Details of Disease

General Information of Disease (ID: DISAPY0H)

• Disease Name: Hemochromatosis
• Synonyms: symptomatic form of classic hemochromatosis; symptomatic form of HFE-related hereditary hemochromatosis; HFE-related hemochromatosis; symptomatic form of hemochromatosis type 1; HFE-associated hereditary hemochromatosis; hemochromatosis; classic hemochromatosis; hemochromatosis type 1; hfe hemochromatosis, modifier of; HFE1; C282Y/C282Y hemochromatosis; hemochromatosis, type 1
• Disease Class: 5C64: Mineral absorption/transport disorder
• Definition: Hemochromatosis type 1 (classic) is the most common form of hereditary hemochromatosis (HH), a group of diseases characterized by excessive tissue iron deposition. Due to its incidence (1/200-1/1000), it is not considered as a rare disease, unlike the other subforms of the disease
• Disease Hierarchy:
  DISVG5MT: Hereditary hemochromatosis
  DISAPY0H: Hemochromatosis
• ICD Code:
  ICD-11: ICD-11: 5C64.1Y
  Expand ICD-11: '5C64.1Y
• Disease Identifiers:
  MONDO ID: MONDO_0021001
  UMLS CUI: C3469186
  OMIM ID: 235200
  MedGen ID: 854011
  Orphanet ID: 139498
  SNOMED CT ID: 1186847009

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 3 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
LJPC-401	DMVM13R	Phase 2	Peptide	[1]
PTG-300	DMOYS8A	Phase 2	Peptide	[2]
Hepcidin	DM7H7NR	Phase 1	NA	[3]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 7 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
BMP2	TTP3IGX	Strong	Biomarker	[4]
PCSK7	TTD30LY	Strong	Genetic Variation	[5]
SLC40A1	TT6Y1PG	Strong	Genetic Variation	[6]
SLC46A1	TTY8Z2E	Strong	Genetic Variation	[7]
SUCNR1	TT4FX9Y	Strong	Biomarker	[8]
TF	TT8WXAV	Strong	Genetic Variation	[9]
TMPRSS6	TTL9KE7	Strong	Genetic Variation	[10]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
BCO1	DE6BOK3	Strong	Genetic Variation	[11]

This Disease Is Related to 16 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CP	OTM8JE4Y	Limited	Biomarker	[12]
CYBRD1	OTUTVBES	Limited	Genetic Variation	[13]
BTBD9	OTWQ6GA3	Strong	Genetic Variation	[10]
EAF2	OTSOET5L	Strong	Genetic Variation	[14]
FTL	OTYQA8A6	Strong	Genetic Variation	[15]
GAB3	OTKX1KEC	Strong	Genetic Variation	[14]
HEPH	OTZ2F15Z	Strong	Altered Expression	[16]
HLA-F	OT76CM19	Strong	Genetic Variation	[17]
MCIDAS	OTK1JVAH	Strong	Genetic Variation	[18]
NMBR	OTBJEGPN	Strong	Genetic Variation	[19]
NUP42	OTADT64E	Strong	Biomarker	[20]
PPP1R11	OTSHYPPW	Strong	Biomarker	[21]
TFR2	OTMYCCEO	Strong	Genetic Variation	[22]
TNMD	OTHLVA9G	Strong	Biomarker	[23]
TRIM31	OT7VW6RP	Strong	Biomarker	[20]
HFE	OTDD93KB	Definitive	Autosomal recessive	[24]

