Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQHBHM9)

• DOT Name: Statherin (STATH)
• Gene Name: STATH
• Related Disease:
  Autosomal dominant polycystic kidney disease
  Nephropathy
  Amyotrophic neuralgia
  Anorexia nervosa cachexia
  Attention deficit hyperactivity disorder
  Autism
  Autosomal recessive polycystic kidney disease
  Brain cancer
  Breast neoplasm
  CHARGE syndrome
  Chordoma
  Colorectal carcinoma
  Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency
  Costello syndrome
  Early-onset posterior polar cataract
  Fleck corneal dystrophy
  Fragile X syndrome
  Haemophilia A
  Hepatocellular carcinoma
  Huntington disease
  Lung cancer
  Lung carcinoma
  Nasal polyp
  Oral cancer
  Primary congenital glaucoma
  Refractory multiple myeloma
  Retinitis pigmentosa
  Schizophrenia
  Spinal muscular atrophy
  Turner syndrome
  Usher syndrome
  Keratoconus
  Prader-Willi syndrome
  Asthma
  Inflammatory bowel disease
  Intrinsic asthma
  Migraine disorder
  Pneumocystis pneumonia
  Rheumatoid arthritis
• UniProt ID: STAT_HUMAN
• Pfam ID: PF03875
• Sequence:
  MKFLVFAFILALMVSMIGADSSEEKFLRRIGRFGYGYGPYQPVPEQPLYPQPYQPQYQQY
  TF
• Function: Salivary protein that stabilizes saliva supersaturated with calcium salts by inhibiting the precipitation of calcium phosphate salts. It also modulates hydroxyapatite crystal formation on the tooth surface.
• Tissue Specificity: Secreted by parotid and submandibular glands.
• KEGG Pathway: Salivary secretion (hsa04970)

Molecular Interaction Atlas (MIA) of This DOT

39 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal dominant polycystic kidney disease	DISBHWUI	Definitive	Genetic Variation	[1]
Nephropathy	DISXWP4P	Definitive	Genetic Variation	[2]
Amyotrophic neuralgia	DISOTIUZ	Strong	Genetic Variation	[3]
Anorexia nervosa cachexia	DISFO5RQ	Strong	Biomarker	[4]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[5]
Autism	DISV4V1Z	Strong	Biomarker	[6]
Autosomal recessive polycystic kidney disease	DISPUS40	Strong	Genetic Variation	[7]
Brain cancer	DISBKFB7	Strong	Genetic Variation	[8]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[9]
CHARGE syndrome	DISKD3CW	Strong	Biomarker	[10]
Chordoma	DISCHJE7	Strong	Biomarker	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[12]
Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	DIS3HGIB	Strong	Genetic Variation	[13]
Costello syndrome	DISXVJH3	Strong	Biomarker	[14]
Early-onset posterior polar cataract	DISJFK9W	Strong	Genetic Variation	[15]
Fleck corneal dystrophy	DISERQJ1	Strong	Biomarker	[16]
Fragile X syndrome	DISE8W3A	Strong	Genetic Variation	[17]
Haemophilia A	DIS0RQ2E	Strong	Genetic Variation	[18]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[12]
Huntington disease	DISQPLA4	Strong	Biomarker	[13]
Lung cancer	DISCM4YA	Strong	Altered Expression	[19]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[19]
Nasal polyp	DISLP3XE	Strong	Altered Expression	[8]
Oral cancer	DISLD42D	Strong	Biomarker	[20]
Primary congenital glaucoma	DISY7HN4	Strong	Biomarker	[21]
Refractory multiple myeloma	DIS606GH	Strong	Genetic Variation	[22]
Retinitis pigmentosa	DISCGPY8	Strong	Genetic Variation	[23]
Schizophrenia	DISSRV2N	Strong	Biomarker	[24]
Spinal muscular atrophy	DISTLKOB	Strong	Genetic Variation	[25]
Turner syndrome	DIS2035C	Strong	Genetic Variation	[26]
Usher syndrome	DIS9YIS7	Strong	Genetic Variation	[27]
Keratoconus	DISOONXH	moderate	Genetic Variation	[28]
Prader-Willi syndrome	DISYWMLU	moderate	Biomarker	[29]
Asthma	DISW9QNS	Limited	Biomarker	[30]
Inflammatory bowel disease	DISGN23E	Limited	Genetic Variation	[31]
Intrinsic asthma	DIS2U1Q9	Limited	Genetic Variation	[32]
Migraine disorder	DISFCQTG	Limited	Genetic Variation	[33]
Pneumocystis pneumonia	DISFSOM3	Limited	Biomarker	[34]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Statherin (STATH).	[36]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Statherin (STATH).	[37]

