Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNMH6OS)

• DOT Name: Keratinocyte differentiation factor 1 (KDF1)
• Gene Name: KDF1
• Related Disease:
  Ectodermal dysplasia
  Ectodermal dysplasia 12, hypohidrotic/hair/tooth/nail type
  X-linked hypohidrotic ectodermal dysplasia
  Autosomal dominant hypohidrotic ectodermal dysplasia
• UniProt ID: KDF1_HUMAN
• Pfam ID: PF15551
• Sequence:
  MPRPGHPRPASGPPRLGPWERPTELCLETYDKPPQPPPSRRTRRPDPKDPGHHGPESITF
  ISGSAEPALESPTCCLLWRPWVWEWCRAAFCFRRCRDCLQRCGACVRGCSPCLSTEDSTE
  GTAEANWAKEHNGVPPSPDRAPPSRRDGQRLKSTMGSSFSYPDVKLKGIPVYPYPRATSP
  APDADSCCKEPLADPPPMRHSLPSTFASSPRGSEEYYSFHESDLDLPEMGSGSMSSREID
  VLIFKKLTELFSVHQIDELAKCTSDTVFLEKTSKISDLISSITQDYHLDEQDAEGRLVRG
  IIRISTRKSRARPQTSEGRSTRAAAPTAAAPDSGHETMVGSGLSQDELTVQISQETTADA
  IARKLRPYGAPGYPASHDSSFQGTDTDSSGAPLLQVYC
• Function: Plays a role in the regulation of the epidermis formation during early development. Required both as an inhibitor of basal cell proliferation and a promoter of differentiation of basal progenitor cell progeny.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ectodermal dysplasia	DISLRS4M	Strong	Biomarker	[1]
Ectodermal dysplasia 12, hypohidrotic/hair/tooth/nail type	DISZ97RP	Strong	Autosomal dominant	[2]
X-linked hypohidrotic ectodermal dysplasia	DISST0XM	Strong	Genetic Variation	[1]
Autosomal dominant hypohidrotic ectodermal dysplasia	DISGWW7F	Supportive	Autosomal dominant	[1]

2 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 Keratinocyte differentiation factor 1 (KDF1).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Keratinocyte differentiation factor 1 (KDF1).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Keratinocyte differentiation factor 1 (KDF1).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Keratinocyte differentiation factor 1 (KDF1).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Keratinocyte differentiation factor 1 (KDF1).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Keratinocyte differentiation factor 1 (KDF1).	[8]

References

• [1] KDF1, encoding keratinocyte differentiation factor 1, is mutated in a multigenerational family with ectodermal dysplasia. Hum Genet. 2017 Jan;136(1):99-105. doi: 10.1007/s00439-016-1741-z. Epub 2016 Nov 12.
• [2] Estradiol, reproductive cycle and preference behavior in a northern swordtail. Gen Comp Endocrinol. 2011 Jan 15;170(2):381-90. doi: 10.1016/j.ygcen.2010.10.012. Epub 2010 Oct 25.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [7] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [8] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.