Details of Disease

General Information of Disease (ID: DISI8ECS)

• Disease Name: Neurofibromatosis type 2
• Synonyms: acoustic Schwannomas, bilateral; neurofibromatosis, type 2; neurofibromatosis, type II; acoustic schwannomas bilateral; acoustic neurinoma bilateral; neurofibromatosis type II; neurofibromatosis, central type; acoustic neurinoma, bilateral; neurofibromatosis central type; acoustic neurofibromatosis; NF2; neurofibromatosis type 2; central neurofibromatosis; bilateral acoustic neurofibromatosis; neurofibromatosis 2
• Disease Class: LD2D: Phakomatoses/hamartoneoplastic syndrome
• Definition: A tumor-prone disorder characterized by the development of multiple schwannomas and meningiomas.
• Disease Hierarchy:
  DIS5N2R6: Neurofibromatosis
  DISI8ECS: Neurofibromatosis type 2
• ICD Code:
  ICD-11: ICD-11: LD2D.11
  Expand ICD-11: 'LD2D.11
• Disease Identifiers:
  MONDO ID: MONDO_0007039
  MESH ID: D016518
  UMLS CUI: C0027832
  OMIM ID: 101000
  MedGen ID: 18014
  Orphanet ID: 637
  SNOMED CT ID: 92503002

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
BXCL101	DMFJARS	Phase 1/2	NA	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 6 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
EZR	TTE47YC	Limited	Biomarker	[2]
LIMK2	TTASMD8	Limited	Altered Expression	[3]
PTPRJ	TTWMKXP	Limited	Biomarker	[4]
AMOT	TTI48OS	Strong	Biomarker	[5]
NF2	TTZIK7P	Definitive	Autosomal dominant	[6]
PAK1	TTFN95D	Definitive	Biomarker	[7]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC17A6	DT5LHCR	Limited	Biomarker	[8]

