Gene description
The HLA-DQA1 gene encodes a protein that plays an important role in the immune system. It helps the immune system distinguish the body’s own proteins from proteins made by foreign invaders such as viruses and bacteria (Ref).
Mutations of this gene can cause many different autoimmune disorders, diabetes, celiac disease, narcolepsy, and arthritis (Ref).
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. idiopathic inflammatory myopathy Genetics Home Reference provides information about idiopathic inflammatory myopathy. juvenile idiopathic arthritis Genetics Home Reference provides information about juvenile idiopathic arthritis. narcolepsy Genetics Home Reference provides information about narcolepsy. type 1 diabetes 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, autoimmune disorders 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. other disorders Normal variations in the HLA-DQA1 gene can affect the body’s ability to recognize and react to foreign invaders (pathogens).
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.
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).
Gene function
Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues.
The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases.
Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components.
Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer.
Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide).
The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO.
Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading.
Disease association
- Breast Cancer
- Schizophrenia
- Obesity
- Leukemia
- Lung Cancer
- Myocardial Infarction
- Colorectal Cancer
- Hepatitis
- Prostate Cancer
- Prostatitis
- Adenocarcinoma
- Thyroiditis
- Artery Disease
- Gastric Cancer
- Asthma
- Coronary Artery Disease
- Lupus Erythematosus
- Osteoarthritis
- Systemic Lupus Erythematosus
- Bipolar Disorder
- Open-Angle Glaucoma
- Crohn’s Disease
- Esophagitis
- Graves’ Disease
- Hepatitis C
- Alcohol Dependence
- Melanoma
- Myeloid Leukemia
- Tuberculosis
- Acute Leukemia
- Arthritis
- Lymphoblastic Leukemia
- Polycystic Ovary Syndrome
- Allergic Rhinitis
- Cleft Lip
- Familial Breast Cancer
- Leprosy
- Malaria
- Ovarian Cancer
- Psoriasis
- Rhinitis
- Atherosclerosis
- Bipolar I Disorder
- Cerebritis
- Infertility
- Kawasaki Disease
- Myelodysplastic Syndrome
- Myeloma
- Myopia
- Osteoporosis
- Rheumatoid Arthritis
- Acute Non Lymphoblastic Leukemia
- Atrial Fibrillation
- Autoimmune Thyroiditis
- Cervicitis
- Child Syndrome
- Congenital Heart Disease
- Down Syndrome
- Dyslexia
- Endotheliitis
- Follicular Lymphoma
- Hepatitis C Virus
- Hepatocellular Carcinoma
- Hyperlipidemia Type 3
- Kid Syndrome
- Lymphatic System Disease
- Male Infertility
- Neuronitis
- Oral Cancer
- Periodontitis
- Adult Lymphoma
- Alzheimer Disease
- Azoospermia
- Blood Protein Disease
- Bone Marrow Cancer
- Brain Injury
- Burkitt Lymphoma
- Cardiomyopathy
- Celiac Disease
- Chromosomal Disease
- Chronic Fatigue Syndrome
- Chronic Lymphocytic Leukemia
- Chronic Monocytic Leukemia
- Cystic Fibrosis
- Endometriosis
- Essential Tremor
- Hemochromatosis
- Hepatitis B
- Hiv-1
- Hypersensitivity Reaction Type Iv Disease
- Intellectual Disability
- Leber Congenital Amaurosis
- Leukemia, Acute Myeloid
- Lymphatic Neoplasm
- Lymphatic System Cancer
- Lymphosarcoma
- Measles
- Multiple Myeloma
- Myasthenia Gravis
- Myelofibrosis
- Nasopharyngitis
- Oligospermia
- Pancreatitis
