Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3F8J6Y)

• DOT Name: Filamin-C (FLNC)
• Synonyms: FLN-C; FLNc; ABP-280-like protein; ABP-L; Actin-binding-like protein; Filamin-2; Gamma-filamin
• Gene Name: FLNC
• Related Disease:
  Dilated cardiomyopathy
  Dilated cardiomyopathy 1A
  Myofibrillar myopathy 5
  Neuromuscular disease
  Advanced cancer
  Allergic rhinitis
  Aortic valve stenosis
  Arrhythmia
  Arrhythmogenic right ventricular cardiomyopathy
  Carcinoma
  Cardiomyopathy
  Cardiovascular disease
  Cystic fibrosis
  Deafness
  Distal myopathy
  Esophageal squamous cell carcinoma
  Frontotemporal dementia
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  Hypertrophic cardiomyopathy
  Hypertrophic cardiomyopathy 26
  leukaemia
  Leukemia
  Limb-girdle muscular dystrophy
  Long QT syndrome
  Mitochondrial disease
  Muscular dystrophy
  Myofibrillar myopathy
  Myopathy
  Neoplasm
  Obstructive sleep apnea
  Prostate cancer
  Prostate carcinoma
  Respiratory failure
  Restrictive cardiomyopathy
  Stomach cancer
  Asthma
  Cardiomyopathy, familial restrictive, 1
  Distal myopathy with posterior leg and anterior hand involvement
  Familial hypertrophic cardiomyopathy
  Gastric cancer
  Obesity
  Obsolete familial isolated restrictive cardiomyopathy
  Colorectal carcinoma
  Colorectal neoplasm
  Gallbladder cancer
  Gallbladder carcinoma
  Heart arrhythmia
  Pick disease
• UniProt ID: FLNC_HUMAN
• PDB ID: 1V05; 2D7M; 2D7N; 2D7O; 2D7P; 2D7Q; 2K9U; 2NQC; 3V8O; 4MGX; 7OUU; 7OUV; 7P0E
• Pfam ID: PF00307 ; PF00630
• Sequence:
  MMNNSGYSDAGLGLGDETDEMPSTEKDLAEDAPWKKIQQNTFTRWCNEHLKCVGKRLTDL
  QRDLSDGLRLIALLEVLSQKRMYRKFHPRPNFRQMKLENVSVALEFLEREHIKLVSIDSK
  AIVDGNLKLILGLIWTLILHYSISMPMWEDEDDEDARKQTPKQRLLGWIQNKVPQLPITN
  FNRDWQDGKALGALVDNCAPGLCPDWEAWDPNQPVENAREAMQQADDWLGVPQVIAPEEI
  VDPNVDEHSVMTYLSQFPKAKLKPGAPVRSKQLNPKKAIAYGPGIEPQGNTVLQPAHFTV
  QTVDAGVGEVLVYIEDPEGHTEEAKVVPNNDKDRTYAVSYVPKVAGLHKVTVLFAGQNIE
  RSPFEVNVGMALGDANKVSARGPGLEPVGNVANKPTYFDIYTAGAGTGDVAVVIVDPQGR
  RDTVEVALEDKGDSTFRCTYRPAMEGPHTVHVAFAGAPITRSPFPVHVSEACNPNACRAS
  GRGLQPKGVRVKEVADFKVFTKGAGSGELKVTVKGPKGTEEPVKVREAGDGVFECEYYPV
  VPGKYVVTITWGGYAIPRSPFEVQVSPEAGVQKVRAWGPGLETGQVGKSADFVVEAIGTE
  VGTLGFSIEGPSQAKIECDDKGDGSCDVRYWPTEPGEYAVHVICDDEDIRDSPFIAHILP
  APPDCFPDKVKAFGPGLEPTGCIVDKPAEFTIDARAAGKGDLKLYAQDADGCPIDIKVIP
  NGDGTFRCSYVPTKPIKHTIIISWGGVNVPKSPFRVNVGEGSHPERVKVYGPGVEKTGLK
  ANEPTYFTVDCSEAGQGDVSIGIKCAPGVVGPAEADIDFDIIKNDNDTFTVKYTPPGAGR
  YTIMVLFANQEIPASPFHIKVDPSHDASKVKAEGPGLNRTGVEVGKPTHFTVLTKGAGKA
