Details of Drug Off-Target (DOT)

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

• DOT Name: Probable E3 SUMO-protein ligase RNF212 (RNF212)
• Synonyms: EC 2.3.2.-; Probable E3 SUMO-protein transferase RNF212; RING finger protein 212
• Gene Name: RNF212
• Related Disease:
  Male infertility
  Spermatogenic failure 62
• UniProt ID: RN212_HUMAN
• EC Number: 2.3.2.-
• Pfam ID: PF14634
• Sequence:
  MANWVFCNRCFQPPHRTSCFSLTNCGHVYCDACLGKGKKNECLICKAPCRTVLLSKHTDA
  DIQAFFMSIDSLCKKYSRETSQILEFQEKHRKRLLAFYREKISRLEESLRKSVLQIEQLQ
  SMRSSQQTAFSTIKSSVSTKPHGCLLPPHSSAPDRLESMEVDLSPSPIRKSEIAAGPARI
  SMISPPQDGRMGPHLTASFCFIPWLTLSKPPVPGECVISRGSPCFCIDVCPHWLLLLAFS
  SGRHGELTNSKTLPIYAEVQRAVLFPFQQAEGTLDTFRTPAVSVVFPLCQFERKKSF
• Function: SUMO E3 ligase that acts as a regulator of crossing-over during meiosis: required to couple chromosome synapsis to the formation of crossover-specific recombination complexes. Localizes to recombination sites and stabilizes meiosis-specific recombination factors, such as MutS-gamma complex proteins (MSH4 and MSH5) and TEX11. May mediate sumoylation of target proteins MSH4 and/or MSH5, leading to enhance their binding to recombination sites. Acts as a limiting factor for crossover designation and/or reinforcement and plays an antagonist role with CCNB1IP1/HEI10 in the regulation of meiotic recombination.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Male infertility	DISY3YZZ	Strong	Biomarker	[1]
Spermatogenic failure 62	DISDIJP8	Limited	Autosomal recessive	[2]

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 Probable E3 SUMO-protein ligase RNF212 (RNF212).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Probable E3 SUMO-protein ligase RNF212 (RNF212).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Probable E3 SUMO-protein ligase RNF212 (RNF212).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Probable E3 SUMO-protein ligase RNF212 (RNF212).	[4]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Probable E3 SUMO-protein ligase RNF212 (RNF212).	[5]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Probable E3 SUMO-protein ligase RNF212 (RNF212).	[8]

References

• [1] Sequencing of a 'mouse azoospermia' gene panel in azoospermic men: identification of RNF212 and STAG3 mutations as novel genetic causes of meiotic arrest.Hum Reprod. 2019 Jun 4;34(6):978-988. doi: 10.1093/humrep/dez042.
• [2] An ENU-induced mutation in the mouse Rnf212 gene is associated with male meiotic failure and infertility. Reproduction. 2015 Jan;149(1):67-74. doi: 10.1530/REP-14-0122. Epub 2014 Oct 23.
• [3] 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.
• [4] 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.
• [5] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [6] 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.
• [7] 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.
• [8] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.