- Primary Malignant Lymphoma
- Respiratory System Disease
- Retinitis
- Thrombocytopenia
- Tremor
- Acute Lymphoblastic Leukemia, Childhood
- Acute Lymphocytic Leukemia
- Adenomyosis
- Adult Acute Lymphocytic Leukemia
- Aggressive Periodontitis
- Anxiety Disorder
- Aplastic Anemia
- Attention Deficit-Hyperactivity Disorder
- Autism Spectrum Disorder
- Bardet-Biedl Syndrome
- Biliary Cirrhosis, Primary, 1
- Bone Cancer
- Cataract
- Chordoma
- Chromosomal Triplication
- Colitis
- Congenital Nervous System Abnormality
- Congenital Toxoplasmosis
- Digeorge Syndrome
- Dysphagia
- Eclampsia
- Edwards Syndrome
- Encephalopathy
- Exanthem
- Eye Disease
- Food Allergy
- Gallbladder Cancer
- Gastroenteritis
- Gastrointestinal System Disease
- Generalized Anxiety Disorder
- Globe Disease
- Huntington Disease
- Hypertrophic Pyloric Stenosis
- Intestinal Disease
- Leiomyoma
- Leukemia, Acute Lymphoblastic
- Lipid Metabolism Disorder
- Long Qt Syndrome
- Lymphoblastic Lymphoma
- Lymphoid Leukemia
- Malignant Pleural Mesothelioma
- Marchiafava Bignami Disease
- Mastitis
- Mesothelioma
- Montefiore Syndrome
- Mosaic Trisomy 13
- Mouth Disease
- Neuroblastoma
- Nutritional Deficiency Disease
- Pain Disorder
- Pancreatic Ductal Adenocarcinoma
- Paranoid Schizophrenia
- Patau Syndrome
- Peripheral Artery Disease
- Placenta Disease
- Prader-Willi Syndrome
- Pre-Eclampsia
- Precursor Lymphoblastic Lymphoma/leukemia
- Prion Disease
- Pulmonary Fibrosis
- Pyloric Stenosis
- Retinal Disease
- Retinitis Pigmentosa
- Retinoblastoma
- Root Resorption
- Rubella
- Sarcoma
- Smith-Magenis Syndrome
- Spasticity
- Spiradenoma
- Thalassemia
- Toxoplasmosis
- Turner Syndrome
- Ulcerative Colitis
- Vascular Disease
- 1p36 Deletion Syndrome
- 1q21.1 Microdeletion
- 22q11.2 Duplication
- Acute Myocardial Infarction
- Adolescent Idiopathic Scoliosis
- Adrenal Gland Disease
- Adrenoleukodystrophy
- Adult Heart Tumor
- Adult Syndrome
- Alcohol Abuse
- Alopecia
- Alopecia Areata
- Aneurysm
- Angelman Syndrome
- Anorexia Nervosa
- Apraxia
- Arteriovenous Malformation
- Astrocytoma
- Atopic Dermatitis
- Atrial Fibrillation, Familial, 1
- Atrial Fibrillation, Familial, 11
- Atrial Fibrillation, Familial, 2
- Atrial Fibrillation, Familial, 3
- Atrial Fibrillation, Familial, 5
- Autosomal Recessive Disease
- B-Cell Lymphomas
- Background Diabetic Retinopathy
- Beckwith-Wiedemann Syndrome
- Behcet’s Disease
- Benign Metastasizing Leiomyoma
- Bilateral Breast Cancer
- Bone Fracture
- Bone Lymphoma
- Bone Mineral Density, Low
- Bone Remodeling Disease
- Bone Structure Disease
- Borderline Personality Disorder
- Breast Disease
- Bronchial Disease
- Bronchial Neoplasm
- Bronchopulmonary Dysplasia
- Bronchus Carcinoma
- Burns
- C Syndrome
- Canavan Disease
- Cannabis Dependence
- Capillary Leak Syndrome
- Carotid Stenosis
- Cayler Cardiofacial Syndrome
- Central Nervous System Cancer
- Central Nervous System Disease
- Cerebral Hemorrhage
- Cerebral Hypoxia
- Cerebral Palsy
- Charcot-Marie-Tooth Disease
- Charge Syndrome
- Childhood Absence Epilepsy
- Childhood Leukemia
- Chromosome 1p Deletion
- Chromosome 1p Duplication
- Chromosome 1p36 Deletion Syndrome
- Chromosome 22q Deletion
- Chromosome 22q Duplication
- Chronic Intestinal Failure
- Clubfoot
- Coloboma
- Colonic Disease
- Composite Lymphoma
- Conduct Disorder
- Connective Tissue Disease
- Conversion Disorder
- Core Binding Factor Acute Myeloid Leukemia
- Cork-Handlers’ Disease
- Coronary Heart Disease 5
- Coronary Heart Disease 8
