVRLT
  RHTGRKQPPVSESHWRTLLQDMLTMQQNVYTCLDSDACYEIFTESLLCSSRLENIHLAGQ
  MMHCSACSENPPAGIAHKGKPHYRVSYEKSIDLVLAASREYFNSSTNLTDSCMDLARCCL
  QLITDRPPAIQEELDLIQAVGCLEEFGVKILPLQVRLCPDRISLIKECISQSPTCYKQST
  KLLGLAELLRVAGENPEERRGQVLILLVEQALRFHDYKAASMHCQELMATGYPKSWDVCS
  QLGQSEGYQDLATRQELMAFALTHCPPSSIELLLAASSSLQTEILYQRVNFQIHHEGGEN
  ISASPLTSKAVQEDEVGVPGSNSADLLRWTTATTMKVLSNTTTTTKAVLQAVSDGQWWKK
  SLTYLRPLQGQKCGGAYQIGTTANEDLEKQGCHPFYESVISNPFVAESEGTYDTYQHVPV
  ESFAEVLLRTGKLAEAKNKGEVFPTTEVLLQLASEALPNDMTLALAYLLALPQVLDANRC
  FEKQSPSALSLQLAAYYYSLQIYARLAPCFRDKCHPLYRADPKELIKMVTRHVTRHEHEA
  WPEDLISLTKQLHCYNERLLDFTQAQILQGLRKGVDVQRFTADDQYKRETILGLAETLEE
  SVYSIAISLAQRYSVSRWEVFMTHLEFLFTDSGLSTLEIENRAQDLHLFETLKTDPEAFH
  QHMVKYIYPTIGGFDHERLQYYFTLLENCGCADLGNCAIKPETHIRLLKKFKVVASGLNY
  KKLTDENMSPLEALEPVLSSQNILSISKLVPKIPEKDGQMLSPSSLYTIWLQKLFWTGDP
  HLIKQVPGSSPEWLHAYDVCMKYFDRLHPGDLITVVDAVTFSPKAVTKLSVEARKEMTRK
  AIKTVKHFIEKPRKRNSEDEAQEAKDSKVTYADTLNHLEKSLAHLETLSHSFILSLKNSE
  QETLQKYSHLYDLSRSEKEKLHDEAVAICLDGQPLAMIQQLLEVAVGPLDISPKDIVQSA
  IMKIISALSGGSADLGGPRDPLKVLEGVVAAVHASVDKGEELVSPEDLLEWLRPFCADDA
  WPVRPRIHVLQILGQSFHLTEEDSKLLVFFRTEAILKASWPQRQVDIADIENEENRYCLF
  MELLESSHHEAEFQHLVLLLQAWPPMKSEYVITNNPWVRLATVMLTRCTMENKEGLGNEV
  LKMCRSLYNTKQMLPAEGVKELCLLLLNQSLLLPSLKLLLESRDEHLHEMALEQITAVTT
  VNDSNCDQELLSLLLDAKLLVKCVSTPFYPRIVDHLLASLQQGRWDAEELGRHLREAGHE
  AEAGSLLLAVRGTHQAFRTFSTALRAAQHWV
• Function: Involved in Golgi-to-endoplasmic reticulum (ER) retrograde transport; the function is proposed to depend on its association in the NRZ complex which is believed to play a role in SNARE assembly at the ER. Required for normal embryonic development. May play a role in the nonsense-mediated decay pathway of mRNAs containing premature stop codons.
• Tissue Specificity: Broadly expressed, with highest levels in heart and skeletal muscle, and lowest levels in liver, small intestine and thymus. Well expressed in retinal ganglion cells, epidermal skin cells, and leukocytes. Up-regulated together with N-myc in some neuroblastoma cell lines.
• Reactome Pathway: COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Infantile liver failure syndrome 2	DISGPJDM	Definitive	Autosomal recessive	[1]
Osteogenesis imperfecta	DIS7XQSD	Definitive	Genetic Variation	[2]
Short stature-optic atrophy-Pelger-HuC+t anomaly syndrome	DISJCA0A	Definitive	Autosomal recessive	[2]
Type-1/2 diabetes	DISIUHAP	Definitive	Biomarker	[3]
Adenocarcinoma	DIS3IHTY	Strong	Genetic Variation	[4]
Adenoma	DIS78ZEV	Strong	Biomarker	[5]
Adrenocortical carcinoma	DISZF4HX	Strong	Altered Expression	[5]
Aplasia cutis congenita	DISMDAYM	Strong	Biomarker	[5]
Appendicitis	DIS4GOLF	Strong	Biomarker	[6]
Burkitt lymphoma	DIS9D5XU	Strong	Altered Expression	[7]
Cardiac failure	DISDC067	Strong	Genetic Variation	[8]
Chronic kidney disease	DISW82R7	Strong	Altered Expression	[9]
Congestive heart failure	DIS32MEA	Strong	Genetic Variation	[8]
