Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE0YZJO)

DOT Name Short stature homeobox protein (SHOX)
Synonyms Pseudoautosomal homeobox-containing osteogenic protein; Short stature homeobox-containing protein
Gene Name SHOX
Related Disease
Langer mesomelic dysplasia ( )
Leri-Weill dyschondrosteosis ( )
Achondroplasia ( )
Becker muscular dystrophy ( )
Bone osteosarcoma ( )
Dorfman-Chanarin disease ( )
Duchenne muscular dystrophy ( )
Hypochondroplasia ( )
Intervertebral disc degeneration ( )
Kallmann syndrome ( )
Klinefelter syndrome ( )
Melanocytic nevus ( )
Mesomelic dysplasia ( )
Morquio syndrome ( )
Muscular dystrophy ( )
Noonan syndrome ( )
Osteoarthritis ( )
Osteochondrodysplasia ( )
Osteosarcoma ( )
Peters anomaly ( )
Skeletal dysplasia ( )
2q37 microdeletion syndrome ( )
Fetal growth restriction ( )
SHOX-related short stature ( )
Aromatase deficiency ( )
Estrogen resistance syndrome ( )
Chromosomal disorder ( )
Timothy syndrome ( )
Tourette syndrome ( )
Tuberous sclerosis ( )
UniProt ID
SHOX_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00046 ; PF03826
Sequence
MEELTAFVSKSFDQKSKDGNGGGGGGGGKKDSITYREVLESGLARSRELGTSDSSLQDIT
EGGGHCPVHLFKDHVDNDKEKLKEFGTARVAEGIYECKEKREDVKSEDEDGQTKLKQRRS
RTNFTLEQLNELERLFDETHYPDAFMREELSQRLGLSEARVQVWFQNRRAKCRKQENQMH
KGVILGTANHLDACRVAPYVNMGALRMPFQQVQAQLQLEGVAHAHPHLHPHLAAHAPYLM
FPPPPFGLPIASLAESASAAAVVAAAAKSNSKNSSIADLRLKARKHAEALGL
Function Controls fundamental aspects of growth and development.
Tissue Specificity
SHOXA is expressed in skeletal muscle, placenta, pancreas, heart and bone marrow fibroblast and SHOXB is highly expressed in bone marrow fibroblast followed by kidney and skeletal muscle. SHOXB is not expressed in brain, kidney, liver and lung. Highly expressed in osteogenic cells.

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Langer mesomelic dysplasia DISCXVK3 Definitive X-linked [1]
Leri-Weill dyschondrosteosis DISDPMVZ Definitive X-linked [2]
Achondroplasia DISYWN2O Strong Genetic Variation [3]
Becker muscular dystrophy DIS5IYHL Strong Genetic Variation [4]
Bone osteosarcoma DIST1004 Strong Altered Expression [5]
Dorfman-Chanarin disease DISKKT3R Strong Genetic Variation [6]
Duchenne muscular dystrophy DISRQ3NV Strong Altered Expression [7]
Hypochondroplasia DISHNE51 Strong Genetic Variation [8]
Intervertebral disc degeneration DISG3AIM Strong Biomarker [9]
Kallmann syndrome DISO3HDG Strong Genetic Variation [10]
Klinefelter syndrome DISOUI7W Strong Biomarker [11]
Melanocytic nevus DISYS32D Strong Altered Expression [7]
Mesomelic dysplasia DISKJI1E Strong Biomarker [12]
Morquio syndrome DIS2Y2P2 Strong Genetic Variation [13]
Muscular dystrophy DISJD6P7 Strong Genetic Variation [4]
Noonan syndrome DIS7Q7DN Strong Genetic Variation [14]
Osteoarthritis DIS05URM Strong Biomarker [15]
Osteochondrodysplasia DIS9SPWW Strong Genetic Variation [16]
Osteosarcoma DISLQ7E2 Strong Altered Expression [5]
Peters anomaly DISERK0M Strong Genetic Variation [17]
Skeletal dysplasia DIS5Z8U6 Strong Genetic Variation [16]
2q37 microdeletion syndrome DISZYHCB moderate Genetic Variation [18]
Fetal growth restriction DIS5WEJ5 moderate Genetic Variation [19]
SHOX-related short stature DIS4A87B Supportive Autosomal dominant [20]
Aromatase deficiency DISMDRRM Disputed Biomarker [21]
Estrogen resistance syndrome DIS2SYXC Disputed Biomarker [21]
Chromosomal disorder DISM5BB5 Limited Biomarker [22]
Timothy syndrome DISBXBZP Limited Biomarker [23]
Tourette syndrome DISX9D54 Limited Biomarker [23]
Tuberous sclerosis DISEMUGZ Limited Biomarker [23]
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⏷ Show the Full List of 30 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Short stature homeobox protein (SHOX). [24]
DTI-015 DMXZRW0 Approved DTI-015 decreases the expression of Short stature homeobox protein (SHOX). [25]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Short stature homeobox protein (SHOX). [26]
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References

