Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZJT4KN)

• DOT Name: Anosmin-1 (ANOS1)
• Synonyms: Adhesion molecule-like X-linked; Kallmann syndrome protein
• Gene Name: ANOS1
• Related Disease:
  Hypogonadism
  Hypogonadotropic hypogonadism 1 with or without anosmia
  Renal agenesis
  Renal hypodysplasia/aplasia 1
  Adult glioblastoma
  Atopic dermatitis
  Bilateral renal agenesis
  Brain neoplasm
  Chromosomal disorder
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Hypogonadotropic hypogonadism 7 with or without anosmia
  Hypopituitarism
  Immunodeficiency
  Intellectual disability
  Kaposi sarcoma
  Mental disorder
  Neoplasm
  Non-syndromic ichthyosis
  Obesity
  Oral cancer
  Panhypopituitarism
  Plasma cell myeloma
  Renal agenesis, unilateral
  Retinoblastoma
  Schizophrenia
  Squamous cell carcinoma
  Turner syndrome
  Vesicoureteral reflux
  X-linked adrenal hypoplasia congenita
  Advanced cancer
  Anosmia
  Cryptorchidism
  Hypogonadotropic hypogonadism 2 with or without anosmia
  Recessive X-linked ichthyosis
  Kallmann syndrome
  Gastric cancer
  Hypogonadotropic hypogonadism
  Kabuki syndrome
  Klinefelter syndrome
  Septooptic dysplasia
  Stomach cancer
• UniProt ID: KALM_HUMAN
• PDB ID: 1ZLG
• Pfam ID: PF17869 ; PF00041 ; PF00095
• Sequence:
  MVPGVPGAVLTLCLWLAASSGCLAAGPGAAAARRLDESLSAGSVQRARCASRCLSLQITR
  ISAFFQHFQNNGSLVWCQNHKQCSKCLEPCKESGDLRKHQCQSFCEPLFPKKSYECLTSC
  EFLKYILLVKQGDCPAPEKASGFAAACVESCEVDNECSGVKKCCSNGCGHTCQVPKTLYK
  GVPLKPRKELRFTELQSGQLEVKWSSKFNISIEPVIYVVQRRWNYGIHPSEDDATHWQTV
  AQTTDERVQLTDIRPSRWYQFRVAAVNVHGTRGFTAPSKHFRSSKDPSAPPAPANLRLAN
  STVNSDGSVTVTIVWDLPEEPDIPVHHYKVFWSWMVSSKSLVPTKKKRRKTTDGFQNSVI
  LEKLQPDCDYVVELQAITYWGQTRLKSAKVSLHFTSTHATNNKEQLVKTRKGGIQTQLPF
  QRRRPTRPLEVGAPFYQDGQLQVKVYWKKTEDPTVNRYHVRWFPEACAHNRTTGSEASSG
  MTHENYIILQDLSFSCKYKVTVQPIRPKSHSKAEAVFFTTPPCSALKGKSHKPVGCLGEA
  GHVLSKVLAKPENLSASFIVQDVNITGHFSWKMAKANLYQPMTGFQVTWAEVTTESRQNS
  LPNSIISQSQILPSDHYVLTVPNLRPSTLYRLEVQVLTPGGEGPATIKTFRTPELPPSSA
  HRSHLKHRHPHHYKPSPERY
• Function: Has a dual branch-promoting and guidance activity, which may play an important role in the patterning of mitral and tufted cell collaterals to the olfactory cortex. Chemoattractant for fetal olfactory epithelial cells.
• Tissue Specificity: Expressed in the cerebellum (at protein level).
