Details of Disease

General Information of Disease (ID: DIS6ZFQQ)

• Disease Name: Von hippel-lindau disease
• Synonyms: Von Hippel-Lindau syndrome, Modifiers of; VHL syndrome; Von Hippel Lindau disease; VHL; von Hippel-Lindau disease; Von Hippel-Lindau syndrome; Hippel Lindau syndrome; Lindau disease; familial cerebelloretinal angiomatosis; von Hippel-Lindau syndrome, modifier of; von Hippel-Lindau syndrome; Von Hippel-Lindau syndrome (VHL); cerebroretinal angiomatosis
• Disease Class: 5A75: Adrenomedullary hyperfunction
• Definition: A familial cancer predisposition syndrome associated with a variety of malignant and benign neoplasms, most frequently retinal, cerebellar, and spinal hemangioblastoma, renal cell carcinoma (RCC), and pheochromocytoma.
• Disease Hierarchy:
  DISNC82H: Neurocutaneous syndrome
  DIS6ZFQQ: Von hippel-lindau disease
• ICD Code:
  ICD-11: ICD-11: 5A75
  ICD-10: ICD-10: E27.5
  ICD-9: ICD-9: 759.6
  Expand ICD-11: '5A75
  Expand ICD-10: 'E27.5
  Expand ICD-9: 759.6
• Disease Identifiers:
  MONDO ID: MONDO_0008667
  MESH ID: D006623
  UMLS CUI: C0019562
  OMIM ID: 193300
  MedGen ID: 42458
  Orphanet ID: 892
  SNOMED CT ID: 46659004

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 2 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Belzutifan	DML1KTO	Approved	NA	[1]
Bevacizumab	DMSD1UN	Approved	Monoclonal antibody	[2]

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

Drug Name	Drug ID	Highest Status	Drug Type	REF
PT2385	DMCSN69	Phase 2	NA	[3]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 40 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
VHL	OT2C3JRN	Definitive	Autosomal dominant	[4]
CHGA	OTXYX5JH	Limited	Biomarker	[21]
ATP1B1	OTTO6ZP4	Strong	Biomarker	[22]
ATP2B2	OT1NPZ9T	Strong	Genetic Variation	[23]
BRK1	OTTUB5KS	Strong	Biomarker	[24]
CBLL2	OTB4AD3V	Strong	Biomarker	[25]
CDC73	OT6JASZ1	Strong	Genetic Variation	[26]
DERL3	OTRZRT6Q	Strong	Genetic Variation	[16]
ELL	OTCBN5LF	Strong	Altered Expression	[27]
ELOA	OTOQTF5K	Strong	Altered Expression	[28]
ELOB	OTZ3X84T	Strong	Biomarker	[29]
ELOC	OT0XHHWP	Strong	Biomarker	[29]
FLCN	OTVM78XM	Strong	Genetic Variation	[30]
HILPDA	OTEID3ZM	Strong	Altered Expression	[31]
HYLS1	OT3SW5UC	Strong	Biomarker	[32]
JADE1	OTBPJIRI	Strong	Altered Expression	[33]
JMJD6	OTILR7E4	Strong	Altered Expression	[34]
KLRD1	OTMYLOV4	Strong	Altered Expression	[35]
LHX1	OT6WI2XS	Strong	Altered Expression	[36]
MAX	OTKZ0YKM	Strong	Genetic Variation	[37]
MUL1	OT2JC9YR	Strong	Biomarker	[38]
PIAS4	OTB7SVMZ	Strong	Biomarker	[39]
PRKN	OTJBN41W	Strong	Biomarker	[38]
RBMXL1	OTMGCWWB	Strong	Genetic Variation	[40]
RBMY1A1	OTM2F25H	Strong	Genetic Variation	[40]
RBX1	OTYA1UIO	Strong	Biomarker	[29]
RHEB	OTFLTSEC	Strong	Altered Expression	[18]
RWDD3	OTE76DY5	Strong	Altered Expression	[41]
SARDH	OTQ49Q27	Strong	Biomarker	[15]
SDHAF2	OT0UG9H5	Strong	Biomarker	[15]
SDHC	OTC8G2MX	Strong	Biomarker	[42]
SDS	OT5WTJ2M	Strong	Biomarker	[15]
SEC13	OTSR4WWM	Strong	Biomarker	[43]
SIX2	OTYOVGSC	Strong	Genetic Variation	[44]
SLC49A4	OTXL3KAM	Strong	Biomarker	[45]
TCP1	OT1MGUX9	Strong	Biomarker	[46]
TDRD9	OTS4UBI8	Strong	Biomarker	[32]
TMEM127	OTYHUXC1	Strong	Genetic Variation	[47]
MEN1	OTN6U6V0	Definitive	Biomarker	[48]
SESN2	OT889IXY	Definitive	Altered Expression	[31]

This Disease Is Related to 15 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
APEH	TTYWEDQ	Strong	Genetic Variation	[5]
CCND1	TTFCJ7S	Strong	Altered Expression	[6]
DDIT4	TTVEOY6	Strong	Altered Expression	[7]
EPAS1	TTWPA54	Strong	Genetic Variation	[8]
EPOR	TTAUX24	Strong	Biomarker	[9]
FECH	TTQ6VF4	Strong	Altered Expression	[10]
MAZ	TT059DA	Strong	Biomarker	[11]
PBRM1	TTH8ZRL	Strong	Genetic Variation	[12]
PYGM	TTZHY6R	Strong	Genetic Variation	[13]
RHBDF2	TTH1ZOP	Strong	Biomarker	[14]
SORD	TTLSRBZ	Strong	Biomarker	[15]
SYVN1	TT8XKYM	Strong	Genetic Variation	[16]
THRB	TTGER3L	Strong	Genetic Variation	[17]
SETD2	TTPC3H4	Definitive	Altered Expression	[18]
VHL	TTEMWSD	Definitive	Autosomal dominant	[4]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC18A1	DTM953D	Strong	Altered Expression	[19]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
EGLN3	DEMQTKH	Strong	Biomarker	[20]