1 Complete SHOX deficiency causes Langer mesomelic dysplasia. Am J Med Genet. 2002 Jun 15;110(2):158-63. doi: 10.1002/ajmg.10422.
2 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
3 New roles of SHOX as regulator of target genes.Pediatr Endocrinol Rev. 2012 May;9 Suppl 2:733-8.
4 Novel SHOX gene mutation in a short boy with Becker muscular dystrophy: double trouble in two adjacent genes.Horm Res. 2008;69(2):124-8. doi: 10.1159/000111816. Epub 2007 Dec 5.
5 SHOX triggers the lysosomal pathway of apoptosis via oxidative stress.Hum Mol Genet. 2014 Mar 15;23(6):1619-30. doi: 10.1093/hmg/ddt552. Epub 2013 Nov 1.
6 Allelic and nonallelic heterogeneity in dyschondrosteosis (Leri-Weill syndrome).Am J Med Genet. 2001 Winter;106(4):272-4. doi: 10.1002/ajmg.10228.
7 Turner syndrome and Xp deletions: clinical and molecular studies in 47 patients.J Clin Endocrinol Metab. 2001 Nov;86(11):5498-508. doi: 10.1210/jcem.86.11.8058.
8 New proposed clinico-radiologic and molecular criteria in hypochondroplasia: FGFR 3 gene mutations are not the only cause of hypochondroplasia.Am J Med Genet A. 2012 Oct;158A(10):2456-62. doi: 10.1002/ajmg.a.35564. Epub 2012 Aug 17.
9 Replacing Shox2 with human SHOX leads to congenital disc degeneration of the temporomandibular joint in mice.Cell Tissue Res. 2014 Feb;355(2):345-54. doi: 10.1007/s00441-013-1743-2. Epub 2013 Nov 19.
10 Short stature in a mother and daughter caused by familial der(X)t(X;X)(p22.1-3;q26).Am J Med Genet. 2001 Jul 22;102(1):81-5. doi: 10.1002/1096-8628(20010722)102:1<81::aid-ajmg1375>3.0.co;2-v.
11 Novel genetic aspects of Klinefelter's syndrome.Mol Hum Reprod. 2010 Jun;16(6):386-95. doi: 10.1093/molehr/gaq019. Epub 2010 Mar 12.
12 SHOX intragenic microsatellite analysis in patients with short stature.J Pediatr Endocrinol Metab. 2002 Feb;15(2):139-48. doi: 10.1515/jpem.2002.15.2.139.
13 Auxological and anthropometric evaluation in skeletal dysplasias.J Endocrinol Invest. 2010 Jun;33(6 Suppl):19-25.
14 An Association of PTPN11 and SHOX Mutations in a Male Presenting With Syndromic Growth Failure.Front Endocrinol (Lausanne). 2018 Sep 20;9:557. doi: 10.3389/fendo.2018.00557. eCollection 2018.
15 Expressing human SHOX in Shox2SHOX KI/KI mice leads to congenital osteoarthritislike disease of the temporomandibular joint in postnatal mice.Mol Med Rep. 2016 Oct;14(4):3676-82. doi: 10.3892/mmr.2016.5715. Epub 2016 Sep 5.
16 Retinoic acid catabolizing enzyme CYP26C1 is a genetic modifier in SHOX deficiency.EMBO Mol Med. 2016 Dec 1;8(12):1455-1469. doi: 10.15252/emmm.201606623. Print 2016 Dec.
17 Brachymesomelic dysplasia with Peters anomaly of the eye results from disruptions of the X chromosome near the SHOX and SOX3 genes.Am J Med Genet A. 2007 Dec 1;143A(23):2785-95. doi: 10.1002/ajmg.a.32036.
18 HDAC8 Loss of Function and SHOX Haploinsufficiency: Two Independent Genetic Defects Responsible for a Complex Phenotype.Cytogenet Genome Res. 2019;157(3):135-140. doi: 10.1159/000499174. Epub 2018 Mar 26.
19 Association of intrauterine growth retardation with monosomy of the terminal segment of the short arm of the X chromosome in patients with Turner's syndrome.Gynecol Obstet Invest. 2000;50(4):237-41. doi: 10.1159/000010323.
20 Clinical Practice Guidelines for Rare Diseases: The Orphanet Database. PLoS One. 2017 Jan 18;12(1):e0170365. doi: 10.1371/journal.pone.0170365. eCollection 2017.
21 Short stature homeobox-containing gene duplication on the der(X) chromosome in a female with 45,X/46,X, der(X), gonadal dysgenesis, and tall stature.J Clin Endocrinol Metab. 2000 Aug;85(8):2927-30. doi: 10.1210/jcem.85.8.6745.
22 Duplication of Yq- and proximal Yp-arms with deletion of almost all PAR1 (including SHOX) in a young man with non-obstructive azoospermia, short stature and skeletal defects.J Appl Genet. 2017 Nov;58(4):481-486. doi: 10.1007/s13353-017-0412-7. Epub 2017 Oct 6.
23 Phenotypes Associated with SHOX Deficiency.J Clin Endocrinol Metab. 2001 Dec;86(12):5674-80. doi: 10.1210/jcem.86.12.8125.
24 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.
25 Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
26 Transcriptomic?pathway?and?benchmark dose analysis of Bisphenol A, Bisphenol S, Bisphenol F, and 3,3',5,5'-Tetrabromobisphenol A in H9 human embryonic stem cells. Toxicol In Vitro. 2021 Apr;72:105097. doi: 10.1016/j.tiv.2021.105097. Epub 2021 Jan 18.