Reviewed July 2010
What is the official name of the HLA-B gene?
The official name of this gene is “major histocompatibility complex, class I, B.”
HLA-B is the gene's official symbol. The HLA-B gene is also known by other names, listed below.
What is the normal function of the HLA-B gene?
The HLA-B gene provides instructions for making a protein that plays a critical role in the immune system. HLA-B is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders such as viruses and bacteria.
HLA is the human version of the major histocompatibility complex (MHC), a gene family that occurs in many species. Genes in this complex are categorized into three basic groups: class I, class II, and class III. In humans, the HLA-B gene and two related genes, HLA-A and HLA-C, are the main genes in MHC class I.
MHC class I genes provide instructions for making proteins that are present on the surface of almost all cells. On the cell surface, these proteins are bound to protein fragments (peptides) that have been exported from within the cell. MHC class I proteins display these peptides to the immune system. If the immune system recognizes the peptides as foreign (such as viral or bacterial peptides), it responds by triggering the infected cell to self-destruct.
The HLA-B gene has many possible variations, allowing each person's immune system to react to a wide range of foreign invaders. Hundreds of versions (alleles) of the HLA-B gene are known, each of which is given a particular number (such as HLA-B27). Closely related alleles are categorized together; for example, more than 60 very similar alleles are subtypes of HLA-B27. These subtypes are designated as HLA-B*2701 to HLA-B*2763.
Does the HLA-B gene share characteristics with other genes?
The HLA-B gene belongs to a family of genes called HLA (histocompatibility complex genes). It also belongs to a family of genes called immunoglobulin superfamily, C1-set domain containing (immunoglobulin superfamily, C1-set domain containing).
A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.
How are changes in the HLA-B gene related to health conditions?
- ankylosing spondylitis - increased risk from variations of the HLA-B gene
A version of the HLA-B gene called HLA-B27 increases the risk of developing ankylosing spondylitis. It is uncertain how HLA-B27 causes this increased risk. Researchers speculate that HLA-B27 may abnormally display peptides that trigger an immune reaction, resulting in the inflammatory process that causes arthritis. Other research suggests that the joint inflammation characteristic of this disorder may result from improper folding of the HLA-B27 protein or the presence of abnormal forms of the protein on the cell surface. Although many people with ankylosing spondylitis have the HLA-B27 variation, most people with this version of the HLA-B gene never develop the disorder. Additional genetic and environmental factors, many of which are unknown, affect the chances of developing ankylosing spondylitis and influence its progression.
- Behçet disease - increased risk from variations of the HLA-B gene
Another version of the HLA-B gene, HLA-B51, is associated with an increased risk of developing Behçet disease, a chronic inflammatory condition that affects many parts of the body. This association is strongest in people from Japan, the Middle East, and other parts of Asia. Researchers do not know how HLA-B51 increases the risk of this disorder. Although many people with Behçet disease have the HLA-B51 variation, most people with this version of the HLA-B gene never develop the condition. It appears likely that other factors, such as viral or bacterial infections and changes in other genes, also influence the development of this complex disorder.
- other disorders - associated with the HLA-B gene
The HLA-B27 variant is associated with a group of inflammatory joint diseases related to ankylosing spondylitis. These conditions are known as spondyloarthropathies. Some of these disorders are associated with a common skin condition called psoriasis or with chronic disorders that cause inflammation of the intestinal walls (inflammatory bowel disease). One of the spondyloarthropathies, reactive arthritis, is typically triggered by bacterial infections of the gastrointestinal or genital tract. Following an infection, affected individuals may develop arthritis, back pain, and eye inflammation. Like ankylosing spondylitis, many factors probably contribute to the development of reactive arthritis and other spondyloarthropathies.
Other variations of the HLA-B gene are associated with adverse reactions to certain drugs. For example, two specific versions of this gene are related to increased drug sensitivity among the Han Chinese population and possibly other Asian populations. Individuals who have the variation HLA-B*1502 are more likely to experience a severe skin disorder called Stevens-Johnson syndrome in response to carbamazepine (a drug used to treat seizures). Another version, HLA-B*5801, is associated with an increased risk of severe skin reactions in people treated with allopurinol (a drug used to treat gout, which is a form of arthritis caused by a buildup of uric acid in the joints).
Among people with human immunodeficiency virus (HIV) infection, a version of the HLA-B gene designated HLA-B*5701 increases the risk of an adverse reaction to the drug abacavir. This medication slows the spread of the HIV-1 virus in the body. People with abacavir hypersensitivity often develop a fever, chills, rash, upset stomach, and other symptoms when treated with this drug.
Several variations of the HLA-B gene appear to play a role in the progression of HIV infection to acquired immunodeficiency syndrome (AIDS). AIDS is a disease that damages the immune system, preventing it from effectively defending the body against infections. The signs and symptoms of AIDS may not appear until 10 or more years after infection with HIV. Studies suggest that people with HIV infection who have HLA-B27 or HLA-B57 tend to progress more slowly than usual to AIDS. On the other hand, researchers believe that HIV-positive individuals who have HLA-B35 tend to develop the signs and symptoms of AIDS more quickly than usual. Other factors also influence the progression of HIV infection to AIDS.
