Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWUBDV0)

• DOT Name: Protein SSUH2 homolog (SSUH2)
• Synonyms: Protein ssu-2 homolog
• Gene Name: SSUH2
• Related Disease:
  Dentin dysplasia
  Rippling muscle disease 2
  Dentin dysplasia type I
  Long QT syndrome
• UniProt ID: SSUH2_HUMAN
• Sequence:
  MDRDLNEDDSVVDLSFEAESPLAPPTELLERLPSYDWLLQGGRGQIFFPPLEAPGRPQEQ
  RSWPSFLEHRVPAMTEEVAREALLSFVDSKCCYSSTVAGDLVIQELKRQTLCRYRLETFS
  ESRISEWTFQPFTNHSVDGPQRGASPRLWDIKVQGPPMFQEDTRKFQVPHSSLVKECHKC
  HGRGRYKCSGCHGAGTVRCPSCCGAKRKAKQSRRCQLCAGSGRRRCSTCSGRGNKTCATC
  KGEKKLLHFIQLVIMWKNSLFEFVSEHRLNCPRELLAKAKGENLFKDENSVVYPIVDFPL
  RDISLASQRGIAEHSAALASRARVLQQRQTIELIPLTEVHYWYQGKTYVYYIYGTDHQVY
  AVDYPERYCCGCTIV
• Function: Plays a role in odontogenesis.
• Tissue Specificity: Expressed in enterocytes of small and large intestinal mucosa (at protein level). Expressed in chromaffine and interstitial cells. Expressed in peripheral blood and gingival cells .

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Dentin dysplasia	DISCGIX8	Strong	Biomarker	[1]
Rippling muscle disease 2	DISVFPSL	Strong	Genetic Variation	[2]
Dentin dysplasia type I	DISS0DLW	Supportive	Autosomal dominant	[1]
Long QT syndrome	DISMKWS3	Limited	CausalMutation	[3]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Protein SSUH2 homolog (SSUH2).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein SSUH2 homolog (SSUH2).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein SSUH2 homolog (SSUH2).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein SSUH2 homolog (SSUH2).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein SSUH2 homolog (SSUH2).	[7]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Protein SSUH2 homolog (SSUH2).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein SSUH2 homolog (SSUH2).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein SSUH2 homolog (SSUH2).	[11]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE increases the expression of Protein SSUH2 homolog (SSUH2).	[7]

References

• [1] Mutation in SSUH2 Causes Autosomal-Dominant Dentin Dysplasia Type I. Hum Mutat. 2017 Jan;38(1):95-104. doi: 10.1002/humu.23130. Epub 2016 Oct 19.
• [2] Targeted Re-Sequencing Emulsion PCR Panel for Myopathies: Results in 94 Cases.J Neuromuscul Dis. 2016 May 27;3(2):209-225. doi: 10.3233/JND-160151.
• [3] Rippling is not always electrically silent in rippling muscle disease.Muscle Nerve. 2011 Apr;43(4):601-5. doi: 10.1002/mus.21947.
• [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] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [8] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [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.
• [10] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [11] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.