Details of Drug Off-Target (DOT)

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

• DOT Name: Cilia- and flagella-associated protein 221 (CFAP221)
• Synonyms: Primary ciliary dyskinesia protein 1
• Gene Name: CFAP221
• Related Disease:
  Attention deficit hyperactivity disorder
  Chronic bronchitis
  Chronic obstructive pulmonary disease
  Primary ciliary dyskinesia 1
  Primary ciliary dyskinesia
• UniProt ID: PCDP1_HUMAN
• Sequence:
  MAVVKTPSRGLKNAKEPFNNASPHLLKNLVEEPKKRKEVPNHLLESKVYAKLVNNKVIQA
  RPGIIHFGGYQVEKQHQQILHLVNVSNEDTRVHILPPQTKYFEINYVRKEHHLVPGLSLT
  VTVTFSPDEWRYYYDCIRVHCKGDDTLLVPIHAYPVMNSLDFPSFINLSNVLLGESKTYV
  IPLQCSCPVDFEFYITLIQSHQAFAIEPTSGIIPANGKMTVTIKFTPFQYGTAQIKMQLW
  ISQFNSQPYECVFTGTCYPNMALPLEEFERLNTLSKKVNVPPEKAMMHINFHRPPAKPKP
  QKVKEIEYQNLRFPVDLSNPFAVATVLNQEPGKLKIKELREVLDQGTEISKTRQMKEALF
  EQKVRQDIHEEMENHLKWQVHLGKDPMSFKLKKELTEEWQKACAKYKLDRGDPILDEEFQ
  RLKTEVSHKRVVRNQEEKIKEFHPTFDPLINNTWLSRSRAQKRFQQVARKVMIQGRLFNM
  LSAVREMDKESILRKIGQAKQSIAQEANFFKFFLRRISQDDYTSRFSVSPKEVLPFAFPD
  CSPPQDSNELAPDGLGLVPIKSSEVQIKQSYSFFNLQVPQLYKIKRYQPFSVHKSSTSYR
  PQKLARALKQGAEDEVTTITALPKQDSTTQLSGKTSVLSMKPPEALAMSLDYDPLYVFNP
  NPGLFAVMHPLTYAETLIDYHLCSHPKYKFTKESRHGSSIPVTQKQFLHHTDIIPGIMHW
  KSFQSLVLSSLPDPSKMETTKSCDSFNSFMLPIDVPAILDALPEEDRLETVERELCEQNV
  EVMLTPEMIKVEFPMLNYKDIRKEKEVKDQAQPAEKAGEKLLEEMRNLRGKALNTYLILE
• Function: May play a role in cilium morphogenesis.
• Tissue Specificity: Expressed in ciliated respiratory epithelial cells and brain ependymal cells (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[1]
Chronic bronchitis	DISS8O8V	Strong	Genetic Variation	[2]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[2]
Primary ciliary dyskinesia 1	DISPGX6H	Strong	GermlineCausalMutation	[3]
Primary ciliary dyskinesia	DISOBC7V	Moderate	Autosomal recessive	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cilia- and flagella-associated protein 221 (CFAP221).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Cilia- and flagella-associated protein 221 (CFAP221).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cilia- and flagella-associated protein 221 (CFAP221).	[7]

References

• [1] Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies.J Neural Transm (Vienna). 2008 Nov;115(11):1573-85. doi: 10.1007/s00702-008-0119-3. Epub 2008 Oct 7.
• [2] Genetic susceptibility for chronic bronchitis in chronic obstructive pulmonary disease.Respir Res. 2014 Sep 21;15(1):113. doi: 10.1186/s12931-014-0113-2.
• [3] Identification of genetic variants in CFAP221 as a cause of primary ciliary dyskinesia. J Hum Genet. 2020 Jan;65(2):175-180. doi: 10.1038/s10038-019-0686-1. Epub 2019 Oct 21.
• [4] 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.
• [5] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [6] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [7] 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.