- Craniosynostosis
- Creutzfeldt-Jakob Disease
- Cri-Du-Chat Syndrome
- Cytogenetically Normal Acute Myeloid Leukemia
- Deficiency Anemia
- Degenerative Myopia
- Dementia
- Dengue Shock Syndrome
- Dental Caries
- Dermatitis
- Desmin-Related Myopathy with Mallory Body-Like Inclusions
- Diabetes Insipidus
- Diabetic Angiopathy
- Diabetic Macular Edema
- Diffuse Large B-Cell Lymphoma
- Drug Addiction
- Dwarfism
- Eating Disorder
- Endometrial Cancer
- Epidermolysis Bullosa
- Esophagus Lymphoma
- Ewing Sarcoma
- Eye Carcinoma
- Eye Degenerative Disease
- Factor V Leiden Thrombophilia
- Familial Atrial Fibrillation
- Familial Long Qt Syndrome
- Familial/multiple Cancer
- Farber Lipogranulomatosis
- Fatty Liver Disease
- Febrile Seizures
- Female Breast Carcinoma
- Female Reproductive Organ Cancer
- Female Reproductive System Disease
- Focal Segmental Glomerulosclerosis
- Functional Colonic Disease
- Gallbladder Disease
- Gastrointestinal Lymphoma
- Gastroparesis
- Gingivitis
- Glioblastoma
- Glomerulonephritis
- Glomerulosclerosis
- Glucocorticoid Therapy, Response to
- Glucose Metabolism Disease
- Glycerol Kinase Deficiency
- Gonadal Disease
- Gonadal Dysgenesis
- Gout
- Gray Platelet Syndrome
- Growth Hormone Deficiency
- Head Injury
- Heart Cancer
- Heart Tumor
- Heart Valve Disease
- Hellp Syndrome
- Hemangiopericytoma
- Hematopoietic Stem Cell Transplantation
- Hereditary Colorectal Cancer
- Hereditary Mixed Polyposis Syndrome
- Hereditary Vascular Retinopathy
- Heroin Dependence
- Hidradenitis
- Hidradenitis Suppurativa
- Histiocytosis
- Hodgkin Lymphoma
- Hodgkin’s Granuloma
- Hodgkin’s Paragranuloma
- Hyperinsulinism
- Hyperparathyroidism
- Hypertension, Essential
- Hypertrichosis
- Hypertriglyceridemia
- Hypertrophic Cardiomyopathy
- Hyperuricemia
- Hypoparathyroidism
- Hypothyroidism
- Hypotonia
- Hypotrichosis
- Hypoxia
- Idiopathic Generalized Epilepsy
- Idiopathic Scoliosis
- Impaired Renal Function Disease
- Influenza
- Inner Ear Disease
- Iron Deficiency Anemia
- Irritable Bowel Syndrome
- Ischemic Heart Disease
- Jacobsen Syndrome
- Kashin-Beck Disease
- Keloids
- Keratomalacia
- Kidney Disease
- Large Intestine Cancer
- Laryngitis
- Lateral Sclerosis
- Learning Disability
- Lepromatous Leprosy
- Leukemia, Acute Lymphoblastic 2
- Leukemia, Acute Lymphoblastic 3
- Leukocyte Disease
- Leukoplakia
- Li-Fraumeni Syndrome
- Limb-Girdle Muscular Dystrophy
- Liver Disease
- Lyme Disease
- Lymph Node Cancer
- Lymph Node Disease
- Lymphoma, Non-Hodgkin
- Lynch Syndrome
- Machado-Joseph Disease
- Macroglobulinemia
- Macular Degeneration, Age-Related, 1
- Macular Degeneration, Age-Related, 10
- Macular Degeneration, Age-Related, 2
- Macular Dystrophy, Dominant Cystoid
- Macular Dystrophy, Retinal, 2
- Macular Retinal Edema
- Malignant Histiocytosis
- Membranous Glomerulonephritis
- Metabolic Syndrome X
- Microcephaly
- Microphthalmia
- Microvascular Complications of Diabetes 5
- Mineral Metabolism Disease
- Monosomy 21
- Monosomy 22
- Mood Disorder
- Morbid Obesity
- Mosaic Monosomy 18
- Mosaic Monosomy 22
- Mosaic Monosomy X
- Mosaic Trisomy 1
- Mosaic Trisomy 14
- Mosaic Trisomy 22
- Motor Neuron Disease
- Movement Disease
- Mumps
- Muscular Dystrophy
- Mycobacterium Abscessus
- Myopathy
- Myotonic Dystrophy
- N Syndrome
- Narcolepsy
- Narcolepsy 1
- Nasopharyngeal Carcinoma
- Neonatal Diabetes Mellitus
- Neonatal Respiratory Failure
- Nervous System Cancer
- Neural Tube Defects
- Neuroendocrine Tumor
- Neurologic Diseases
