Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6GS3XQ)

• DOT Name: Refilin-A (RFLNA)
• Synonyms: Regulator of filamin protein A; RefilinA
• Gene Name: RFLNA
• Related Disease:
  Spondylocarpotarsal synostosis syndrome
  Advanced cancer
  Non-insulin dependent diabetes
  Schizophrenia
  Endometriosis
  Clubfoot
• UniProt ID: RFLA_HUMAN
• Pfam ID: PF15068
• Sequence:
  MVGHLHLQGMEDSLKEQGREGLLDSPDSGLPPSPSPSPPFYSLAPGILDARAGGAGASSE
  PPGPSEARAPPSQLPNPPASEMRPRMLPVFFGESIKVNPEPTHEIRCNSEVKYASEKHFQ
  DKVFYAPVPTVTAYSETIVAAPNCTWRNYRSQLTLEPRPRALRFRSTTIIFPKHARSTFR
  TTLHCSLGRPSRWFTASVQLQLCQDPAPSLLGPATL
• Function: Involved in the regulation of the perinuclear actin network and nuclear shape through interaction with filamins. Plays an essential role in actin cytoskeleton formation in developing cartilaginous cells.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Spondylocarpotarsal synostosis syndrome	DISF9VP3	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[3]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[4]
Endometriosis	DISX1AG8	moderate	Genetic Variation	[5]
Clubfoot	DISLXT4S	Limited	Genetic Variation	[6]

3 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 Refilin-A (RFLNA).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Refilin-A (RFLNA).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Refilin-A (RFLNA).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Refilin-A (RFLNA).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Refilin-A (RFLNA).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Refilin-A (RFLNA).	[10]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Refilin-A (RFLNA).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Refilin-A (RFLNA).	[13]

References

• [1] Identification of a homozygous frameshift variant in RFLNA in a patient with a typical phenotype of spondylocarpotarsal synostosis syndrome.J Hum Genet. 2019 May;64(5):467-471. doi: 10.1038/s10038-019-0581-9. Epub 2019 Feb 22.
• [2] AMPA Receptor Antagonist CFM-2 Decreases Survivin Expression in Cancer Cells.Anticancer Agents Med Chem. 2018;18(4):591-596. doi: 10.2174/1871520618666180228123406.
• [3] Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes.Nat Commun. 2018 Jul 27;9(1):2941. doi: 10.1038/s41467-018-04951-w.
• [4] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
• [5] New variants near RHOJ and C2, HLA-DRA region and susceptibility to endometriosis in the Polish population-The genome-wide association study.Eur J Obstet Gynecol Reprod Biol. 2017 Oct;217:106-112. doi: 10.1016/j.ejogrb.2017.08.037. Epub 2017 Sep 1.
• [6] Genome-wide association study identifies new disease loci for isolated clubfoot.J Med Genet. 2014 May;51(5):334-9. doi: 10.1136/jmedgenet-2014-102303. Epub 2014 Mar 25.
• [7] 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.
• [8] 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.
• [9] Inorganic arsenic exposure promotes malignant progression by HDAC6-mediated down-regulation of HTRA1. J Appl Toxicol. 2023 Aug;43(8):1214-1224. doi: 10.1002/jat.4457. Epub 2023 Mar 11.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] 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.
• [13] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [14] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.