Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZHO8WU)

• DOT Name: Metal transporter CNNM2 (CNNM2)
• Synonyms: Ancient conserved domain-containing protein 2; Cyclin-M2
• Gene Name: CNNM2
• Related Disease:
  Hypomagnesemia, seizures, and intellectual disability 1
  Anxiety
  Arrhythmia
  Attention deficit hyperactivity disorder
  Bipolar disorder
  Coronary atherosclerosis
  Coronary heart disease
  Familial primary hypomagnesemia
  High blood pressure
  Intellectual disability
  Major depressive disorder
  Migraine disorder
  Myocardial infarction
  Nephropathy
  Parkinson disease
  Renal hypomagnesemia 6
  Epilepsy
  Familial primary hypomagnesemia with normocalciuria and normocalcemia
  Schizophrenia
  Type-1/2 diabetes
• UniProt ID: CNNM2_HUMAN
• PDB ID: 4IY0; 4IY2; 4IY4; 4IYS; 6DJ3; 6N7E; 8F6D
• Pfam ID: PF00571 ; PF01595
• Sequence:
  MIGCGACEPKVKMAGGQAAAALPTWKMAARRSLSARGRGILQAAAGRLLPLLLLSCCCGA
  GGCAAVGENEETVIIGLRLEDTNDVSFMEGGALRVSERTRVKLRVYGQNINNETWSRIAF
  TEHERRRHSPGERGLGGPAPPEPDSGPQRCGIRTSDIIILPHIILNRRTSGIIEIEIKPL
  RKMEKSKSYYLCTSLSTPALGAGGSGSTGGAVGGKGGSGVAGLPPPPWAETTWIYHDGED
  TKMIVGEEKKFLLPFWLQVIFISLLLCLSGMFSGLNLGLMALDPMELRIVQNCGTEKEKN
  YAKRIEPVRRQGNYLLCSLLLGNVLVNTTLTILLDDIAGSGLVAVVVSTIGIVIFGEIVP
  QAICSRHGLAVGANTIFLTKFFMMMTFPASYPVSKLLDCVLGQEIGTVYNREKLLEMLRV
  TDPYNDLVKEELNIIQGALELRTKTVEDVMTPLRDCFMITGEAILDFNTMSEIMESGYTR
  IPVFEGERSNIVDLLFVKDLAFVDPDDCTPLKTITKFYNHPLHFVFNDTKLDAMLEEFKK
  GKSHLAIVQRVNNEGEGDPFYEVLGIVTLEDVIEEIIKSEILDETDLYTDNRTKKKVAHR
  ERKQDFSAFKQTDSEMKVKISPQLLLAMHRFLATEVEAFSPSQMSEKILLRLLKHPNVIQ
  ELKYDEKNKKAPEYYLYQRNKPVDYFVLILQGKVEVEAGKEGMKFEASAFSYYGVMALTA
  SPVPLSLSRTFVVSRTELLAAGSPGENKSPPRPCGLNHSDSLSRSDRIDAVTPTLGSSNN
  QLNSSLLQVYIPDYSVRALSDLQFVKISRQQYQNALMASRMDKTPQSSDSENTKIELTLT
  ELHDGLPDETANLLNEQNCVTHSKANHSLHNEGAI
• Function: Divalent metal cation transporter. Mediates transport of divalent metal cations in an order of Mg(2+) > Co(2+) > Mn(2+) > Sr(2+) > Ba(2+) > Cu(2+) > Fe(2+).
• Tissue Specificity: Widely expressed. Expressed at higher level in brain, kidney and placenta, while it is weakly expressed in skeletal muscle. In the kidney, it is expressed in the distal convoluted tubule and the thick ascending limb of Henle loop.

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hypomagnesemia, seizures, and intellectual disability 1	DIST3YHO	Definitive	Semidominant	[1]
Anxiety	DISIJDBA	Strong	Genetic Variation	[2]
Arrhythmia	DISFF2NI	Strong	Biomarker	[3]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[4]
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[5]
Coronary atherosclerosis	DISKNDYU	Strong	Genetic Variation	[6]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[7]
Familial primary hypomagnesemia	DIS6TTKI	Strong	Genetic Variation	[8]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[6]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[8]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[4]
Migraine disorder	DISFCQTG	Strong	Genetic Variation	[9]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[10]
Nephropathy	DISXWP4P	Strong	Biomarker	[3]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[11]
Renal hypomagnesemia 6	DISQZQ94	Strong	Autosomal dominant	[12]
Epilepsy	DISBB28L	moderate	Genetic Variation	[8]
Familial primary hypomagnesemia with normocalciuria and normocalcemia	DISZNFLZ	Supportive	Autosomal dominant	[12]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[13]
Type-1/2 diabetes	DISIUHAP	Limited	Genetic Variation	[14]

18 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 Metal transporter CNNM2 (CNNM2).	[15]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Metal transporter CNNM2 (CNNM2).	[16]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Metal transporter CNNM2 (CNNM2).	[17]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Metal transporter CNNM2 (CNNM2).	[18]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Metal transporter CNNM2 (CNNM2).	[19]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Metal transporter CNNM2 (CNNM2).	[20]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Metal transporter CNNM2 (CNNM2).	[21]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Metal transporter CNNM2 (CNNM2).	[22]
Marinol	DM70IK5	Approved	Marinol increases the expression of Metal transporter CNNM2 (CNNM2).	[23]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Metal transporter CNNM2 (CNNM2).	[24]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Metal transporter CNNM2 (CNNM2).	[25]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Metal transporter CNNM2 (CNNM2).	[26]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Metal transporter CNNM2 (CNNM2).	[27]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Metal transporter CNNM2 (CNNM2).	[28]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Metal transporter CNNM2 (CNNM2).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Metal transporter CNNM2 (CNNM2).	[32]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Metal transporter CNNM2 (CNNM2).	[33]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Metal transporter CNNM2 (CNNM2).	[34]

3 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 increases the methylation of Metal transporter CNNM2 (CNNM2).	[30]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Metal transporter CNNM2 (CNNM2).	[31]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Metal transporter CNNM2 (CNNM2).	[31]

References

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