Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMSCW5I)

• DOT Name: Neurofilament heavy polypeptide (NEFH)
• Synonyms: NF-H; 200 kDa neurofilament protein; Neurofilament triplet H protein
• Gene Name: NEFH
• Related Disease:
  Charcot-Marie-Tooth disease axonal type 2CC
  Intellectual disability
  Neurofibromatosis type 2
  Ovarian cancer
  Ovarian neoplasm
  Rabies
  Subarachnoid hemorrhage
  Advanced cancer
  Alzheimer disease
  Amyloidosis
  Charcot marie tooth disease
  Clear cell renal carcinoma
  Congenital hypothyroidism
  Cytomegalovirus infection
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Essential hypertension
  Familial amyotrophic lateral sclerosis
  Frontotemporal dementia
  Hepatocellular carcinoma
  High blood pressure
  Huntington disease
  Hypothyroidism
  Kennedy disease
  Motor neurone disease
  Neoplasm
  Optic neuritis
  Parkinson disease
  Pick disease
  Renal cell carcinoma
  Schizophrenia
  Sciatic neuropathy
  Spinal muscular atrophy
  Maternal phenylketonuria
  Phenylketonuria
  Breast cancer
  Breast carcinoma
  Amyotrophic lateral sclerosis
  Axonal neuropathy
  Focal segmental glomerulosclerosis
  Membranous glomerulonephritis
  Nervous system disease
  Neuroblastoma
  Ocular hypertension
• UniProt ID: NFH_HUMAN
• Pfam ID: PF07142 ; PF00038
• Sequence:
  MMSFGGADALLGAPFAPLHGGGSLHYALARKGGAGGTRSAAGSSSGFHSWTRTSVSSVSA
  SPSRFRGAGAASSTDSLDTLSNGPEGCMVAVATSRSEKEQLQALNDRFAGYIDKVRQLEA
  HNRSLEGEAAALRQQQAGRSAMGELYEREVREMRGAVLRLGAARGQLRLEQEHLLEDIAH
  VRQRLDDEARQREEAEAAARALARFAQEAEAARVDLQKKAQALQEECGYLRRHHQEEVGE
  LLGQIQGSGAAQAQMQAETRDALKCDVTSALREIRAQLEGHAVQSTLQSEEWFRVRLDRL
  SEAAKVNTDAMRSAQEEITEYRRQLQARTTELEALKSTKDSLERQRSELEDRHQADIASY
  QEAIQQLDAELRNTKWEMAAQLREYQDLLNVKMALDIEIAAYRKLLEGEECRIGFGPIPF
  SLPEGLPKIPSVSTHIKVKSEEKIKVVEKSEKETVIVEEQTEETQVTEEVTEEEEKEAKE
  EEGKEEEGGEEEEAEGGEEETKSPPAEEAASPEKEAKSPVKEEAKSPAEAKSPEKEEAKS
  PAEVKSPEKAKSPAKEEAKSPPEAKSPEKEEAKSPAEVKSPEKAKSPAKEEAKSPAEAKS
  PEKAKSPVKEEAKSPAEAKSPVKEEAKSPAEVKSPEKAKSPTKEEAKSPEKAKSPEKAKS
  PEKEEAKSPEKAKSPVKAEAKSPEKAKSPVKAEAKSPEKAKSPVKEEAKSPEKAKSPVKE
  EAKSPEKAKSPVKEEAKTPEKAKSPVKEEAKSPEKAKSPEKAKTLDVKSPEAKTPAKEEA
  RSPADKFPEKAKSPVKEEVKSPEKAKSPLKEDAKAPEKEIPKKEEVKSPVKEEEKPQEVK
  VKEPPKKAEEEKAPATPKTEEKKDSKKEEAPKKEAPKPKVEEKKEPAVEKPKESKVEAKK
  EEAEDKKKVPTPEKEAPAKVEVKEDAKPKEKTEVAKKEPDDAKAKEPSKPAEKKEAAPEK
  KDTKEEKAKKPEEKPKTEAKAKEDDKTLSKEPSKPKAEKAEKSSSTDQKDSKPPEKATED
  KAAKGK
• Function: Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. NEFH has an important function in mature axons that is not subserved by the two smaller NF proteins. May additionally cooperate with the neuronal intermediate filament proteins PRPH and INA to form neuronal filamentous networks.
• KEGG Pathway:
  Amyotrophic lateral sclerosis (hsa05014)
  Pathways of neurodegeneration - multiple diseases (hsa05022)

