LRBA

Summary

LRBA (LPS responsive beige-like anchor protein, HGNC:1742) is a protein-coding gene on chromosome 4q31.3, encoding Lipopolysaccharide-responsive and beige-like anchor protein (P50851). Involved in coupling signal transduction and vesicle trafficking to enable polarized secretion and/or membrane deposition of immune effector molecules.

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 leading intracellular vesicles to activated receptor complexes, which aids in the secretion and/or membrane deposition of immune effector molecules. Defects in this gene are associated with the disorder common variable immunodeficiency-8 with autoimmunity. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 987 — RefSeq curated summary.

At a glance

• Gene–disease (curated): combined immunodeficiency due to LRBA deficiency (Definitive, ClinGen)
• GWAS associations: 11
• Clinical variants (ClinVar): 2,683 total — 124 pathogenic, 79 likely-pathogenic (top 1% of genes corpus-wide)
• GTEx eGene: eQTL in 32 tissues, sQTL in 9 (q < 0.05)
• Phenotypes (HPO): 45
• Constraint (gnomAD): pLI 0.01 (LoF-tolerant), LOEUF 0.52 (moderately constrained)
• MANE Select transcript: NM_001364905

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1742
Approved symbol	LRBA
Name	LPS responsive beige-like anchor protein
Location	4q31.3
Locus type	gene with protein product
Status	Approved
Aliases	BGL, LAB300, LBA, uc.147
Ensembl gene	ENSG00000198589
Ensembl biotype	protein_coding
OMIM	606453
Entrez	987

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 22 protein_coding, 4 protein_coding_CDS_not_defined, 4 retained_intron, 3 nonsense_mediated_decay

MANE Select: ENST00000651943

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 2, TSL 3: 3, TSL 4: 1, TSL 5: 2

ENST00000651943, ENST00000357115, ENST00000502839, ENST00000503716, ENST00000507224, ENST00000508396, ENST00000508606, ENST00000510157, ENST00000510413, ENST00000510841, ENST00000513021, ENST00000514435, ENST00000515096, ENST00000648626, ENST00000648823, ENST00000648878, ENST00000649874, ENST00000651035, ENST00000651695, ENST00000697127, ENST00000697128, ENST00000697129, ENST00000697130, ENST00000911749, ENST00000911750, ENST00000911751, ENST00000911752, ENST00000911753, ENST00000977229, ENST00001111081, ENST00001111082, ENST00001126221, ENST00001139958

RefSeq mRNA: 8 — MANE Select: NM_001364905 NM_001199282, NM_001364905, NM_001367550, NM_001440430, NM_001440431, NM_001440432, NM_001440433, NM_006726

CCDS: CCDS3773, CCDS58928, CCDS93649, CCDS93650

Canonical transcript exons

ENST00000651943 — 57 exons

Exon	Start	End
ENSE00000740094	150928516	150928616
ENSE00000740095	150921198	150921293
ENSE00000740096	150915608	150915727
ENSE00000740097	150914195	150914341
ENSE00000740098	150908660	150908857
ENSE00000740099	150908334	150908467
ENSE00000740100	150906297	150906405
ENSE00000740101	150900049	150900217
ENSE00000740104	150868182	150868305
ENSE00000740106	150867671	150867863
ENSE00000740109	150850724	150850902
ENSE00000821053	150870525	150870606
ENSE00000821054	150871345	150871453
ENSE00000821057	150872663	150872755
ENSE00000821058	150893052	150893149
ENSE00000821060	150897739	150897818
ENSE00000821061	150905838	150905990
ENSE00000821062	150916401	150916527
ENSE00001081815	150321191	150321368
ENSE00001081818	150798081	150798142
ENSE00001081820	150828180	150828621
ENSE00001081822	150844658	150844779
ENSE00001081823	150808320	150808398
ENSE00001081824	150831817	150831976
ENSE00001081825	150848818	150848998
ENSE00001081826	150806271	150806404
ENSE00001081827	150849422	150849575
ENSE00001081828	150844100	150844207
ENSE00001081829	150817124	150817257
ENSE00001081830	150735258	150735366
ENSE00001200926	150851885	150852943
ENSE00001250081	150683551	150683717
ENSE00001250470	150896394	150896456
ENSE00001250476	150928834	150929065
ENSE00001428255	151014427	151014861
ENSE00001619686	150761783	150761847
ENSE00001777660	150916617	150916738
ENSE00003487176	150310229	150310384
ENSE00003487821	150467673	150467785
ENSE00003576042	150277853	150278004
ENSE00003583036	150435589	150435708
ENSE00003591436	150436724	150436864
ENSE00003613524	150315561	150315623
ENSE00003613781	150588048	150588184
ENSE00003621548	150487732	150487834
ENSE00003623119	150285933	150286034
ENSE00003626043	150325809	150325898
ENSE00003637749	150490918	150491035
ENSE00003661993	150471624	150471739
ENSE00003670996	150349992	150350159
ENSE00003683208	150590713	150590859
ENSE00003683395	150415438	150415590
ENSE00003688095	150599007	150599131
ENSE00003692138	150282450	150282646
ENSE00003692871	150302625	150302792
ENSE00003900801	150264435	150265812
ENSE00003902903	151015202	151015284

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 95.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.3310 / max 403.3496, expressed in 1806 samples.