Corpus callosum, agenesis of	DISO9P40	Strong	Biomarker	[5]
Dentatorubral-pallidoluysian atrophy	DISHWE0K	Strong	Altered Expression	[10]
Focal segmental glomerulosclerosis	DISJNHH0	Strong	Biomarker	[11]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[12]
Glomerulosclerosis	DISJF20Z	Strong	Biomarker	[13]
Hepatitis	DISXXX35	Strong	Genetic Variation	[14]
Hepatitis A virus infection	DISUMFQV	Strong	Genetic Variation	[14]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[12]
Immunodeficiency	DIS093I0	Strong	Biomarker	[2]
Inborn error of immunity	DISNGCMN	Strong	Genetic Variation	[15]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[16]
Liver failure	DISLGEL6	Strong	Genetic Variation	[17]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[18]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Nephropathy	DISXWP4P	Strong	Biomarker	[19]
Neuroblastoma	DISVZBI4	Strong	Genetic Variation	[2]
Oculocerebrorenal syndrome	DIS8TEDY	Strong	Biomarker	[20]
Panic disorder	DISD3VNY	Strong	Biomarker	[21]
Pelger-Huet anomaly	DISCW4OI	Strong	Biomarker	[17]
Polyp	DISRSLYF	Strong	Genetic Variation	[22]
Psoriasis	DIS59VMN	Strong	Genetic Variation	[23]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[24]
Urolithiasis	DISNFTKT	Strong	Biomarker	[25]
Plasma cell myeloma	DIS0DFZ0	moderate	Biomarker	[26]
Arteriosclerosis	DISK5QGC	Disputed	Biomarker	[27]
Atherosclerosis	DISMN9J3	Disputed	Biomarker	[27]
Non-insulin dependent diabetes	DISK1O5Z	Disputed	Biomarker	[27]
Acute liver failure	DIS5EZKX	Limited	Biomarker	[28]
Chronic hepatitis B virus infection	DISHL4NT	Limited	Genetic Variation	[29]
Cystitis	DIS2D4B9	Limited	Altered Expression	[30]
Gastric cancer	DISXGOUK	Limited	Genetic Variation	[24]
Malignant pleural mesothelioma	DIST2R60	Limited	Altered Expression	[31]
Vibrio cholerae infection	DISW7E3U	Limited	Genetic Variation	[32]

9 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 NBAS subunit of NRZ tethering complex (NBAS).	[33]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of NBAS subunit of NRZ tethering complex (NBAS).	[34]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of NBAS subunit of NRZ tethering complex (NBAS).	[35]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of NBAS subunit of NRZ tethering complex (NBAS).	[36]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of NBAS subunit of NRZ tethering complex (NBAS).	[37]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of NBAS subunit of NRZ tethering complex (NBAS).	[38]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of NBAS subunit of NRZ tethering complex (NBAS).	[39]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of NBAS subunit of NRZ tethering complex (NBAS).	[40]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of NBAS subunit of NRZ tethering complex (NBAS).	[41]

References

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