Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2Y5D15)

• DOT Name: NF-X1-type zinc finger protein NFXL1 (NFXL1)
• Synonyms: Ovarian zinc finger protein; hOZFP
• Gene Name: NFXL1
• Related Disease:
  Cholestasis
  Language disorder
  Specific language impairment
• UniProt ID: NFXL1_HUMAN
• Pfam ID: PF01422
• Sequence:
  MEASWRQVAGGRGRSRGRATAAPSGNGVHLRGAGGGREKGSVGAVPSGTSPGGVATTAAA
  GSRHSPAGSQALQTTAASELMSQKKFEEIKKANQAAARKLVEEQFSSSSEEGDEDFEGKQ
  GKILANTFITYTTQTDGDTRELERTKQYVNEAFQAGAMTCLICIASVKRNQAVWSCSGCF
  CIFHMPCIQKWAKDSQFLVSSVTDDDFGKKDCPWPCPKCRFEYKRSETPSRYYCYCGKVE
  DPPLDPWLVPHSCGQVCEREFKPPCGHKCLLLCHPGPCPPCPKMVTTTCYCKKAKPIPRR
  CSAKEWSCQLPCGQKLLCGQHKCENPCHAGSCQPCPRVSRQKCVCGKKVAERSCASPLWH
  CDQVCGKTLPCGNHTCEQVCHVGACGECPRSGKRFCPCQKSKFSLPCTEDVPTCGDSCDK
  VLECGIHRCSQRCHRGPCETCRQEVEKHCRCGKHTKRMPCHKPYLCETKCVKMRDCQKHQ
  CRRKCCPGNCPPCDQNCGRTLGCRNHKCPSVCHRGSCYPCPETVDVKCNCGNTKVTVPCG
  RERTTRPPKCKEQCSRPPTCHHTSQEKHRCHFGSCPPCHQPCQKVLEKCGHLCPAPCHDQ
  ALIKQTGRHQPTGPWEQPSEPAFIQTALPCPPCQVPIPMECLGKHEVSPLPCHAVGPYSC
  KRVCGRILDCQNHTCMKECHKVTKTDGCTGKNKAGPECLHCEEGCSKSRPLGCLHPCILR
  CHPGECPPCVQMLRIKCHCKITSLYVECRKITTADVNEKNLLSCCKNQCPKELPCGHRCK
  EMCHPGECPFNCNQKVKLRCPCKRIKKELQCNKVRENQVSIECDTTCKEMKRKASEIKEA
  EAKAALEEEKRRQQAELEAFENRLKGRRKKNRKRDEVAVELSLWQKHKYYLISVCGVVVV
  VFAWYITHDVN

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cholestasis	DISDJJWE	Strong	Biomarker	[1]
Language disorder	DISTLKP7	Limited	Genetic Variation	[2]
Specific language impairment	DISEKRML	Limited	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of NF-X1-type zinc finger protein NFXL1 (NFXL1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of NF-X1-type zinc finger protein NFXL1 (NFXL1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of NF-X1-type zinc finger protein NFXL1 (NFXL1).	[4]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of NF-X1-type zinc finger protein NFXL1 (NFXL1).	[5]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of NF-X1-type zinc finger protein NFXL1 (NFXL1).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of NF-X1-type zinc finger protein NFXL1 (NFXL1).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of NF-X1-type zinc finger protein NFXL1 (NFXL1).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of NF-X1-type zinc finger protein NFXL1 (NFXL1).	[9]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of NF-X1-type zinc finger protein NFXL1 (NFXL1).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of NF-X1-type zinc finger protein NFXL1 (NFXL1).	[10]
Octanal	DMTN0OK	Investigative	Octanal increases the methylation of NF-X1-type zinc finger protein NFXL1 (NFXL1).	[12]

References

• [1] Classification of Cholestatic and Necrotic Hepatotoxicants Using Transcriptomics on Human Precision-Cut Liver Slices.Chem Res Toxicol. 2016 Mar 21;29(3):342-51. doi: 10.1021/acs.chemrestox.5b00491. Epub 2016 Mar 9.
• [2] Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment.PLoS Genet. 2015 Mar 17;11(3):e1004925. doi: 10.1371/journal.pgen.1004925. eCollection 2015 Mar.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [6] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [7] 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.
• [8] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [9] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [10] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [11] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
• [12] DNA Methylome Analysis of Saturated Aliphatic Aldehydes in Pulmonary Toxicity. Sci Rep. 2018 Jul 12;8(1):10497. doi: 10.1038/s41598-018-28813-z.