Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOI8TRJ)

• DOT Name: Synemin (SYNM)
• Synonyms: Desmuslin
• Gene Name: SYNM
• Related Disease:
  Neuroblastoma
  Adenoma
  Adult glioblastoma
  Advanced cancer
  Alzheimer disease
  Amyloidosis
  Attention deficit hyperactivity disorder
  Autism
  Autism spectrum disorder
  Brain neoplasm
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Central diabetes insipidus
  Cerebellar ataxia
  Constipation
  Depression
  Dermatomyositis
  Duchenne muscular dystrophy
  Epilepsy
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  Inclusion body myositis
  Irritable bowel syndrome
  Liver cirrhosis
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Major depressive disorder
  Meningioma
  Neoplasm
  Neuralgia
  Parkinson disease
  Parkinsonian disorder
  Rheumatoid arthritis
  Tuberculosis
  Varicose veins
  Vascular dementia
  Small-cell lung cancer
  Dilated cardiomyopathy
  Cognitive impairment
  Lewy body dementia
  Metastatic malignant neoplasm
  Myopathy
  Post-traumatic stress disorder
• UniProt ID: SYNEM_HUMAN
• PDB ID: 6EWO
• Pfam ID: PF00038
• Sequence:
  MLSWRLQTGPEKAELQELNARLYDYVCRVRELERENLLLEEELRGRRGREGLWAEGQARC
  AEEARSLRQQLDELSWATALAEGERDALRRELRELQRLDAEERAARGRLDAELGAQQREL
  QEALGARAALEALLGRLQAERRGLDAAHERDVRELRARAASLTMHFRARATGPAAPPPRL
  REVHDSYALLVAESWRETVQLYEDEVRELEEALRRGQESRLQAEEETRLCAQEAEALRRE
  ALGLEQLRARLEDALLRMREEYGIQAEERQRVIDCLEDEKATLTLAMADWLRDYQDLLQV
  KTGLSLEVATYRALLEGESNPEIVIWAEHVENMPSEFRNKSYHYTDSLLQRENERNLFSR
  QKAPLASFNHSSALYSNLSGHRGSQTGTSIGGDARRGFLGSGYSSSATTQQENSYGKAVS
  SQTNVRTFSPTYGLLRNTEAQVKTFPDRPKAGDTREVPVYIGEDSTIARESYRDRRDKVA
  AGASESTRSNERTVILGKKTEVKATREQERNRPETIRTKPEEKMFDSKEKASEERNLRWE
  ELTKLDKEARQRESQQMKEKAKEKDSPKEKSVREREVPISLEVSQDRRAEVSPKGLQTPV
  KDAGGGTGREAEARELRFRLGTSDATGSLQGDSMTETVAENIVTSILKQFTQSPETEASA
  DSFPDTKVTYVDRKELPGERKTKTEIVVESKLTEDVDVSDEAGLDYLLSKDIKEVGLKGK
  SAEQMIGDIINLGLKGREGRAKVVNVEIVEEPVSYVSGEKPEEFSVPFKVEEVEDVSPGP
  WGLVKEEEGYGESDVTFSVNQHRRTKQPQENTTHVEEVTEAGDSEGEQSYFVSTPDEHPG
  GHDRDDGSVYGQIHIEEESTIRYSWQDEIVQGTRRRTQKDGAVGEKVVKPLDVPAPSLEG
  DLGSTHWKEQARSGEFHAEPTVIEKEIKIPHEFHTSMKGISSKEPRQQLVEVIGQLEETL
  PERMREELSALTREGQGGPGSVSVDVKKVQGAGGSSVTLVAEVNVSQTVDADRLDLEELS
  KDEASEMEKAVESVVRESLSRQRSPAPGSPDEEGGAEAPAAGIRFRRWATRELYIPSGES
  EVAGGASHSSGQRTPQGPVSATVEVSSPTGFAQSQVLEDVSQAARHIKLGPSEVWRTERM
  SYEGPTAEVVEVSAGGDLSQAASPTGASRSVRHVTLGPGQSPLSREVIFLGPAPACPEAW
  GSPEPGPAESSADMDGSGRHSTFGCRQFHAEKEIIFQGPISAAGKVGDYFATEESVGTQT
  SVRQLQLGPKEGFSGQIQFTAPLSDKVELGVIGDSVHMEGLPGSSTSIRHISIGPQRHQT
  TQQIVYHGLVPQLGESGDSESTVHGEGSADVHQATHSHTSGRQTVMTEKSTFQSVVSESP
  QEDSAEDTSGAEMTSGVSRSFRHIRLGPTETETSEHIAIRGPVSRTFVLAGSADSPELGK
  LADSSRTLRHIAPGPKETSFTFQMDVSNVEAIRSRTQEAGALGVSDRGSWRDADSRNDQA
  VGVSFKASAGEGDQAHREQGKEQAMFDKKVQLQRMVDQRSVISDEKKVALLYLDNEEEEN
  DGHWF
• Function: Type-VI intermediate filament (IF) which plays an important cytoskeletal role within the muscle cell cytoskeleton. It forms heteromeric IFs with desmin and/or vimentin, and via its interaction with cytoskeletal proteins alpha-dystrobrevin, dystrophin, talin-1, utrophin and vinculin, is able to link these heteromeric IFs to adherens-type junctions, such as to the costameres, neuromuscular junctions, and myotendinous junctions within striated muscle cells.
• Tissue Specificity: Isoform 2 is strongly detected in adult heart, fetal skeletal muscles and fetal heart. Isoform 1 is weakly detected in fetal heart and also in fetal skeletal muscle. Isoform 1 and isoform 2 are detected in adult bladder (at protein level). The mRNA is predominantly expressed in heart and muscle with some expression in brain which may be due to tissue-specific isoforms.

