Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOW8R6H)

• DOT Name: Anoctamin-5 (ANO5)
• Synonyms: Gnathodiaphyseal dysplasia 1 protein; Transmembrane protein 16E
• Gene Name: ANO5
• Related Disease:
  Autosomal recessive limb-girdle muscular dystrophy
  Amyloidosis
  Autosomal recessive limb-girdle muscular dystrophy type 2A
  Autosomal recessive limb-girdle muscular dystrophy type 2L
  Becker muscular dystrophy
  Bone disease
  Cardiovascular disease
  Congenital muscular dystrophy
  Distal myopathy
  Gnathodiaphyseal dysplasia
  Limb-girdle muscular dystrophy
  Miyoshi muscular dystrophy 3
  Muscle-eye-brain disease
  Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4
  Muscular dystrophy-dystroglycanopathy, type A
  Myopathy
  Neoplasm
  Qualitative or quantitative defects of dysferlin
  Scott syndrome
  Hereditary fructose intolerance
  Dilated cardiomyopathy
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid gland follicular carcinoma
  Thyroid gland papillary carcinoma
  Thyroid tumor
• UniProt ID: ANO5_HUMAN
• Pfam ID: PF16178 ; PF04547
• Sequence:
  MGDPDLLEVLAEEGEKVNKHIDYSFQMSEQSLSSRETSFLINEETMPAKRFNLFLRRRLM
  FQKNQQSKDSIFFRDGIRQIDFVLSYVDDVKKDAELKAERRKEFETNLRKTGLELEIEDK
  RDSEDGRTYFVKIHAPWEVLVTYAEVLGIKMPIKESDIPRPKHTPISYVLGPVRLPLSVK
  YPHPEYFTAQFSRHRQELFLIEDQATFFPSSSRNRIVYYILSRCPFGIEDGKKRFGIERL
  LNSNTYSSAYPLHDGQYWKPSEPPNPTNERYTLHQNWARFSYFYKEQPLDLIKNYYGEKI
  GIYFVFLGFYTEMLFFAAVVGLACFIYGLLSMEHNTSSTEICDPEIGGQMIMCPLCDQVC
  DYWRLNSTCLASKFSHLFDNESTVFFAIFMGIWVTLFLEFWKQRQARLEYEWDLVDFEEE
  QQQLQLRPEFEAMCKHRKLNAVTKEMEPYMPLYTRIPWYFLSGATVTLWMSLVVTSMVAV
  IVYRLSVFATFASFMESDASLKQVKSFLTPQITTSLTGSCLNFIVILILNFFYEKISAWI
  TKMEIPRTYQEYESSLTLKMFLFQFVNFYSSCFYVAFFKGKFVGYPGKYTYLFNEWRSEE
  CDPGGCLIELTTQLTIIMTGKQIFGNIKEAIYPLALNWWRRRKARTNSEKLYSRWEQDHD
  LESFGPLGLFYEYLETVTQFGFVTLFVASFPLAPLLALINNIVEIRVDAWKLTTQYRRTV
  ASKAHSIGVWQDILYGMAVLSVATNAFIVAFTSDIIPRLVYYYAYSTNATQPMTGYVNNS
  LSVFLIADFPNHTAPSEKRDFITCRYRDYRYPPDDENKYFHNMQFWHVLAAKMTFIIVME
  HVVFLVKFLLAWMIPDVPKDVVERIKREKLMTIKILHDFELNKLKENLGINSNEFAKHVM
  IEENKAQLAKSTL
• Function: Plays a role in plasma membrane repair in a process involving annexins. Does not exhibit calcium-activated chloride channel (CaCC) activity.
• Tissue Specificity: Highly expressed in brain, heart, kidney, lung, and skeletal muscle. Weakly expressed in bone marrow, fetal liver, placenta, spleen, thymus, osteoblasts and periodontal ligament cells.
• KEGG Pathway: Efferocytosis (hsa04148)
• Reactome Pathway:
  Induction of Cell-Cell Fusion (R-HSA-9733458)
  Stimuli-sensing channels (R-HSA-2672351)

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal recessive limb-girdle muscular dystrophy	DISWPGLM	Definitive	Autosomal recessive	[1]
Amyloidosis	DISHTAI2	Strong	Biomarker	[2]
Autosomal recessive limb-girdle muscular dystrophy type 2A	DISIHX4S	Strong	Genetic Variation	[3]
Autosomal recessive limb-girdle muscular dystrophy type 2L	DIS31BGJ	Strong	Autosomal recessive	[4]
Becker muscular dystrophy	DIS5IYHL	Strong	Biomarker	[5]
Bone disease	DISE1F82	Strong	Genetic Variation	[6]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[7]
Congenital muscular dystrophy	DISKY7OY	Strong	Genetic Variation	[8]
Distal myopathy	DIS7F5R0	Strong	Genetic Variation	[9]
Gnathodiaphyseal dysplasia	DISTWRZO	Strong	Autosomal dominant	[10]
Limb-girdle muscular dystrophy	DISI9Y1Z	Strong	Genetic Variation	[11]
Miyoshi muscular dystrophy 3	DISR9FAQ	Strong	Autosomal recessive	[4]
Muscle-eye-brain disease	DISJUOQB	Strong	Genetic Variation	[8]
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4	DISGM0K5	Strong	Genetic Variation	[8]
Muscular dystrophy-dystroglycanopathy, type A	DISZTBC4	Strong	Genetic Variation	[8]
Myopathy	DISOWG27	Strong	Genetic Variation	[11]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[12]
Qualitative or quantitative defects of dysferlin	DIS59VEJ	Strong	Genetic Variation	[13]
Scott syndrome	DIS4N4IB	Strong	Genetic Variation	[14]
Hereditary fructose intolerance	DISWLA0D	moderate	CausalMutation	[15]
Dilated cardiomyopathy	DISX608J	Limited	Genetic Variation	[16]
Thyroid cancer	DIS3VLDH	Limited	Altered Expression	[17]
Thyroid gland carcinoma	DISMNGZ0	Limited	Altered Expression	[17]
Thyroid gland follicular carcinoma	DISFK2QT	Limited	Altered Expression	[17]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Altered Expression	[17]
Thyroid tumor	DISLVKMD	Limited	Altered Expression	[17]

