Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6WRQOX)

• DOT Name: Sterile alpha motif domain-containing protein 11 (SAMD11)
• Synonyms: SAM domain-containing protein 11
• Gene Name: SAMD11
• Related Disease: Retinitis pigmentosa
• UniProt ID: SAM11_HUMAN
• Pfam ID: PF07647
• Sequence:
  MSKGILQVHPPICDCPGCRISSPVNRGRLADKRTVALPAARNLKKERTPSFSASDGDSDG
  SGPTCGRRPGLKQEDGPHIRIMKRRVHTHWDVNISFREASCSQDGNLPTLISSVHRSRHL
  VMPEHQSRCEFQRGSLEIGLRPAGDLLGKRLGRSPRISSDCFSEKRARSESPQEALLLPR
  ELGPSMAPEDHYRRLVSALSEASTFEDPQRLYHLGLPSHGEDPPWHDPPHHLPSHDLLRV
  RQEVAAAALRGPSGLEAHLPSSTAGQRRKQGLAQHREGAAPAAAPSFSERELPQPPPLLS
  PQNAPHVALGPHLRPPFLGVPSALCQTPGYGFLPPAQAEMFAWQQELLRKQNLARLELPA
  DLLRQKELESARPQLLAPETALRPNDGAEELQRRGALLVLNHGAAPLLALPPQGPPGSGP
  PTPSRDSARRAPRKGGPGPASARPSESKEMTGARLWAQDGSEDEPPKDSDGEDPETAAVG
  CRGPTPGQAPAGGAGAEGKGLFPGSTLPLGFPYAVSPYFHTGAVGGLSMDGEEAPAPEDV
  TKWTVDDVCSFVGGLSGCGEYTRVFREQGIDGETLPLLTEEHLLTNMGLKLGPALKIRAQ
  VARRLGRVFYVASFPVALPLQPPTLRAPERELGTGEQPLSPTTATSPYGGGHALAGQTSP
  KQENGTLALLPGAPDPSQPLC
• Function: May play a role in photoreceptor development.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Retinitis pigmentosa	DISCGPY8	Limited	Autosomal recessive	[1]

4 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 Sterile alpha motif domain-containing protein 11 (SAMD11).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Sterile alpha motif domain-containing protein 11 (SAMD11).	[10]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Sterile alpha motif domain-containing protein 11 (SAMD11).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Sterile alpha motif domain-containing protein 11 (SAMD11).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Sterile alpha motif domain-containing protein 11 (SAMD11).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Sterile alpha motif domain-containing protein 11 (SAMD11).	[4]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Sterile alpha motif domain-containing protein 11 (SAMD11).	[5]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Sterile alpha motif domain-containing protein 11 (SAMD11).	[6]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Sterile alpha motif domain-containing protein 11 (SAMD11).	[7]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Sterile alpha motif domain-containing protein 11 (SAMD11).	[8]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Sterile alpha motif domain-containing protein 11 (SAMD11).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Sterile alpha motif domain-containing protein 11 (SAMD11).	[11]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Sterile alpha motif domain-containing protein 11 (SAMD11).	[14]

References

• [1] 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.
• [2] 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.
• [3] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [6] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [7] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [8] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [9] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [10] 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.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [13] 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.
• [14] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.