Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL4A57N)

DOT Name	Osteocrin (OSTN)
Synonyms	Musclin
Gene Name	OSTN
Related Disease	Alzheimer disease ( ) Amyloidosis ( ) Congestive heart failure ( ) Myocardial infarction ( ) Lateral meningocele syndrome ( ) Limb-mammary syndrome ( )
UniProt ID	OSTN_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF11037
Sequence	MLDWRLASAHFILAVTLTLWSSGKVLSVDVTTTEAFDSGVIDVQSTPTVREEKSATDLTA KLLLLDELVSLENDVIETKKKRSFSGFGSPLDRLSAGSVDHKGKQRKVVDHPKRRFGIPM DRIGRNRLSNSRG
Function	Hormone that acts as a regulator of dendritic growth in the developing cerebral cortex in response to sensory experience. Induced in the brain following membrane depolarization and inhibits dendritic branching in neurons of the developing cortex. Probably acts by binding to natriuretic peptide receptor NPR3/NPR-C, thereby preventing binding between NPR3/NPR-C and natriuretic peptides, leading to increase cGMP production.
Tissue Specificity	Enriched in neocortical regions of the developing cerebral cortex . Not expressed in other compartments of the neocortical wall or in brain regions such as the hippocampus, striatum, mediodorsal nucleus of the thalamus and cerebellum . Also expressed in bone . In developing neonatal rib bone, present at high level in osteoblasts on bone-forming surfaces, in newly incorporated osteocytes and in some late hypertrophic chondrocytes (at protein level) . In adult bone, localizes specifically to osteoblasts and young osteocytes at bone-forming sites (at protein level) .

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Amyloidosis	DISHTAI2	Strong	Biomarker	[2]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[3]
Myocardial infarction	DIS655KI	Strong	Biomarker	[3]
Lateral meningocele syndrome	DISG74RP	Limited	Altered Expression	[4]
Limb-mammary syndrome	DIS7H4FP	Limited	Altered Expression	[4]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Osteocrin (OSTN).	[5]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Osteocrin (OSTN).	[6]
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References

1	GWAS of cerebrospinal fluid tau levels identifies risk variants for Alzheimer's disease.Neuron. 2013 Apr 24;78(2):256-68. doi: 10.1016/j.neuron.2013.02.026. Epub 2013 Apr 4.
2	Sex-specific genetic predictors of Alzheimer's disease biomarkers.Acta Neuropathol. 2018 Dec;136(6):857-872. doi: 10.1007/s00401-018-1881-4. Epub 2018 Jul 2.
3	A New Secretory Peptide of Natriuretic Peptide Family, Osteocrin, Suppresses the Progression of Congestive Heart Failure After Myocardial Infarction.Circ Res. 2018 Mar 2;122(5):742-751. doi: 10.1161/CIRCRESAHA.117.312624. Epub 2018 Jan 11.
4	Gene expression signatures of primary and metastatic uterine leiomyosarcoma.Hum Pathol. 2014 Apr;45(4):691-700. doi: 10.1016/j.humpath.2013.11.003. Epub 2013 Nov 13.
5	The PPAR gamma agonist troglitazone induces musclin mRNA expression in human myotubes. Horm Metab Res. 2006 Sep;38(9):614-6. doi: 10.1055/s-2006-951310.
6	Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.