Highest expression (Bgee): upper leg skin, bronchial epithelial cell, epithelium of bronchus, colonic epithelium, gingival epithelium.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LRBA is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 32 tissues and its splicing (sQTL) in 9 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 41 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	4.2e-35	-1.21	4:150394895:C:T
Cells Cultured fibroblasts	eqtl	1.7e-08	-0.17	4:150394895:C:T
Brain Cerebellum	eqtl	3.4e-08	-0.33	4:150508563:T:C
Nerve Tibial	eqtl	4.2e-08	+0.20	4:150476607:A:G
Colon Transverse	eqtl	3.4e-05	-0.12	4:150524906:C:T
Brain Anterior cingulate cortex BA24	eqtl	5.1e-05	-2.14	4:150574897:G:C
Brain Caudate basal ganglia	eqtl	2.9e-04	-0.81	4:150438228:A:T
Pancreas	eqtl	4.9e-04	+0.14	4:150547193:T:C
Brain Cerebellar Hemisphere	eqtl	1.1e-03	+0.30	4:150879091:C:T
Muscle Skeletal	eqtl	1.2e-03	-0.13	4:150884164:C:T
Skin Not Sun Exposed Suprapubic	sqtl	1.4e-03	+0.35	4:150266516:T:TCTC
Cells EBV-transformed lymphocytes	eqtl	1.5e-03	-0.19	4:150520091:T:C
Brain Putamen basal ganglia	eqtl	2.3e-03	-0.67	4:150330552:T:C
Brain Hippocampus	eqtl	2.5e-03	-0.47	4:150281800:T:C
Esophagus Mucosa	eqtl	2.8e-03	-0.08	4:150330667:T:C
Brain Hypothalamus	eqtl	3.0e-03	+0.30	4:150703148:G:A
Spleen	eqtl	3.1e-03	-0.17	4:150562298:T:C
Skin Sun Exposed Lower leg	sqtl	3.8e-03	+0.29	4:150277928:G:A
Skin Sun Exposed Lower leg	eqtl	4.2e-03	+0.08	4:150382166:G:A
Artery Aorta	eqtl	6.5e-03	+0.14	4:150245085:C:T

FANTOM5 promoters

10 alternative TSS:

Promoter ID	TPM avg	Samples expressed
54335	11.1964	1776
54334	7.3897	1419
54333	2.5744	923
54336	0.4726	277
54332	0.2125	109
54307	0.1538	84
54308	0.1273	78
54310	0.0843	50
54309	0.0723	41
54306	0.0476	21

Top tissues by expression

showing 100 of 289 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	95.01	gold quality
bronchial epithelial cell	CL:0002328	94.99	gold quality
epithelium of bronchus	UBERON:0002031	93.59	gold quality
colonic epithelium	UBERON:0000397	93.55	gold quality
gingival epithelium	UBERON:0001949	93.19	gold quality
bronchus	UBERON:0002185	93.04	gold quality
esophagus squamous epithelium	UBERON:0006920	92.84	gold quality
epithelium of nasopharynx	UBERON:0001951	92.80	gold quality
corpus epididymis	UBERON:0004359	92.79	gold quality
gingiva	UBERON:0001828	92.57	gold quality
right uterine tube	UBERON:0001302	92.54	gold quality
choroid plexus epithelium	UBERON:0003911	92.49	gold quality
pigmented layer of retina	UBERON:0001782	92.33	gold quality
skin of hip	UBERON:0001554	92.27	gold quality
mucosa of sigmoid colon	UBERON:0004993	92.18	gold quality
tonsil	UBERON:0002372	91.97	gold quality
pancreatic ductal cell	CL:0002079	91.91	gold quality
squamous epithelium	UBERON:0006914	91.90	gold quality
colonic mucosa	UBERON:0000317	91.78	gold quality
epithelium of esophagus	UBERON:0001976	91.66	gold quality
oviduct epithelium	UBERON:0004804	91.66	gold quality
calcaneal tendon	UBERON:0003701	91.51	gold quality
caput epididymis	UBERON:0004358	91.48	gold quality
sperm	CL:0000019	91.40	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.06	gold quality
lower esophagus mucosa	UBERON:0035834	90.95	gold quality
adrenal tissue	UBERON:0018303	90.72	gold quality
upper arm skin	UBERON:0004263	90.66	gold quality
islet of Langerhans	UBERON:0000006	90.54	gold quality
nephron tubule	UBERON:0001231	90.52	gold quality
tibia	UBERON:0000979	90.40	gold quality
esophagus mucosa	UBERON:0002469	90.14	gold quality
nasal cavity mucosa	UBERON:0001826	89.98	gold quality
skin of leg	UBERON:0001511	89.95	gold quality
skin of abdomen	UBERON:0001416	89.93	gold quality
zone of skin	UBERON:0000014	89.79	gold quality
adenohypophysis	UBERON:0002196	89.68	gold quality
pituitary gland	UBERON:0000007	89.57	gold quality
sigmoid colon	UBERON:0001159	89.26	gold quality
rectum	UBERON:0001052	89.23	gold quality
renal medulla	UBERON:0000362	89.21	gold quality
large intestine	UBERON:0000059	89.18	gold quality
colon	UBERON:0001155	89.11	gold quality
epithelium of mammary gland	UBERON:0003244	88.99	gold quality
kidney	UBERON:0002113	88.90	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.81	gold quality
intestine	UBERON:0000160	88.74	gold quality
transverse colon	UBERON:0001157	88.71	gold quality
adult mammalian kidney	UBERON:0000082	88.69	gold quality
muscle layer of sigmoid colon	UBERON:0035805	88.62	gold quality
oral cavity	UBERON:0000167	88.42	gold quality
mammary duct	UBERON:0001765	88.37	gold quality
fallopian tube	UBERON:0003889	88.34	gold quality
pancreas	UBERON:0001264	88.22	gold quality
mouth mucosa	UBERON:0003729	88.16	gold quality
cervix squamous epithelium	UBERON:0006922	88.11	gold quality
cervix epithelium	UBERON:0004801	88.09	gold quality
minor salivary gland	UBERON:0001830	87.88	gold quality
male germ cell	CL:0000015	87.84	gold quality
germinal epithelium of ovary	UBERON:0001304	87.81	gold quality
kidney epithelium	UBERON:0004819	87.79	gold quality
duodenum	UBERON:0002114	87.70	gold quality
saliva-secreting gland	UBERON:0001044	87.51	gold quality
right adrenal gland cortex	UBERON:0035827	87.41	gold quality
bone marrow cell	CL:0002092	87.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.38	gold quality
metanephros cortex	UBERON:0010533	87.36	gold quality
mammalian vulva	UBERON:0000997	87.35	gold quality
cortex of kidney	UBERON:0001225	87.25	gold quality
thoracic mammary gland	UBERON:0005200	87.13	gold quality
jejunal mucosa	UBERON:0000399	87.12	gold quality
mucosa of transverse colon	UBERON:0004991	87.06	gold quality
mucosa of paranasal sinus	UBERON:0005030	87.06	gold quality
nasal cavity epithelium	UBERON:0005384	87.06	gold quality
right adrenal gland	UBERON:0001233	87.05	gold quality
mammary gland	UBERON:0001911	87.05	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.98	gold quality
small intestine	UBERON:0002108	86.97	gold quality
palpebral conjunctiva	UBERON:0001812	86.96	gold quality
adrenal gland	UBERON:0002369	86.94	gold quality
metanephros	UBERON:0000081	86.91	gold quality
body of pancreas	UBERON:0001150	86.84	gold quality
left adrenal gland	UBERON:0001234	86.65	gold quality
endometrium	UBERON:0001295	86.55	gold quality
left adrenal gland cortex	UBERON:0035825	86.53	gold quality
stomach	UBERON:0000945	86.41	gold quality
parotid gland	UBERON:0001831	86.24	gold quality
liver	UBERON:0002107	85.99	gold quality
vagina	UBERON:0000996	85.98	gold quality
body of stomach	UBERON:0001161	85.96	gold quality
sural nerve	UBERON:0015488	85.95	gold quality
adrenal cortex	UBERON:0001235	85.86	gold quality
thyroid gland	UBERON:0002046	85.79	gold quality
parietal pleura	UBERON:0002400	85.75	gold quality
left lobe of thyroid gland	UBERON:0001120	85.74	gold quality
endometrium epithelium	UBERON:0004811	85.72	gold quality
urinary bladder	UBERON:0001255	85.70	gold quality
ventricular zone	UBERON:0003053	85.64	gold quality
pleura	UBERON:0000977	85.55	gold quality
uterine cervix	UBERON:0000002	85.53	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	49.94
E-ANND-3	yes	9.34

