LRBA

LPS responsive beige-like anchor protein, the group of Armadillo like helical domain containing|WD repeat domain containing|BEACH domain containing

Basic information

Region (hg38): 4:150264435-151015727

Previous symbols: [ "CDC4L" ]

Links

ENSG00000198589 ∙ NCBI:987 ∙ OMIM:606453 ∙ HGNC:1742 ∙ Uniprot:P50851 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• combined immunodeficiency due to LRBA deficiency (Strong), mode of inheritance: AR
• combined immunodeficiency due to LRBA deficiency (Strong), mode of inheritance: AR
• combined immunodeficiency due to LRBA deficiency (Supportive), mode of inheritance: AR
• combined immunodeficiency due to LRBA deficiency (Strong), mode of inheritance: AR
• combined immunodeficiency due to LRBA deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Common variable immunodeficiency 8, with autoimmunity	AR	Allergy/Immunology/Infectious; Hematologic	Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; The condition may include autoimmune phenomena including hematologic manifestations (eg, thrombocytopenia, anemia), and surveillance and early diagnosis and treatment may be beneficial; Automimune manifestations (interstitial lung disease, enteritis) have been reported as responding to a CTLA4-immunoglobin fusion drug	Allergy/Immunology/Infectious; Cardiovascular; Endocrine; Hematologic	22608502; 22981790; 25468195; 26206937
The condition may include infectious and autoimmune manifestations

ClinVar

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

• Combined immunodeficiency due to LRBA deficiency (59 variants)
• not provided (4 variants)
• Colobomatous microphthalmia-rhizomelic dysplasia syndrome (3 variants)
• not specified (1 variants)
• Severe combined immunodeficiency due to CORO1A deficiency (1 variants)
• Inherited Immunodeficiency Diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LRBA 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			13	376	19	408
missense	1		891	13	13	918
nonsense	29	12	1			42
start loss			1			1
frameshift	32	14				46
inframe indel			12			12
splice donor/acceptor (+/-2bp)	3	23	1			27
splice region			57	68	6	131
non coding	3	7	21	239	86	356
Total	68	56	940	628	118

Highest pathogenic variant AF is 0.0000394

Variants in LRBA

This is a list of pathogenic ClinVar variants found in the LRBA region.

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

Position	Type	Phenotype	Significance	ClinVar
4-150265713-C-A		not specified	Conflicting classifications of pathogenicity (Feb 03, 2020)
4-150265729-C-T		Combined immunodeficiency due to LRBA deficiency	Uncertain significance (Jul 19, 2022)
4-150265730-G-A		not specified • Combined immunodeficiency due to LRBA deficiency • LRBA-related disorder	Conflicting classifications of pathogenicity (Mar 01, 2024)
4-150265731-G-C		Combined immunodeficiency due to LRBA deficiency	Likely benign (May 12, 2021)
4-150265747-T-C		LRBA-related disorder	Uncertain significance (Dec 22, 2022)
4-150265750-C-T		Combined immunodeficiency due to LRBA deficiency	Uncertain significance (Jun 04, 2018)
4-150265752-C-A		Combined immunodeficiency due to LRBA deficiency	Likely benign (Dec 31, 2023)
4-150265753-C-T		Combined immunodeficiency due to LRBA deficiency • LRBA-related disorder	Uncertain significance (May 25, 2022)
4-150265754-G-A		Combined immunodeficiency due to LRBA deficiency	Uncertain significance (Apr 05, 2022)
4-150265755-G-A		Combined immunodeficiency due to LRBA deficiency	Likely benign (Apr 15, 2023)
4-150265763-CGTT-C		Combined immunodeficiency due to LRBA deficiency	Uncertain significance (Aug 23, 2022)
4-150265764-G-A		Combined immunodeficiency due to LRBA deficiency • not specified • Inborn genetic diseases	Likely benign (Jun 17, 2024)
4-150265766-T-C		Combined immunodeficiency due to LRBA deficiency • LRBA-related disorder	Uncertain significance (Aug 17, 2022)
4-150265768-T-G		Combined immunodeficiency due to LRBA deficiency • See cases	Uncertain significance (Jul 05, 2022)
4-150265770-A-AAAT		Combined immunodeficiency due to LRBA deficiency	Uncertain significance (Aug 08, 2022)
4-150265775-G-C		Combined immunodeficiency due to LRBA deficiency	Uncertain significance (Apr 05, 2021)
4-150265781-T-C		Combined immunodeficiency due to LRBA deficiency	Uncertain significance (Jul 03, 2022)
4-150265782-G-T		Combined immunodeficiency due to LRBA deficiency	Uncertain significance (Sep 10, 2021)
4-150265800-A-G		Combined immunodeficiency due to LRBA deficiency	Likely benign (Sep 06, 2022)
4-150265813-C-G		Combined immunodeficiency due to LRBA deficiency	Uncertain significance (Aug 03, 2022)
4-150265822-G-A		Combined immunodeficiency due to LRBA deficiency	Likely benign (Mar 07, 2021)
4-150265825-C-G		Combined immunodeficiency due to LRBA deficiency	Likely benign (Feb 16, 2023)
4-150265825-C-CAG		Combined immunodeficiency due to LRBA deficiency	Likely benign (Jun 09, 2021)
4-150265829-GAGA-G		Combined immunodeficiency due to LRBA deficiency	Likely benign (Jul 18, 2023)
4-150265859-A-AGAGAT			Benign (Nov 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LRBA	protein_coding	protein_coding	ENST00000357115	57	751286

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.15e-12	1.00	125416	0	332	125748	0.00132

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.692	1419	1.49e+3	0.950	0.0000778	18715
Missense in Polyphen		758	827.65	0.91584		10422
Synonymous	-1.13	569	536	1.06	0.0000286	5535
Loss of Function	7.59	49	149	0.329	0.00000832	1783

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00364	0.00340
Ashkenazi Jewish	0.000306	0.000298
East Asian	0.00270	0.00250
Finnish	0.00140	0.00134
European (Non-Finnish)	0.00120	0.00113
Middle Eastern	0.00270	0.00250
South Asian	0.00155	0.00131
Other	0.00135	0.00130

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be involved in coupling signal transduction and vesicle trafficking to enable polarized secretion and/or membrane deposition of immune effector molecules. {ECO:0000250}.
• Disease: DISEASE: Immunodeficiency, common variable, 8, with autoimmunity (CVID8) [MIM:614700]: An autosomal recessive immunologic disorder associated with defective B-cell differentiation and decreased or absent antibody production. Affected individuals have early- childhood onset of recurrent infections, particularly respiratory infections, and also develop variable autoimmune disorders, including idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, and inflammatory bowel disease. {ECO:0000269|PubMed:22608502}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• loftool: 0.749
• rvis_EVS: -2.51
• rvis_percentile_EVS: 0.93

Haploinsufficiency Scores

• pHI: 0.316
• hipred: N
• hipred_score: 0.478
• ghis: 0.583

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.872

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lrba
• Phenotype: immune system phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: biological_process
• Cellular component: lysosome;endoplasmic reticulum;Golgi apparatus;plasma membrane;membrane;integral component of membrane
• Molecular function: molecular_function