5 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 Anoctamin-5 (ANO5).	[18]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Anoctamin-5 (ANO5).	[19]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Anoctamin-5 (ANO5).	[20]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Anoctamin-5 (ANO5).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Anoctamin-5 (ANO5).	[23]

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 affects the methylation of Anoctamin-5 (ANO5).	[22]

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] Amyloidosis and exercise intolerance in ANO5 muscular dystrophy.Neuromuscul Disord. 2012 Jan;22(1):13-5. doi: 10.1016/j.nmd.2011.07.005. Epub 2011 Aug 4.
• [3] Autosomal recessive limb-girdle muscular dystrophies in the Czech Republic.BMC Neurol. 2014 Aug 19;14:154. doi: 10.1186/s12883-014-0154-7.
• [4] [Hyperviscosity syndrome in plasma cell dyscrasia]. Harefuah. 1979 Feb 1;96(3):161-3.
• [5] Reliability and accuracy of skeletal muscle imaging in limb-girdle muscular dystrophies.Neurology. 2012 Oct 16;79(16):1716-23. doi: 10.1212/WNL.0b013e31826e9b73. Epub 2012 Oct 3.
• [6] Gain of function of TMEM16E/ANO5 scrambling activity caused by a mutation associated with gnathodiaphyseal dysplasia.Cell Mol Life Sci. 2018 May;75(9):1657-1670. doi: 10.1007/s00018-017-2704-9. Epub 2017 Nov 9.
• [7] Genome-wide association study identifies genes for biomarkers of cardiovascular disease: serum urate and dyslipidemia.Am J Hum Genet. 2008 Jan;82(1):139-49. doi: 10.1016/j.ajhg.2007.11.001.
• [8] Muscular dystrophies due to glycosylation defects.Neurotherapeutics. 2008 Oct;5(4):627-32. doi: 10.1016/j.nurt.2008.08.005.
• [9] Clinical spectrum and gene mutations in a Chinese cohort with anoctaminopathy.Neuromuscul Disord. 2019 Aug;29(8):628-633. doi: 10.1016/j.nmd.2019.06.005. Epub 2019 Jun 12.
• [10] The novel gene encoding a putative transmembrane protein is mutated in gnathodiaphyseal dysplasia (GDD). Am J Hum Genet. 2004 Jun;74(6):1255-61. doi: 10.1086/421527. Epub 2004 Apr 29.
• [11] ANO5 mutations in the Polish limb girdle muscular dystrophy patients: Effects on the protein structure.Sci Rep. 2019 Aug 8;9(1):11533. doi: 10.1038/s41598-019-47849-3.
• [12] Whole exome sequencing links dental tumor to an autosomal-dominant mutation in ANO5 gene associated with gnathodiaphyseal dysplasia and muscle dystrophies.Sci Rep. 2016 May 24;6:26440. doi: 10.1038/srep26440.
• [13] ANO5-muscular dystrophy: clinical, pathological and molecular findings.Eur J Neurol. 2013 Oct;20(10):1383-9. doi: 10.1111/ene.12191. Epub 2013 May 12.
• [14] Physiological roles and diseases of Tmem16/Anoctamin proteins: are they all chloride channels?.Acta Pharmacol Sin. 2011 Jun;32(6):685-92. doi: 10.1038/aps.2011.48.
• [15] Next generation sequencing on patients with LGMD and nonspecific myopathies: Findings associated with ANO5 mutations.Neuromuscul Disord. 2015 Jul;25(7):533-41. doi: 10.1016/j.nmd.2015.03.011. Epub 2015 Mar 30.
• [16] Dilated cardiomyopathy in patients with mutations in anoctamin 5.Int J Cardiol. 2013 Sep 20;168(1):76-9. doi: 10.1016/j.ijcard.2012.09.070. Epub 2012 Oct 3.
• [17] Anoctamin5 regulates cell migration and invasion in thyroid cancer.Int J Oncol. 2017 Oct;51(4):1311-1319. doi: 10.3892/ijo.2017.4113. Epub 2017 Sep 1.
• [18] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [19] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [20] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [21] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [22] 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.
• [23] 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.