HLA-DQB1

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Major histocompatibility complex, class II, DQ beta 1
1UVQ.png
Structure of HLA-DQB1 (green) complexed with HLA-DQA1 (cyan) and HCRT (magenta) based on PDB 1uvq.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols HLA-DQB1 ; CELIAC1; HLA-DQB; IDDM1
External IDs OMIM604305 HomoloGene1603 GeneCards: HLA-DQB1 Gene
RNA expression pattern
PBB GE HLA-DQB1 209823 x at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 3119 14961
Ensembl ENSG00000179344 ENSMUSG00000073421
UniProt P01920 P14483
RefSeq (mRNA) NM_001243961 NM_207105
RefSeq (protein) NP_001230890 NP_996988
Location (UCSC) Chr 6:
32.63 – 32.64 Mb
Chr 17:
34.26 – 34.27 Mb
PubMed search [1] [2]

Major histocompatibility complex, class II, DQ beta 1, also known as HLA-DQB1, is a human gene and also denotes the genetic locus that contains this gene.[1] The protein encoded by this gene is one of two proteins that are required to form the DQ heterodimer, a cell surface receptor essential to the function of the immune system.

Function[edit]

HLA-DQB1 belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen-presenting cells (APC: B lymphocytes, dendritic cells, macrophages).[1]

Gene structure and polymorphisms[edit]

The beta chain is approximately 26-28 kDa and it contains 5 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular protein domains, exon 4 encodes the transmembrane domain, and exon 5 encodes the cytoplasmic tail. Within the DQ molecule, both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to 4 different molecules. Typing for these polymorphisms is routinely done for bone marrow transplantation.[1][2]

Disease association[edit]

Diabetes[edit]

Several alleles of HLA-DQB1 are associated with an increased risk of developing type 1 diabetes.[3][4][5] The locus also has the genetic name IDDM1 as it is the highest genetic risk for type 1 diabetes. Again the DQB1*0201 and DQB1*0302 alleles, particularly the phenotype DQB1*0201/*0302 has a high risk of late onset type 1 diabetes. The risk is partially shared with the HLA-DR locus (DR3 and DR4 serotypes).

Celiac disease[edit]

Celiac1 is a genetic name for DQB1, the HLA DQB1*0201, *0202, and *0302 encode genes that mediate the autoimmune coeliac disease. Homozygotes of DQB1*0201 have a higher risk of developing the celiac disease, relative to any other genetic locus.[6]

Multiple sclerosis[edit]

Certain HLA-DQB1 alleles are also linked to a modest increased risk of multiple sclerosis.[7][8]

Narcolepsy[edit]

Other HLA-DQB1 alleles are associated with a predisposition to narcolepsy,[9] specifically HLA-DQB1*0602, which is carried by over 90% of patients with narcolepsy-cataplexy.[10]

Alleles[edit]

HLA-DQB1 alleles
Serotype DQB1 allele
DQ2 *0201
*0202
*0203
DQ4 *0401
*0402
DQ5 *0501
*0502
*0503
*0504
DQ6 *0601
*0602
*0603
*0604
*0605
*0609
DQ7 *0301
*0304
DQ8 *0302
*0305
DQ9 *0303

See also[edit]

References[edit]

  1. ^ a b c "Entrez Gene: HLA-DQB1 major histocompatibility complex, class II, DQ beta 1". 
  2. ^ Lau M, Terasaki PI, Park MS (1994). "International Cell Exchange, 1994". Clin Transpl: 467–88. PMID 7547576. 
  3. ^ Todd JA (April 1990). "Genetic control of autoimmunity in type 1 diabetes". Immunol. Today 11 (4): 122–9. doi:10.1016/0167-5699(90)90049-F. PMID 2187469. 
  4. ^ Todd JA (March 1997). "Genetics of type 1 diabetes". Pathol. Biol. 45 (3): 219–27. PMID 9296067. 
  5. ^ Redondo MJ, Fain PR, Eisenbarth GS (2001). "Genetics of type 1A diabetes". Recent Prog. Horm. Res. 56: 69–89. doi:10.1210/rp.56.1.69. PMID 11237226. 
  6. ^ Murray JA, Moore SB, Van Dyke CT, et al. (December 2007). "HLA DQ gene dosage and risk and severity of celiac disease". Clin. Gastroenterol. Hepatol. 5 (12): 1406–12. doi:10.1016/j.cgh.2007.08.013. PMC 2175211. PMID 17919990. 
  7. ^ Dyment DA, Sadovnick AD, Ebers GC, Sadnovich AD (1997). "Genetics of multiple sclerosis". Hum. Mol. Genet. 6 (10): 1693–8. doi:10.1093/hmg/6.10.1693. PMID 9300661. 
  8. ^ Schmidt H, Williamson D, Ashley-Koch A (May 2007). "HLA-DR15 haplotype and multiple sclerosis: a HuGE review". Am. J. Epidemiol. 165 (10): 1097–109. doi:10.1093/aje/kwk118. PMID 17329717. 
  9. ^ Kadotani H, Faraco J, Mignot E (May 1998). "Genetic studies in the sleep disorder narcolepsy". Genome Res. 8 (5): 427–34. doi:10.1101/gr.8.5.427. PMID 9582188. 
  10. ^ "Narcolepsy Research - FAQs". Retrieved 3 January 2014.