Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQY8SJ3)

• DOT Name: Short-chain dehydrogenase/reductase family 9C member 7 (SDR9C7)
• Synonyms: EC 1.1.1.-; Orphan short-chain dehydrogenase/reductase; SDR-O; RDH-S
• Gene Name: SDR9C7
• Related Disease:
  Congenital ichthyosiform erythroderma
  Esophageal squamous cell carcinoma
  Ichthyosis, congenital, autosomal recessive 13
  Neoplasm
  Open-angle glaucoma
  Non-syndromic ichthyosis
  Lamellar ichthyosis
  Lung carcinoma
• UniProt ID: DR9C7_HUMAN
• EC Number: 1.1.1.-
• Pfam ID: PF00106
• Sequence:
  MAALTDLSFMYRWFKNCNLVGNLSEKYVFITGCDSGFGNLLAKQLVDRGMQVLAACFTEE
  GSQKLQRDTSYRLQTTLLDVTKSESIKAAAQWVRDKVGEQGLWALVNNAGVGLPSGPNEW
  LTKDDFVKVINVNLVGLIEVTLHMLPMVKRARGRVVNMSSSGGRVAVIGGGYCVSKFGVE
  AFSDSIRRELYYFGVKVCIIEPGNYRTAILGKENLESRMRKLWERLPQETRDSYGEDYFR
  IYTDKLKNIMQVAEPRVRDVINSMEHAIVSRSPRIRYNPGLDAKLLYIPLAKLPTPVTDF
  ILSRYLPRPADSV
• Function: Displays weak conversion of all-trans-retinal to all-trans-retinol in the presence of NADH. Has apparently no steroid dehydrogenase activity.
• Tissue Specificity: Expressed in the skin . Expressed in granular and cornified layers of the epidermis (at protein level) . Highly expressed in liver .
• Reactome Pathway: The canonical retinoid cycle in rods (twilight vision) (R-HSA-2453902)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital ichthyosiform erythroderma	DISV8HQX	Strong	GermlineCausalMutation	[1]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[2]
Ichthyosis, congenital, autosomal recessive 13	DISSPGQX	Strong	Autosomal recessive	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Open-angle glaucoma	DISSZEE8	Strong	Genetic Variation	[4]
Non-syndromic ichthyosis	DISZ9QBQ	moderate	Biomarker	[5]
Lamellar ichthyosis	DIS714UN	Supportive	Autosomal recessive	[1]
Lung carcinoma	DISTR26C	Limited	Genetic Variation	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Short-chain dehydrogenase/reductase family 9C member 7 (SDR9C7).	[7]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Short-chain dehydrogenase/reductase family 9C member 7 (SDR9C7).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Short-chain dehydrogenase/reductase family 9C member 7 (SDR9C7).	[10]

1 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 Short-chain dehydrogenase/reductase family 9C member 7 (SDR9C7).	[9]

References

• [1] Identification of mutations in SDR9C7 in six families with autosomal recessive congenital ichthyosis. Br J Dermatol. 2018 Mar;178(3):e207-e209. doi: 10.1111/bjd.15994. Epub 2018 Jan 21.
• [2] SDR9C7 promotes lymph node metastases in patients with esophageal squamous cell carcinoma.PLoS One. 2013;8(1):e52184. doi: 10.1371/journal.pone.0052184. Epub 2013 Jan 14.
• [3] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [4] Genome-wide association study of primary open angle glaucoma risk and quantitative traits.Mol Vis. 2012;18:1083-92. Epub 2012 Apr 28.
• [5] SDR9C7 catalyzes critical dehydrogenation of acylceramides for skin barrier formation.J Clin Invest. 2020 Feb 3;130(2):890-903. doi: 10.1172/JCI130675.
• [6] Genome-wide association study of familial lung cancer.Carcinogenesis. 2018 Sep 21;39(9):1135-1140. doi: 10.1093/carcin/bgy080.
• [7] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [8] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [9] 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.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.