Details of Drug Off-Target (DOT)

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

• DOT Name: Sodium/bile acid cotransporter 7 (SLC10A7)
• Synonyms: Na(+)/bile acid cotransporter 7; Solute carrier family 10 member 7
• Gene Name: SLC10A7
• Related Disease: Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis
• UniProt ID: NTCP7_HUMAN
• Pfam ID: PF13593
• Sequence:
  MRLLERMRKDWFMVGIVLAIAGAKLEPSIGVNGGPLKPEITVSYIAVATIFFNSGLSLKT
  EELTSALVHLKLHLFIQIFTLAFFPATIWLFLQLLSITPINEWLLKGLQTVGCMPPPVSS
  AVILTKAVGGNEAAAIFNSAFGSFLGIVITPLLLLLFLGSSSSVPFTSIFSQLFMTVVVP
  LIIGQIVRRYIKDWLERKKPPFGAISSSVLLMIIYTTFCDTFSNPNIDLDKFSLVLILFI
  IFSIQLSFMLLTFIFSTRNNSGFTPADTVAIIFCSTHKSLTLGIPMLKIVFAGHEHLSLI
  SVPLLIYHPAQILLGSVLVPTIKSWMVSRQKGVKLTRPTV
• Function: Involved in teeth and skeletal development. Has an essential role in the biosynthesis and trafficking of glycosaminoglycans and glycoproteins, to produce a proper functioning extracellular matrix. Required for extracellular matrix mineralization. Also involved in the regulation of cellular calcium homeostasis. Does not show transport activity towards bile acids or steroid sulfates (including taurocholate, cholate, chenodeoxycholate, estrone-3-sulfate, dehydroepiandrosterone sulfate (DHEAS) and pregnenolone sulfate).
• Tissue Specificity: Widely expressed . Expressed at high levels in liver and at lower levels in prostate, placenta, kidney, heart, lung, thymus and spleen . Strongly expressed in testis and also detected in brain, ovary, colon and small intestine . Weakly expressed in testis and not detected in brain, ovary, colon or small intestine . Isoform 1: Expressed in liver, testis and placenta . Isoform 4: Expressed in liver, testis and placenta .

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis	DIS3SAPB	Strong	Autosomal recessive	[1]

1 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 Sodium/bile acid cotransporter 7 (SLC10A7).	[2]

11 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 Sodium/bile acid cotransporter 7 (SLC10A7).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Sodium/bile acid cotransporter 7 (SLC10A7).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sodium/bile acid cotransporter 7 (SLC10A7).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Sodium/bile acid cotransporter 7 (SLC10A7).	[6]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Sodium/bile acid cotransporter 7 (SLC10A7).	[6]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Sodium/bile acid cotransporter 7 (SLC10A7).	[7]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Sodium/bile acid cotransporter 7 (SLC10A7).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Sodium/bile acid cotransporter 7 (SLC10A7).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Sodium/bile acid cotransporter 7 (SLC10A7).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Sodium/bile acid cotransporter 7 (SLC10A7).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Sodium/bile acid cotransporter 7 (SLC10A7).	[12]

References

• [1] Integrating glycomics and genomics uncovers SLC10A7 as essential factor for bone mineralization by regulating post-Golgi protein transport and glycosylation. Hum Mol Genet. 2018 Sep 1;27(17):3029-3045. doi: 10.1093/hmg/ddy213.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [7] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [8] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [9] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [10] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [11] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.