LRBA Gene: Lipopolysaccharide Responsive Beige-Like Anchor Protein
A critical regulator of immune homeostasis and vesicle trafficking, associated with primary immunodeficiency and autoimmunity.
Gene Information Card
| Symbol | LRBA |
|---|---|
| Full Name | Lipopolysaccharide Responsive Beige-Like Anchor Protein |
| Gene Type | Protein coding |
| Chromosomal Location | 4q31.3 |
| NCBI Gene ID | 987 ncbi.nlm.nih.gov/gene/987 |
| Ensembl ID | ENSG00000138698 |
| UniProt ID | P50851 |
| OMIM ID | 606453 |
| HGNC ID | 6692 |
| Aliases | BGL, CDC4L, LBA, LBP, LPS-responsive vesicle trafficking, beige-like anchor |
Description
The LRBA gene encodes a large, multidomain protein involved in vesicle trafficking, endosomal sorting, and immune regulation. It is essential for the proper recycling and expression of CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) on regulatory T cells, thereby maintaining immune tolerance. Loss-of-function mutations in LRBA cause a primary immunodeficiency characterized by autoimmunity, enteropathy, and recurrent infections.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| LRBA deficiency (primary immunodeficiency with autoimmunity) | Loss-of-function mutations impair CTLA-4 recycling, leading to defective immune regulation and T-cell hyperactivity. | ClinVar, OMIM |
| Common variable immunodeficiency (CVID) | Biallelic LRBA mutations result in a CVID-like phenotype with hypogammaglobulinemia and autoimmune manifestations. | ClinVar, OMIM |
| Inflammatory bowel disease (IBD)-like enteropathy | LRBA deficiency disrupts intestinal immune homeostasis, causing chronic inflammation. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 11.8 | Medium |
| Whole blood | 8.2 | Medium |
| Small intestine | 7.1 | Medium |
| Lung | 5.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| B-lymphocytes (GM12878) | 15.2 | High expression |
| T-lymphocytes (Jurkat) | 12.8 | Medium expression |
| Monocytes (THP-1) | 10.5 | Medium expression |
| HeLa | 4.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2450C>T (p.Pro817Leu) | Missense | Rare | Likely pathogenic; disrupts protein stability |
| c.3451C>T (p.Arg1151*) | Nonsense | Rare | Loss-of-function; premature truncation |
| c.4977_4981del (p.Glu1659Aspfs*2) | Frameshift deletion | Rare | Loss-of-function; protein truncation |
| c.6766C>T (p.Arg2256*) | Nonsense | Rare | Loss-of-function; nonsense-mediated decay |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations in LRBA cause LRBA deficiency, a primary immunodeficiency with defective CTLA-4 recycling, leading to autoimmunity and immune dysregulation.
Gain of Function (GOF)
No gain-of-function mutations have been reported for LRBA.
Dominant Negative (DN)
No dominant-negative mutations have been described for LRBA.
View complete mutation data：
Gene Ontology (GO)
Pathways
• CTLA-4 recycling pathway (Reactome: R-HSA-389359)
• Vesicle-mediated transport (Reactome: R-HSA-5653656)
• Endosomal sorting complex required for transport (ESCRT) (Reactome: R-HSA-917729)
Protein Summary
The LRBA protein (UniProt P50851) is a large, 2863-amino-acid cytoplasmic protein containing multiple domains, including a BEACH domain, WD40 repeats, and a PH-like domain. It functions as a scaffold in vesicle trafficking, particularly in the endosomal recycling of CTLA-4. By facilitating CTLA-4 surface expression on regulatory T cells, LRBA is critical for maintaining peripheral immune tolerance. Loss of LRBA function leads to CTLA-4 deficiency, unchecked T-cell activation, and autoimmune pathology.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LRBA Knockout HEK293 Cell Line | EDJ-KQ3784 | Human | 987 | Details Get a Quote |
| LRBA Knockout A-549 Cell Line | EDJ-KQ24523 | Human | 987 | Details Get a Quote |
| LRBA Knockout HCT 116 Cell Line | EDJ-KQ25883 | Human | 987 | Details Get a Quote |
| LRBA Knockout HeLa Cell Line | EDJ-KQ25884 | Human | 987 | Details Get a Quote |
| LRBA Knockout Jurkat Cell Line | EDJ-KZ338 | Human | 987 | Details Get a Quote |
