Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDMJ75N)

• DOT Name: Spectrin beta chain, non-erythrocytic 2 (SPTBN2)
• Synonyms: Beta-III spectrin; Spinocerebellar ataxia 5 protein
• Gene Name: SPTBN2
• Related Disease:
  Cerebellar degeneration
  Microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability
  Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2
  Ataxia-telangiectasia
  Autosomal recessive spinocerebellar ataxia 14
  Cardiac arrest
  Cerebellar disorder
  Cholangiocarcinoma
  Dentatorubral-pallidoluysian atrophy
  Dowling-Degos disease
  Hepatocellular carcinoma
  Huntington disease
  Malignant peripheral nerve sheath tumor
  Niemann-Pick disease, type C1
  Schizophrenia
  Schwartz-Jampel syndrome
  Spinocerebellar ataxia type 14
  Spinocerebellar ataxia type 5
  Toxic epidermal necrolysis
  West syndrome
  Mitochondrial DNA depletion syndrome 7 (hepatocerebral type)
  Cerebellar ataxia
  Spinocerebellar ataxia
  Spinocerebellar ataxia type 3
• UniProt ID: SPTN2_HUMAN
• PDB ID: 1WJM; 1WYQ; 6ANU
• Pfam ID: PF00307 ; PF15410 ; PF00435
• Sequence:
  MSSTLSPTDFDSLEIQGQYSDINNRWDLPDSDWDNDSSSARLFERSRIKALADEREAVQK
  KTFTKWVNSHLARVTCRVGDLYSDLRDGRNLLRLLEVLSGEILPKPTKGRMRIHCLENVD
  KALQFLKEQKVHLENMGSHDIVDGNHRLTLGLVWTIILRFQIQDISVETEDNKEKKSAKD
  ALLLWCQMKTAGYPNVNVHNFTTSWRDGLAFNAIVHKHRPDLLDFESLKKCNAHYNLQNA
  FNLAEKELGLTKLLDPEDVNVDQPDEKSIITYVATYYHYFSKMKALAVEGKRIGKVLDHA
  MEAERLVEKYESLASELLQWIEQTIVTLNDRQLANSLSGVQNQLQSFNSYRTVEKPPKFT
  EKGNLEVLLFTIQSKLRANNQKVYTPREGRLISDINKAWERLEKAEHERELALRTELIRQ
  EKLEQLAARFDRKAAMRETWLSENQRLVSQDNFGLELAAVEAAVRKHEAIETDIVAYSGR
  VQAVDAVAAELAAERYHDIKRIAARQHNVARLWDFLRQMVAARRERLLLNLELQKVFQDL
  LYLMDWMEEMKGRLQSQDLGRHLAGVEDLLQLHELVEADIAVQAERVRAVSASALRFCNP
  GKEYRPCDPQLVSERVAKLEQSYEALCELAAARRARLEESRRLWRFLWEVGEAEAWVREQ
  QHLLASADTGRDLTGALRLLNKHTALRGEMSGRLGPLKLTLEQGQQLVAEGHPGASQASA
  RAAELQAQWERLEALAEERAQRLAQAASLYQFQADANDMEAWLVDALRLVSSPELGHDEF