This Disease Is Related to 25 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
AJUBA	OTNW7YPK	Limited	Genetic Variation	[9]
BIN2	OT4S45WJ	Limited	Biomarker	[10]
CAPN5	OTQ8QM7K	Limited	Biomarker	[11]
CRYBB2	OTL0Z8E6	Limited	Biomarker	[12]
CRYBB3	OTTGTQIQ	Limited	Biomarker	[13]
DCAF1	OT3ZDVOE	Limited	Genetic Variation	[14]
EIF3C	OTR8RF9X	Limited	Biomarker	[15]
ELF4	OT167PR5	Limited	Biomarker	[16]
HARS1	OTHOEOTS	Limited	Biomarker	[17]
HGS	OTCYYCAC	Limited	Biomarker	[17]
IGLL5	OT9XQFL5	Limited	Genetic Variation	[18]
MN1	OTVQR4R9	Limited	Genetic Variation	[19]
MORC2	OT52A8BJ	Limited	Biomarker	[20]
RDX	OTNSYUN6	Limited	Biomarker	[21]
SAV1	OTSAEV92	Limited	Biomarker	[22]
SEMA3F	OTQFMS8S	Limited	Biomarker	[23]
SMARCE1	OTAX4ITH	Limited	Biomarker	[24]
SRSF5	OTC5WP98	Limited	Biomarker	[17]
TEAD2	OTM8YMYT	Limited	Altered Expression	[25]
ETV5	OTE2OBM4	Strong	Biomarker	[26]
MSN	OTZJ4J6G	Strong	Biomarker	[21]
TCHP	OTVDMHSY	Strong	Altered Expression	[27]
EPB41L3	OTS6CHG2	Definitive	Biomarker	[28]
NEFH	OTMSCW5I	Definitive	Biomarker	[29]
NF2	OT6E5ACG	Definitive	Autosomal dominant	[6]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Merlin/ERM proteins regulate growth factor-induced macropinocytosis and receptor recycling by organizing the plasma membrane:cytoskeleton interface.Genes Dev. 2018 Sep 1;32(17-18):1201-1214. doi: 10.1101/gad.317354.118. Epub 2018 Aug 24.
• [3] LIM domain kinases as potential therapeutic targets for neurofibromatosis type 2.Oncogene. 2014 Jul 3;33(27):3571-82. doi: 10.1038/onc.2013.320. Epub 2013 Aug 12.
• [4] Loss of PTPRJ/DEP-1 enhances NF2/Merlin-dependent meningioma development.J Neurol Sci. 2020 Jan 15;408:116553. doi: 10.1016/j.jns.2019.116553. Epub 2019 Nov 9.
• [5] Angiomotin regulates prostate cancer cell proliferation by signaling through the Hippo-YAP pathway.Oncotarget. 2017 Feb 7;8(6):10145-10160. doi: 10.18632/oncotarget.14358.
• [6] 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.
• [7] A high-throughput kinome screen reveals serum/glucocorticoid-regulated kinase 1 as a therapeutic target for NF2-deficient meningiomas.Oncotarget. 2015 Jul 10;6(19):16981-97. doi: 10.18632/oncotarget.4858.
• [8] Merlin modulates process outgrowth and synaptogenesis in the cerebellum.Brain Struct Funct. 2019 Jul;224(6):2121-2142. doi: 10.1007/s00429-019-01897-7. Epub 2019 Jun 4.
• [9] LIM-domain protein AJUBA suppresses malignant mesothelioma cell proliferation via Hippo signaling cascade.Oncogene. 2015 Jan 2;34(1):73-83. doi: 10.1038/onc.2013.528. Epub 2013 Dec 16.
• [10] Analysis of YAP1 and TAZ expression by immunohistochemical staining in malignant mesothelioma and reactive mesothelial cells.Oncol Lett. 2018 May;15(5):6825-6830. doi: 10.3892/ol.2018.8225. Epub 2018 Mar 9.
• [11] First insight into the somatic mutation burden of neurofibromatosis type 2-associated grade I and grade II meningiomas: a case report comprehensive genomic study of two cranial meningiomas with vastly different clinical presentation.BMC Cancer. 2017 Feb 13;17(1):127. doi: 10.1186/s12885-017-3127-6.
• [12] Neurofibromatosis type 2 appears to be a genetically homogeneous disease.Am J Hum Genet. 1992 Sep;51(3):486-96.
• [13] Direct assignment of the human beta B2 and beta B3 crystallin genes to 22q11.2----q12: markers for neurofibromatosis 2.Cytogenet Cell Genet. 1991;56(3-4):171-5. doi: 10.1159/000133080.
• [14] Combined Inhibition of NEDD8-Activating Enzyme and mTOR Suppresses NF2 Loss-Driven Tumorigenesis.Mol Cancer Ther. 2017 Aug;16(8):1693-1704. doi: 10.1158/1535-7163.MCT-16-0821. Epub 2017 May 3.
• [15] Schwannomin inhibits tumorigenesis through direct interaction with the eukaryotic initiation factor subunit c (eIF3c).Hum Mol Genet. 2006 Apr 1;15(7):1059-70. doi: 10.1093/hmg/ddl021. Epub 2006 Feb 23.
• [16] Loss of NF2 Induces TGF Receptor 1-mediated Noncanonical and Oncogenic TGF Signaling: Implication of the Therapeutic Effect of TGF Receptor 1 Inhibitor on NF2 Syndrome.Mol Cancer Ther. 2018 Nov;17(11):2271-2284. doi: 10.1158/1535-7163.MCT-17-1210. Epub 2018 Aug 22.
• [17] Neurofibromatosis 2 (NF2) tumor suppressor schwannomin and its interacting protein HRS regulate STAT signaling.Hum Mol Genet. 2002 Dec 1;11(25):3179-89. doi: 10.1093/hmg/11.25.3179.
• [18] Neurofibromatosis 2: clinical and DNA linkage studies of a large kindred.N Engl J Med. 1988 Aug 4;319(5):278-83. doi: 10.1056/NEJM198808043190505.
• [19] Exome sequencing on malignant meningiomas identified mutations in neurofibromatosis type 2 (NF2) and meningioma 1 (MN1) genes.Discov Med. 2014 Dec;18(101):301-311.
• [20] Epigenetic restriction of Hippo signaling by MORC2 underlies stemness of hepatocellular carcinoma cells.Cell Death Differ. 2018 Dec;25(12):2086-2100. doi: 10.1038/s41418-018-0095-6. Epub 2018 Mar 19.
• [21] VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation.Oncogene. 2008 Jul 3;27(29):4056-64. doi: 10.1038/onc.2008.44. Epub 2008 Mar 10.
• [22] Hippo pathway gene mutations in malignant mesothelioma: revealed by RNA and targeted exon sequencing.J Thorac Oncol. 2015 May;10(5):844-851. doi: 10.1097/JTO.0000000000000493.
• [23] Merlin/NF2 regulates angiogenesis in schwannomas through a Rac1/semaphorin 3F-dependent mechanism.Neoplasia. 2012 Feb;14(2):84-94. doi: 10.1593/neo.111600.
• [24] Targeted next-generation sequencing for differential diagnosis of neurofibromatosis type 2, schwannomatosis, and meningiomatosis.Neuro Oncol. 2018 Jun 18;20(7):917-929. doi: 10.1093/neuonc/noy009.
• [25] Neurofibromatosis 2 (NF2) controls the invasiveness of glioblastoma through YAP-dependent expression of CYR61/CCN1 and miR-296-3p.Biochim Biophys Acta. 2016 Apr;1859(4):599-611. doi: 10.1016/j.bbagrm.2016.02.010. Epub 2016 Feb 24.
• [26] Childhood neurofibromatosis type 2 (NF2) and related disorders: from bench to bedside and biologically targeted therapies.Acta Otorhinolaryngol Ital. 2016 Oct;36(5):345-367. doi: 10.14639/0392-100X-1093.
• [27] Neurofibromatosis type 2 tumor suppressor protein is expressed in oligodendrocytes and regulates cell proliferation and process formation.PLoS One. 2018 May 1;13(5):e0196726. doi: 10.1371/journal.pone.0196726. eCollection 2018.
• [28] Pathological classification and molecular genetics of meningiomas.J Neurooncol. 2010 Sep;99(3):379-91. doi: 10.1007/s11060-010-0342-2. Epub 2010 Sep 1.
• [29] Presymptomatic DNA and MRI diagnosis of neurofibromatosis 2 with mild clinical course in an extended pedigree.Neurology. 1995 Jul;45(7):1314-22. doi: 10.1212/wnl.45.7.1314.