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Olfactory bulb	tissue	67.5
Choroid plexus	tissue	65.6
Parathyroid gland	tissue	34.9	high
Nucleus accumbens	tissue	24.1
Breast	tissue	23.8	medium
Kidney	tissue	23.7	medium
Skin 1	tissue	23.5	medium
Prostate	tissue	22.1	medium
Cerebellum	tissue	20.6	medium
Colon	tissue	20.3	high
Epididymis	tissue	20.3	high
Rectum	tissue	20.1	high
Thymus	tissue	19.5
Caudate putamen	tissue	19.4
Tonsil	tissue	19.0	medium
Thyroid gland	tissue	18.8	medium
Postcentral gyrus	tissue	18.4
Lymph node	tissue	18.1	low
Stomach 1	tissue	17.7	high
Locus coeruleus	tissue	17.5
Hippocampus	tissue	16.5	low
Retina	tissue	15.6
Salivary gland	tissue	15.6	medium
Liver	tissue	15.6	low
Duodenum	tissue	15.6	high
Superior colliculi	tissue	15.4
Esophagus	tissue	15.3	high
Fallopian tube	tissue	15.1	medium
Periaqueductal gray	tissue	14.9
Basal ganglia	tissue	14.8	low
Putamen	tissue	14.7
Pancreas	tissue	14.6	high
Ventral forebrain	tissue	14.6
Septum	tissue	14.2
Small intestine	tissue	13.9	high
Amygdala	tissue	13.4
Hippocampal formation	tissue	13.4
Entorhinal cortex	tissue	13.4
Cervix	tissue	13.3	medium
Urinary bladder	tissue	13.1	high
Thalamus	tissue	12.9
Medulla oblongata	tissue	12.8
Hypothalamus	tissue	12.7
Midbrain	tissue	12.6
Cerebral cortex	tissue	12.4	medium
Temporal cortex	tissue	12.4
Occipital cortex	tissue	12.2
Pons	tissue	12.1
Adrenal gland	tissue	12.1	medium
Spinal cord	tissue	11.9
Somatosensory cortex	tissue	11.9
Substantia nigra	tissue	11.8
Lung	tissue	11.7	medium
Corpus callosum	tissue	11.7
Frontal cortex	tissue	11.6
Retrosplenial and cingulate cortex	tissue	11.6
Insular cortex	tissue	11.6
Gallbladder	tissue	11.2	high
Retrosplenial cortex	tissue	11.2
Appendix	tissue	11.2	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Ventral periolivary nuclei (32.9), Flocculonodular lobe (31.3), Nuclei of the trapezoid body (31.3), Vermis (31.3), Cerebellar cortex (31.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, TP53

miRNA regulators (miRDB)

Targeting LRBA by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 88 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-3121-3P	99.82	71.96	3630

Functional genomics

gnomAD constraint: pLI 0.00996, LOEUF 0.515, missense Z 1.37 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000651943 — one region, missense o/e 0.95.

