Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5CE7LO)

• DOT Name: Neurochondrin (NCDN)
• Gene Name: NCDN
• Related Disease:
  Cerebellar ataxia
  High blood pressure
  Neurodevelopmental disorder with infantile epileptic spasms
  Spinal muscular atrophy
  Autosomal recessive non-syndromic intellectual disability
  Type-1 diabetes
• UniProt ID: NCDN_HUMAN
• Pfam ID: PF05536
• Sequence:
  MSCCDLAAAGQLGKASIMASDCEPALNQAEGRNPTLERYLGALREAKNDSEQFAALLLVT
  KAVKAGDIDAKTRRRIFDAVGFTFPNRLLTTKEAPDGCPDHVLRALGVALLACFCSDPEL
  AAHPQVLNKIPILSTFLTARGDPDDAARRSMIDDTYQCLTAVAGTPRGPRHLIAGGTVSA
  LCQAYLGHGYGFDQALALLVGLLAAAETQCWKEAEPDLLAVLRGLSEDFQKAEDASKFEL
  CQLLPLFLPPTTVPPECYRDLQAGLARILGSKLSSWQRNPALKLAARLAHACGSDWIPAG
  SSGSKFLALLVNLACVEVRLALEETGTEVKEDVVTACYALMELGIQECTRCEQSLLKEPQ
  KVQLVSVMKEAIGAVIHYLLQVGSEKQKEPFVFASVRILGAWLAEETSSLRKEVCQLLPF
  LVRYAKTLYEEAEEANDLSQQVANLAISPTTPGPTWPGDALRLLLPGWCHLTVEDGPREI
  LIKEGAPSLLCKYFLQQWELTSPGHDTSVLPDSVEIGLQTCCHIFLNLVVTAPGLIKRDA
  CFTSLMNTLMTSLPALVQQQGRLLLAANVATLGLLMARLLSTSPALQGTPASRGFFAAAI
  LFLSQSHVARATPGSDQAVLALSPEYEGIWADLQELWFLGMQAFTGCVPLLPWLAPAALR
  SRWPQELLQLLGSVSPNSVKPEMVAAYQGVLVELARANRLCREAMRLQAGEETASHYRMA
  ALEQCLSEP
• Function: Probably involved in signal transduction in the nervous system, via increasing cell surface localization of GRM5/mGluR5 and positively regulating its signaling. Required for the spatial learning process. Acts as a negative regulator of Ca(2+)-calmodulin-dependent protein kinase 2 (CaMK2) phosphorylation. May play a role in modulating melanin-concentrating hormone-mediated functions via its interaction with MCHR1 that interferes with G protein-coupled signal transduction. May be involved in bone metabolism. May also be involved in neurite outgrowth (Probable).
• Tissue Specificity: Abundantly expressed in whole adult brain and in all individual brain regions examined, including spinal cord. Weakly expressed in ovary, testis, fetal brain and small intestine.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebellar ataxia	DIS9IRAV	Strong	Biomarker	[1]
High blood pressure	DISY2OHH	Strong	Biomarker	[2]
Neurodevelopmental disorder with infantile epileptic spasms	DIS7JC0O	Strong	Autosomal dominant	[3]
Spinal muscular atrophy	DISTLKOB	Strong	Biomarker	[4]
Autosomal recessive non-syndromic intellectual disability	DISJWRZZ	Supportive	Autosomal recessive	[3]
Type-1 diabetes	DIS7HLUB	Limited	Altered Expression	[5]

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 Neurochondrin (NCDN).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Neurochondrin (NCDN).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Neurochondrin (NCDN).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Neurochondrin (NCDN).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Neurochondrin (NCDN).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Neurochondrin (NCDN).	[10]
Selenium	DM25CGV	Approved	Selenium increases the expression of Neurochondrin (NCDN).	[11]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Neurochondrin (NCDN).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Neurochondrin (NCDN).	[12]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Neurochondrin (NCDN).	[13]

References

• [1] Neurochondrin Antibody Serum Positivity in Three Cases of Autoimmune Cerebellar Ataxia.Cerebellum. 2019 Dec;18(6):1137-1142. doi: 10.1007/s12311-019-01048-y.
• [2] Evaluation of 12 Novel Molecular Markers for Degenerated Nucleus Pulposus in a Chinese Population.Spine (Phila Pa 1976). 2015 Aug 15;40(16):1252-60. doi: 10.1097/BRS.0000000000000929.
• [3] Monoallelic and bi-allelic variants in NCDN cause neurodevelopmental delay, intellectual disability, and epilepsy. Am J Hum Genet. 2021 Apr 1;108(4):739-748. doi: 10.1016/j.ajhg.2021.02.015. Epub 2021 Mar 11.
• [4] Neurochondrin interacts with the SMN protein suggesting a novel mechanism for spinal muscular atrophy pathology.J Cell Sci. 2018 Apr 17;131(8):jcs211482. doi: 10.1242/jcs.211482.
• [5] Comprehensive evaluation of differential lncRNA and gene expression in patients with intervertebral disc degeneration.Mol Med Rep. 2018 Aug;18(2):1504-1512. doi: 10.3892/mmr.2018.9128. Epub 2018 Jun 5.
• [6] 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.
• [7] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [8] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [9] 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.
• [10] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [11] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [12] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] 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.