Details of Disease

General Information of Disease (ID: DISDCGAG)

• Disease Name: Hemangioma
• Synonyms: benign angioma; angioma; hemangioma; hemangioma, benign; benign hemangioma
• Disease Class: 2E81-2F2Y: Hemangioma
• Definition: A benign vascular lesion characterized by the formation of capillary-sized or cavernous vascular channels.
• Disease Hierarchy:
  DISVQL8F: Benign blood vessel neoplasm
  DISYCU8Q: Benign epithelial neoplasm
  DISDCGAG: Hemangioma
• ICD Code: ICD-11: ICD-11: 2E81-2F2Y
• Disease Identifiers:
  MONDO ID: MONDO_0006500
  MESH ID: D006391
  UMLS CUI: C0018916
  MedGen ID: 5477
  HPO ID: HP:0001028
  SNOMED CT ID: 253053003

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
Propranolol	DM79NTF	Approved	Small molecular drug	[1]
Sodium Tetradecyl Sulfate	DM4QFXJ	Approved	Small molecular drug	[2]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 17 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
DUSP5	TTZN92A	Strong	Biomarker	[3]
FLT4	TTDCBX5	Strong	Biomarker	[4]
GLI2	TT045OH	Strong	Altered Expression	[5]
GNA11	TTSRXJW	Strong	Genetic Variation	[6]
GNAQ	TTL1SRG	Strong	Genetic Variation	[7]
HSD17B2	TT0PT1R	Strong	Genetic Variation	[8]
ID1	TTBXVDE	Strong	Biomarker	[9]
IDH1	TTV2A1R	Strong	Biomarker	[10]
KAT6A	TT6O1J0	Strong	CausalMutation	[11]
LYVE1	TTG8DNU	Strong	Biomarker	[12]
MAG	TT9XFON	Strong	Biomarker	[13]
PNPLA6	TTWAQU2	Strong	Biomarker	[7]
PORCN	TTNFBTO	Strong	Biomarker	[14]
PTK2B	TTTEFBV	Strong	Altered Expression	[15]
TEK	TT9VGXW	Strong	Biomarker	[16]
VHL	TTEMWSD	Strong	Genetic Variation	[17]
YAP1	TT8UN2D	Strong	Biomarker	[18]

This Disease Is Related to 17 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
IDH2	OTTQA4PB	Limited	Genetic Variation	[19]
SOX18	OTPUMHWA	Limited	Genetic Variation	[20]
C1GALT1C1	OTRTZUF5	Strong	Altered Expression	[21]
CIZ1	OT3UKHPI	Strong	Biomarker	[22]
CNTNAP1	OT5Y03EU	Strong	Genetic Variation	[23]
EMCN	OTS03CZC	Strong	Altered Expression	[24]
FKBP11	OTY2GC67	Strong	Altered Expression	[25]
GNA14	OTYZ1ZI0	Strong	Genetic Variation	[6]
HOMER1	OTWFD3SI	Strong	Biomarker	[26]
NDC80	OTS7D306	Strong	Biomarker	[16]
PAPLN	OTCJD85N	Strong	Biomarker	[14]
PIGF	OTJKE6VW	Strong	Biomarker	[27]
RNF213	OT4OVE9O	Strong	Genetic Variation	[28]
TBRG1	OTMV5L8H	Strong	Biomarker	[29]
THSD1	OTKPGFHS	Strong	Genetic Variation	[30]
TPD52	OTPKSK43	Strong	Altered Expression	[31]
PNPLA2	OTR3ERMR	Definitive	Biomarker	[32]

