HLA-DRB4 (major histocompatibility complex, class II, DR beta 4)

Gene

• Entrez ID: 3126
• Gene name: Major histocompatibility complex, class II, DR beta 4
• Gene symbol: HLA-DRB4
• Synonyms (NCBI Gene): DR4, DRB4, HLA-DR4B, HLA-DRB, HLA-DRB4*
• Chromosome: 6
• Chromosome location: 6p21.3
• Summary: HLA-DRB4 belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DRA) and a beta (DRB) chain, both anchored in the membrane. It plays a central role in the immune system by presenting peptides der

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1048470	hsa-miR-4699-5p	CLIP-seq
MIRT1048471	hsa-miR-4709-3p	CLIP-seq
MIRT2011024	hsa-miR-320a	CLIP-seq
MIRT2011025	hsa-miR-320b	CLIP-seq
MIRT2011026	hsa-miR-320c	CLIP-seq
MIRT2011027	hsa-miR-320d	CLIP-seq
MIRT2011028	hsa-miR-4429	CLIP-seq
MIRT2243305	hsa-miR-298	CLIP-seq
MIRT2011024	hsa-miR-320a	CLIP-seq
MIRT2011025	hsa-miR-320b	CLIP-seq
MIRT2011026	hsa-miR-320c	CLIP-seq
MIRT2011027	hsa-miR-320d	CLIP-seq
MIRT2243306	hsa-miR-320e	CLIP-seq
MIRT2011028	hsa-miR-4429	CLIP-seq
MIRT2243307	hsa-miR-4457	CLIP-seq
MIRT2243308	hsa-miR-4731-5p	CLIP-seq
MIRT2243309	hsa-miR-486-3p	CLIP-seq
MIRT2243310	hsa-miR-518a-5p	CLIP-seq
MIRT2243311	hsa-miR-527	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
CIITA	Unknown	10886240
RFX5	Unknown	11258423
RFXANK	Unknown	11258423
RFXAP	Unknown	11258423

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000139	Component	Golgi membrane	TAS
GO:0002250	Process	Adaptive immune response	IEA
GO:0002376	Process	Immune system process	IEA
GO:0002503	Process	Peptide antigen assembly with MHC class II protein complex	IBA
GO:0002504	Process	Antigen processing and presentation of peptide or polysaccharide antigen via MHC class II	IEA
GO:0005764	Component	Lysosome	IEA
GO:0005765	Component	Lysosomal membrane	IBA
GO:0005765	Component	Lysosomal membrane	IDA	18305173
GO:0005765	Component	Lysosomal membrane	IEA
GO:0005765	Component	Lysosomal membrane	TAS
GO:0005768	Component	Endosome	IEA
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005794	Component	Golgi apparatus	IEA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0006955	Process	Immune response	IEA
GO:0010008	Component	Endosome membrane	IEA
GO:0012507	Component	ER to Golgi transport vesicle membrane	TAS
GO:0016020	Component	Membrane	IEA
GO:0019882	Process	Antigen processing and presentation	IEA
GO:0019886	Process	Antigen processing and presentation of exogenous peptide antigen via MHC class II	IBA
GO:0023026	Function	MHC class II protein complex binding	IBA
GO:0030658	Component	Transport vesicle membrane	TAS
GO:0030666	Component	Endocytic vesicle membrane	TAS
GO:0030669	Component	Clathrin-coated endocytic vesicle membrane	TAS
GO:0031902	Component	Late endosome membrane	IBA
GO:0031902	Component	Late endosome membrane	IDA	18305173, 19117940
GO:0031902	Component	Late endosome membrane	IEA
GO:0032588	Component	Trans-Golgi network membrane	TAS
GO:0042605	Function	Peptide antigen binding	IBA
GO:0042613	Component	MHC class II protein complex	IBA
GO:0042613	Component	MHC class II protein complex	IEA
GO:0050778	Process	Positive regulation of immune response	IBA
GO:0050870	Process	Positive regulation of T cell activation	IBA
GO:0098553	Component	Lumenal side of endoplasmic reticulum membrane	TAS

Other IDs

• MIM: HGNC
• HGNC: 4952
• e!Ensembl: N/A

Protein

• UniProt ID: P13762
• Protein name: HLA class II histocompatibility antigen, DR beta 4 chain (MHC class II antigen DRB4)
• Protein 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. T
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00969	MHC_II_beta	42 → 116	Class II histocompatibility antigen, beta domain	Domain
  PF07654	C1-set	128 → 209	Immunoglobulin C1-set domain	Domain

• Sequence:

