Reviewed October 2006
What is the official name of the HFE2 gene?
The official name of this gene is “hemochromatosis type 2 (juvenile).”
HFE2 is the gene's official symbol. The HFE2 gene is also known by other names, listed below.
What is the normal function of the HFE2 gene?
The HFE2 gene provides instructions for making a protein called hemojuvelin. This protein is made in the liver, heart, and muscles used for movement (skeletal muscles). Researchers recently discovered that hemojuvelin plays a role in maintaining iron balance in the body. Although its exact function is unclear, hemojuvelin appears to regulate the levels of another protein called hepcidin. Hepcidin also plays a key role in maintaining proper iron levels in the body.
How are changes in the HFE2 gene related to health conditions?
- hereditary hemochromatosis - caused by mutations in the HFE2 gene
Researchers have identified more than 20 HFE2 gene mutations that cause type 2 hemochromatosis, a form of hereditary hemochromatosis that begins during childhood or adolescence. Most HFE2 gene mutations change one of the protein building blocks (amino acids) used to make hemojuvelin. Most frequently, the amino acid glycine is replaced by the amino acid valine at protein position 320 (written as Gly320Val). Other mutations create a premature stop signal in the instructions for making the hemojuvelin protein. As a result, an abnormally small protein is made.
Mutations in the HFE2 gene lead to an altered hemojuvelin protein that cannot function properly. Without adequate hemojuvelin, levels of the protein hepcidin are reduced and iron balance is disturbed. As a result, too much iron is absorbed during digestion, which leads to iron overload and damage to tissues and organs in the body.
Where is the HFE2 gene located?
Cytogenetic Location: 1q21.1
Molecular Location on chromosome 1: base pairs 146,017,468 to 146,021,822
(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/148738))
The HFE2 gene is located on the long (q) arm of chromosome 1 at position 21.1.
More precisely, the HFE2 gene is located from base pair 146,017,468 to base pair 146,021,822 on chromosome 1.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about HFE2?
You and your healthcare professional may find the following resources about HFE2 helpful.
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1170)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for HFE2 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=148738%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28%28HFE2%5BTIAB%5D%29%20OR%20%28hemochromatosis%20type%202%5BTIAB%5D%29%20OR%20%28hemochromatosis%20AND%201q%5BTIAB%5D%29%29%20OR%20%28%28hemojuvelin%5BTIAB%5D%29%20OR%20%28HFE2A%5BTIAB%5D%29%20OR%20%28HJV%5BTIAB%5D%29%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/608374)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_HFE2.html)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=4887)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/148738)
What other names do people use for the HFE2 gene or gene products?
- RGM domain family, member C
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding HFE2?
amino acid ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Babitt JL, Huang FW, Wrighting DM, Xia Y, Sidis Y, Samad TA, Campagna JA, Chung RT, Schneyer AL, Woolf CJ, Andrews NC, Lin HY. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet. 2006 May;38(5):531-9. Epub 2006 Apr 9. (http://www.ncbi.nlm.nih.gov/pubmed/16604073?dopt=Abstract)
- Beutler L, Beutler E. Hematologically important mutations: iron storage diseases. Blood Cells Mol Dis. 2004 Jul-Aug;33(1):40-4. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15223009?dopt=Abstract)
- Lanzara C, Roetto A, Daraio F, Rivard S, Ficarella R, Simard H, Cox TM, Cazzola M, Piperno A, Gimenez-Roqueplo AP, Grammatico P, Volinia S, Gasparini P, Camaschella C. Spectrum of hemojuvelin gene mutations in 1q-linked juvenile hemochromatosis. Blood. 2004 Jun 1;103(11):4317-21. Epub 2004 Feb 24. (http://www.ncbi.nlm.nih.gov/pubmed/14982873?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/148738)
- Papanikolaou G, Samuels ME, Ludwig EH, MacDonald ML, Franchini PL, Dubé MP, Andres L, MacFarlane J, Sakellaropoulos N, Politou M, Nemeth E, Thompson J, Risler JK, Zaborowska C, Babakaiff R, Radomski CC, Pape TD, Davidas O, Christakis J, Brissot P, Lockitch G, Ganz T, Hayden MR, Goldberg YP. Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis. Nat Genet. 2004 Jan;36(1):77-82. Epub 2003 Nov 30. (http://www.ncbi.nlm.nih.gov/pubmed/14647275?dopt=Abstract)
- Pissia M, Polonifi K, Politou M, Lilakos K, Sakellaropoulos N, Papanikolaou G. Prevalence of the G320V mutation of the HJV gene, associated with juvenile hemochromatosis, in Greece. Haematologica. 2004 Jun;89(6):742-3. (http://www.ncbi.nlm.nih.gov/pubmed/15194541?dopt=Abstract)
- Roetto A, Totaro A, Cazzola M, Cicilano M, Bosio S, D'Ascola G, Carella M, Zelante L, Kelly AL, Cox TM, Gasparini P, Camaschella C. Juvenile hemochromatosis locus maps to chromosome 1q. Am J Hum Genet. 1999 May;64(5):1388-93. (http://www.ncbi.nlm.nih.gov/pubmed/10205270?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.