Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKDX01I)

DOT Name Calcium permeable stress-gated cation channel 1 (TMEM63C)
Synonyms Transmembrane protein 63C
Gene Name TMEM63C
Related Disease
Focal segmental glomerulosclerosis ( )
Spastic paraplegia 87, autosomal recessive ( )
UniProt ID
CSC1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF14703 ; PF02714 ; PF13967
Sequence
MSASPDDLSTGGRLQNMTVDECFQSRNTVLQGQPFGGVPTVLCLNIALWVLVLVVYSFLR
KAAWDYGRLALLIHNDSLTSLIYGEQSEKTSPSETSLEMERRDKGFCSWFFNSITMKDED
LINKCGDDARIYIVFQYHLIIFVLIICIPSLGIILPINYTGSVLDWSSHFARTTIVNVST
ESKLLWLHSLLSFFYFITNFMFMAHHCLGFAPRNSQKVTRTLMITYVPKDIEDPELIIKH
FHEAYPGSVVTRVHFCYDVRNLIDLDDQRRHAMRGRLFYTAKAKKTGKVMIRIHPCARLC
FCKCWTCFKEVDAEQYYSELEEQLTDEFNAELNRVPLKRLDLIFVTFQDSRMAKRVRKDY
KYVQCGVQPQQSSVTTIVKSYYWRVTMAPHPKDIIWKHLSVRRFFWWARFIAINTFLFFL
FFFLTTPAIIMNTIDMYNVTRPIEKLQNPIVTQFFPSVMLWGFTVILPLIVYFSAFLEAH
WTRSSQNLVMVHKCYIFLVFMVVILPSMGLTSLDVFLRWLFDIYYLEQASIRFQCVFLPD
NGAFFVNYVITAALLGTGMELLRLGSLFCYSTRLFFSRSEPERVNIRKNQAIDFQFGREY
AWMMNVFSVVMAYSITCPIIVPFGLLYLCMKHLTDRYNMYYSFAPTKLNEQIHMAAVSQA
IFAPLLGLFWMLFFSILRLGSLHAITIFSLSTLLIAMVIAFVGIFLGKLRMVADYEPEEE
EIQTVFDMEPSSTSSTPTSLLYVATVLQEPELNLTPASSPARHTYGTMNNQPEEGEEESG
LRGFARELDSAQFQEGLELEGQNQYH
Function Acts as an osmosensitive calcium-permeable cation channel. Required for the functional integrity of the kidney glomerular filtration barrier.
Tissue Specificity Expressed in podocytes of kidney glomeruli . Significantly reduced expression in patients with focal segmental glomerulosclerosis .

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Focal segmental glomerulosclerosis DISJNHH0 Strong Biomarker [1]
Spastic paraplegia 87, autosomal recessive DISO39YP Limited Autosomal recessive [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 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 Calcium permeable stress-gated cation channel 1 (TMEM63C). [3]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Calcium permeable stress-gated cation channel 1 (TMEM63C). [5]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Calcium permeable stress-gated cation channel 1 (TMEM63C). [8]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Calcium permeable stress-gated cation channel 1 (TMEM63C). [10]
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5 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Estradiol DMUNTE3 Approved Estradiol increases the expression of Calcium permeable stress-gated cation channel 1 (TMEM63C). [4]
Triclosan DMZUR4N Approved Triclosan increases the expression of Calcium permeable stress-gated cation channel 1 (TMEM63C). [6]
Niclosamide DMJAGXQ Approved Niclosamide increases the expression of Calcium permeable stress-gated cation channel 1 (TMEM63C). [7]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Calcium permeable stress-gated cation channel 1 (TMEM63C). [9]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde increases the expression of Calcium permeable stress-gated cation channel 1 (TMEM63C). [11]
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References

1 Analysis of the genomic architecture of a complex trait locus in hypertensive rat models links Tmem63c to kidney damage.Elife. 2019 Mar 22;8:e42068. doi: 10.7554/eLife.42068.
2 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
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 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
5 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
6 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
7 Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
8 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.
9 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.
10 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
11 Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.