Literature-anchored findings (GeneRIF, showing 36)

• The crystal structure of the aPH-BEACH domains of LRBA were studied. (PMID:15554694)
• mutations in LRBA cause an immune deficiency characterized by defects in B cell activation and autophagy and by susceptibility to apoptosis, associated with a clinical phenotype of hypogammaglobulinemia and autoimmunity (PMID:22608502)
• A truncating mutation in LRBA, which abolished protein expression, was identified as the most likely candidate in a consanguineous family with chronic inflammatory bowel disease-like disorder and combined immunodeficiency. (PMID:22721650)
• LRBA deficiency is a novel cause of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome and Treg cell deficiency associated with metabolic dysfunction and increased apoptosis of Treg cells. (PMID:25468195)
• A homozygous missense mutation in lipopolysaccharide-responsive and beige-like anchor gene is associated with inflammatory bowel disease. (PMID:25479458)
• LRBA mutation was associated with an autoimmune lymphoproliferative syndrome-like disease characterized by splenomegaly and lymphadenopathy, cytopenia, elevated double negative T cells and raised serum Fas ligand levels. (PMID:25931386)
• Variants of LRBA were associated with common variable immunodeficiency. (PMID:26122175)
• Patients with LRBA deficiency manifested a dramatic and sustained improvement in response to abatacept, a CTLA4 (cytotoxic T lymphocyte antigen-4)-immunoglobulin fusion drug. (PMID:26206937)
• homozygous frame shift mutation results in refractory Celiac dsease (PMID:26686526)
• mutations result in various immunodeficiency phenotypes (PMID:26707784)
• diagnosis of LRBA deficiency was confirmed by a fluorescence-activated cell sorting-based immunoassay (PMID:26745254)
• Among 2 brothers homozygous for LPS responsive beige-like anchor protein (LRBA) mutation, one developed Evans syndrome and deceased at age 8.5, and his brother carried the same homozygous LRBA mutation with early-onset erosive polyarthritis. (PMID:27057999)
• Case Report: potential causative role of LRBA gene mutations in juvenile arthritis. (PMID:28134088)
• Assessing total CTLA-4 expression levels was found to be optimal when restricting analysis to the CD45RA(-)Foxp3(+) fraction. CTLA-4 induction following stimulation, and the use of lysosomal-blocking compounds, distinguished CTLA-4 from LRBA mutations (PMID:28159733)
• As diabetes was the presenting feature in six of nine individuals, we recommend that testing for LRBA mutations is considered in all patients with newly diagnosed neonatal diabetes and in those with infancy-onset diabetes (<12 months), especially when a recessive inheritance is suspected or additional autoimmune features are present (PMID:28473463)
• cTFH cell dysregulation in patients with LRBA deficiency reflects impaired control of TFH cell differentiation because of profoundly decreased CTLA4 expression on regulatory T cells and probably contributes to autoimmunity in patients with this disease. Serial monitoring of cTFH cell frequencies is highly useful in gauging the clinical response of LRBA-deficient patients to CTLA4-Ig therapy. (PMID:28601686)
• LRBA is required for hair bundle maintenance in cochlear hair cells and for hearing. (PMID:28893864)
• The present results suggest that LRBA SNPs are associated with CWP susceptibility in a Chinese population. (PMID:28953250)
• Mutations found in 7 out of 18 children with Evans syndrome (ES) involved lipopolysaccharide-responsive beige-like anchor protein (LRBA) and cytotoxic T-lymphocyte protein 4 (CTLA-4). (PMID:29330115)
• LRBA Deficiency in Siblings. (PMID:29461210)
• This easy flow cytometry-based assay allows a fast screening of patients with suspicion of LRBA deficiency reducing therefore the number of patients requiring LRBA sequencing and accelerating the treatment implementation. Detection of biallelic mutations in LRBA is however required for a definitive diagnosis. (PMID:29740429)
• Our findings demonstrated an imbalance in Th subsets, mainly in Th1-like Th17 and Treg cells and their corresponding cytokines in LRBA deficiency, which might be important in the immunopathogenesis of autoimmunity and enteropathy. (PMID:29806698)
• We are the first to report normal CTLA-4 expression and normal Treg-cell function in the face of overactive TH17 immunity in an LRBA-deficient patient, illustrating that loss of CTLA-4 is not a prerequisite for autoimmunity in LRBA deficiency (PMID:30193839)
• CTLA-4 Expression in CD4+ T Cells From Patients With LRBA Deficiency. (PMID:30530390)
• lymphocyte chromosomal radiosensitivity in patients with LPS responsive beige-like anchor protein (LRBA) deficiency (PMID:30714845)
• Dissecting the localization of lipopolysaccharide-responsive and beige-like anchor protein (LRBA) in the endomembrane system. (PMID:31883622)
• Clinical Phenotypes and Immunological Characteristics of 18 Egyptian LRBA Deficiency Patients. (PMID:32506362)
• Evaluation of Expression of LRBA and CTLA-4 Proteins in Common Variable Immunodeficiency Patients. (PMID:33191838)
• Pulmonary manifestations of immune dysregulation in CTLA-4 haploinsufficiency and LRBA deficiency. (PMID:33710794)
• Case Report: Refractory Autoimmune Gastritis Responsive to Abatacept in LRBA Deficiency. (PMID:33717114)
• Comprehensive comparison between 222 CTLA-4 haploinsufficiency and 212 LRBA deficiency patients: a systematic review. (PMID:33788257)
• Novel compound heterozygous LRBA deletions in a 6-month-old with neonatal diabetes. (PMID:33845048)
• Comparing the levels of CTLA-4-dependent biological defects in patients with LRBA deficiency and CTLA-4 insufficiency. (PMID:35491430)
• Clinically Complex LRBA Deficiency Due to a Founder Allele in the Georgian Jewish Population. (PMID:36063261)
• Various phenotypes of LRBA gene with compound heterozygous variation: A case series report of pediatric cytopenia patients. (PMID:36074705)
• Arf1-dependent LRBA recruitment to Rab4 endosomes is required for endolysosome homeostasis. (PMID:39325073)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrba	ENSDARG00000031108
mus_musculus	Lrba	ENSMUSG00000028080
rattus_norvegicus	Lrba	ENSRNOG00000023453
caenorhabditis_elegans		WBGENE00004760
caenorhabditis_elegans		WBGENE00007752

