Details of Drug Off-Target (DOT)

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

• DOT Name: Clathrin heavy chain 1 (CLTC)
• Synonyms: Clathrin heavy chain on chromosome 17; CLH-17
• Gene Name: CLTC
• Related Disease:
  T-cell acute lymphoblastic leukaemia
  Acute myelogenous leukaemia
  Adult glioblastoma
  Advanced cancer
  Anaplastic large cell lymphoma
  Androgen insensitivity syndrome
  B-cell neoplasm
  Blastic plasmacytoid dendritic cell neoplasm
  Cholangiocarcinoma
  Chronic hepatitis B virus infection
  Congenital contractural arachnodactyly
  DiGeorge syndrome
  Epilepsy
  Glioblastoma multiforme
  Haemophilia A
  Hemophilia
  Hepatitis B virus infection
  Hepatitis C virus infection
  Hepatitis D virus infection
  Hepatocellular carcinoma
  Hypercholesterolemia, familial, 4
  Intellectual disability, autosomal dominant 56
  Isolated congenital microcephaly
  Liver cirrhosis
  Movement disorder
  Neoplasm
  Renal carcinoma
  Renal cell carcinoma
  Velocardiofacial syndrome
  Adrenoleukodystrophy
  Hepatitis
  Neuroblastoma
  Rhabdomyosarcoma
  Autosomal dominant non-syndromic intellectual disability
  Undetermined early-onset epileptic encephalopathy
  Breast cancer
  Breast carcinoma
  Melanoma
  Pancreatic cancer
  Adult lymphoma
  B-cell lymphoma
  Chronic renal failure
  Cryohydrocytosis
  End-stage renal disease
  Hepatitis A virus infection
  Lymphoma
  Multinodular goiter
  Pediatric lymphoma
• UniProt ID: CLH1_HUMAN
• PDB ID: 2XZG; 4G55; 6E4L; 6QNN; 6QNP; 7BN1; 7BN2; 7ZX4
• Pfam ID: PF00637 ; PF09268 ; PF13838 ; PF01394
• Sequence:
  MAQILPIRFQEHLQLQNLGINPANIGFSTLTMESDKFICIREKVGEQAQVVIIDMNDPSN
  PIRRPISADSAIMNPASKVIALKAGKTLQIFNIEMKSKMKAHTMTDDVTFWKWISLNTVA
  LVTDNAVYHWSMEGESQPVKMFDRHSSLAGCQIINYRTDAKQKWLLLTGISAQQNRVVGA
  MQLYSVDRKVSQPIEGHAASFAQFKMEGNAEESTLFCFAVRGQAGGKLHIIEVGTPPTGN
  QPFPKKAVDVFFPPEAQNDFPVAMQISEKHDVVFLITKYGYIHLYDLETGTCIYMNRISG
  ETIFVTAPHEATAGIIGVNRKGQVLSVCVEEENIIPYITNVLQNPDLALRMAVRNNLAGA
  EELFARKFNALFAQGNYSEAAKVAANAPKGILRTPDTIRRFQSVPAQPGQTSPLLQYFGI
  LLDQGQLNKYESLELCRPVLQQGRKQLLEKWLKEDKLECSEELGDLVKSVDPTLALSVYL
  RANVPNKVIQCFAETGQVQKIVLYAKKVGYTPDWIFLLRNVMRISPDQGQQFAQMLVQDE
  EPLADITQIVDVFMEYNLIQQCTAFLLDALKNNRPSEGPLQTRLLEMNLMHAPQVADAIL
  GNQMFTHYDRAHIAQLCEKAGLLQRALEHFTDLYDIKRAVVHTHLLNPEWLVNYFGSLSV
  EDSLECLRAMLSANIRQNLQICVQVASKYHEQLSTQSLIELFESFKSFEGLFYFLGSIVN
  FSQDPDVHFKYIQAACKTGQIKEVERICRESNCYDPERVKNFLKEAKLTDQLPLIIVCDR
  FDFVHDLVLYLYRNNLQKYIEIYVQKVNPSRLPVVIGGLLDVDCSEDVIKNLILVVRGQF
  STDELVAEVEKRNRLKLLLPWLEARIHEGCEEPATHNALAKIYIDSNNNPERFLRENPYY
  DSRVVGKYCEKRDPHLACVAYERGQCDLELINVCNENSLFKSLSRYLVRRKDPELWGSVL
  LESNPYRRPLIDQVVQTALSETQDPEEVSVTVKAFMTADLPNELIELLEKIVLDNSVFSE
  HRNLQNLLILTAIKADRTRVMEYINRLDNYDAPDIANIAISNELFEEAFAIFRKFDVNTS
  AVQVLIEHIGNLDRAYEFAERCNEPAVWSQLAKAQLQKGMVKEAIDSYIKADDPSSYMEV
  VQAANTSGNWEELVKYLQMARKKARESYVETELIFALAKTNRLAELEEFINGPNNAHIQQ
  VGDRCYDEKMYDAAKLLYNNVSNFGRLASTLVHLGEYQAAVDGARKANSTRTWKEVCFAC
  VDGKEFRLAQMCGLHIVVHADELEELINYYQDRGYFEELITMLEAALGLERAHMGMFTEL
  AILYSKFKPQKMREHLELFWSRVNIPKVLRAAEQAHLWAELVFLYDKYEEYDNAIITMMN
