Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB9EM6C)

• DOT Name: Spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein 2 (SOHLH2)
• Gene Name: SOHLH2
• Related Disease:
  Advanced cancer
  Epithelial ovarian cancer
  Neoplasm
  Female hypogonadism
  Metastatic malignant neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Breast cancer
  Breast carcinoma
• UniProt ID: SOLH2_HUMAN
• Pfam ID: PF00010
• Sequence:
  MASSIICQEHCQISGQAKIDILLVGDVTVGYLADTVQKLFANIAEVTITISDTKEAAALL
  DDCIFNMVLLKVPSSLSAEELEAIKLIRFGKKKNTHSLFVFIIPENFKGCISGHGMDIAL
  TEPLTMEKMSNVVKYWTTCPSNTVKTENATGPEELGLPLQRSYSEHLGYFPTDLFACSES
  LRNGNGLELNASLSEFEKNKKISLLHSSKEKLRRERIKYCCEQLRTLLPYVKGRKNDAAS
  VLEATVDYVKYIREKISPAVMAQITEALQSNMRFCKKQQTPIELSLPGTVMAQRENSVMS
  TYSPERGLQFLTNTCWNGCSTPDAESSLDEAVRVPSSSASENAIGDPYKTHISSAALSLN
  SLHTVRYYSKVTPSYDATAVTNQNISIHLPSAMPPVSKLLPRHCTSGLGQTCTTHPNCLQ
  QFWAY
• 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

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Female hypogonadism	DISWASB4	moderate	Biomarker	[3]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[4]
Ovarian cancer	DISZJHAP	moderate	Posttranslational Modification	[4]
Ovarian neoplasm	DISEAFTY	moderate	Posttranslational Modification	[4]
Breast cancer	DIS7DPX1	Limited	Biomarker	[2]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[2]

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 Spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein 2 (SOHLH2).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein 2 (SOHLH2).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein 2 (SOHLH2).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein 2 (SOHLH2).	[8]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein 2 (SOHLH2).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein 2 (SOHLH2).	[10]

References

• [1] Sohlh2 alleviates malignancy of EOC cells under hypoxia via inhibiting the HIF1/CA9 signaling pathway.Biol Chem. 2020 Feb 25;401(2):263-271. doi: 10.1515/hsz-2019-0119.
• [2] Sohlh2 inhibits breast cancer cell proliferation by suppressing Wnt/-catenin signaling pathway.Mol Carcinog. 2019 Jun;58(6):1008-1018. doi: 10.1002/mc.22989. Epub 2019 Mar 5.
• [3] Novel variants in the SOHLH2 gene are implicated in human premature ovarian failure.Fertil Steril. 2014 Apr;101(4):1104-1109.e6. doi: 10.1016/j.fertnstert.2014.01.001. Epub 2014 Feb 10.
• [4] Sohlh2 inhibits human ovarian cancer cell invasion and metastasis by transcriptional inactivation of MMP9.Mol Carcinog. 2016 Jul;55(7):1127-37. doi: 10.1002/mc.22355. Epub 2015 Jul 8.
• [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] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [7] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [8] Characterization of DOK1, a candidate tumor suppressor gene, in epithelial ovarian cancer. Mol Oncol. 2011 Oct;5(5):438-53. doi: 10.1016/j.molonc.2011.07.003. Epub 2011 Jul 26.
• [9] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [10] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.