Details of Drug Off-Target (DOT)

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

• DOT Name: Radial spoke head protein 4 homolog A (RSPH4A)
• Synonyms: Radial spoke head-like protein 3
• Gene Name: RSPH4A
• Related Disease:
  Primary ciliary dyskinesia 11
  Bronchiectasis
  Primary ciliary dyskinesia 1
  Rhinitis
  Primary ciliary dyskinesia
  Otitis media
  Sinusitis
• UniProt ID: RSH4A_HUMAN
• PDB ID: 8J07
• Pfam ID: PF04712
• Sequence:
  MEDSTSPKQEKENQEELGETRRPWEGKTAASPQYSEPESSEPLEAKQGPETGRQSRSSRP
  WSPQSRAKTPLGGPAGPETSSPAPVSPREPSSSPSPLAPARQDLAAPPQSDRTTSVIPEA
  GTPYPDPLEQSSDKRESTPHHTSQSEGNTFQQSQQPKPHLCGRRDVSYNNAKQKELRFDV
  FQEEDSNSDYDLQQPAPGGSEVAPSMLEITIQNAKAYLLKTSSNSGFNLYDHLSNMLTKI
  LNERPENAVDIFENISQDVKMAHFSKKFDALQNENELLPTYEIAEKQKALFLQGHLEGVD
  QELEDEIAENALPNVMESAFYFEQAGVGLGTDETYRIFLALKQLTDTHPIQRCRFWGKIL
  GLEMNYIVAEVEFREGEDEEEVEEEDVAEERDNGESEAHEDEEDELPKSFYKAPQAIPKE
  ESRTGANKYVYFVCNEPGRPWVKLPPVIPAQIVIARKIKKFFTGRLDAPIISYPPFPGNE
  SNYLRAQIARISAGTHVSPLGFYQFGEEEGEEEEEAEGGRNSFEENPDFEGIQVIDLVES
  LSNWVHHVQHILSQGRCNWFNSIQKNEEEEEEEDEEKDDSDYIEQEVGLPLLTPISEDLE
  IQNIPPWTTRLSSNLIPQYAIAVLQSNLWPGAYAFSNGKKFENFYIGWGHKYSPDNYTPP
  VPPPVYQEYPSGPEITEMDDPSVEEEQAFRAAQEAVLLAAENEESEEDEDEEDDYD
• Function: Component of the axonemal radial spoke head which plays an important role in ciliary motility. Essential for triplet radial spokes (RS1, RS2 and RS3) head assembly in the motile cilia.
• Tissue Specificity: Expressed in trachea, lungs, and testes . Very strong expression is detected in nasal brushings .

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Primary ciliary dyskinesia 11	DISDAJNA	Definitive	Autosomal recessive	[1]
Bronchiectasis	DIS5MYEE	Strong	Biomarker	[2]
Primary ciliary dyskinesia 1	DISPGX6H	Strong	CausalMutation	[3]
Rhinitis	DISKLMN7	Strong	Biomarker	[2]
Primary ciliary dyskinesia	DISOBC7V	Supportive	Autosomal dominant	[4]
Otitis media	DISGZDUO	Disputed	Biomarker	[2]
Sinusitis	DISX5NCF	Disputed	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Radial spoke head protein 4 homolog A (RSPH4A).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Radial spoke head protein 4 homolog A (RSPH4A).	[6]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Radial spoke head protein 4 homolog A (RSPH4A).	[7]

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] RSPH3 Mutations Cause Primary Ciliary Dyskinesia with Central-Complex Defects and a Near Absence of Radial Spokes. Am J Hum Genet. 2015 Jul 2;97(1):153-62. doi: 10.1016/j.ajhg.2015.05.004. Epub 2015 Jun 11.
• [3] Unexpected genetic heterogeneity for primary ciliary dyskinesia in the Irish Traveller population.Eur J Hum Genet. 2015 Feb;23(2):210-7. doi: 10.1038/ejhg.2014.79. Epub 2014 May 14.
• [4] Primary Ciliary Dyskinesia. 2007 Jan 24 [updated 2019 Dec 5]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [7] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.