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 (1944 variants)
Inborn_genetic_diseases (378 variants)
not_provided (260 variants)
LRBA-related_disorder (69 variants)
not_specified (45 variants)
Colobomatous_microphthalmia-rhizomelic_dysplasia_syndrome (13 variants)
See_cases (5 variants)
Meniere_disease (4 variants)
Inherited_Immunodeficiency_Diseases (4 variants)
LRBA_deficiency (3 variants)
MAB21L2-related_disorder (2 variants)
Severe_combined_immunodeficiency_due_to_CORO1A_deficiency (2 variants)
Spastic_paraplegia,_intellectual_disability,_nystagmus,_and_obesity (1 variants)
Schizophrenia (1 variants)
Long_QT_syndrome (1 variants)
Hirschsprung_disease,_susceptibility_to,_1 (1 variants)
EBV-positive_nodal_T-_and_NK-cell_lymphoma (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. These statistics are base on transcript: NM_001364905.1. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			12 clinvar	470 clinvar	19 clinvar	501
missense	4 clinvar	1 clinvar	1013 clinvar	39 clinvar	11 clinvar	1068
nonsense	40 clinvar	15 clinvar	1 clinvar			56
start loss			1			1
frameshift	47 clinvar	27 clinvar				74
splice donor/acceptor (+/-2bp)	7 clinvar	26 clinvar	1 clinvar			34
Total	98	69	1028	509	30

Highest pathogenic variant AF is 0.00007188921

Loading clinvar variants...

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