References

• [1] ClinicalTrials.gov (NCT03395704) A Study of LJPC-401 for the Treatment of Iron Overload in Adult Patients With Hereditary Hemochromatosis. U.S. National Institutes of Health.
• [2] ClinicalTrials.gov (NCT04202965) PTG-300 in Subjects With Hereditary Hemochromatosis. U.S. National Institutes of Health.
• [3] A first-in-human phase 1 study of a hepcidin monoclonal antibody, LY2787106, in cancer-associated anemia. J Hematol Oncol. 2017 Mar 21;10(1):73.
• [4] Endothelial Bone Morphogenetic Protein 2 (Bmp2) Knockout Exacerbates Hemochromatosis in Homeostatic Iron Regulator (Hfe) Knockout Mice but not Bmp6 Knockout Mice.Hepatology. 2020 Aug;72(2):642-655. doi: 10.1002/hep.31048. Epub 2020 May 22.
• [5] Proprotein convertase 7 rs236918 associated with liver fibrosis in Italian patients with HFE-related hemochromatosis.J Gastroenterol Hepatol. 2016 Jul;31(7):1342-8. doi: 10.1111/jgh.13315.
• [6] Molecular model of the ferroportin intracellular gate and implications for the human iron transport cycle and hemochromatosis type 4A.FASEB J. 2019 Dec;33(12):14625-14635. doi: 10.1096/fj.201901857R. Epub 2019 Nov 5.
• [7] Heme carrier protein 1 (HCP1) genetic variants in the Hemochromatosis and Iron Overload Screening (HEIRS) Study participants.Blood Cells Mol Dis. 2009 Mar-Apr;42(2):150-4. doi: 10.1016/j.bcmd.2008.11.003. Epub 2009 Jan 26.
• [8] Increased Retinal Expression of the Pro-Angiogenic Receptor GPR91 via BMP6 in a Mouse Model of Juvenile Hemochromatosis.Invest Ophthalmol Vis Sci. 2016 Apr;57(4):1612-9. doi: 10.1167/iovs.15-17437.
• [9] Genome-wide association study identifies TF as a significant modifier gene of iron metabolism in HFE hemochromatosis.J Hepatol. 2015 Mar;62(3):664-72. doi: 10.1016/j.jhep.2014.10.017. Epub 2014 Oct 18.
• [10] Genetic factors influencing hemoglobin levels in 15,567 blood donors: results from the Danish Blood Donor Study.Transfusion. 2019 Jan;59(1):226-231. doi: 10.1111/trf.15075. Epub 2018 Dec 7.
• [11] Genetic variants influencing biomarkers of nutrition are not associated with cognitive capability in middle-aged and older adults.J Nutr. 2013 May;143(5):606-12. doi: 10.3945/jn.112.171520. Epub 2013 Mar 6.
• [12] Brain iron dysregulation and the risk of ageing white matter lesions.Neuromolecular Med. 2011 Dec;13(4):289-99. doi: 10.1007/s12017-011-8161-y. Epub 2011 Oct 7.
• [13] Analysis of polymorphism and hepatic expression of duodenal cytochrome b in chronic hepatitis C.J Gastroenterol Hepatol. 2017 Feb;32(2):482-486. doi: 10.1111/jgh.13495.
• [14] Genome-wide association study of iron traits and relation to diabetes in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL): potential genomic intersection of iron and glucose regulation?.Hum Mol Genet. 2017 May 15;26(10):1966-1978. doi: 10.1093/hmg/ddx082.
• [15] Raised serum ferritin concentration in hereditary hyperferritinemia cataract syndrome is not a marker for iron overload.Hepatology. 2014 Mar;59(3):1204-6. doi: 10.1002/hep.26681. Epub 2014 Jan 27.
• [16] Duodenal cytochrome b and hephaestin expression in patients with iron deficiency and hemochromatosis.Gastroenterology. 2003 Sep;125(3):746-54. doi: 10.1016/s0016-5085(03)01063-1.
• [17] 46,XX, inv(6)(p21.1p23) in a pedigree with hereditary haemochromatosis.J Med Genet. 1997 Jan;34(1):24-7. doi: 10.1136/jmg.34.1.24.
• [18] Evaluation of HFE (hemochromatosis) mutations as genetic modifiers in sporadic AD and MCI.Neurobiol Aging. 2004 Apr;25(4):465-74. doi: 10.1016/j.neurobiolaging.2003.06.008.
• [19] Impact of natural neuromedin-B receptor variants on iron metabolism.Am J Hematol. 2020 Feb;95(2):167-177. doi: 10.1002/ajh.25679. Epub 2019 Dec 16.
• [20] Localization of seven new genes around the HLA-A locus.Hum Mol Genet. 1993 Jan;2(1):55-60. doi: 10.1093/hmg/2.1.55.
• [21] Cloning of a human homologue of the mouse Tctex-5 gene within the MHC class I region.Immunogenetics. 1996;44(5):331-9. doi: 10.1007/BF02602777.
• [22] Identification of novel mutations in HFE, HFE2, TfR2, and SLC40A1 genes in Chinese patients affected by hereditary hemochromatosis.Int J Hematol. 2017 Apr;105(4):521-525. doi: 10.1007/s12185-016-2150-8. Epub 2016 Nov 28.
• [23] Hereditary hemochromatosis of a young girl: detection of early iron deposition in liver cell lysosomes using transmission electron microscopy and electron energy loss spectroscopy.Ultrastruct Pathol. 2002 Jan-Feb;26(1):23-6. doi: 10.1080/01913120252934297.
• [24] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.