Paralogs (7): NSMAF (ENSG00000035681), WDFY4 (ENSG00000128815), LYST (ENSG00000143669), NBEAL1 (ENSG00000144426), NBEAL2 (ENSG00000160796), WDFY3 (ENSG00000163625), NBEA (ENSG00000172915)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1933162) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 22 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased circulating chloride level	2
abnormal ear position	1
increased circulating calcium level	1
increased circulating HDL cholesterol level	1
increased circulating alkaline phosphatase level	1
increased circulating bicarbonate level	1
increased length of allograft survival	1
increased regulatory T cell number	1
impaired natural killer cell mediated cytotoxicity	1
increased circulating cholesterol level	1
increased circulating creatinine level	1
increased blood urea nitrogen level	1
increased circulating total protein level	1
decreased circulating sodium level	1
decreased susceptibility to graft versus host disease	1
increased urine sodium level	1
absent pinna reflex	1
increased susceptibility to induced colitis	1
increased circulating amylase level	1
abnormal NK cell physiology	1
isosthenuria	1
increased myeloid cell number	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5REE6	99.5%	Diamond
Bos taurus	Q0VC24	96.2%	Diamond
Caenorhabditis briggsae	A8XSV3	89.7%	Diamond
Gallus gallus	Q9DDD5	87.2%	Diamond
Oryza sativa Japonica Group	P49027	80.1%	Diamond
Arabidopsis thaliana	F4HZB2	77.6%	Diamond
Drosophila melanogaster	Q9W4E2	64.7%	Diamond
Dictyostelium discoideum	Q54RQ8	60.0%	Diamond
Saccharomyces cerevisiae S288C	P25356	54.4%	Diamond
Schizosaccharomyces pombe 972h-	Q7LKZ7	46.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MAB21L2	protein-coding	10586
DCLK2	protein-coding	166614
LRBA-AS1	ncRNA	729558
SNORD73B	snoRNA	114655
RPS3A	protein-coding	6189
IQCM	protein-coding	285423
SH3D19-AS1	ncRNA	107986196
SH3D19	protein-coding	152503
SNORD73A	snoRNA	8944

Protein

Protein identifiers

Lipopolysaccharide-responsive and beige-like anchor protein — P50851 (reviewed: P50851)

Alternative names: Beige-like protein, CDC4-like protein

All UniProt accessions (14): P50851, A0A3B3IS13, A0A3B3ISK3, A0A3B3IU76, A0A494BZW2, A0A494C0R9, A0A494C1L5, A0A8V8TKR0, A0A8V8TL26, A0A8V8TLZ6, A0A8V8TM79, E9PEM5, H0Y9N9, H0YA17

UniProt curated annotations — full annotation on UniProt →

Function. Involved in coupling signal transduction and vesicle trafficking to enable polarized secretion and/or membrane deposition of immune effector molecules. Involved in phagophore growth during mitophagy by regulating ATG9A trafficking to mitochondria.

Subunit / interactions. Interacts with TOM1 and TOLLIP.

Subcellular location. Cell membrane. Endoplasmic reticulum membrane. Golgi apparatus. trans-Golgi network membrane. Lysosome membrane.

Tissue specificity. Ubiquitous.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Induction. By bacterial lipopolysaccharides (LPS).

Isoforms (2)

UniProt ID	Names	Canonical?
P50851-1	1	yes
P50851-2	2

RefSeq proteins (8): NP_001186211, NP_001351834, NP_001354479, NP_001427359, NP_001427360, NP_001427361, NP_001427362, NP_006717 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000409	BEACH_dom	Domain
IPR001680	WD40_rpt	Repeat
IPR010508	NBEA-like_DUF1088	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR023362	PH-BEACH_dom	Domain
IPR031570	NBEA/BDCP_DUF4704	Domain
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR036372	BEACH_dom_sf	Homologous_superfamily
IPR046851	NBCH_WD40	Domain
IPR046852	Neurobeachin_a-sol	Domain
IPR050865	BEACH_Domain	Family

Pfam: PF02138, PF06469, PF13385, PF14844, PF15787, PF20425, PF20426

UniProt features (95 total): helix 25, modified residue 17, sequence variant 11, strand 10, compositionally biased region 7, repeat 6, region of interest 6, sequence conflict 3, domain 2, splice variant 2, turn 2, initiator methionine 1, chain 1, coiled-coil region 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
1T77	Crystal structure of the PH-BEACH domains of human LRBA/BGL	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