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neuroblastoma	DISVZBI4	Definitive	Altered Expression	[1]
Adenoma	DIS78ZEV	Strong	Biomarker	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Amyloidosis	DISHTAI2	Strong	Biomarker	[5]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Biomarker	[6]
Autism	DISV4V1Z	Strong	Genetic Variation	[7]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[6]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[4]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[4]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[4]
Central diabetes insipidus	DISJ4P9O	Strong	Biomarker	[9]
Cerebellar ataxia	DIS9IRAV	Strong	Biomarker	[10]
Constipation	DISRQXWI	Strong	Biomarker	[11]
Depression	DIS3XJ69	Strong	Biomarker	[12]
Dermatomyositis	DIS50C5O	Strong	Biomarker	[13]
Duchenne muscular dystrophy	DISRQ3NV	Strong	Altered Expression	[14]
Epilepsy	DISBB28L	Strong	Biomarker	[15]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[8]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[16]
Inclusion body myositis	DISZXXG5	Strong	Biomarker	[13]
Irritable bowel syndrome	DIS27206	Strong	Biomarker	[11]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[17]
Lung cancer	DISCM4YA	Strong	Biomarker	[18]
Lung carcinoma	DISTR26C	Strong	Biomarker	[18]
Lung neoplasm	DISVARNB	Strong	Biomarker	[19]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[20]
Meningioma	DISPT4TG	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[21]
Neuralgia	DISWO58J	Strong	Biomarker	[22]
Parkinson disease	DISQVHKL	Strong	Biomarker	[23]
Parkinsonian disorder	DISHGY45	Strong	Genetic Variation	[10]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[24]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[25]
Varicose veins	DISIMBN2	Strong	Altered Expression	[26]
Vascular dementia	DISVO82H	Strong	Biomarker	[27]
Small-cell lung cancer	DISK3LZD	moderate	Biomarker	[28]
Dilated cardiomyopathy	DISX608J	Disputed	Genetic Variation	[29]
Cognitive impairment	DISH2ERD	Limited	Biomarker	[30]
Lewy body dementia	DISAE66J	Limited	Biomarker	[31]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[32]
Myopathy	DISOWG27	Limited	Altered Expression	[13]
Post-traumatic stress disorder	DISHL1EY	Limited	Biomarker	[33]

3 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 Synemin (SYNM).	[34]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Synemin (SYNM).	[41]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Synemin (SYNM).	[49]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Synemin (SYNM).	[35]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Synemin (SYNM).	[36]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Synemin (SYNM).	[37]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Synemin (SYNM).	[38]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Synemin (SYNM).	[39]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Synemin (SYNM).	[40]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Synemin (SYNM).	[42]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Synemin (SYNM).	[43]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Synemin (SYNM).	[44]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Synemin (SYNM).	[45]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Synemin (SYNM).	[46]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Synemin (SYNM).	[47]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Synemin (SYNM).	[48]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Synemin (SYNM).	[50]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Synemin (SYNM).	[51]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Synemin (SYNM).	[52]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Synemin (SYNM).	[53]

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