• Reactome Pathway:
  Negative regulation of FGFR1 signaling (R-HSA-5654726)
  FGFR1c ligand binding and activation (R-HSA-190373)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hypogonadism	DISICMNI	Definitive	Genetic Variation	[1]
Hypogonadotropic hypogonadism 1 with or without anosmia	DISVQKUG	Definitive	X-linked	[2]
Renal agenesis	DIS0M9AF	Definitive	Biomarker	[3]
Renal hypodysplasia/aplasia 1	DISOH8XN	Definitive	Biomarker	[3]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[4]
Atopic dermatitis	DISTCP41	Strong	Biomarker	[5]
Bilateral renal agenesis	DISOR5IA	Strong	Biomarker	[3]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[4]
Chromosomal disorder	DISM5BB5	Strong	Genetic Variation	[6]
Colon cancer	DISVC52G	Strong	Altered Expression	[7]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[8]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Posttranslational Modification	[9]
Hypogonadotropic hypogonadism 7 with or without anosmia	DISPBWEU	Strong	Biomarker	[10]
Hypopituitarism	DIS1QT3G	Strong	Genetic Variation	[11]
Immunodeficiency	DIS093I0	Strong	Biomarker	[12]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[13]
Kaposi sarcoma	DISC1H1Z	Strong	Genetic Variation	[14]
Mental disorder	DIS3J5R8	Strong	Genetic Variation	[15]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[16]
Non-syndromic ichthyosis	DISZ9QBQ	Strong	Genetic Variation	[17]
Obesity	DIS47Y1K	Strong	Biomarker	[18]
Oral cancer	DISLD42D	Strong	Biomarker	[19]
Panhypopituitarism	DISAKJ4T	Strong	Genetic Variation	[20]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[16]
Renal agenesis, unilateral	DIS53ZJ8	Strong	Genetic Variation	[14]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[21]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[22]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[19]
Turner syndrome	DIS2035C	Strong	Biomarker	[23]
Vesicoureteral reflux	DISUL6SA	Strong	Genetic Variation	[15]
X-linked adrenal hypoplasia congenita	DISNMXY8	Strong	Altered Expression	[18]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[24]
Anosmia	DISNRJVL	moderate	CausalMutation	[25]
Cryptorchidism	DISYUD2P	moderate	Genetic Variation	[26]
Hypogonadotropic hypogonadism 2 with or without anosmia	DISRVFVX	moderate	CausalMutation	[25]
Recessive X-linked ichthyosis	DISZY56W	moderate	Biomarker	[27]
Kallmann syndrome	DISO3HDG	Supportive	Autosomal dominant	[28]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[29]
Hypogonadotropic hypogonadism	DIS8JSKR	Limited	Biomarker	[30]
Kabuki syndrome	DISZN97H	Limited	Genetic Variation	[31]
Klinefelter syndrome	DISOUI7W	Limited	Biomarker	[30]
Septooptic dysplasia	DISXYR1H	Limited	Genetic Variation	[11]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Anosmin-1 (ANOS1).	[32]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Anosmin-1 (ANOS1).	[33]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Anosmin-1 (ANOS1).	[34]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Anosmin-1 (ANOS1).	[35]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Anosmin-1 (ANOS1).	[36]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Anosmin-1 (ANOS1).	[37]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Anosmin-1 (ANOS1).	[38]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Anosmin-1 (ANOS1).	[39]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Anosmin-1 (ANOS1).	[40]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Anosmin-1 (ANOS1).	[41]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Anosmin-1 (ANOS1).	[42]

References

• [1] The prevalence of intragenic deletions in patients with idiopathic hypogonadotropic hypogonadism and Kallmann syndrome.Mol Hum Reprod. 2008 Jun;14(6):367-70. doi: 10.1093/molehr/gan027. Epub 2008 May 7.
• [2] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [3] Renal dysgenesis and KAL1 gene defects in patients with sporadic Kallmann syndrome.Fertil Steril. 2007 Nov;88(5):1311-7. doi: 10.1016/j.fertnstert.2006.12.044. Epub 2007 Jul 2.
• [4] Anosmin-1 contributes to brain tumor malignancy through integrin signal pathways.Endocr Relat Cancer. 2013 Dec 20;21(1):85-99. doi: 10.1530/ERC-13-0181. Print 2014 Feb.
• [5] Keratinocyte-derived anosmin-1, an extracellular glycoprotein encoded by the X-linked Kallmann syndrome gene, is involved in modulation of epidermal nerve density in atopic dermatitis.J Dermatol Sci. 2010 Apr;58(1):64-71. doi: 10.1016/j.jdermsci.2010.02.010. Epub 2010 Feb 20.
• [6] Two human myeloma cell lines, amylase-producing KMS-12-PE and amylase-non-producing KMS-12-BM, were established from a patient, having the same chromosome marker, t(11;14)(q13;q32).Br J Haematol. 1989 Oct;73(2):199-204. doi: 10.1111/j.1365-2141.1989.tb00252.x.
• [7] Anosmin-1 involved in neuronal cell migration is hypoxia inducible and cancer regulated.Cell Cycle. 2009 Nov 15;8(22):3770-6. doi: 10.4161/cc.8.22.10066. Epub 2009 Nov 14.
• [8] Study on molecular mechanism of ANOS1 promoting development of colorectal cancer.PLoS One. 2017 Aug 30;12(8):e0182964. doi: 10.1371/journal.pone.0182964. eCollection 2017.
• [9] Translational implication of Kallmann syndrome-1 gene expression in hepatocellular carcinoma.Int J Oncol. 2015;46(6):2546-54. doi: 10.3892/ijo.2015.2965. Epub 2015 Apr 16.
• [10] Exogenous kisspeptin administration as a probe of GnRH neuronal function in patients with idiopathic hypogonadotropic hypogonadism.J Clin Endocrinol Metab. 2014 Dec;99(12):E2762-71. doi: 10.1210/jc.2014-2233.
• [11] Novel application of luciferase assay for the invitro functional assessment of KAL1 variants in three females with septo-optic dysplasia (SOD).Mol Cell Endocrinol. 2015 Dec 5;417:63-72. doi: 10.1016/j.mce.2015.09.010. Epub 2015 Sep 14.
• [12] Synergistic combination therapy with cotyleninA and vincristine in multiple myeloma models.Int J Oncol. 2015 Apr;46(4):1801-9. doi: 10.3892/ijo.2015.2882. Epub 2015 Feb 9.
