HLA-DRB1

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

Basic information

Region (hg38): 6:32577901-32589848

Previous symbols: [ "HLA-DR1B" ]

Links

ENSG00000196126 ∙ NCBI:3123 ∙ OMIM:142857 ∙ HGNC:4948 ∙ Uniprot:P01911 ∙ 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-DRB1 gene.

• not provided (16 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HLA-DRB1 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				8		8
missense			1	1	3	5
nonsense						0
start loss						0
frameshift				1	1	2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	1	10	4

Variants in HLA-DRB1

This is a list of pathogenic ClinVar variants found in the HLA-DRB1 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-32580254-C-T			Likely benign (Feb 01, 2024)
6-32580255-T-G			Likely benign (Apr 01, 2024)
6-32580272-T-C		Multiple sclerosis, susceptibility to	Likely pathogenic (Mar 26, 2024)
6-32580745-C-G			Likely benign (Feb 01, 2024)
6-32581554-C-T			Likely benign (Apr 01, 2024)
6-32581719-C-T			Uncertain significance (-)
6-32581726-G-A			Likely benign (Mar 01, 2024)
6-32581763-C-T		HLA-DRB1-related disorder	Likely benign (Dec 17, 2020)
6-32581807-C-T			Likely benign (Aug 01, 2023)
6-32581830-T-C			Uncertain significance (-)
6-32584143-G-A			Likely benign (Aug 01, 2023)
6-32584172-C-G		Peritoneal Gliomatosis	Uncertain significance (Aug 01, 2019)
6-32584176-C-A			Likely benign (Jan 01, 2023)
6-32584178-G-GCT		HLA-DRB1-related disorder	Likely benign (Dec 17, 2020)
6-32584182-C-T			Likely benign (Mar 01, 2024)
6-32584237-T-A		Pulmonary artery atresia	Pathogenic (-)
6-32584279-AC-A			Likely benign (Dec 01, 2023)
6-32584282-G-A			Benign (Jan 18, 2019)
6-32584282-G-T			Benign (Jan 18, 2019)
6-32584283-A-AG			Benign (Dec 01, 2023)
6-32584314-G-T			Benign (Jan 01, 2023)
6-32584351-TCCC-T		Multiple sclerosis, susceptibility to	Uncertain significance (Mar 29, 2024)
6-32584360-G-GA		HLA-DRB1-related disorder	Likely benign (Dec 17, 2020)
6-32584361-G-GA		not specified	Benign (-)
6-32584361-G-GTA		HLA-DRB1-related disorder	Likely benign (Dec 17, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HLA-DRB1	protein_coding	protein_coding	ENST00000360004	6	11080

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00110	0.845	125037	0	1	125038	0.00000400

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.18	84	120	0.698	0.00000570	1549
Missense in Polyphen		18	42.282	0.42571		569
Synonymous	1.06	39	48.4	0.805	0.00000233	472
Loss of Function	1.23	6	10.2	0.586	4.63e-7	127

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
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;Vitamin D Receptor Pathway;Cytokines and Inflammatory Response;the co-stimulatory signal during t-cell activation;lck and fyn tyrosine kinases in initiation of tcr activation;role of mef2d in t-cell apoptosis;il 4 signaling pathway;activation of csk by camp-dependent protein kinase inhibits signaling through the t cell receptor;antigen processing and presentation;t cell receptor signaling pathway;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;IL12 signaling mediated by STAT4;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;CXCR4-mediated signaling events;Interferon gamma signaling;Interferon Signaling;TCR signaling in naïve CD4+ T cells;IL12-mediated signaling events;CD4 T cell receptor signaling-JNK cascade;CD4 T cell receptor signaling-NFkB cascade;CD4 T cell receptor signaling (Consensus)

Intolerance Scores

• loftool: 1.00
• rvis_EVS: 2.97
• rvis_percentile_EVS: 99.19

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.204
• ghis: 0.487

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.786

Gene Damage Prediction

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

Gene ontology

• Biological process: polysaccharide assembly with MHC class II protein complex;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;cell surface;ER to Golgi transport vesicle membrane;membrane;transport vesicle membrane;endocytic vesicle membrane;clathrin-coated endocytic vesicle membrane;late endosome membrane;trans-Golgi network membrane;MHC class II protein complex;extracellular exosome;integral component of lumenal side of endoplasmic reticulum membrane
• Molecular function: MHC class II protein complex binding;peptide antigen binding