No AlphaFold model available for P50851 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Disease related genes, Human disease related genes, Primary immunodeficiency

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus; cytosol

Antibody reliability (HPA): IH approved · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (17)

Type	Positions
N-acetylalanine	2
Phosphoserine	10, 979, 1003, 1100, 1135, 1139, 1233, 1247, 1261, 1488, 1498, 1605, 1767, 1770, 2064, 2496

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 329 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_VACUOLE_ORGANIZATION, KAAB_FAILED_HEART_ATRIUM_DN, GOCC_VACUOLAR_MEMBRANE, TTTGTAG_MIR520D, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, CAGCTG_AP4_Q5, GOBP_MACROAUTOPHAGY, KYNG_DNA_DAMAGE_BY_GAMMA_RADIATION, GENTILE_UV_HIGH_DOSE_DN, ATTCTTT_MIR186, GOBP_ORGANELLE_ASSEMBLY, ZHANG_BREAST_CANCER_PROGENITORS_UP, CUI_TCF21_TARGETS_2_DN, CTTTGTA_MIR524

GO Biological Process (2): mitophagy (GO:0000423), protein localization to phagophore assembly site (GO:0034497)

GO Molecular Function (2): protein kinase binding (GO:0019901), protein binding (GO:0005515)

GO Cellular Component (7): lysosomal membrane (GO:0005765), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), cytoplasm (GO:0005737)

GO top-level categories

18 GO namespaces:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
autophagy of mitochondrion	1
macroautophagy	1
autophagosome assembly	1
intracellular protein localization	1
kinase binding	1
binding	1
lysosome	1
lytic vacuole membrane	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 11 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
mitophagy	BP	mutant phenotype
protein localization to phagophore assembly site	BP	mutant phenotype
Golgi apparatus	CC	direct assay
membrane	CC	high-throughput assay

Protein interactions and networks

STRING

showing 16 of 1,042 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRBA	RBP3	P10745	723
LRBA	MYL3	P08590	661
LRBA	SLC9C1	Q4G0N8	653
LRBA	PIK3R4	Q99570	646
LRBA	FBXW7	Q969H0	620
LRBA	SPINK1	P00995	609
LRBA	CTLA4	P16410	606
LRBA	TTC7A	Q9ULT0	600
LRBA	IL10RA	Q13651	565
LRBA	TNFRSF13B	O14836	549
LRBA	STXBP2	Q15833	542
LRBA	PRKACB	P22694	538
LRBA	DOCK8	Q8NF50	537
LRBA	PRKACA	P17612	536
LRBA	ADCY10	Q96PN6	498
LRBA	SDHC	Q99643	498

IntAct

Human interaction partners of LRBA in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

10 partners by confidence:

Partner	Interaction type	MIscore	Records
CTLA4	physical association	0.670	2
ABL1	physical association	0.400	1
FYN	physical association	0.400	1
H3C13	physical association	0.400	1
SENP1	physical association	0.400	1
CAPN5	association	0.350	1
RD3	association	0.350	1
SLC27A4	association	0.350	1
HSPA13	physical association	0.000	1
TUSC2	physical association	0.000	1

BioGRID (245 interactions; top human partners by supporting records): CT55 (Affinity Capture-MS; 3 records), RD3 (Affinity Capture-MS; 3 records), RIC3 (Affinity Capture-MS; 3 records), ALK (Proximity Label-MS; 2 records), EPHA1 (Affinity Capture-MS; 2 records), FAM196A (Affinity Capture-MS; 2 records), FGFR1 (Proximity Label-MS; 2 records), GYPB (Affinity Capture-MS; 2 records), LAMP1 (Proximity Label-MS; 2 records), NCR3LG1 (Affinity Capture-MS; 2 records), PVR (Affinity Capture-MS; 2 records), RAB11A (Proximity Label-MS; 2 records), RAB4A (Proximity Label-MS; 2 records), RAB9A (Proximity Label-MS; 2 records), TGOLN2 (Affinity Capture-MS; 2 records)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
E2F1	“up-regulates quantity by expression”	LRBA	“transcriptional regulation”
TP53	“down-regulates quantity by repression”	LRBA	“transcriptional regulation”

Disease & clinical

Genetic variants

Variant evidence for LRBA: 2,683 ClinVar records (203 pathogenic / likely pathogenic); 11 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

2,683 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	124
Likely pathogenic	79
Uncertain significance	1268
Likely benign	925
Benign	94

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 203 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
35455	NM_001364905.1(LRBA):c.7937T>G (p.Ile2646Ser)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
1176175	NM_001364905.1(LRBA):c.7009C>T (p.Arg2337Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
35456	NM_001364905.1(LRBA):c.5047C>T (p.Arg1683Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
827717	NM_001364905.1(LRBA):c.4522C>T (p.Gln1508Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
973590	NM_001364905.1(LRBA):c.4333C>T (p.Arg1445Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
1458881	NM_001364905.1(LRBA):c.2836_2839del (p.Glu945_Glu946insTer)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1495928	NM_001364905.1(LRBA):c.5646-2A>T	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2146562	NM_001364905.1(LRBA):c.7282C>T (p.Arg2428Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
3720595	NM_001364905.1(LRBA):c.544C>T (p.Arg182Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
4763783	NM_001364905.1(LRBA):c.6382C>T (p.Arg2128Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
973589	NM_001364905.1(LRBA):c.4159-1G>T	Likely pathogenic	criteria provided, multiple submitters, no conflicts	5
2900567	NM_001364905.1(LRBA):c.5518+2T>C	Likely pathogenic	criteria provided, multiple submitters, no conflicts	4
3235014	NM_001364905.1(LRBA):c.4759_4762del (p.Thr1587fs)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
859600	NM_001364905.1(LRBA):c.5519-1G>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
968938	NM_001364905.1(LRBA):c.1923_1924+11del	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2