- Neutropenia
- Neutropenia, Severe Congenital, 5, Autosomal Recessive
- Newcastle Disease
- Night Blindness
- Noonan Syndrome 1
- Obsessive-Compulsive Disorder
- Opioid Abuse
- Oral Cavity Cancer
- Oral Squamous Cell Carcinoma
- Ornithine Transcarbamylase Deficiency
- Osteonecrosis
- Osteoporotic Fracture
- Otosclerosis
- Ovarian Cyst
- Ovarian Disease
- Overnutrition
- Pallister-Killian Syndrome
- Pancreatic Cancer
- Panic Disorder
- Papilloma
- Parathyroid Gland Disease
- Perinatal Necrotizing Enterocolitis
- Periodic Fever, Familial
- Personality Disorder
- Plasma Cell Neoplasm
- Plasmodium Falciparum Malaria
- Polycystic Ovary Syndrome 1
- Precocious Puberty
- Premature Ovarian Failure
- Primary Angle-Closure Glaucoma
- Primary Bone Lymphoma
- Primary Hyperoxaluria
- Primary Hyperparathyroidism
- Psoriatic Arthritis
- Psychotic Disorder
- Pulmonary Alveolar Microlithiasis
- Pulmonary Tuberculosis
- Pulmonary Valve Insufficiency
- Radiation Induced Cancer
- Recessive Dystrophic Epidermolysis Bullosa
- Refractive Error
- Renal Artery Disease
- Renal Hypertension
- Renovascular Hypertension
- Reproductive System Disease
- Respiratory Failure
- Retinal Degeneration
- Retinal Vascular Disease
- Rett Syndrome
- Rhabdomyosarcoma
- Ring Chromosome 18
- Salla Disease
- Schistosomiasis
- Schizophrenia 10
- Scoliosis
- Secondary Syphilis
- Seizure Disorder
- Sexual Disorder
- Skin Benign Neoplasm
- Sleep Disorder
- Smallpox
- Spastic Cerebral Palsy
- Spastic Diplegia
- Spastic Paraparesis
- Spondylitis
- Spondylosis
- Sporadic Breast Cancer
- Stomatitis
- Stroke, Ischemic
- Substance Abuse
- Substance Dependence
- Sudden Infant Death with Dysgenesis of the Testes Syndrome
- Swallowing Disorders
- Systemic Capillary Leak Syndrome
- Testicular Germ Cell Tumor
- Tetrasomy 12p
- Thoracic Cancer
- Thrombophilia
- Tooth Disease
- Transitional Cell Carcinoma
- Trichohepatoenteric Syndrome 1
- Trisomy 11 Mosaicism
- Trisomy 22
- Tropical Spastic Paraparesis
- Tumor Necrosis Factor Receptor 1 Associated Periodic Syndrome
- Uniparental Disomy of Chromosome 2
- Vascular Cancer
- Vascular Hemostatic Disease
- Vasculitis
- Velocardiofacial Syndrome
- Waldenstrom Macroglobulinemia
- Walker-Warburg Syndrome
- Wisconsin Syndrome
- Yellow Fever
Advanced information
The following transcription factors affect gene expression (R):
- c-Myc
- STAT1
- STAT1alpha
- STAT1beta
- c-Rel
Gene Pathways:
- Immune System
- Systemic lupus erythematosus
- Antigen processing and presentation
- Type I diabetes mellitus
- Intestinal immune network for IgA production
- Autoimmune thyroid disease
- Asthma
- Phagosome
- Graft-versus-host disease
- Viral myocarditis
- Cell adhesion molecules (CAMs)
- Rheumatoid arthritis
- Tuberculosis
- Leishmaniasis
- Staphylococcus aureus infection
- Toxoplasmosis
- Allograft rejection
Molecular Function:
- Mhc Class Ii Receptor Activity
- Peptide Antigen Binding
Biological Processes:
- Antigen Processing And Presentation Of Exogenous Peptide Antigen Via Mhc Class Ii
- Immune Response
- Interferon-Gamma-Mediated Signaling Pathway
- T Cell Costimulation
- T Cell Receptor Signaling Pathway
Synonyms/Aliases/Alternative Names of the Gene:
CELIAC1| DC-1 alpha chain| DC-alpha| DQ-A1| HLA class II histocompatibility antigen, DQ alpha 1 chain| HLA-DCA| HLA-DQA| major histocompatibility complex, class II, DQ alpha 1-like| Mamu-DQA| MHC class II antigen| MHC class II DQA1| MHC class II HLA-DQ-alpha-1| MHC HLA-DQ alpha| hla-dqa1| hypothetical protein