HLA-DQB1

major histocompatibility complex, class II, DQ beta 1, the group of Histocompatibility complex|C1-set domain containing

Basic information

Region (hg38): 6:32659466-32668383

Previous symbols: [ "HLA-DQB" ]

Links

ENSG00000179344 ∙ NCBI:3119 ∙ OMIM:604305 ∙ HGNC:4944 ∙ Uniprot:P01920 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HLA-DQB1 gene.

• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HLA-DQB1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3		3
missense						0
nonsense						0
start loss						0
frameshift					1	1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	0	3	1

Variants in HLA-DQB1

This is a list of pathogenic ClinVar variants found in the HLA-DQB1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-32664858-A-G			Likely benign (Jul 01, 2022)
6-32666524-T-G			Likely benign (Jan 01, 2024)
6-32666527-G-A			Likely benign (Feb 01, 2023)
6-32666527-G-GAA			Benign (Mar 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HLA-DQB1	protein_coding	protein_coding	ENST00000374943	6	8917

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00893	0.942	124521	0	10	124531	0.0000402

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.31	91	134	0.680	0.00000691	1624
Missense in Polyphen		31	46.582	0.66549		621
Synonymous	2.25	31	51.6	0.601	0.00000267	495
Loss of Function	1.70	5	11.1	0.449	5.64e-7	133

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000444	0.000436
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000567	0.0000558
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.0000567	0.0000558
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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.
• Pathway: Antigen processing and presentation - Homo sapiens (human);Cell adhesion molecules (CAMs) - Homo sapiens (human);Type I diabetes mellitus - Homo sapiens (human);Allograft rejection - Homo sapiens (human);Graft-versus-host disease - Homo sapiens (human);Viral myocarditis - Homo sapiens (human);Influenza A - Homo sapiens (human);Systemic lupus erythematosus - Homo sapiens (human);Autoimmune thyroid disease - Homo sapiens (human);Inflammatory bowel disease (IBD) - Homo sapiens (human);Phagosome - Homo sapiens (human);Asthma - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Staphylococcus aureus infection - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);Leishmaniasis - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Rheumatoid arthritis - Homo sapiens (human);Hematopoietic cell lineage - Homo sapiens (human);Intestinal immune network for IgA production - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Allograft Rejection;Cytokine Signaling in Immune system;Phosphorylation of CD3 and TCR zeta chains;Generation of second messenger molecules;Translocation of ZAP-70 to Immunological synapse;Downstream TCR signaling;TCR signaling;PD-1 signaling;Costimulation by the CD28 family;CD4 T cell receptor signaling-ERK cascade;MHC class II antigen presentation;Immune System;Adaptive Immune System;Interferon gamma signaling;Interferon Signaling;CD4 T cell receptor signaling-JNK cascade;CD4 T cell receptor signaling-NFkB cascade;CD4 T cell receptor signaling (Consensus)

Intolerance Scores

• loftool: 0.972
• rvis_EVS: 7.7
• rvis_percentile_EVS: 99.92

Haploinsufficiency Scores

• pHI: 0.122
• hipred: N
• hipred_score: 0.328
• ghis: 0.497

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.164

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: H2-Ab1
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; cellular phenotype; renal/urinary system phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; muscle phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: immunoglobulin production involved in immunoglobulin mediated immune response;humoral immune response mediated by circulating immunoglobulin;immune response;antigen processing and presentation of exogenous peptide antigen via MHC class II;T cell receptor signaling pathway;interferon-gamma-mediated signaling pathway
• Cellular component: Golgi membrane;lysosomal membrane;plasma membrane;endosome membrane;ER to Golgi transport vesicle membrane;membrane;transport vesicle membrane;endocytic vesicle membrane;clathrin-coated endocytic vesicle membrane;trans-Golgi network membrane;MHC class II protein complex;integral component of lumenal side of endoplasmic reticulum membrane
• Molecular function: protein binding;MHC class II receptor activity;peptide antigen binding