Per-variant reference — Sugi Variant

Explore LRBA’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 38 predictions of 6,501):

Position(s)	Effect	Δscore	Sites
4:150265813–150265814	acceptor_loss	1.0000	2
4:150266459	acceptor_gain	1.0000
4:150302623–150302624	donor_loss	1.0000	5
4:150302793–150302794	acceptor_loss	1.0000	6
4:150310385–150310386	acceptor_loss	1.0000	6
4:150315624	acceptor_loss	1.0000	2
4:150315635	acceptor_gain	1.0000
4:150349990–150349991	donor_loss	1.0000	4
4:150350160–150350161	acceptor_loss	1.0000	5
4:150415436–150415437	donor_loss	1.0000	6

AlphaMissense

6,100 missense substitutions predicted likely pathogenic (of 18,757 scored), across 1,480 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M1855	9	0.977	0.999
M451	9	0.913	0.995
M1544	9	0.900	0.998
M2510	9	0.897	0.990
D2617	8	0.993	0.999
F1874	8	0.992	0.999
H2637	8	0.992	0.997
D2663	8	0.992	0.999
H448	8	0.985	0.997
D2334	8	0.983	0.991
D1511	8	0.978	0.993
N856	8	0.977	0.998
D914	8	0.977	0.994
F1818	8	0.977	0.998
H2696	8	0.977	0.993
D2425	8	0.974	0.994
D2572	8	0.974	0.991
D845	8	0.968	0.988
D1817	8	0.968	0.991
F2333	8	0.968	0.996

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	5.36e-10

Disease associations

OMIM: gene MIM:606453 | disease phenotypes: MIM:614700, MIM:615877, MIM:615401

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
combined immunodeficiency due to LRBA deficiency	Strong	Autosomal recessive	5

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
combined immunodeficiency due to LRBA deficiency	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (12 panels, 11 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

12 panels:

Panel	Rating
COVID-19 research	green
Childhood interstitial lung disease	green
DDG2P	green
Diabetes with additional phenotypes suggestive of a monogenic aetiology	green
Familial diabetes	green
Infantile enterocolitis & monogenic inflammatory bowel disease	green
Intestinal failure or congenital diarrhoea	green
Multi-organ autoimmune diabetes	green
Neonatal diabetes	green
Paediatric disorders	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green
Gastrointestinal epithelial barrier disorders	amber

Mondo (3): combined immunodeficiency due to LRBA deficiency (MONDO:0013863), colobomatous microphthalmia-rhizomelic dysplasia syndrome (MONDO:0014380), severe combined immunodeficiency due to CORO1A deficiency (MONDO:0014168)

Orphanet (3): Syndromic autoimmune enteropathy due to LRBA deficiency (Orphanet:445018), Colobomatous microphthalmia-rhizomelic dysplasia syndrome (Orphanet:424099), Severe combined immunodeficiency due to CORO1A deficiency (Orphanet:228003)

HPO phenotypes

45 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000403	Recurrent otitis media
HP:0000509	Conjunctivitis
HP:0000554	Uveitis
HP:0000821	Hypothyroidism
HP:0001045	Vitiligo
HP:0001369	Arthritis
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001744	Splenomegaly
HP:0001873	Thrombocytopenia
HP:0001876	Pancytopenia
HP:0001890	Autoimmune hemolytic anemia
HP:0001973	Autoimmune thrombocytopenia
HP:0002028	Chronic diarrhea
HP:0002037	Inflammation of the large intestine
HP:0002090	Pneumonia
HP:0002099	Asthma
HP:0002110	Bronchiectasis
HP:0002205	Recurrent respiratory infections
HP:0002582	Atrophic gastritis
HP:0002583	Colitis
HP:0002665	Lymphoma
HP:0002716	Lymphadenopathy
HP:0002719	Recurrent infections
HP:0002720	Decreased circulating IgA concentration
HP:0002721	Immunodeficiency
HP:0002850	Decreased circulating IgM concentration
HP:0004315	Decreased circulating IgG concentration
HP:0005523	Lymphoproliferative disorder
HP:0006528	Chronic lung disease
HP:0006532	Recurrent pneumonia
HP:0008940	Generalized lymphadenopathy
HP:0010976	Decreased total B cell count
HP:0011108	Recurrent sinusitis
HP:0011473	Villous atrophy
HP:0012219	Erythema nodosum
HP:0025526	Psoriasiform lesion
HP:0030388	Decreased class-switched memory B cell proportion
HP:0032140	Decreased specific antibody response to vaccination
HP:0100646	Thyroiditis
HP:0100651	Type I diabetes mellitus
HP:0100759	Clubbing of fingers
HP:0100806	Sepsis
HP:0410252	Persistently decreased total neutrophil count

GWAS associations

11 associations:

Study	Trait	p-value
GCST007209_5	Gallstone disease	5e-27
GCST90013406_218	Liver enzyme levels (alkaline phosphatase)	2e-26
GCST90011900_64	Serum alkaline phosphatase levels	3e-18
GCST90002398_281	Neutrophil count	1e-13
GCST90002407_91	White blood cell count	1e-13
GCST006628_39	Systolic blood pressure	4e-10
GCST004079_1	Drug-induced hepatocellular liver injury	5e-9
GCST002997_2	Helix rolling	2e-8
GCST003001_5	Ear morphology	4e-8
GCST001715_3	Bipolar disorder with mood-incongruent psychosis	1e-7
GCST010397_96	Gut microbiota (bacterial taxa, rank normal transformation method)	5e-6

