Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ9HA3I)

• DOT Name: Coiled-coil domain-containing protein 141 (CCDC141)
• Synonyms: Coiled-coil protein associated with myosin II and DISC1
• Gene Name: CCDC141
• Related Disease:
  Atrial fibrillation
  Cognitive impairment
  Hypogonadotropic hypogonadism 7 with or without anosmia
  Klinefelter syndrome
  Mental disorder
  Kallmann syndrome
  Hypogonadotropic hypogonadism
• UniProt ID: CC141_HUMAN
• Pfam ID: PF07679 ; PF00435
• Sequence:
  MSSQGSPSVALSTTTVSSVAVQAGDSKIVIAVIKCGKWVQLQLAESQPNLLEIGSSQDET
  KKLLHDHELLLAKLKALEDRVWELLQEADKTAEENKDQSQVYDAMAETLGEAWAALVSML
  ERRTELLRLTSEFFENALEFAIKIDQAEDFLQNTHEFESAESLKSLLQLHEHHTKELLER
  SLALLNKSQQLTDFIEKFKCEGPNVNPELTQGAHSSCLKVDRLLELLQDRRRQLDKYLKQ
  QWQELSQVLQICQWDQQENQVTCWFQKTIRNLQEQSLGSSLSDNEDRIHKQEELIIKAKE
  WNSAVEKLKSEALRILLSKDYVEKEHLQLSHQKLSQLQEEFGQLMVERNTWLKKANEFFN
  SANKAFDVLGRVEAYLKLLKSEGLSLAVLAVRHEELHRKIKDCTTDALQKGQTLISQVDS
  CSSQVSGIHEMMGCIKRRVDHLTEQCSAHKEYALKKQQLTASVEGYLRKVEMSIQKISPV
  LSNAMDVGSTRSESEKILNKYLELDIQAKETSHELEAAAKTMMEKNEFVSDEMVSLSSKA
  RWLAEELNLFGQSIDYRSQVLQTYVAFLKSSEEVEMQFQSLKEFYETEIPQKEQDDAKAK
  HCSDSAEKQWQLFLKKSFITQDLGLEFLNLINMAKENEILDVKNEVYLMKNTMENQKAER
  EELSLLRLAWQLKATESKPGKQQWAAFKEQLKKTSHNLKLLQEALMPVSALDLGGSLQFI
  LDLRQKWNDMKPQFQQLNDEVQYIMKESEELTGRGAPVKEKSQQLKDLIHFHQKQKERIQ
  DYEDILYKVVQFHQVKEELGRLIKSRELEFVEQPKELGDAHDVQIHLRCSQEKQARVDHL
  HRLALSLGVDIISSVQRPHCSNVSAKNLQQQLELLEEDSMKWRAKAEEYGRTLSRSVEYC
  AMRDEINELKDSFKDIKKKFNNLKFNYTKKNEKSRNLKALKYQIQQVDMYAEKMQALKRK
  MEKVSNKTSDSFLNYPSDKVNVLLEVMKDLQKHVDDFDKVVTDYKKNLDLTEHFQEVIEE
  CHFWYEDASATVVRVGKYSTECKTKEAVKILHQQFNKFIAPSVPQQEERIQEATDLAQHL
  YGLEEGQKYIEKIVTKHKEVLESVTELCESLTELEEKLKQGDVLKMNPNLEDFHYDYIDL
  LKEPAKNKQTIFNEERNKGQVQVADLLGINGTGEERLPQDLKVSTDKEGGVQDLLLPEDM
  LSGEEYECVSPDDISLPPLPGSPESPLAPSDMEVEEPVSSSLSLHISSYGVQAGTSSPGD
  AQESVLPPPVAFADACNDKRETFSSHFERPYLQFKAEPPLTSRGFVEKSTALHRISAEHP
  ESMMSEVHERALQQHPQAQGGLLETREKMHADNNFTKTQDRLHASSDAFSGLRFQSGTSR
  GYQRQMVPREEIKSTSAKSSVVSLADQAPNFSRLLSNVTVMEGSPVTLEVEVTGFPEPTL
  TWYKKGQKLSADGHLQVLHKETRHSVFIPKVCKADAGLYVARAQNSSGALSSNVILHVTG
  NCRLPITRVNWITLCVVYVSVSLMYWLLTQ
• Function: Plays a critical role in cortical radial and GnRH neurons migration during brain development. Regulates cortical radial migration by negatively controlling the activity of histone deacetylase 6 (HDAC6) and promotes centrosome maturation. CAMDI is required for dilation formation of cortical neurons during radial migration. Plays a critical role in learning and memory performance through regulation of AMPA-selective glutamate receptors (AMPARs) cell surface expression in competition with KIBRA.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[1]
Cognitive impairment	DISH2ERD	Strong	Biomarker	[2]
Hypogonadotropic hypogonadism 7 with or without anosmia	DISPBWEU	Strong	Genetic Variation	[3]
Klinefelter syndrome	DISOUI7W	Strong	Genetic Variation	[4]
Mental disorder	DIS3J5R8	Strong	Biomarker	[2]
Kallmann syndrome	DISO3HDG	Supportive	Autosomal dominant	[3]
Hypogonadotropic hypogonadism	DIS8JSKR	Limited	Autosomal dominant	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Coiled-coil domain-containing protein 141 (CCDC141).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Coiled-coil domain-containing protein 141 (CCDC141).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Coiled-coil domain-containing protein 141 (CCDC141).	[8]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Coiled-coil domain-containing protein 141 (CCDC141).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Coiled-coil domain-containing protein 141 (CCDC141).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Coiled-coil domain-containing protein 141 (CCDC141).	[11]

References

• [1] Genome-wide DNA methylation analysis in permanent atrial fibrillation.Mol Med Rep. 2017 Oct;16(4):5505-5514. doi: 10.3892/mmr.2017.7221. Epub 2017 Aug 10.
• [2] CAMDI interacts with the human memory-associated protein KIBRA and regulates AMPAR cell surface expression and cognition.PLoS One. 2019 Nov 15;14(11):e0224967. doi: 10.1371/journal.pone.0224967. eCollection 2019.
• [3] CCDC141 Mutations in Idiopathic Hypogonadotropic Hypogonadism. J Clin Endocrinol Metab. 2017 Jun 1;102(6):1816-1825. doi: 10.1210/jc.2016-3391.
• [4] CCDC141 Mutation Identified in Anosmic Hypogonadotropic Hypogonadism (Kallmann Syndrome) Alters GnRH Neuronal Migration.Endocrinology. 2016 May;157(5):1956-66. doi: 10.1210/en.2015-1846. Epub 2016 Mar 25.
• [5] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [6] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [7] 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.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [10] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [11] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.