  HPTDAWKEGQFKDIITKVANVELYYRAIQFYLEFKPLLLNDLLMVLSPRLDHTRAVNYFS
  KVKQLPLVKPYLRSVQNHNNKSVNESLNNLFITEEDYQALRTSIDAYDNFDNISLAQRLE
  KHELIEFRRIAAYLFKGNNRWKQSVELCKKDSLYKDAMQYASESKDTELAEELLQWFLQE
  EKRECFGACLFTCYDLLRPDVVLETAWRHNIMDFAMPYFIQVMKEYLTKVDKLDASESLR
  KEEEQATETQPIVYGQPQLMLTAGPSVAVPPQAPFGYGYTAPPYGQPQPGFGYSM
• Function: Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Two different adapter protein complexes link the clathrin lattice either to the plasma membrane or to the trans-Golgi network. Acts as a component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge. The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension. Plays a role in early autophagosome formation. Interaction with DNAJC6 mediates the recruitment of HSPA8 to the clathrin lattice and creates local destabilization of the lattice promoting uncoating.
• KEGG Pathway:
  Lysosome (hsa04142)
  Endocytosis (hsa04144)
  Sy.ptic vesicle cycle (hsa04721)
  Endocrine and other factor-regulated calcium reabsorption (hsa04961)
  Huntington disease (hsa05016)
  Bacterial invasion of epithelial cells (hsa05100)
• Reactome Pathway:
  Retrograde neurotrophin signalling (R-HSA-177504)
  Gap junction degradation (R-HSA-190873)
  Formation of annular gap junctions (R-HSA-196025)
  EPH-ephrin mediated repulsion of cells (R-HSA-3928665)
  Recycling pathway of L1 (R-HSA-437239)
  WNT5A-dependent internalization of FZD4 (R-HSA-5099900)
  WNT5A-dependent internalization of FZD2, FZD5 and ROR2 (R-HSA-5140745)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  VLDLR internalisation and degradation (R-HSA-8866427)
  LDL clearance (R-HSA-8964038)
  RHOU GTPase cycle (R-HSA-9013420)
  RHOV GTPase cycle (R-HSA-9013424)
  ALK mutants bind TKIs (R-HSA-9700645)
  Signaling by ALK fusions and activated point mutants (R-HSA-9725370)
  Nuclear events stimulated by ALK signaling in cancer (R-HSA-9725371)
  Entry of Influenza Virion into Host Cell via Endocytosis (R-HSA-168275)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
T-cell acute lymphoblastic leukaemia	DIS17AI2	Definitive	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Anaplastic large cell lymphoma	DISP4D1R	Strong	Genetic Variation	[5]
Androgen insensitivity syndrome	DISUZBBO	Strong	Biomarker	[6]
B-cell neoplasm	DISVY326	Strong	Biomarker	[5]
Blastic plasmacytoid dendritic cell neoplasm	DISLEJU7	Strong	Biomarker	[7]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[8]
Chronic hepatitis B virus infection	DISHL4NT	Strong	Genetic Variation	[9]
Congenital contractural arachnodactyly	DISOM1K7	Strong	Biomarker	[8]
DiGeorge syndrome	DIST1RKO	Strong	Biomarker	[10]
Epilepsy	DISBB28L	Strong	Genetic Variation	[11]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[3]
Haemophilia A	DIS0RQ2E	Strong	Biomarker	[12]
Hemophilia	DIS1S8P6	Strong	Biomarker	[12]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[13]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[14]
Hepatitis D virus infection	DISESSLZ	Strong	Biomarker	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[16]