  MVCLKLPGGSCMAALTVTLTVLSSPLALAGDTQPRFLEQAKCECHFLNGTERVWNLIRYI
  YNQEEYARYNSDLGEYQAVTELGRPDAEYWNSQKDLLERRRAEVDTYCRYNYGVVESFTV
  QRRVQPKVTVYPSKTQPLQHHNLLVCSVNGFYPGSIEVRWFRNGQEEKAGVVSTGLIQNG
  DWTFQTLVMLETVPRSGEVYTCQVEHPSMMSPLTVQWSARSESAQSKMLSGVGGFVLGLL
  FLGTGLFIYFRNQKGHSGLQPTGLLS

• Sequence length: 266

Pathways

KEGG:

Phagosome
Cell adhesion molecules
Antigen processing and presentation
Hematopoietic cell lineage
Th1 and Th2 cell differentiation
Th17 cell differentiation
Intestinal immune network for IgA production
Type I diabetes mellitus
Leishmaniasis
Toxoplasmosis
Staphylococcus aureus infection
Tuberculosis
Influenza A
Human T-cell leukemia virus 1 infection
Herpes simplex virus 1 infection
Epstein-Barr virus infection
Asthma
Autoimmune thyroid disease
Inflammatory bowel disease
Systemic lupus erythematosus
Rheumatoid arthritis
Allograft rejection
Graft-versus-host disease
Viral myocarditis

Reactome:

Downstream TCR signaling
Phosphorylation of CD3 and TCR zeta chains
Translocation of ZAP-70 to Immunological synapse
Generation of second messenger molecules
MHC class II antigen presentation
PD-1 signaling
Interferon gamma signaling