  STQALARQHRALEEEIRSHRPTLDALREQAAALPPTLSRTPEVQSRVPTLERHYEELQAR
  AGERARALEAALALYTMLSEAGACGLWVEEKEQWLNGLALPERLEDLEVVQQRFETLEPE
  MNTLAAQITAVNDIAEQLLKANPPGKDRIVNTQEQLNHRWQQFRRLADGKKAALTSALSI
  QNYHLECTETQAWMREKTKVIESTQGLGNDLAGVLALQRKLAGTERDLEAIAARVGELTR
  EANALAAGHPAQAVAINARLREVQTGWEDLRATMRRREESLGEARRLQDFLRSLDDFQAW
  LGRTQTAVASEEGPATLPEAEALLAQHAALRGEVERAQSEYSRLRALGEEVTRDQADPQC
  LFLRQRLEALGTGWEELGRMWESRQGRLAQAHGFQGFLRDARQAEGVLSSQEYVLSHTEM
  PGTLQAADAAIKKLEDFMSTMDANGERIHGLLEAGRQLVSEGNIHADKIREKADSIERRH
  KKNQDAAQQFLGRLRDNREQQHFLQDCHELKLWIDEKMLTAQDVSYDEARNLHTKWQKHQ
  AFMAELAANKDWLDKVDKEGRELTLEKPELKALVSEKLRDLHRRWDELETTTQAKARSLF
  DANRAELFAQSCCALESWLESLQAQLHSDDYGKDLTSVNILLKKQQMLEWEMAVREKEVE
  AIQAQAKALAQEDQGAGEVERTSRAVEEKFRALCQPMRERCRRLQASREQHQFHRDVEDE
  ILWVTERLPMASSMEHGKDLPSVQLLMKKNQTLQKEIQGHEPRIADLRERQRALGAAAAG
  PELAELQEMWKRLGHELELRGKRLEDALRAQQFYRDAAEAEAWMGEQELHMMGQEKAKDE
  LSAQAEVKKHQVLEQALADYAQTIHQLAASSQDMIDHEHPESTRISIRQAQVDKLYAGLK
  ELAGERRERLQEHLRLCQLRRELDDLEQWIQEREVVAASHELGQDYEHVTMLRDKFREFS
  RDTSTIGQERVDSANALANGLIAGGHAARATVAEWKDSLNEAWADLLELLDTRGQVLAAA
  YELQRFLHGARQALARVQHKQQQLPDGTGRDLNAAEALQRRHCAYEHDIQALSPQVQQVQ
  DDGHRLQKAYAGDKAEEIGRHMQAVAEAWAQLQGSSAARRQLLLDTTDKFRFFKAVRELM
  LWMDEVNLQMDAQERPRDVSSADLVIKNQQGIKAEIEARADRFSSCIDMGKELLARSHYA
  AEEISEKLSQLQARRQETAEKWQEKMDWLQLVLEVLVFGRDAGMAEAWLCSQEPLVRSAE
  LGCTVDEVESLIKRHEAFQKSAVAWEERFCALEKLTALEEREKERKRKREEEERRKQPPA
  PEPTASVPPGDLVGGQTASDTTWDGTQPRPPPSTQAPSVNGVCTDGEPSQPLLGQQRLEH
  SSFPEGPGPGSGDEANGPRGERQTRTRGPAPSAMPQSRSTESAHAATLPPRGPEPSAQEQ
  MEGMLCRKQEMEAFGKKAANRSWQNVYCVLRRGSLGFYKDAKAASAGVPYHGEVPVSLAR
  AQGSVAFDYRKRKHVFKLGLQDGKEYLFQAKDEAEMSSWLRVVNAAIATASSASGEPEEP
  VVPSTTRGMTRAMTMPPVSPVGAEGPVVLRSKDGREREREKRFSFFKKNK
• Function: Probably plays an important role in neuronal membrane skeleton.
• Tissue Specificity: Highly expressed in brain, kidney, pancreas, and liver, and at lower levels in lung and placenta.