Another version of the HLA-B gene, HLA-B53, has been shown to help protect against severe malaria. HLA-B53 is most common in West African populations, where malaria is a frequent cause of death in children. Researchers suggest that this version of the HLA-B gene may help the immune system respond more effectively to the parasite that causes malaria.
Where is the HLA-B gene located?
Cytogenetic Location: 6p21.3
Molecular Location on chromosome 6: base pairs 31,353,871 to 31,357,211
The HLA-B gene is located on the short (p) arm of chromosome 6 at position 21.3.
More precisely, the HLA-B gene is located from base pair 31,353,871 to base pair 31,357,211 on chromosome 6.
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 HLA-B?
You and your healthcare professional may find the following resources about HLA-B helpful.
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=%28HLA-B*%5BTI%5D%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%20360%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog
- HUMAN IMMUNODEFICIENCY VIRUS TYPE 1, SUSCEPTIBILITY TO (http://omim.org/entry/609423)
- MAJOR HISTOCOMPATIBILITY COMPLEX, CLASS I, B (http://omim.org/entry/142830)
- SEVERE CUTANEOUS ADVERSE REACTION, SUSCEPTIBILITY TO TOXIC EPIDERMAL NECROLYSIS, SUSCEPTIBILITY TO, INCLUDED (http://omim.org/entry/608579)
Research Resources - Tools for researchers
- Anthony Nolan Research Institute: Nomenclature for Factors of the HLA System (http://hla.alleles.org/nomenclature/nomenclature_2009.html)
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_HLA-B.html)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=3106)
- HGNC Gene Family: Histocompatibility complex (http://www.genenames.org/genefamilies/HLA)
- HGNC Gene Family: Immunoglobulin superfamily / C1-set domain containing (http://www.genenames.org/genefamilies/C1SET)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=4932)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/3106)
What other names do people use for the HLA-B gene or gene products?
- HLA class I histocompatibility antigen, B alpha chain
- leukocyte antigen B
- MHC class I HLA-B heavy chain
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 HLA-B?
acquired immunodeficiency syndrome ;
immune system ;
joint inflammation ;
uric acid ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Brown MA, Crane AM, Wordsworth BP. Genetic aspects of susceptibility, severity, and clinical expression in ankylosing spondylitis. Curr Opin Rheumatol. 2002 Jul;14(4):354-60. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12118167?dopt=Abstract)
- Carrington M, O'Brien SJ. The influence of HLA genotype on AIDS. Annu Rev Med. 2003;54:535-51. Epub 2001 Dec 3. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12525683?dopt=Abstract)
- Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC, Wu JY, Chen YT. Medical genetics: a marker for Stevens-Johnson syndrome. Nature. 2004 Apr 1;428(6982):486. (http://www.ncbi.nlm.nih.gov/pubmed/15057820?dopt=Abstract)
- Colbert RA. The immunobiology of HLA-B27: variations on a theme. Curr Mol Med. 2004 Feb;4(1):21-30. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15011956?dopt=Abstract)
- Colmegna I, Cuchacovich R, Espinoza LR. HLA-B27-associated reactive arthritis: pathogenetic and clinical considerations. Clin Microbiol Rev. 2004 Apr;17(2):348-69. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15084505?dopt=Abstract)
- de Menthon M, Lavalley MP, Maldini C, Guillevin L, Mahr A. HLA-B51/B5 and the risk of Behçet's disease: a systematic review and meta-analysis of case-control genetic association studies. Arthritis Rheum. 2009 Oct 15;61(10):1287-96. doi: 10.1002/art.24642. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19790126?dopt=Abstract)
- Ferrell PB Jr, McLeod HL. Carbamazepine, HLA-B*1502 and risk of Stevens-Johnson syndrome and toxic epidermal necrolysis: US FDA recommendations. Pharmacogenomics. 2008 Oct;9(10):1543-6. doi: 10.2217/146224184.108.40.2063. (http://www.ncbi.nlm.nih.gov/pubmed/18855540?dopt=Abstract)
- Gao X, Nelson GW, Karacki P, Martin MP, Phair J, Kaslow R, Goedert JJ, Buchbinder S, Hoots K, Vlahov D, O'Brien SJ, Carrington M. Effect of a single amino acid change in MHC class I molecules on the rate of progression to AIDS. N Engl J Med. 2001 May 31;344(22):1668-75. (http://www.ncbi.nlm.nih.gov/pubmed/11386265?dopt=Abstract)
