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The official name of this gene is “major histocompatibility complex, class II, DQ alpha 1.”
HLA-DQA1 is the gene's official symbol. The HLA-DQA1 gene is also known by other names, listed below.
The HLA-DQA1 gene provides instructions for making a protein that plays a critical role in the immune system. The HLA-DQA1 gene 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.
The HLA complex is the human version of the major histocompatibility complex (MHC), a gene family that occurs in many species. The HLA-DQA1 gene belongs to a group of MHC genes called MHC class II. MHC class II genes provide instructions for making proteins that are present on the surface of certain immune system cells. These proteins attach to protein fragments (peptides) outside the cell. MHC class II proteins display these peptides to the immune system. If the immune system recognizes the peptides as foreign (such as viral or bacterial peptides), it triggers a response to attack the invading viruses or bacteria.
The protein produced from the HLA-DQA1 gene attaches (binds) to the protein produced from another MHC class II gene, HLA-DQB1. Together, they form a functional protein complex called an antigen-binding DQαβ heterodimer. This complex displays foreign peptides to the immune system to trigger the body's immune response.
Each MHC class II gene has many possible variations, allowing the immune system to react to a wide range of foreign invaders. Researchers have identified hundreds of different versions (alleles) of the HLA-DQA1 gene, each of which is given a particular number (such as HLA-DQA1*05:01).
The HLA-DQA1 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.
Certain normal variations of the HLA-DQA1 gene have been associated with increased risk of autoimmune disorders, which occur when the immune system malfunctions and attacks the body's own tissues and organs. It is unclear how different versions of the HLA-DQA1 gene influence the risk of developing autoimmune disorders. These conditions are thought to result from a combination of multiple environmental and genetic factors. Changes in other HLA and non-HLA genes, some of which remain unknown, also likely contribute to the risk of developing these complex conditions.
At least two specific combinations of HLA gene variants (HLA haplotypes) have been found to increase the risk of developing celiac disease, a disorder in which inflammation damages the intestinal tract and other organs and tissues. One of these haplotypes, known as DQ2, is composed of the protein produced from HLA-DQA1 gene variants known as HLA-DQA1*05:01 or HLA-DQA1*05:05 bound to the protein produced from HLA-DQB1 gene variants known as HLA-DQB1*02:01 or HLA-DQB1*02:02. The other haplotype, known as DQ8, is composed of the protein produced from HLA-DQA1 gene variants known as HLA-DQA1*03:01 or HLA-DQA1*03:02 bound to the protein produced from the HLA-DQB1 gene variant known as HLA-DQB1*03:02.
The DQ2 and DQ8 haplotypes, which may occur separately or together, seem to increase the risk of an inappropriate immune response to the protein gluten, which is found in wheat, rye, and barley. This immune system malfunction results in the damage to the body's organs and tissues that occurs in celiac disease. However, the DQ2 and DQ8 haplotypes are also found in 30 percent of the general population, and only 3 percent of individuals with these haplotypes develop celiac disease.
Combinations of variations in the HLA-DQA1 gene and other HLA genes affect the risk of type 1 diabetes. Type 1 diabetes is characterized by high blood sugar levels resulting from a shortage of the hormone insulin and is caused by autoimmune damage to insulin-producing cells in the pancreas.
Type 1 diabetes risk is most increased by two HLA haplotypes involving variations of the HLA-DQA1 and HLA-DQB1 genes and another HLA gene called HLA-DRB1. One haplotype, written as DRB1*03:01-DQA1*05:01-DQB1*02, is called DR3. The other haplotype, written as DRB1*04:01/02/04/05/08-DQA1*03:01-DQB1*02, is called DR4. People at highest risk of developing type 1 diabetes have one copy of the DR3 haplotype and one copy of the DR4 haplotype in each cell. Other HLA haplotypes only mildly increase the risk of type 1 diabetes, while some haplotypes seem to protect against developing this condition. Variations in other genes and environmental factors are also thought to affect the risk of this complex disorder.
Normal variations in the HLA-DQA1 gene can affect the body's ability to recognize and react to foreign invaders (pathogens). For example, variations of this gene have been shown to increase or decrease a person's chance of getting infections such as hepatitis B and leprosy or may affect the severity of illness if infection occurs.
A particular variant of the HLA-DQA1 gene known as HLA-DQA1*02:01 increases the risk of liver damage in women with advanced breast cancer treated with a drug called lapatinib. Researchers suggest that the variant may increase immune system sensitivity to the drug, resulting in inflammation that damages the liver.
Cytogenetic Location: 6p21.3
Molecular Location on chromosome 6: base pairs 32,637,391 to 32,654,684
The HLA-DQA1 gene is located on the short (p) arm of chromosome 6 at position 21.3.
More precisely, the HLA-DQA1 gene is located from base pair 32,637,391 to base pair 32,654,684 on chromosome 6.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
You and your healthcare professional may find the following resources about HLA-DQA1 helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
arthritis ; autoimmune ; bacteria ; cancer ; cell ; class ; diabetes ; gene ; haplotype ; hepatitis ; HLA ; hormone ; idiopathic ; immune response ; immune system ; infection ; inflammation ; insulin ; juvenile ; leukocyte ; MHC ; pancreas ; population ; protein ; sensitivity
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).
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 healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.