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
BIPOLAR DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERSENSITIVITY	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PARANOIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PARANOID SCHIZOPHRENIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute monocytic leukemia	Monocytic Leukemia	BEFREE	17893434		★☆☆☆☆ Found in Text Mining only
Arthritis	Arthritis	BEFREE	10527388		★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	BEFREE	24838153		★☆☆☆☆ Found in Text Mining only
Astrocytoma	Astrocytoma	BEFREE	19706813		★☆☆☆☆ Found in Text Mining only
Autoimmune Chronic Hepatitis	Autoimmune hepatitis	BEFREE	10406258, 15763345, 9021941		★☆☆☆☆ Found in Text Mining only
Autoimmune Diseases	Autoimmune Diseases	BEFREE	25523449, 28059022, 30455401		★☆☆☆☆ Found in Text Mining only
Autoimmune thyroiditis	Autoimmune Thyroiditis	LHGDN	15046556		★☆☆☆☆ Found in Text Mining only
Bipolar Disorder	Bipolar Disorder	PSYGENET_DG	12109964		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Bladder Neoplasm	Bladder Neoplasm	BEFREE	25955868		★☆☆☆☆ Found in Text Mining only
Cancer of Nasopharynx	Nasopharyngeal Cancer	BEFREE	10762627		★☆☆☆☆ Found in Text Mining only
Carcinoma of bladder	Bladder carcinoma	BEFREE	25955868		★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	19203830		★☆☆☆☆ Found in Text Mining only
Celiac Disease	Celiac disease	BEFREE	11061289, 11862400, 28585303		★☆☆☆☆ Found in Text Mining only
Childhood Acute Lymphoblastic Leukemia	Lymphoblastic Leukemia	BEFREE	10397736		★☆☆☆☆ Found in Text Mining only
Chronic Lymphocytic Leukemia	Lymphocytic Leukemia	BEFREE	11291046, 12148880, 25232063		★☆☆☆☆ Found in Text Mining only
Coffin-Siris syndrome	Coffin-Siris Syndrome	BEFREE	17763415		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	26518902		★☆☆☆☆ Found in Text Mining only
Crohn Disease	Crohn Disease	BEFREE	10323339		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Insulin-Dependent	Diabetes Mellitus	BEFREE	24838153, 26740600, 30455401, 31127057		★☆☆☆☆ Found in Text Mining only
Encephalitis	Encephalitis	BEFREE	28026046		★☆☆☆☆ Found in Text Mining only
FNAITP	Fetal and neonatal alloimmune thrombocytopenia	BEFREE	28019029		★☆☆☆☆ Found in Text Mining only
Granulomatosis with polyangiitis	Granulomatosis With Polyangiitis	BEFREE	25523449		★☆☆☆☆ Found in Text Mining only
Graves Disease	Graves Disease	BEFREE	11895223		★☆☆☆☆ Found in Text Mining only
Hamartoma Syndrome, Multiple	Hamartoma	BEFREE	11061289		★☆☆☆☆ Found in Text Mining only
Hashimoto Disease	Hashimoto Disease	BEFREE	15055474, 24285682		★☆☆☆☆ Found in Text Mining only
Hashimoto Disease	Hashimoto Disease	LHGDN	15055474		★☆☆☆☆ Found in Text Mining only
Head and Neck Carcinoma	Head And Neck Carcinoma	BEFREE	26718429		★☆☆☆☆ Found in Text Mining only
Immune System Diseases	Immune System Diseases	BEFREE	9021941		★☆☆☆☆ Found in Text Mining only
Iron deficiency anemia	Iron deficiency anemia	BEFREE	29472772		★☆☆☆☆ Found in Text Mining only
Leprosy	Leprosy	LHGDN	18053473		★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	17237562, 17893434, 29472772		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	22401174		★☆☆☆☆ Found in Text Mining only
Liver Failure	Liver failure	BEFREE	9021941		★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus, Systemic	Lupus Erythematosus	BEFREE	26919467, 8456439		★☆☆☆☆ Found in Text Mining only
Malignant Head and Neck Neoplasm	Head and neck cancer	BEFREE	26718429		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of liver	Liver Cancer	BEFREE	22401174		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	19203830		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of nasopharynx	Nasopharyngeal carcinoma	BEFREE	10762627		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of urinary bladder	Urinary bladder cancer	BEFREE	25955868		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	10762627		★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	BEFREE	10684854		★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple Sclerosis	GWASDB_DG	23472185		★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple Sclerosis	GWASCAT_DG	23472185		★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple Sclerosis	BEFREE	29683085		★☆☆☆☆ Found in Text Mining only
Myeloid Leukemia, Chronic	Myeloid Leukemia	BEFREE	12879429		★☆☆☆☆ Found in Text Mining only
MYOTONIC DYSTROPHY 1	Myotonic dystrophy	BEFREE	15237707		★☆☆☆☆ Found in Text Mining only
Narcolepsy	Narcolepsy	BEFREE	9534039		★☆☆☆☆ Found in Text Mining only
Narcolepsy type 1	Narcolepsy	BEFREE	31577807		★☆☆☆☆ Found in Text Mining only
Nasopharyngeal carcinoma	Nasopharyngeal Carcinoma	BEFREE	10762627		★☆☆☆☆ Found in Text Mining only
Neonatal Alloimmune Thrombocytopenia	Alloimmune Thrombocytopenia	BEFREE	22671039		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	28026046		★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	BEFREE	14999771		★☆☆☆☆ Found in Text Mining only
Paranoia	Paranoia	PSYGENET_DG	16786814		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Paranoid Schizophrenia	Paranoid Schizophrenia	PSYGENET_DG	16786814		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Polyendocrinopathies, Autoimmune	Autoimmune Polyendocrinopathy	LHGDN	15046556		★☆☆☆☆ Found in Text Mining only
Precursor Cell Lymphoblastic Leukemia Lymphoma	Lymphoblastic Leukemia	LHGDN	12008082		★☆☆☆☆ Found in Text Mining only
Purpura, Thrombotic Thrombocytopenic	Thrombotic thrombocytopenic purpura	BEFREE	19922436		★☆☆☆☆ Found in Text Mining only
Refractory anemias	Anemia	BEFREE	20584722		★☆☆☆☆ Found in Text Mining only
Rheumatoid Arthritis	Rheumatoid arthritis	BEFREE	14558083, 1686751, 2001978, 20584722, 2510739, 25636569, 26919467, 31451934, 8162639, 8894643		★☆☆☆☆ Found in Text Mining only
Sarcoidosis	Sarcoidosis	BEFREE	14508706, 17559577		★☆☆☆☆ Found in Text Mining only
Spina Bifida	Spina Bifida	BEFREE	12209103		★☆☆☆☆ Found in Text Mining only
Thyroiditis	Thyroiditis	BEFREE	17010173		★☆☆☆☆ Found in Text Mining only
Ulcerative Colitis	Ulcerative colitis	BEFREE	10323339		★☆☆☆☆ Found in Text Mining only
Uveomeningoencephalitic Syndrome	Uveomeningoencephalitic Syndrome	BEFREE	7906684, 8781122		★☆☆☆☆ Found in Text Mining only
Vasculitis	Vasculitis	BEFREE	17763415		★☆☆☆☆ Found in Text Mining only
Vitiligo	Vitiligo	BEFREE	11453913, 17021767		★☆☆☆☆ Found in Text Mining only
VITILIGO-ASSOCIATED MULTIPLE AUTOIMMUNE DISEASE SUSCEPTIBILITY 1 (finding)	Vitiligo-associated SYSTEMIC LUPUS ERYTHEMATOSUS	BEFREE	11453913, 17021767		★☆☆☆☆ Found in Text Mining only