Details of Drug Off-Target (DOT)

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

DOT Name	Kelch-like protein 6 (KLHL6)
Gene Name	KLHL6
Related Disease	Advanced cancer ( ) Neoplasm ( ) Follicular lymphoma ( ) B-cell lymphoma ( ) B-cell neoplasm ( ) Gastric cancer ( ) Small lymphocytic lymphoma ( ) Stomach cancer ( )
UniProt ID	KLHL6_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF07707 ; PF00651 ; PF01344
Sequence	MLMAGQRGAWTMGDVVEKSLEGPLAPSTDEPSQKTGDLVEILNGEKVKFDDAGLSLILQN GLETLRMENALTDVILCVDIQEFSCHRVVLAAASNYFRAMFCNDLKEKYEKRIIIKGVDA ETMHTLLDYTYTSKALITKQNVQRVLEAANLFQFLRMVDACASFLTEALNPENCVGILRL ADTHSLDSLKKQVQSYIIQNFVQILNSEEFLDLPVDTLHHILKSDDLYVTEEAQVFETVM SWVRHKPSERLCLLPYVLENVRLPLLDPWYFVETVEADPLIRQCPEVFPLLQEARMYHLS GNEIISERTKPRMHEFQSEVFMIIGGCTKDERFVAEVTCLDPLRRSRLEVAKLPLTEHEL ESENKKWVEFACVTLKNEVYISGGKETQHDVWKYNSSINKWIQIEYLNIGRWRHKMVVLG GKVYVIGGFDGLQRINNVETYDPFHNCWSEAAPLLVHVSSFAATSHKKKLYVIGGGPNGK LATDKTQCYDPSTNKWSLKAAMPVEAKCINAVSFRDRIYVVGGAMRALYAYSPLEDSWCL VTQLSHERASCGIAPCNNRLYITGGRDEKNEVIATVLCWDPEAQKLTEECVLPRGVSHHG SVTIRKSYTHIRRIVPGAVSV
Function	Involved in B-lymphocyte antigen receptor signaling and germinal center formation.
Tissue Specificity	Found in germinal center B-cells.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Follicular lymphoma	DISVEUR6	Disputed	Biomarker	[2]
B-cell lymphoma	DISIH1YQ	Limited	Biomarker	[1]
B-cell neoplasm	DISVY326	Limited	Biomarker	[1]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[3]
Small lymphocytic lymphoma	DIS30POX	Limited	Genetic Variation	[4]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[3]
------------------------------------------------------------------------------------


⏷ Show the Full List of 8 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Kelch-like protein 6 (KLHL6).	[5]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Kelch-like protein 6 (KLHL6).	[6]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Kelch-like protein 6 (KLHL6).	[8]
------------------------------------------------------------------------------------

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Kelch-like protein 6 (KLHL6).	[7]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Kelch-like protein 6 (KLHL6).	[9]
------------------------------------------------------------------------------------

References

1	KLHL6 is a tumor suppressor gene in diffuse large B-cell lymphoma.Cell Cycle. 2019 Feb;18(3):249-256. doi: 10.1080/15384101.2019.1568765. Epub 2019 Jan 24.
2	KLHL6 Is Preferentially Expressed in Germinal Center-Derived B-Cell Lymphomas.Am J Clin Pathol. 2017 Nov 20;148(6):465-476. doi: 10.1093/ajcp/aqx099.
3	Prognostic value of the cancer oncogene Kelch-like 6 in gastric cancer.Br J Surg. 2017 Dec;104(13):1847-1856. doi: 10.1002/bjs.10628. Epub 2017 Oct 17.
4	Routine sequencing in CLL has prognostic implications and provides new insight into pathogenesis and targeted treatments.Br J Haematol. 2019 Jun;185(5):852-864. doi: 10.1111/bjh.15877. Epub 2019 Mar 28.
5	Gene expression profile induced by arsenic trioxide in chronic lymphocytic leukemia cells reveals a central role for heme oxygenase-1 in apoptosis and regulation of matrix metalloproteinase-9. Oncotarget. 2016 Dec 13;7(50):83359-83377.
6	Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
7	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.
8	Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
9	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.