2 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 decreases the methylation of Statherin (STATH).	[38]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Statherin (STATH).	[39]

References

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• [2] The genetic background difference between diabetic patients with and without nephropathy in a Taiwanese population by linkage disequilibrium mapping using 382 autosomal STR markers.Genet Test Mol Biomarkers. 2010 Jun;14(3):433-8. doi: 10.1089/gtmb.2009.0179.
• [3] A sequence-ready BAC/PAC contig and partial transcript map of approximately 1.5 Mb in human chromosome 17q25 comprising multiple disease genes.Genomics. 1999 Dec 1;62(2):242-50. doi: 10.1006/geno.1999.5991.
• [4] Linkage analysis of anorexia nervosa incorporating behavioral covariates.Hum Mol Genet. 2002 Mar 15;11(6):689-96. doi: 10.1093/hmg/11.6.689.
• [5] Association between the alpha-2C-adrenergic receptor gene and attention deficit hyperactivity disorder in a Korean sample.Neurosci Lett. 2008 Dec 3;446(2-3):108-11. doi: 10.1016/j.neulet.2008.09.058.
• [6] Hypo-phosphorylation of salivary peptidome as a clue to the molecular pathogenesis of autism spectrum disorders.J Proteome Res. 2008 Dec;7(12):5327-32. doi: 10.1021/pr8004088.
• [7] Birth of a healthy infant following preimplantation PKHD1 haplotyping for autosomal recessive polycystic kidney disease using multiple displacement amplification.J Assist Reprod Genet. 2010 Jul;27(7):397-407. doi: 10.1007/s10815-010-9432-5. Epub 2010 May 20.
• [8] Gene expression profiles in human nasal polyp tissues studied by means of DNA microarray.J Allergy Clin Immunol. 2004 Oct;114(4):783-90. doi: 10.1016/j.jaci.2004.04.052.
• [9] Four regions of allelic imbalance on 17q12-qter associated with high-grade breast tumors.Genes Chromosomes Cancer. 1997 Dec;20(4):354-62.
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• [11] Corroboration of a familial chordoma locus on chromosome 7q and evidence of genetic heterogeneity using single nucleotide polymorphisms (SNPs).Int J Cancer. 2005 Sep 1;116(3):487-91. doi: 10.1002/ijc.21006.
• [12] Polymorphism of T-cell receptor gamma short tandem repeats as a susceptibility risk factor of hepatocellular carcinoma.Anticancer Res. 2006 Sep-Oct;26(5B):3787-91.
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• [14] Paternal uniparental disomy with segmental loss of heterozygosity of chromosome 11 are hallmark characteristics of syndromic and sporadic embryonal rhabdomyosarcoma.Am J Med Genet A. 2016 Dec;170(12):3197-3206. doi: 10.1002/ajmg.a.37949. Epub 2016 Sep 2.
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• [16] Age-severity relationships in families linked to FCD2 with retroillumination photography.Invest Ophthalmol Vis Sci. 2010 Dec;51(12):6298-302. doi: 10.1167/iovs.10-5187. Epub 2010 Sep 1.
• [17] Chromosome fragility at FRAXA in human cleavage stage embryos at risk for fragile X syndrome.Am J Med Genet A. 2015 Oct;167A(10):2306-13. doi: 10.1002/ajmg.a.37149. Epub 2015 May 7.
• [18] Prenatal diagnosis in hemophilia A using factor VIII gene polymorphism--Indian experience.Ann Hematol. 2003 Jul;82(7):427-30. doi: 10.1007/s00277-003-0670-9. Epub 2003 May 24.
• [19] Forensic evaluation of STR typing reliability in lung cancer.Leg Med (Tokyo). 2018 Jan;30:38-41. doi: 10.1016/j.legalmed.2017.11.004. Epub 2017 Nov 11.
