LRBA Gene

The LRBA gene (LRBA stands for "LPS Responsive Beige-Like Anchor Protein") is a protein-coding gene located on chromosome 4q31.3. Two transcript variants have been found for this gene, coding for different isoforms

The protein encoded by this gene is a member of the WDL-BEACH-WD (WBW) gene family. Its expression is induced in B cells and macrophages by bacterial lipopolysaccharides (LPS). The encoded protein associates with protein kinase A and may be involved in directing intracellular vesicles to activated receptor complexes, supporting secretion and/or membrane deposition of immune effector molecules.

Diseases associated with LRBA include variable immunodeficiency syndrome 8 with autoimmunity and mutations in the LRBA gene.

The encoded LRBA protein is involved in the coupling of signal transduction and vesicle transport to enable polarized secretion and/or membrane deposition of immune effector molecules. It is further involved in the growth of phagophores (= membranous structures that form as precursors of autophagosomes) during mitophagy by regulating ATG9A transport to mitochondria (Nguyen TN et al. 2021).

Note: see also under autophagy.

1. Alangari A et al. (2012) LPS-responsive beige-like anchor (LRBA) gene mutation in a family with inflammatory bowel disease and combined immunodeficiency. J Allergy Clin Immun 130: 481-488.
2. Burns SO et al (2012) LRBA gene deletion in a patient presenting with autoimmunity without hypogammaglobulinemia. (Letter) J Allergy Clin Immun 130: 1428-1432.
3. Charbonnier L-M et al (2015) Regulatory T-cell deficiency and immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like disorder caused by loss-of-function mutations in LRBA. J Allergy Clin Immun 135: 217-227.
4. Nguyen TN et al. (2021) ATG4 family proteins drive phagophore growth independently of the LC3/GABARAP lipidation system. Mol Cell 81:2013-2030.