Hypercholesterolemia, familial, 4	DISFLNLI	Strong	Biomarker	[17]
Intellectual disability, autosomal dominant 56	DISUQE1E	Strong	Autosomal dominant	[18]
Isolated congenital microcephaly	DISUXHZ6	Strong	Genetic Variation	[11]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[16]
Movement disorder	DISOJJ2D	Strong	Genetic Variation	[19]
Neoplasm	DISZKGEW	Strong	Biomarker	[20]
Renal carcinoma	DISER9XT	Strong	Genetic Variation	[21]
Renal cell carcinoma	DISQZ2X8	Strong	Genetic Variation	[21]
Velocardiofacial syndrome	DISOSBTY	Strong	Biomarker	[10]
Adrenoleukodystrophy	DISTUD1F	moderate	Biomarker	[22]
Hepatitis	DISXXX35	moderate	Biomarker	[23]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[24]
Rhabdomyosarcoma	DISNR7MS	moderate	Biomarker	[25]
Autosomal dominant non-syndromic intellectual disability	DISD6L06	Supportive	Autosomal dominant	[18]
Undetermined early-onset epileptic encephalopathy	DISISEI2	Supportive	Autosomal dominant	[18]
Breast cancer	DIS7DPX1	Disputed	Biomarker	[1]
Breast carcinoma	DIS2UE88	Disputed	Biomarker	[1]
Melanoma	DIS1RRCY	Disputed	Biomarker	[1]
Pancreatic cancer	DISJC981	Disputed	Biomarker	[1]
Adult lymphoma	DISK8IZR	Limited	Genetic Variation	[26]
B-cell lymphoma	DISIH1YQ	Limited	Biomarker	[27]
Chronic renal failure	DISGG7K6	Limited	Genetic Variation	[28]
Cryohydrocytosis	DISMQHL3	Limited	Biomarker	[29]
End-stage renal disease	DISXA7GG	Limited	Genetic Variation	[28]
Hepatitis A virus infection	DISUMFQV	Limited	Biomarker	[23]
Lymphoma	DISN6V4S	Limited	Genetic Variation	[26]
Multinodular goiter	DISZQJH7	Limited	Altered Expression	[30]
Pediatric lymphoma	DIS51BK2	Limited	Genetic Variation	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Clathrin heavy chain 1 (CLTC).	[31]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Clathrin heavy chain 1 (CLTC).	[32]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Clathrin heavy chain 1 (CLTC).	[33]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Clathrin heavy chain 1 (CLTC).	[34]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Clathrin heavy chain 1 (CLTC).	[35]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Clathrin heavy chain 1 (CLTC).	[36]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Clathrin heavy chain 1 (CLTC).	[37]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Clathrin heavy chain 1 (CLTC).	[31]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Clathrin heavy chain 1 (CLTC).	[39]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Clathrin heavy chain 1 (CLTC).	[42]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of Clathrin heavy chain 1 (CLTC).	[43]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Decitabine	DMQL8XJ	Approved	Decitabine affects the methylation of Clathrin heavy chain 1 (CLTC).	[38]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Clathrin heavy chain 1 (CLTC).	[40]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Clathrin heavy chain 1 (CLTC).	[41]

References

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