• [20] Allelic alterations at the STR markers in the buccal tissue cells of oral cancer patients and the oral epithelial cells of healthy betel quid-chewers: an evaluation of forensic applicability.Forensic Sci Int. 2002 Oct 9;129(3):158-67. doi: 10.1016/s0379-0738(02)00205-0.
• [21] Confirmation and further mapping of the GLC3C locus in primary congenital glaucoma.Front Biosci (Landmark Ed). 2011 Jun 1;16(6):2052-9. doi: 10.2741/3838.
• [22] Genetic heterogeneity in families with hereditary multiple exostoses.Am J Hum Genet. 1993 Jul;53(1):71-9.
• [23] Nonsense mutation in MERTK causes autosomal recessive retinitis pigmentosa in a consanguineous Pakistani family.Br J Ophthalmol. 2010 Aug;94(8):1094-9. doi: 10.1136/bjo.2009.171892. Epub 2010 Jun 10.
• [24] Initial genome-wide scan for linkage with schizophrenia in the Japanese Schizophrenia Sib-Pair Linkage Group (JSSLG) families.Am J Med Genet B Neuropsychiatr Genet. 2003 Jul 1;120B(1):22-8. doi: 10.1002/ajmg.b.20022.
• [25] Heterozygosity assessment of five STR loci located at 5q13 region for preimplantation genetic diagnosis of spinal muscular atrophy.Mol Biol Rep. 2013 Jan;40(1):67-72. doi: 10.1007/s11033-012-2011-3. Epub 2012 Nov 7.
• [26] Diagnosis of Down syndrome and other aneuploidies using quantitative polymerase chain reaction and small tandem repeat polymorphisms.Hum Mol Genet. 1993 Jan;2(1):43-50. doi: 10.1093/hmg/2.1.43.
• [27] Genetic analysis through OtoSeq of Pakistani families segregating prelingual hearing loss.Otolaryngol Head Neck Surg. 2013 Sep;149(3):478-87. doi: 10.1177/0194599813493075. Epub 2013 Jun 14.
• [28] Mutation analysis of VSX1 and SOD1 in Iranian patients with keratoconus.Mol Vis. 2011;17:3128-36. Epub 2011 Nov 30.
• [29] Molecular genetic diagnostics of Prader-Willi Syndrome: a validation of linkage analysis for the Chinese population.J Genet Genomics. 2007 Oct;34(10):885-91. doi: 10.1016/S1673-8527(07)60100-3.
• [30] The polymorphisms of protein-tyrosine phosphatase receptor-type delta gene and its association with pediatric asthma in the Taiwanese population.Eur J Hum Genet. 2008 Oct;16(10):1283-8. doi: 10.1038/ejhg.2008.79. Epub 2008 Apr 16.
• [31] Characterization of genotype-phenotype relationships and stratification by the CARD15 variant genotype for inflammatory bowel disease susceptibility loci using multiple short tandem repeat genetic markers.Hum Mutat. 2005 Feb;25(2):156-66. doi: 10.1002/humu.20129.
• [32] Discovery of genetic difference between asthmatic children with high IgE level and normal IgE level by whole genome linkage disequilibrium mapping using 763 autosomal STR markers.J Hum Genet. 2005;50(5):249-258. doi: 10.1007/s10038-005-0248-6. Epub 2005 May 21.
• [33] Association between migraine and a functional polymorphism at the dopamine beta-hydroxylase locus.Neurogenetics. 2009 Jul;10(3):199-208. doi: 10.1007/s10048-009-0176-2. Epub 2009 Feb 14.
• [34] Diversity of Pneumocystis jirovecii Across Europe: A Multicentre Observational Study.EBioMedicine. 2017 Aug;22:155-163. doi: 10.1016/j.ebiom.2017.06.027. Epub 2017 Jun 29.
• [35] Association of familial and sporadic rheumatoid arthritis with a single corticotropin-releasing hormone genomic region (8q12.3) haplotype.Arthritis Rheum. 2002 Jan;46(1):75-82. doi: 10.1002/1529-0131(200201)46:1<75::AID-ART10034>3.0.CO;2-3.
• [36] Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells. Toxicol Appl Pharmacol. 2017 Sep 15;331:154-163.
• [37] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [38] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [39] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.