References

• [1] Propranolol FDA Label
• [2] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 040541.
• [3] Serendipitous discovery of light-induced (In Situ) formation of an Azo-bridged dimeric sulfonated naphthol as a potent PTP1B inhibitor.BMC Biochem. 2017 May 31;18(1):10. doi: 10.1186/s12858-017-0083-3.
• [4] Neuropilin-2 and vascular endothelial growth factor receptor-3 are up-regulated in human vascular malformations.Angiogenesis. 2013 Jan;16(1):137-46. doi: 10.1007/s10456-012-9305-x. Epub 2012 Sep 9.
• [5] Transcriptional activation of Hedgehog pathway components in aggressive haemangioma.Exp Dermatol. 2017 Oct;26(10):934-939. doi: 10.1111/exd.13346. Epub 2017 Aug 15.
• [6] High frequency of GNA14, GNAQ, and GNA11 mutations in cherry hemangioma: a histopathological and molecular study of 85 cases indicating GNA14 as the most commonly mutated gene in vascular neoplasms.Mod Pathol. 2019 Nov;32(11):1657-1665. doi: 10.1038/s41379-019-0284-y. Epub 2019 Jun 12.
• [7] GNAQ Mutations in Diffuse and Solitary Choroidal Hemangiomas.Ophthalmology. 2019 May;126(5):759-763. doi: 10.1016/j.ophtha.2018.12.011. Epub 2018 Dec 8.
• [8] Evidence by molecular profiling for a placental origin of infantile hemangioma.Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):19097-102. doi: 10.1073/pnas.0509579102. Epub 2005 Dec 19.
• [9] Knockdown of inhibitor of differentiation 1 suppresses proliferation and induces apoptosis by inactivating PI3K/Akt/mTOR signaling in hemangioma-derived endothelial cells.Biomed Pharmacother. 2019 Mar;111:236-243. doi: 10.1016/j.biopha.2018.12.072. Epub 2018 Dec 22.
• [10] Widespread and debilitating hemangiomas in a patient with enchondromatosis and D-2-hydroxyglutaric aciduria.Skeletal Radiol. 2018 Nov;47(11):1577-1582. doi: 10.1007/s00256-018-2963-z. Epub 2018 May 10.
• [11] Dominant mutations in KAT6A cause intellectual disability with recognizable syndromic features.Am J Hum Genet. 2015 Mar 5;96(3):507-13. doi: 10.1016/j.ajhg.2015.01.016. Epub 2015 Feb 26.
• [12] Infantile hemangioma is a proliferation of LYVE-1-negative blood endothelial cells without lymphatic competence.Mod Pathol. 2006 Feb;19(2):291-8. doi: 10.1038/modpathol.3800537.
• [13] Infantile Hemangioma with Minimal or Arrested Growth: Further Observations on Clinical and Histopathologic Findings of this Unique but Underrecognized Entity.Pediatr Dermatol. 2017 Jan;34(1):64-71. doi: 10.1111/pde.13022. Epub 2016 Nov 22.
• [14] PLGA nanoparticles with CD133 aptamers for targeted delivery and sustained release of propranolol to hemangioma.Nanomedicine (Lond). 2017 Nov;12(21):2611-2624. doi: 10.2217/nnm-2017-0130. Epub 2017 Sep 29.
• [15] Propranolol inhibits proliferation and induces apoptosis of hemangioma-derived endothelial cells via Akt pathway by down-regulating Ang-2 expression. Chem Biol Interact. 2020 Jan 25;316:108925. doi: 10.1016/j.cbi.2019.108925. Epub 2019 Dec 12.
• [16] Disruption and inactivation of the PP2A complex promotes the proliferation and angiogenesis of hemangioma endothelial cells through activating AKT and ERK.Oncotarget. 2015 Sep 22;6(28):25660-76. doi: 10.18632/oncotarget.4705.
• [17] Unique association of non-functioning pheochromocytoma, ganglioneuroma, adrenal cortical adenoma, hepatic and vertebral hemangiomas in a patient with a new intronic variant in the VHL gene.J Endocrinol Invest. 2005 Dec;28(11):1032-7. doi: 10.1007/BF03345345.
• [18] Mono (2-ethylhexyl) phthalate (MEHP) triggers the proliferation of hemangioma-derived endothelial cells via YAP signals.Chem Biol Interact. 2019 Sep 25;311:108773. doi: 10.1016/j.cbi.2019.108773. Epub 2019 Jul 24.
• [19] Constitutional abnormalities of IDH1 combined with secondary mutations predispose a patient with Maffucci syndrome to acute lymphoblastic leukemia.Pediatr Blood Cancer. 2017 Dec;64(12). doi: 10.1002/pbc.26647. Epub 2017 May 24.
• [20] R-propranolol is a small molecule inhibitor of the SOX18 transcription factor in a rare vascular syndrome and hemangioma.Elife. 2019 Jul 30;8:e43026. doi: 10.7554/eLife.43026.
• [21] COSMC is overexpressed in proliferating infantile hemangioma and enhances endothelial cell growth via VEGFR2.PLoS One. 2013;8(2):e56211. doi: 10.1371/journal.pone.0056211. Epub 2013 Feb 12.
• [22] CIZ1 Expression Is Upregulated in Hemangioma of the Tongue.Pathol Oncol Res. 2019 Oct;25(4):1653-1658. doi: 10.1007/s12253-018-0495-4. Epub 2018 Nov 19.
• [23] Novel mutation in CNTNAP1 results in congenital hypomyelinating neuropathy.Muscle Nerve. 2017 May;55(5):761-765. doi: 10.1002/mus.25416. Epub 2017 Feb 3.
• [24] Expression of endomucin, a novel endothelial sialomucin, in normal and diseased human skin.J Invest Dermatol. 2002 Dec;119(6):1388-93. doi: 10.1046/j.1523-1747.2002.19647.x.
• [25] Identification of FKBP11 as a biomarker for hepatocellular carcinoma.Anticancer Res. 2013 Jun;33(6):2763-9.
• [26] Potential role of Homer-2a on cutaneous vascular anomaly.J Korean Med Sci. 2002 Oct;17(5):636-40. doi: 10.3346/jkms.2002.17.5.636.
• [27] Serum cytokine profiles are altered in patients with progressive infantile hemangioma.Biosci Trends. 2018 Sep 19;12(4):438-441. doi: 10.5582/bst.2018.01118. Epub 2018 Aug 26.
• [28] RNF213 variants in a child with PHACE syndrome and moyamoya vasculopathy.Am J Med Genet A. 2017 Sep;173(9):2557-2561. doi: 10.1002/ajmg.a.38258. Epub 2017 Jul 7.
• [29] NIAM-deficient mice are predisposed to the development of proliferative lesions including B-cell lymphomas.PLoS One. 2014 Nov 13;9(11):e112126. doi: 10.1371/journal.pone.0112126. eCollection 2014.
• [30] A recessive truncating variant in thrombospondin-1 domain containing protein 1 gene THSD1 is the underlying cause of nonimmune hydrops fetalis, congenital cardiac defects, and haemangiomas in four patients from a consanguineous family.Am J Med Genet A. 2018 Sep;176(9):1996-2003. doi: 10.1002/ajmg.a.40424. Epub 2018 Jul 28.
• [31] Long non-coding RNA 00152 slicing represses the growth and aggressiveness of hemangioma cell by modulating miR-139-5p.Biomed Pharmacother. 2019 Dec;120:109385. doi: 10.1016/j.biopha.2019.109385. Epub 2019 Sep 19.
• [32] Pigment epithelium-derived factor/vascular endothelial growth factor ratio plays a crucial role in the spontaneous regression of infant hemangioma and in the therapeutic effect of propranolol.Cancer Sci. 2018 Jun;109(6):1981-1994. doi: 10.1111/cas.13611. Epub 2018 May 23.