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

ENSG00000198589NCBI:987OMIM:606453HGNC:1742Uniprot:P50851AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Common variable immunodeficiency 8, with autoimmunityARAllergy/Immunology/Infectious; HematologicAntiinfectious 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 drugAllergy/Immunology/Infectious; Cardiovascular; Endocrine; Hematologic22608502; 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.

EffectPLPVUSLBBSum
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

GeneTypeBio TypeTranscript Coding Exons Length
LRBAprotein_codingprotein_codingENST00000357115 57751286
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
7.15e-121.0012541603321257480.00132
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.69214191.49e+30.9500.000077818715
Missense in Polyphen758827.650.9158410422
Synonymous-1.135695361.060.00002865535
Loss of Function7.59491490.3290.000008321783

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.003640.00340
Ashkenazi Jewish0.0003060.000298
East Asian0.002700.00250
Finnish0.001400.00134
European (Non-Finnish)0.001200.00113
Middle Eastern0.002700.00250
South Asian0.001550.00131
Other0.001350.00130

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

AllRecessiveDominant
MendelianHighMediumHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

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