• KEGG Pathway:
  Cytoskeleton in muscle cells (hsa04820)
  Spinocerebellar ataxia (hsa05017)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
• Reactome Pathway:
  NCAM signaling for neurite out-growth (R-HSA-375165)
  Interaction between L1 and Ankyrins (R-HSA-445095)
  RAF/MAP kinase cascade (R-HSA-5673001)
  COPI-mediated anterograde transport (R-HSA-6807878)
  MHC class II antigen presentation (R-HSA-2132295)

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebellar degeneration	DISPBCM3	Definitive	Genetic Variation	[1]
Microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability	DISFHDE1	Definitive	Genetic Variation	[2]
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	DIS84UUI	Definitive	Genetic Variation	[2]
Ataxia-telangiectasia	DISP3EVR	Strong	Biomarker	[3]
Autosomal recessive spinocerebellar ataxia 14	DISYKOVU	Strong	Autosomal recessive	[4]
Cardiac arrest	DIS9DIA4	Strong	Genetic Variation	[5]
Cerebellar disorder	DIS2O7WM	Strong	Biomarker	[6]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[7]
Dentatorubral-pallidoluysian atrophy	DISHWE0K	Strong	Biomarker	[8]
Dowling-Degos disease	DISGTTEP	Strong	Genetic Variation	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[7]
Huntington disease	DISQPLA4	Strong	Biomarker	[10]
Malignant peripheral nerve sheath tumor	DIS0JTN6	Strong	Altered Expression	[11]
Niemann-Pick disease, type C1	DIS9HUE3	Strong	Altered Expression	[12]
Schizophrenia	DISSRV2N	Strong	Biomarker	[13]
Schwartz-Jampel syndrome	DIS3HCR8	Strong	Biomarker	[14]
Spinocerebellar ataxia type 14	DISMGAYN	Strong	Biomarker	[15]
Spinocerebellar ataxia type 5	DISPYXJ0	Strong	Autosomal dominant	[16]
Toxic epidermal necrolysis	DISIWPFR	Strong	Biomarker	[14]
West syndrome	DISLIAU9	Strong	Biomarker	[4]
Mitochondrial DNA depletion syndrome 7 (hepatocerebral type)	DISWVOY7	moderate	Genetic Variation	[17]
Cerebellar ataxia	DIS9IRAV	Limited	Genetic Variation	[18]
Spinocerebellar ataxia	DISYMHUK	Limited	Genetic Variation	[19]
Spinocerebellar ataxia type 3	DISQBQID	Limited	Genetic Variation	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Spectrin beta chain, non-erythrocytic 2 (SPTBN2).	[20]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Spectrin beta chain, non-erythrocytic 2 (SPTBN2).	[21]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of Spectrin beta chain, non-erythrocytic 2 (SPTBN2).	[22]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Spectrin beta chain, non-erythrocytic 2 (SPTBN2).	[24]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Spectrin beta chain, non-erythrocytic 2 (SPTBN2).	[25]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Spectrin beta chain, non-erythrocytic 2 (SPTBN2).	[26]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Spectrin beta chain, non-erythrocytic 2 (SPTBN2).	[27]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Spectrin beta chain, non-erythrocytic 2 (SPTBN2).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Spectrin beta chain, non-erythrocytic 2 (SPTBN2).	[29]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Spectrin beta chain, non-erythrocytic 2 (SPTBN2).	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Spectrin beta chain, non-erythrocytic 2 (SPTBN2).	[23]

References

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• [2] Genetic analysis of undiagnosed ataxia-telangiectasia-like disorders.Brain Dev. 2019 Feb;41(2):150-157. doi: 10.1016/j.braindev.2018.09.007. Epub 2018 Oct 6.
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• [4] Recessive mutations in SPTBN2 implicate -III spectrin in both cognitive and motor development. PLoS Genet. 2012;8(12):e1003074. doi: 10.1371/journal.pgen.1003074. Epub 2012 Dec 6.
• [5] Spinocerebellar ataxia.Nat Rev Dis Primers. 2019 Apr 11;5(1):24. doi: 10.1038/s41572-019-0074-3.
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• [12] Impact of Reduced Cerebellar EAAT Expression on Purkinje Cell Firing Pattern of NPC1-deficient Mice.Sci Rep. 2018 Feb 20;8(1):3318. doi: 10.1038/s41598-018-21805-z.
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• [17] Infantile-onset spinocerebellar ataxia type 5 associated with a novel SPTBN2 mutation: A case report.Brain Dev. 2019 Aug;41(7):630-633. doi: 10.1016/j.braindev.2019.03.002. Epub 2019 Mar 18.
• [18] Heterozygous Missense Pathogenic Variants Within the Second Spectrin Repeat of SPTBN2 Lead to Infantile-Onset Cerebellar Ataxia.J Child Neurol. 2020 Feb;35(2):106-110. doi: 10.1177/0883073819878917. Epub 2019 Oct 16.
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• [22] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
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