Details of Drug Off-Target (DOT)

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

• DOT Name: Adenylate kinase 7 (AK7)
• Synonyms: AK 7; EC 2.7.4.3; EC 2.7.4.6; ATP-AMP transphosphorylase 7
• Gene Name: AK7
• Related Disease:
  Hydrocephalus
  Male infertility
  Obsolete non-syndromic male infertility due to sperm motility disorder
  Primary ciliary dyskinesia
  Spermatogenic failure 27
• UniProt ID: KAD7_HUMAN
• EC Number: 2.7.4.3; 2.7.4.6
• Pfam ID: PF00406 ; PF05186
• Sequence:
  MAEEEETAALTEKVIRTQRVFINLLDSYSSGNIGKFLSNCVVGASLEEITEEEEEEDENK
  SAMLEASSTKVKEGTFQIVGTLSKPDSPRPDFAVETYSAISREDLLMRLLECDVIIYNIT
  ESSQQMEEAIWAVSALSEEVSHFEKRKLFILLSTVMTWARSKALDPEDSEVPFTEEDYRR
  RKSHPNFLDHINAEKMVLKFGKKARKFAAYVVAAGLQYGAEGGMLHTFFKMAWLGEIPAL
  PVFGDGTNVIPTIHVLDLAGVIQNVIDHVPKPHYLVAVDESVHTLEDIVKCISKNTGPGK
  IQKIPRENAYLTKDLTQDCLDHLLVNLRMEALFVKENFNIRWAAQTGFVENINTILKEYK
  QSRGLMPIKICILGPPAVGKSSIAKELANYYKLHHIQLKDVISEAIAKLEAIVAPNDVGE
  GEEEVEEEEEEENVEDAQELLDGIKESMEQNAGQLDDQYIIRFMKEKLKSMPCRNQGYIL
  DGFPKTYDQAKDLFNQEDEEEEDDVRGRMFPFDKLIIPEFVCALDASDEFLKERVINLPE
  SIVAGTHYSQDRFLRALSNYRDINIDDETVFNYFDELEIHPIHIDVGKLEDAQNRLAIKQ
  LIKEIGEPRNYGLTDEEKAEEERKAAEERLAREAAEEAEREHQEAVEMAEKIARWEEWNK
  RLEEVKREERELLEAQSIPLRNYLMTYVMPTLIQGLNECCNVRPEDPVDFLAEYLFKNNP
  EAQ
• Function: Nucleoside monophosphate (NMP) kinase that catalyzes the reversible transfer of the terminal phosphate group between nucleoside triphosphates and monophosphates. Has highest activity toward AMP, and weaker activity toward dAMP, CMP and dCMP. Also displays broad nucleoside diphosphate kinase activity. Involved in maintaining ciliary structure and function.
• Tissue Specificity: Expressed in sperm and airway epithelial cells (at protein level).
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Thiamine metabolism (hsa00730)
  Metabolic pathways (hsa01100)
  Nucleotide metabolism (hsa01232)
  Biosynthesis of cofactors (hsa01240)
• Reactome Pathway: Interconversion of nucleotide di- and triphosphates (R-HSA-499943)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hydrocephalus	DISIZUF7	Strong	Biomarker	[1]
Male infertility	DISY3YZZ	Strong	Genetic Variation	[2]
Obsolete non-syndromic male infertility due to sperm motility disorder	DISG7641	Supportive	Autosomal recessive	[2]
Primary ciliary dyskinesia	DISOBC7V	Disputed	Autosomal recessive	[3]
Spermatogenic failure 27	DISXWQH3	Limited	Autosomal recessive	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Adenylate kinase 7 (AK7).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Adenylate kinase 7 (AK7).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Adenylate kinase 7 (AK7).	[5]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Adenylate kinase 7 (AK7).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Adenylate kinase 7 (AK7).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Adenylate kinase 7 (AK7).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Adenylate kinase 7 (AK7).	[8]

References

• [1] Congenital hydrocephalus in genetically engineered mice.Vet Pathol. 2012 Jan;49(1):166-81. doi: 10.1177/0300985811415708. Epub 2011 Jul 11.
• [2] Homozygous missense mutation L673P in adenylate kinase 7 (AK7) leads to primary male infertility and multiple morphological anomalies of the flagella but not to primary ciliary dyskinesia. Hum Mol Genet. 2018 Apr 1;27(7):1196-1211. doi: 10.1093/hmg/ddy034.
• [3] 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.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [6] Inter- and intra-laboratory study to determine the reproducibility of toxicogenomics datasets. Toxicology. 2011 Nov 28;290(1):50-8.
• [7] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [8] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.