  KLDVQFAGTAKGEVVRDFEIIDNHDYSYTVKYTAVQQGNMAVTVTYGGDPVPKSPFVVNV
  APPLDLSKIKVQGLNSKVAVGQEQAFSVNTRGAGGQGQLDVRMTSPSRRPIPCKLEPGGG
  AEAQAVRYMPPEEGPYKVDITYDGHPVPGSPFAVEGVLPPDPSKVCAYGPGLKGGLVGTP
  APFSIDTKGAGTGGLGLTVEGPCEAKIECQDNGDGSCAVSYLPTEPGEYTINILFAEAHI
  PGSPFKATIRPVFDPSKVRASGPGLERGKVGEAATFTVDCSEAGEAELTIEILSDAGVKA
  EVLIHNNADGTYHITYSPAFPGTYTITIKYGGHPVPKFPTRVHVQPAVDTSGVKVSGPGV
  EPHGVLREVTTEFTVDARSLTATGGNHVTARVLNPSGAKTDTYVTDNGDGTYRVQYTAYE
  EGVHLVEVLYDEVAVPKSPFRVGVTEGCDPTRVRAFGPGLEGGLVNKANRFTVETRGAGT
  GGLGLAIEGPSEAKMSCKDNKDGSCTVEYIPFTPGDYDVNITFGGRPIPGSPFRVPVKDV
  VDPGKVKCSGPGLGAGVRARVPQTFTVDCSQAGRAPLQVAVLGPTGVAEPVEVRDNGDGT
  HTVHYTPATDGPYTVAVKYADQEVPRSPFKIKVLPAHDASKVRASGPGLNASGIPASLPV
  EFTIDARDAGEGLLTVQILDPEGKPKKANIRDNGDGTYTVSYLPDMSGRYTITIKYGGDE
  IPYSPFRIHALPTGDASKCLVTVSIGGHGLGACLGPRIQIGQETVITVDAKAAGEGKVTC
  TVSTPDGAELDVDVVENHDGTFDIYYTAPEPGKYVITIRFGGEHIPNSPFHVLACDPLPH
  EEEPSEVPQLRQPYAPPRPGARPTHWATEEPVVPVEPMESMLRPFNLVIPFAVQKGELTG
  EVRMPSGKTARPNITDNKDGTITVRYAPTEKGLHQMGIKYDGNHIPGSPLQFYVDAINSR
  HVSAYGPGLSHGMVNKPATFTIVTKDAGEGGLSLAVEGPSKAEITCKDNKDGTCTVSYLP
  TAPGDYSIIVRFDDKHIPGSPFTAKITGDDSMRTSQLNVGTSTDVSLKITESDLSQLTAS
  IRAPSGNEEPCLLKRLPNRHIGISFTPKEVGEHVVSVRKSGKHVTNSPFKILVGPSEIGD
  ASKVRVWGKGLSEGHTFQVAEFIVDTRNAGYGGLGLSIEGPSKVDINCEDMEDGTCKVTY
  CPTEPGTYIINIKFADKHVPGSPFTVKVTGEGRMKESITRRRQAPSIATIGSTCDLNLKI
  PGNWFQMVSAQERLTRTFTRSSHTYTRTERTEISKTRGGETKREVRVEESTQVGGDPFPA
  VFGDFLGRERLGSFGSITRQQEGEASSQDMTAQVTSPSGKVEAAEIVEGEDSAYSVRFVP
  QEMGPHTVAVKYRGQHVPGSPFQFTVGPLGEGGAHKVRAGGTGLERGVAGVPAEFSIWTR
  EAGAGGLSIAVEGPSKAEIAFEDRKDGSCGVSYVVQEPGDYEVSIKFNDEHIPDSPFVVP
  VASLSDDARRLTVTSLQETGLKVNQPASFAVQLNGARGVIDARVHTPSGAVEECYVSELD
  SDKHTIRFIPHENGVHSIDVKFNGAHIPGSPFKIRVGEQSQAGDPGLVSAYGPGLEGGTT
  GVSSEFIVNTLNAGSGALSVTIDGPSKVQLDCRECPEGHVVTYTPMAPGNYLIAIKYGGP
  QHIVGSPFKAKVTGPRLSGGHSLHETSTVLVETVTKSSSSRGSSYSSIPKFSSDASKVVT
  RGPGLSQAFVGQKNSFTVDCSKAGTNMMMVGVHGPKTPCEEVYVKHMGNRVYNVTYTVKE
  KGDYILIVKWGDESVPGSPFKVKVP
• Function: Muscle-specific filamin, which plays a central role in sarcomere assembly and organization. Critical for normal myogenesis, it probably functions as a large actin-cross-linking protein with structural functions at the Z lines in muscle cells. May be involved in reorganizing the actin cytoskeleton in response to signaling events.
• Tissue Specificity: Highly expressed in striated muscles. Weakly expressed in thyroid, fetal brain, fetal lung, retina, spinal cord and bone marrow. Not expressed in testis, pancreas, adrenal gland, placenta, liver and kidney.
