Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8AD4JC)

DOT Name Serine/threonine-protein kinase Nek8 (NEK8)
Synonyms EC 2.7.11.1; Never in mitosis A-related kinase 8; NimA-related protein kinase 8; Nima-related protein kinase 12a
Gene Name NEK8
Related Disease
Renal-hepatic-pancreatic dysplasia 2 ( )
Autosomal dominant polycystic kidney disease ( )
Nephronophthisis 9 ( )
Nephronophthisis 2 ( )
Renal-hepatic-pancreatic dysplasia ( )
UniProt ID
NEK8_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.7.11.1
Pfam ID
PF00069 ; PF00415
Sequence
MEKYERIRVVGRGAFGIVHLCLRKADQKLVIIKQIPVEQMTKEERQAAQNECQVLKLLNH
PNVIEYYENFLEDKALMIAMEYAPGGTLAEFIQKRCNSLLEEETILHFFVQILLALHHVH
THLILHRDLKTQNILLDKHRMVVKIGDFGISKILSSKSKAYTVVGTPCYISPELCEGKPY
NQKSDIWALGCVLYELASLKRAFEAANLPALVLKIMSGTFAPISDRYSPELRQLVLSLLS
LEPAQRPPLSHIMAQPLCIRALLNLHTDVGSVRMRRAEKSVAPSNTGSRTTSVRCRGIPR
GPVRPAIPPPLSSVYAWGGGLGTPLRLPMLNTEVVQVAAGRTQKAGVTRSGRLILWEAPP
LGAGGGSLLPGAVEQPQPQFISRFLEGQSGVTIKHVACGDFFTACLTDRGIIMTFGSGSN
GCLGHGSLTDISQPTIVEALLGYEMVQVACGASHVLALSTERELFAWGRGDSGRLGLGTR
ESHSCPQQVPMPPGQEAQRVVCGIDSSMILTVPGQALACGSNRFNKLGLDHLSLGEEPVP
HQQVEEALSFTLLGSAPLDQEPLLSIDLGTAHSAAVTASGDCYTFGSNQHGQLGTNTRRG
SRAPCKVQGLEGIKMAMVACGDAFTVAIGAESEVYSWGKGARGRLGRRDEDAGLPRPVQL
DETHPYTVTSVSCCHGNTLLAVRSVTDEPVPP
Function
Required for renal tubular integrity. May regulate local cytoskeletal structure in kidney tubule epithelial cells. May regulate ciliary biogenesis through targeting of proteins to the cilia. Plays a role in organogenesis and is involved in the regulation of the Hippo signaling pathway.
Tissue Specificity
Highest expression in thyroid, adrenal gland and skin. Low levels in spleen, colon and uterus. Overexpressed in breast tumors, with highest expression in infiltrating ductal carcinomas and moderate levels in mucinous adenocarcinoma.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Renal-hepatic-pancreatic dysplasia 2 DISI2L8K Definitive Autosomal recessive [1]
Autosomal dominant polycystic kidney disease DISBHWUI Strong Autosomal dominant [1]
Nephronophthisis 9 DIS422XX Strong Autosomal recessive [2]
Nephronophthisis 2 DIS5Y5KV Supportive Autosomal recessive [3]
Renal-hepatic-pancreatic dysplasia DIS3L6GZ Supportive Autosomal recessive [2]
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Molecular Interaction Atlas (MIA) 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
Valproate DMCFE9I Approved Valproate decreases the expression of Serine/threonine-protein kinase Nek8 (NEK8). [4]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of Serine/threonine-protein kinase Nek8 (NEK8). [5]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Serine/threonine-protein kinase Nek8 (NEK8). [6]
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References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 Mutations in NEK8 link multiple organ dysplasia with altered Hippo signalling and increased c-MYC expression. Hum Mol Genet. 2013 Jun 1;22(11):2177-85. doi: 10.1093/hmg/ddt070. Epub 2013 Feb 14.
3 NEK8 mutations affect ciliary and centrosomal localization and may cause nephronophthisis. J Am Soc Nephrol. 2008 Mar;19(3):587-92. doi: 10.1681/ASN.2007040490. Epub 2008 Jan 16.
4 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.
5 Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
6 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.