• [13] Analysis of an interstitial deletion in a patient with Kallmann syndrome, X-linked ichthyosis and mental retardation.Clin Genet. 1998 Jul;54(1):45-51. doi: 10.1111/j.1399-0004.1998.tb03692.x.
• [14] Kallmann syndrome with FGFR1 and KAL1 mutations detected during fetal life.Orphanet J Rare Dis. 2015 Jun 9;10:71. doi: 10.1186/s13023-015-0287-9.
• [15] Familial Kallmann syndrome: a novel splice acceptor mutation in the KAL gene.Hum Mutat. 1998;11(4):340-2.
• [16] An IgG1 Version of the Anti-transferrin Receptor 1 Antibody ch128.1 Shows Significant Antitumor Activity Against Different Xenograft Models of Multiple Myeloma: A Brief Communication.J Immunother. 2020 Feb/Mar;43(2):48-52. doi: 10.1097/CJI.0000000000000304.
• [17] Expanding the genetic spectrum of ANOS1 mutations in patients with congenital hypogonadotropic hypogonadism.Hum Reprod. 2017 Mar 1;32(3):704-711. doi: 10.1093/humrep/dew354.
• [18] Hypogonadotropic hypogonadism.Semin Reprod Med. 2002 Nov;20(4):327-38. doi: 10.1055/s-2002-36707.
• [19] Decreased expression of Kallmann syndrome 1 sequence gene (KAL1) contributes to oral squamous cell carcinoma progression and significantly correlates with poorly differentiated grade.J Oral Pathol Med. 2015 Feb;44(2):109-14. doi: 10.1111/jop.12206. Epub 2014 Jul 24.
• [20] Genetic overlap in Kallmann syndrome, combined pituitary hormone deficiency, and septo-optic dysplasia. J Clin Endocrinol Metab. 2012 Apr;97(4):E694-9. doi: 10.1210/jc.2011-2938. Epub 2012 Feb 8.
• [21] Alteration in the retinoblastoma gene associated with immortalization of human fibroblasts treated with 60Co gamma rays.J Cancer Res Clin Oncol. 1993;119(9):522-6. doi: 10.1007/BF01686461.
• [22] Kallmann syndrome gene (KAL-X) is not mutated in schizophrenia.Am J Med Genet. 1999 Feb 5;88(1):34-7. doi: 10.1002/(sici)1096-8628(19990205)88:1<34::aid-ajmg6>3.0.co;2-6.
• [23] Polymorphic changes in the KAL1 gene: not all of them should be classified as polymorphisms.J Endocrinol Invest. 2004 Sep;27(8):765-9. doi: 10.1007/BF03347520.
• [24] Efficacy and Mechanism of Antitumor Activity of an Antibody Targeting Transferrin Receptor 1 in Mouse Models of Human Multiple Myeloma.J Immunol. 2018 May 15;200(10):3485-3494. doi: 10.4049/jimmunol.1700787. Epub 2018 Apr 13.
• [25] Prioritizing genetic testing in patients with Kallmann syndrome using clinical phenotypes.J Clin Endocrinol Metab. 2013 May;98(5):E943-53. doi: 10.1210/jc.2012-4116. Epub 2013 Mar 26.
• [26] Kallmann's syndrome: a comparison of the reproductive phenotypes in men carrying KAL1 and FGFR1/KAL2 mutations.J Clin Endocrinol Metab. 2008 Mar;93(3):758-63. doi: 10.1210/jc.2007-1168. Epub 2007 Dec 26.
• [27] Xp22.31 Microdeletion due to Microhomology-Mediated Break-Induced Replication in a Boy with Contiguous Gene Deletion Syndrome.Cytogenet Genome Res. 2017;151(1):1-4. doi: 10.1159/000458469. Epub 2017 Mar 3.
• [28] A fertile male patient with Kallmann syndrome and two missense mutations in the KAL1 gene. Fertil Steril. 2011 Apr;95(5):1789.e3-6. doi: 10.1016/j.fertnstert.2010.11.045. Epub 2010 Dec 18.
• [29] Serum levels of ANOS1 serve as a diagnostic biomarker of gastric cancer: a prospective multicenter observational study.Gastric Cancer. 2020 Mar;23(2):203-211. doi: 10.1007/s10120-019-00995-z. Epub 2019 Aug 3.
• [30] Anosmin-1 over-expression increases adult neurogenesis in the subventricular zone and neuroblast migration to the olfactory bulb.Brain Struct Funct. 2016 Jan;221(1):239-60. doi: 10.1007/s00429-014-0904-8. Epub 2014 Oct 10.
• [31] Cutis laxa in Kabuki make-up syndrome.J Am Acad Dermatol. 2005 Nov;53(5 Suppl 1):S247-51. doi: 10.1016/j.jaad.2005.02.007.
• [32] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [33] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [34] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [35] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [36] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [37] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [38] The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat Genet. 2009 Feb;41(2):178-186.
• [39] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [40] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [41] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [42] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.