• KEGG Pathway: Cytoskeleton in muscle cells (hsa04820)
• Reactome Pathway: Cell-extracellular matrix interactions (R-HSA-446353)

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Dilated cardiomyopathy	DISX608J	Definitive	Autosomal dominant	[1]
Dilated cardiomyopathy 1A	DIS0RK9Z	Definitive	Genetic Variation	[2]
Myofibrillar myopathy 5	DIS0XEAW	Definitive	Autosomal dominant	[1]
Neuromuscular disease	DISQTIJZ	Definitive	Genetic Variation	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Allergic rhinitis	DIS3U9HN	Strong	Biomarker	[5]
Aortic valve stenosis	DISW7AQ9	Strong	Biomarker	[6]
Arrhythmia	DISFF2NI	Strong	Genetic Variation	[7]
Arrhythmogenic right ventricular cardiomyopathy	DIS3V2BE	Strong	Genetic Variation	[8]
Carcinoma	DISH9F1N	Strong	Posttranslational Modification	[9]
Cardiomyopathy	DISUPZRG	Strong	Biomarker	[2]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[10]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[11]
Deafness	DISKCLH4	Strong	Genetic Variation	[12]
Distal myopathy	DIS7F5R0	Strong	Genetic Variation	[13]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[14]
Frontotemporal dementia	DISKYHXL	Strong	Genetic Variation	[15]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[16]
Glioma	DIS5RPEH	Strong	Biomarker	[17]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[18]
Hypertrophic cardiomyopathy	DISQG2AI	Strong	Genetic Variation	[7]
Hypertrophic cardiomyopathy 26	DISRSXN5	Strong	Autosomal dominant	[19]
leukaemia	DISS7D1V	Strong	Biomarker	[20]
Leukemia	DISNAKFL	Strong	Biomarker	[20]
Limb-girdle muscular dystrophy	DISI9Y1Z	Strong	Genetic Variation	[21]
Long QT syndrome	DISMKWS3	Strong	Biomarker	[22]
Mitochondrial disease	DISKAHA3	Strong	Genetic Variation	[23]
Muscular dystrophy	DISJD6P7	Strong	Genetic Variation	[24]
Myofibrillar myopathy	DISF24LW	Strong	Genetic Variation	[25]
Myopathy	DISOWG27	Strong	Biomarker	[25]
Neoplasm	DISZKGEW	Strong	Altered Expression	[26]
Obstructive sleep apnea	DIS0SVD1	Strong	Altered Expression	[27]
Prostate cancer	DISF190Y	Strong	Altered Expression	[28]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[28]
Respiratory failure	DISVMYJO	Strong	Genetic Variation	[12]
Restrictive cardiomyopathy	DISFAF31	Strong	Genetic Variation	[29]
Stomach cancer	DISKIJSX	Strong	Biomarker	[30]
Asthma	DISW9QNS	moderate	Biomarker	[31]
Cardiomyopathy, familial restrictive, 1	DIS4AJ17	moderate	Biomarker	[29]
Distal myopathy with posterior leg and anterior hand involvement	DIS0H8C4	Moderate	Autosomal dominant	[32]
Familial hypertrophic cardiomyopathy	DISQ89HN	moderate	Genetic Variation	[33]
Gastric cancer	DISXGOUK	moderate	Biomarker	[30]
Obesity	DIS47Y1K	moderate	Altered Expression	[34]
Obsolete familial isolated restrictive cardiomyopathy	DIS51KNV	Supportive	Autosomal dominant	[35]
Colorectal carcinoma	DIS5PYL0	Disputed	Biomarker	[36]
Colorectal neoplasm	DISR1UCN	Disputed	Biomarker	[36]
Gallbladder cancer	DISXJUAF	Limited	Biomarker	[37]
Gallbladder carcinoma	DISD6ACL	Limited	Biomarker	[37]
Heart arrhythmia	DISLKUNL	Limited	Autosomal dominant	[38]
Pick disease	DISP6X50	Limited	Biomarker	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Filamin-C (FLNC) affects the response to substance of Topotecan.	[55]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Filamin-C (FLNC).	[39]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Filamin-C (FLNC).	[48]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Filamin-C (FLNC).	[51]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Filamin-C (FLNC).	[40]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Filamin-C (FLNC).	[41]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Filamin-C (FLNC).	[42]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Filamin-C (FLNC).	[43]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Filamin-C (FLNC).	[44]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Filamin-C (FLNC).	[45]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Filamin-C (FLNC).	[46]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Filamin-C (FLNC).	[47]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Filamin-C (FLNC).	[49]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Filamin-C (FLNC).	[50]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Filamin-C (FLNC).	[50]
Dactinomycin	DM2YGNW	Approved	Dactinomycin increases the expression of Filamin-C (FLNC).	[50]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Filamin-C (FLNC).	[43]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Filamin-C (FLNC).	[52]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Filamin-C (FLNC).	[53]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Filamin-C (FLNC).	[54]

References

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