Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ96T2F)

• DOT Name: Radial spoke head protein 6 homolog A (RSPH6A)
• Synonyms: Radial spoke head-like protein 1
• Gene Name: RSPH6A
• Related Disease:
  Systemic lupus erythematosus
  Chronic obstructive pulmonary disease
  Coronary heart disease
  Myotonic dystrophy
  Myotonic dystrophy type 1
• UniProt ID: RSH6A_HUMAN
• Pfam ID: PF04712
• Sequence:
  MGDLPPYPERPAQQPPGRRTSQASQRRHSRDQAQALAADPEERQQIPPDAQRNAPGWSQR
  GSLSQQENLLMPQVFQAEEARLGGMEYPSVNTGFPSEFQPQPYSDESRMQVAELTTSLML
  QRLQQGQSSLFQQLDPTFQEPPVNPLGQFNLYQTDQFSEGAQHGPYIRDDPALQFLPSEL
  GFPHYSAQVPEPEPLELAVQNAKAYLLQTSINCDLSLYEHLVNLLTKILNQRPEDPLSVL
  ESLNRTTQWEWFHPKLDTLRDDPEMQPTYKMAEKQKALFTRSGGGTEGEQEMEEEVGETP
  VPNIMETAFYFEQAGVGLSSDESFRIFLAMKQLVEQQPIHTCRFWGKILGIKRSYLVAEV
  EFREGEEEAEEEEVEEMTEGGEVMEAHGEEEGEEDEEKAVDIVPKSVWKPPPVIPKEESR
  SGANKYLYFVCNEPGLPWTRLPHVTPAQIVNARKIKKFFTGYLDTPVVSYPPFPGNEANY
  LRAQIARISAATQVSPLGFYQFSEEEGDEEEEGGAGRDSYEENPDFEGIPVLELVDSMAN
  WVHHTQHILPQGRCTWVNPLQKTEEEEDLGEEEEKADEGPEEVEQEVGPPLLTPLSEDAE
  IMHLAPWTTRLSCSLCPQYSVAVVRSNLWPGAYAYASGKKFENIYIGWGHKYSPESFNPA
  LPAPIQQEYPSGPEIMEMSDPTVEEEQALKAAQEQALGATEEEEEGEEEEEGEETDD
• Function: Functions as part of radial spoke complexes in the axoneme of sperm flagella that play an important part in motility. The triple radial spokes (RS1, RS2 and RS3) are required to modulate beating of the sperm flagellum.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[1]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Genetic Variation	[2]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[2]
Myotonic dystrophy	DISNBEMX	Limited	Genetic Variation	[3]
Myotonic dystrophy type 1	DISJC0OX	Limited	Genetic Variation	[3]

1 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 Radial spoke head protein 6 homolog A (RSPH6A).	[4]

4 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 Radial spoke head protein 6 homolog A (RSPH6A).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Radial spoke head protein 6 homolog A (RSPH6A).	[6]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Radial spoke head protein 6 homolog A (RSPH6A).	[7]
Maleic Acid	DM4L0R7	Investigative	Maleic Acid increases the expression of Radial spoke head protein 6 homolog A (RSPH6A).	[8]

References

• [1] Analysis of variable region genes encoding anti-Sm and anti-cardiolipin antibodies from a systemic lupus erythematosus patient.Immunology. 1995 Nov;86(3):487-94.
• [2] Genetic overlap of chronic obstructive pulmonary disease and cardiovascular disease-related traits: a large-scale genome-wide cross-trait analysis.Respir Res. 2019 Apr 2;20(1):64. doi: 10.1186/s12931-019-1036-8.
• [3] A mammalian radial spokehead-like gene, RSHL1, at the myotonic dystrophy-1 locus.Biochem Biophys Res Commun. 2001 Mar 9;281(4):835-41. doi: 10.1006/bbrc.2001.4465.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [8] Profiling transcriptomes of human SH-SY5Y neuroblastoma cells exposed to maleic acid. PeerJ. 2017 Apr 5;5:e3175.