- Gaudieri S, DeSantis D, McKinnon E, Moore C, Nolan D, Witt CS, Mallal SA, Christiansen FT. Killer immunoglobulin-like receptors and HLA act both independently and synergistically to modify HIV disease progression. Genes Immun. 2005 Dec;6(8):683-90. (http://www.ncbi.nlm.nih.gov/pubmed/16121209?dopt=Abstract)
- Hetherington S, Hughes AR, Mosteller M, Shortino D, Baker KL, Spreen W, Lai E, Davies K, Handley A, Dow DJ, Fling ME, Stocum M, Bowman C, Thurmond LM, Roses AD. Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. Lancet. 2002 Mar 30;359(9312):1121-2. (http://www.ncbi.nlm.nih.gov/pubmed/11943262?dopt=Abstract)
- Hill AV, Allsopp CE, Kwiatkowski D, Anstey NM, Twumasi P, Rowe PA, Bennett S, Brewster D, McMichael AJ, Greenwood BM. Common west African HLA antigens are associated with protection from severe malaria. Nature. 1991 Aug 15;352(6336):595-600. (http://www.ncbi.nlm.nih.gov/pubmed/1865923?dopt=Abstract)
- Hughes CA, Foisy MM, Dewhurst N, Higgins N, Robinson L, Kelly DV, Lechelt KE. Abacavir hypersensitivity reaction: an update. Ann Pharmacother. 2008 Mar;42(3):387-96. doi: 10.1345/aph.1K522. Epub 2008 Feb 26. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18303141?dopt=Abstract)
- Hung SI, Chung WH, Jee SH, Chen WC, Chang YT, Lee WR, Hu SL, Wu MT, Chen GS, Wong TW, Hsiao PF, Chen WH, Shih HY, Fang WH, Wei CY, Lou YH, Huang YL, Lin JJ, Chen YT. Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions. Pharmacogenet Genomics. 2006 Apr;16(4):297-306. (http://www.ncbi.nlm.nih.gov/pubmed/16538176?dopt=Abstract)
- Hung SI, Chung WH, Liou LB, Chu CC, Lin M, Huang HP, Lin YL, Lan JL, Yang LC, Hong HS, Chen MJ, Lai PC, Wu MS, Chu CY, Wang KH, Chen CH, Fann CS, Wu JY, Chen YT. HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):4134-9. Epub 2005 Mar 2. Erratum in: Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):6237. (http://www.ncbi.nlm.nih.gov/pubmed/15743917?dopt=Abstract)
- Inman RD. Mechanisms of disease: infection and spondyloarthritis. Nat Clin Pract Rheumatol. 2006 Mar;2(3):163-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16932676?dopt=Abstract)
- Khan MA, Mathieu A, Sorrentino R, Akkoc N. The pathogenetic role of HLA-B27 and its subtypes. Autoimmun Rev. 2007 Jan;6(3):183-9. Epub 2006 Dec 8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17289555?dopt=Abstract)
- Khan MA. HLA-B27 and its pathogenic role. J Clin Rheumatol. 2008 Feb;14(1):50-2. doi: 10.1097/RHU.0b013e3181637a38. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18431102?dopt=Abstract)
- Kim TH, Uhm WS, Inman RD. Pathogenesis of ankylosing spondylitis and reactive arthritis. Curr Opin Rheumatol. 2005 Jul;17(4):400-5. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15956835?dopt=Abstract)
- Letvin NL, Walker BD. Immunopathogenesis and immunotherapy in AIDS virus infections. Nat Med. 2003 Jul;9(7):861-6. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12835706?dopt=Abstract)
- Martin AM, Nolan D, Gaudieri S, Almeida CA, Nolan R, James I, Carvalho F, Phillips E, Christiansen FT, Purcell AW, McCluskey J, Mallal S. Predisposition to abacavir hypersensitivity conferred by HLA-B*5701 and a haplotypic Hsp70-Hom variant. Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4180-5. Epub 2004 Mar 15. (http://www.ncbi.nlm.nih.gov/pubmed/15024131?dopt=Abstract)
- Meguro A, Inoko H, Ota M, Katsuyama Y, Oka A, Okada E, Yamakawa R, Yuasa T, Fujioka T, Ohno S, Bahram S, Mizuki N. Genetics of Behçet disease inside and outside the MHC. Ann Rheum Dis. 2010 Apr;69(4):747-54. doi: 10.1136/ard.2009.108571. Epub 2009 Aug 13. (http://www.ncbi.nlm.nih.gov/pubmed/19684014?dopt=Abstract)
- Migueles SA, Sabbaghian MS, Shupert WL, Bettinotti MP, Marincola FM, Martino L, Hallahan CW, Selig SM, Schwartz D, Sullivan J, Connors M. HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors. Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2709-14. (http://www.ncbi.nlm.nih.gov/pubmed/10694578?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/3106)
- Smith JA, Märker-Hermann E, Colbert RA. Pathogenesis of ankylosing spondylitis: current concepts. Best Pract Res Clin Rheumatol. 2006 Jun;20(3):571-91. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16777583?dopt=Abstract)
- Young K, Frodsham A, Doumbo OK, Gupta S, Dolo A, Hu JT, Robson KJ, Crisanti A, Hill AV, Gilbert SC. Inverse associations of human leukocyte antigen and malaria parasite types in two West African populations. Infect Immun. 2005 Feb;73(2):953-5. (http://www.ncbi.nlm.nih.gov/pubmed/15664937?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.