References

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• [15] Isocitrate dehydrogenase mutations are rare in pheochromocytomas and paragangliomas.J Clin Endocrinol Metab. 2010 Mar;95(3):1274-8. doi: 10.1210/jc.2009-2170. Epub 2009 Nov 13.
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• [20] Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility.Endocr Relat Cancer. 2010 Dec 21;18(1):73-83. doi: 10.1677/ERC-10-0113. Print 2011 Feb.
• [21] Chromogranin a expression in phaeochromocytomas associated with von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2.Horm Metab Res. 2007 Dec;39(12):876-83. doi: 10.1055/s-2007-993135. Epub 2007 Nov 28.
• [22] Epigenetic silencing of Na,K-ATPase 1 subunit gene ATP1B1 by methylation in clear cell renal cell carcinoma.Epigenetics. 2014 Apr;9(4):579-86. doi: 10.4161/epi.27795. Epub 2014 Jan 22.
• [23] One-megabase yeast artificial chromosome and 400-kilobase cosmid-phage contigs containing the von Hippel-Lindau tumor suppressor and Ca(2+)-transporting adenosine triphosphatase isoform 2 genes.Cancer Res. 1994 May 1;54(9):2486-91.
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• [25] Cancer-causing mutations in a novel transcription-dependent nuclear export motif of VHL abrogate oxygen-dependent degradation of hypoxia-inducible factor.Mol Cell Biol. 2008 Jan;28(1):302-14. doi: 10.1128/MCB.01044-07. Epub 2007 Oct 29.
• [26] A complex endocrine conundrum.Fam Cancer. 2013 Sep;12(3):577-80. doi: 10.1007/s10689-012-9594-7.
• [27] An RNA polymerase II elongation factor encoded by the human ELL gene.Science. 1996 Mar 29;271(5257):1873-6. doi: 10.1126/science.271.5257.1873.
• [28] Expression of the von Hippel-Lindau-binding protein-1 (Vbp1) in fetal and adult mouse tissues.Hum Mol Genet. 1999 Feb;8(2):229-36. doi: 10.1093/hmg/8.2.229.
• [29] An integrated computational approach can classify VHL missense mutations according to risk of clear cell renal carcinoma.Hum Mol Genet. 2014 Nov 15;23(22):5976-88. doi: 10.1093/hmg/ddu321. Epub 2014 Jun 26.
• [30] Loss of the Birt-Hogg-Dub gene product folliculin induces longevity in a hypoxia-inducible factor-dependent manner.Aging Cell. 2013 Aug;12(4):593-603. doi: 10.1111/acel.12081. Epub 2013 May 15.
• [31] Expression of HIF-1 regulated proteins vascular endothelial growth factor, carbonic anhydrase IX and hypoxia inducible gene 2 in hemangioblastomas.Folia Neuropathol. 2014;52(3):234-42. doi: 10.5114/fn.2014.45564.
• [32] Clustering of features of von Hippel-Lindau syndrome: evidence for a complex genetic locus.Lancet. 1991 May 4;337(8749):1052-4. doi: 10.1016/0140-6736(91)91705-y.
• [33] von Hippel-Lindau partner Jade-1 is a transcriptional co-activator associated with histone acetyltransferase activity.J Biol Chem. 2004 Dec 31;279(53):56032-41. doi: 10.1074/jbc.M410487200. Epub 2004 Oct 22.
• [34] Jumonji Domain Containing Protein 6: A Novel Oxygen Sensor in the Human Placenta.Endocrinology. 2015 Aug;156(8):3012-25. doi: 10.1210/en.2015-1262. Epub 2015 Jun 2.
• [35] Natural killer (NK) cell lytic dysfunction and putative NK cell receptor expression abnormality in members of a family with chromosome 3p-linked von Hippel-Lindau disease.J Natl Cancer Inst. 1992 Dec 16;84(24):1897-903. doi: 10.1093/jnci/84.24.1897.
• [36] The Lim1 oncogene as a new therapeutic target for metastatic human renal cell carcinoma.Oncogene. 2019 Jan;38(1):60-72. doi: 10.1038/s41388-018-0413-y. Epub 2018 Aug 3.
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• [38] Role of the VHL (von Hippel-Lindau) gene in renal cancer: a multifunctional tumour suppressor.Biochem Soc Trans. 2008 Jun;36(Pt 3):472-8. doi: 10.1042/BST0360472.
• [39] Hypoxia inactivates the VHL tumor suppressor through PIASy-mediated SUMO modification.PLoS One. 2010 Mar 16;5(3):e9720. doi: 10.1371/journal.pone.0009720.
• [40] Blockade of the vascular endothelial growth factor-receptor 2 pathway inhibits the growth of human renal cell carcinoma, RBM1-IT4, in the kidney but not in the bone of nude mice.Int J Oncol. 2007 Apr;30(4):937-45.
• [41] RSUME inhibits VHL and regulates its tumor suppressor function.Oncogene. 2015 Sep 10;34(37):4855-66. doi: 10.1038/onc.2014.407. Epub 2014 Dec 15.
• [42] Biallelic inactivation of the SDHC gene in renal carcinoma associated with paraganglioma syndrome type 3.Endocr Relat Cancer. 2012 May 3;19(3):283-90. doi: 10.1530/ERC-11-0324. Print 2012 Jun.
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