Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3RBLSK)

• DOT Name: Spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein 1 (SOHLH1)
• Gene Name: SOHLH1
• Related Disease:
  Adult glioblastoma
  Advanced cancer
  Astrocytoma
  Glioblastoma multiforme
  Hypogonadism, male
  Ovarian dysgenesis 5
  Hypogonadism
• UniProt ID: SOLH1_HUMAN
• Pfam ID: PF00010
• Sequence:
  MASRCSEPYPEVSRIPTVRGCNGSLSGALSCCEDSARGSGPPKAPTVAEGPSSCLRRNVI
  SERERRKRMSLSCERLRALLPQFDGRREDMASVLEMSVQFLRLASALGPSQEQHAILASS
  KEMWHSLQEDVLQLTLSSQIQAGVPDPGTGASSGTRTPDVKAFLESPWSLDPASASPEPV
  PHILASSRQWDPASCTSLGTDKCEALLGLCQVRGGLPPFSEPSSLVPWPPGRSLPKAVRP
  PLSWPPFSQQQTLPVMSGEALGWLGQAGPLAMGAAPLGEPAKEDPMLAQEAGSALGSDVD
  DGTSFLLTAGPSSWPGEWGPGFRAGPPA
• Function: Transcription regulator of both male and female germline differentiation. Suppresses genes involved in spermatogonial stem cells maintenance, and induces genes important for spermatogonial differentiation. Coordinates oocyte differentiation without affecting meiosis I.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Astrocytoma	DISL3V18	Strong	Altered Expression	[1]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[1]
Hypogonadism, male	DISV1F5R	Strong	Biomarker	[2]
Ovarian dysgenesis 5	DISI2B1U	Strong	Autosomal recessive	[3]
Hypogonadism	DISICMNI	Limited	Autosomal recessive	[4]

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 Spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein 1 (SOHLH1).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein 1 (SOHLH1).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein 1 (SOHLH1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein 1 (SOHLH1).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein 1 (SOHLH1).	[8]

References

• [1] Sohlh1 suppresses glioblastoma cell proliferation, migration, and invasion by inhibition of Wnt/-catenin signaling.Mol Carcinog. 2018 Apr;57(4):494-502. doi: 10.1002/mc.22774. Epub 2018 Jan 5.
• [2] Mutations in SOHLH1 gene associate with nonobstructive azoospermia.Hum Mutat. 2010 Jul;31(7):788-93. doi: 10.1002/humu.21264.
• [3] Oogenesis requires germ cell-specific transcriptional regulators Sohlh1 and Lhx8. Proc Natl Acad Sci U S A. 2006 May 23;103(21):8090-5. doi: 10.1073/pnas.0601083103. Epub 2006 May 11.
• [4] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [5] 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.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] 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.
• [8] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [9] 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.