EFO canonical traits (from GWAS)

6 canonical traits:

EFO ID	Trait name
EFO:0007670	helix rolling
EFO:0007664	outer ear morphology trait
EFO:0006335	systolic blood pressure
EFO:0007874	gut microbiome measurement
EFO:0004833	neutrophil count
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066253 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.78	Kd	167.1	nM	CHEMBL5653589
6.78	ED50	167.1	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148664: Binding affinity to human LRBA incubated for 45 mins by Kinobead based pull down assay	kd	0.1671	uM

CTD chemical–gene interactions

58 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	8
Aflatoxin B1	increases methylation, affects expression, decreases expression	5
Cisplatin	affects cotreatment, decreases expression, increases expression	3
Valproic Acid	decreases methylation, increases expression, affects expression	3
Acetaminophen	decreases expression	2
Air Pollutants	decreases expression, affects cotreatment, affects expression, affects oxidation, increases abundance	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects oxidation, increases abundance, affects cotreatment, affects expression	1
bisphenol A	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	decreases expression, increases abundance	1
cobaltous chloride	decreases expression	1
ochratoxin A	increases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	decreases methylation	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, affects expression, affects oxidation, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
bicalutamide	increases expression	1
tamibarotene	affects expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651706	Binding	Binding affinity to human LRBA incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E0WI	Ubigene Jurkat, Clone E6-1 LRBA KO	Cancer cell line	Male
CVCL_SV80	HAP1 LRBA (-) 1	Cancer cell line	Male
CVCL_SV81	HAP1 LRBA (-) 2	Cancer cell line	Male
CVCL_SV82	HAP1 LRBA (-) 3	Cancer cell line	Male
CVCL_SV83	HAP1 LRBA (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT01574313	Phase 4	COMPLETED	Effect of Stellate Ganglion Block on Meniere’s Disease
NCT02529475	Phase 4	TERMINATED	Evaluation of Inner Ear and Brain Structures With Contrast-enhanced MRI in Healthy Subjects (HYDROPS)
NCT04815187	Phase 4	ACTIVE_NOT_RECRUITING	Repurposed Use of Allergic Rhinitis and Allergic Asthma Drug to Reduce Vertigo and Hearing Loss in Meniere’s Disease
NCT00000374	Phase 4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	Phase 4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	Phase 4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	Phase 4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	Phase 4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	Phase 4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	Phase 4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	Phase 4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	Phase 4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	Phase 4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	Phase 4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	Phase 4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	Phase 4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	Phase 4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	Phase 4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	Phase 4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	Phase 4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	Phase 4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	Phase 4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	Phase 4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	Phase 4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	Phase 4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	Phase 4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	Phase 4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	Phase 4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	Phase 4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	Phase 4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	Phase 4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	Phase 4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	Phase 4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	Phase 4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	Phase 4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	Phase 4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	Phase 4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	Phase 4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	Phase 4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	Phase 4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	Phase 4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	Phase 4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	Phase 4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety
NCT00177580	Phase 4	COMPLETED	Improving Symptoms of Schizophrenia and Schizoaffective Disorder by Supplementing Medications With Pravastatin
NCT00182442	Phase 4	COMPLETED	Cognition, Functioning and Quality of Life
NCT00182494	Phase 4	UNKNOWN	Diabetes Prevention Program in Schizophrenia [DPPS]
NCT00183625	Phase 4	COMPLETED	Supported Employment and Skills Training in Conjunction With Pharmacotherapy in Schizophrenia Patients
NCT00186771	Phase 4	UNKNOWN	Magnetic Stimulation as a Treatment for Auditory Hallucinations in Schizophrenia
NCT00190749	Phase 4	COMPLETED	Safety Study of Olanzapine and a Comparator in Patients With Schizophrenia and Schizoaffective Disorder
NCT00191555	Phase 4	COMPLETED	Efficacy Study of Switching Stabilized Schizophrenic Patients From Conventional to Atypical Antipsychotic Treatment
NCT00194025	Phase 4	COMPLETED	Valproate in Late Life Schizophrenia
NCT00199940	Phase 4	COMPLETED	Safety And Efficacy Study Of Ziprasidone In Pediatric Psychotic Illness
NCT00202306	Phase 4	COMPLETED	Indicated Prevention of Psychotic Disorders With Low-dose Lithium
NCT00203788	Phase 4	COMPLETED	Improving Work Outcome in People With Recent-onset Schizophrenia
NCT00204061	Phase 4	COMPLETED	Early Pharmacological and Psychological Intervention for Late Prodromal States of Psychosis
NCT00205660	Phase 4	COMPLETED	Changes in Adiposity, Metabolic Measures From Atypicals to Aripiprazole
NCT00206102	Phase 4	COMPLETED	A Study of the Cataractogenic Potential of Seroquel and Risperdal in the Treatment of Participants With Schizophrenia or Schizoaffective Disorder
NCT00208143	Phase 4	COMPLETED	Seroquel Therapy for Substance Use Disorders Comorbid With Schizophrenia
NCT00208169	Phase 4	COMPLETED	Abilify Therapy for Reducing Comorbid Substance Abuse
NCT00214578	Phase 4	COMPLETED	Seroquel on Glucose Metabolism

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for LRBA across ~30M SureChEMBL compounds — explore on Sugi Predict.