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Charcot-Marie-Tooth disease axonal type 2CC	DISK9FMS	Definitive	Autosomal dominant	[1]
Intellectual disability	DISMBNXP	Definitive	Altered Expression	[2]
Neurofibromatosis type 2	DISI8ECS	Definitive	Biomarker	[3]
Ovarian cancer	DISZJHAP	Definitive	Genetic Variation	[4]
Ovarian neoplasm	DISEAFTY	Definitive	Genetic Variation	[4]
Rabies	DISSC4V5	Definitive	Altered Expression	[5]
Subarachnoid hemorrhage	DISI7I8Y	Definitive	Biomarker	[6]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[7]
Alzheimer disease	DISF8S70	Strong	Posttranslational Modification	[8]
Amyloidosis	DISHTAI2	Strong	Biomarker	[9]
Charcot marie tooth disease	DIS3BT2L	Strong	Genetic Variation	[10]
Clear cell renal carcinoma	DISBXRFJ	Strong	Posttranslational Modification	[11]
Congenital hypothyroidism	DISL5XVU	Strong	Biomarker	[12]
Cytomegalovirus infection	DISCEMGC	Strong	Biomarker	[13]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[14]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[15]
Essential hypertension	DIS7WI98	Strong	Biomarker	[16]
Familial amyotrophic lateral sclerosis	DISWZ9CJ	Strong	Genetic Variation	[17]
Frontotemporal dementia	DISKYHXL	Strong	Biomarker	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[18]
High blood pressure	DISY2OHH	Strong	Biomarker	[19]
Huntington disease	DISQPLA4	Strong	Altered Expression	[20]
Hypothyroidism	DISR0H6D	Strong	Therapeutic	[21]
Kennedy disease	DISXZVM1	Strong	Altered Expression	[22]
Motor neurone disease	DISUHWUI	Strong	Biomarker	[23]
Neoplasm	DISZKGEW	Strong	Biomarker	[18]
Optic neuritis	DISDYCHC	Strong	Biomarker	[24]
Parkinson disease	DISQVHKL	Strong	Biomarker	[25]
Pick disease	DISP6X50	Strong	Biomarker	[13]
Renal cell carcinoma	DISQZ2X8	Strong	Posttranslational Modification	[11]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[26]
Sciatic neuropathy	DISMGDKX	Strong	Therapeutic	[27]
Spinal muscular atrophy	DISTLKOB	Strong	Biomarker	[28]
Maternal phenylketonuria	DISAVNUV	moderate	Biomarker	[29]
Phenylketonuria	DISCU56J	moderate	Biomarker	[29]
Breast cancer	DIS7DPX1	Disputed	Biomarker	[30]
Breast carcinoma	DIS2UE88	Disputed	Biomarker	[30]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Autosomal dominant	[1]
Axonal neuropathy	DIS5S2BC	Limited	Genetic Variation	[31]
Focal segmental glomerulosclerosis	DISJNHH0	Limited	Altered Expression	[32]
Membranous glomerulonephritis	DISFSUKQ	Limited	Altered Expression	[32]
Nervous system disease	DISJ7GGT	Limited	Altered Expression	[2]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[33]
Ocular hypertension	DISC2BT9	Limited	Biomarker	[34]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	Neurofilament heavy polypeptide (NEFH) affects the response to substance of Mitoxantrone.	[57]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Neurofilament heavy polypeptide (NEFH).	[35]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Neurofilament heavy polypeptide (NEFH).	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Neurofilament heavy polypeptide (NEFH).	[36]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Neurofilament heavy polypeptide (NEFH).	[37]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Neurofilament heavy polypeptide (NEFH).	[38]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Neurofilament heavy polypeptide (NEFH).	[39]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Neurofilament heavy polypeptide (NEFH).	[40]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Neurofilament heavy polypeptide (NEFH).	[41]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Neurofilament heavy polypeptide (NEFH).	[42]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Neurofilament heavy polypeptide (NEFH).	[43]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Neurofilament heavy polypeptide (NEFH).	[44]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Neurofilament heavy polypeptide (NEFH).	[45]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Neurofilament heavy polypeptide (NEFH).	[46]
Scopolamine	DMOM8AL	Approved	Scopolamine decreases the expression of Neurofilament heavy polypeptide (NEFH).	[47]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Neurofilament heavy polypeptide (NEFH).	[41]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Neurofilament heavy polypeptide (NEFH).	[48]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Neurofilament heavy polypeptide (NEFH).	[51]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Neurofilament heavy polypeptide (NEFH).	[52]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Neurofilament heavy polypeptide (NEFH).	[53]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Neurofilament heavy polypeptide (NEFH).	[54]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Neurofilament heavy polypeptide (NEFH).	[55]
Paraoxon	DMN4ZKC	Investigative	Paraoxon decreases the expression of Neurofilament heavy polypeptide (NEFH).	[56]
tryptanthrin	DMTRYCI	Investigative	tryptanthrin increases the expression of Neurofilament heavy polypeptide (NEFH).	[46]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Neurofilament heavy polypeptide (NEFH).	[49]

References

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