ADGRB1

Summary

ADGRB1 (adhesion G protein-coupled receptor B1, HGNC:943) is a protein-coding gene on chromosome 8q24.3, encoding Adhesion G protein-coupled receptor B1 (O14514). Phosphatidylserine receptor which enhances the engulfment of apoptotic cells.

Angiogenesis is controlled by a local balance between stimulators and inhibitors of new vessel growth and is suppressed under normal physiologic conditions. Angiogenesis has been shown to be essential for growth and metastasis of solid tumors. In order to obtain blood supply for their growth, tumor cells are potently angiogenic and attract new vessels as results of increased secretion of inducers and decreased production of endogenous negative regulators. BAI1 contains at least one ‘functional’ p53-binding site within an intron, and its expression has been shown to be induced by wildtype p53. There are two other brain-specific angiogenesis inhibitor genes, designated BAI2 and BAI3 which along with BAI1 have similar tissue specificities and structures, however only BAI1 is transcriptionally regulated by p53. BAI1 is postulated to be a member of the secretin receptor family, an inhibitor of angiogenesis and a growth suppressor of glioblastomas

Source: NCBI Gene 575 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 246 total — 6 pathogenic
• MANE Select transcript: NM_001702

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:943
Approved symbol	ADGRB1
Name	adhesion G protein-coupled receptor B1
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000181790
Ensembl biotype	protein_coding
OMIM	602682
Entrez	575

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000517894, ENST00000518812, ENST00000518820, ENST00000521208, ENST00000643448

RefSeq mRNA: 3 — MANE Select: NM_001702 NM_001391985, NM_001391986, NM_001702

CCDS: CCDS64985, CCDS94349

Canonical transcript exons

ENST00000517894 — 31 exons

Exon	Start	End
ENSE00001264747	142479693	142479794
ENSE00001264755	142479323	142479487
ENSE00001264770	142477385	142477549
ENSE00001264779	142477114	142477278
ENSE00001264784	142476585	142476695
ENSE00001264792	142475474	142475635
ENSE00001292246	142478187	142478360
ENSE00001749723	142524238	142524304
ENSE00002098138	142463980	142464982
ENSE00003467061	142481254	142481360
ENSE00003467365	142536987	142537082
ENSE00003478204	142489035	142489110
ENSE00003490337	142543403	142543438
ENSE00003545389	142488364	142488507
ENSE00003551359	142522641	142522710
ENSE00003551633	142510932	142511073
ENSE00003554646	142539374	142539413
ENSE00003556732	142543601	142543708
ENSE00003585681	142483977	142484045
ENSE00003604787	142521965	142522115
ENSE00003608783	142526542	142526627
ENSE00003609698	142533295	142533466
ENSE00003614134	142490772	142490815
ENSE00003615097	142481517	142481711
ENSE00003645548	142489336	142489438
ENSE00003651296	142484656	142484764
ENSE00003671264	142518138	142518241
ENSE00003682050	142541941	142542647
ENSE00003687141	142520823	142520925
ENSE00003934213	142449649	142450104
ENSE00003938235	142544220	142545007

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 96.43.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2632 / max 290.3580, expressed in 206 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
91335	0.8426	173
91334	0.2545	104
91333	0.1159	48
91332	0.0503	21

Top tissues by expression

277 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	96.43	gold quality
nucleus accumbens	UBERON:0001882	94.43	gold quality
cingulate cortex	UBERON:0003027	93.83	gold quality
anterior cingulate cortex	UBERON:0009835	93.71	gold quality
amygdala	UBERON:0001876	93.41	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.76	gold quality
caudate nucleus	UBERON:0001873	92.31	gold quality
putamen	UBERON:0001874	92.13	gold quality
prefrontal cortex	UBERON:0000451	91.33	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.16	gold quality
neocortex	UBERON:0001950	89.26	gold quality
cortical plate	UBERON:0005343	89.25	gold quality
frontal cortex	UBERON:0001870	88.78	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.30	gold quality
telencephalon	UBERON:0001893	87.74	gold quality
forebrain	UBERON:0001890	87.34	gold quality
hypothalamus	UBERON:0001898	86.84	gold quality
cerebral cortex	UBERON:0000956	86.76	gold quality
brain	UBERON:0000955	86.21	gold quality
central nervous system	UBERON:0001017	86.05	gold quality
adenohypophysis	UBERON:0002196	85.53	gold quality
pituitary gland	UBERON:0000007	85.42	gold quality
ganglionic eminence	UBERON:0004023	85.17	gold quality
cerebellar cortex	UBERON:0002129	84.84	gold quality
cerebellar hemisphere	UBERON:0002245	84.84	gold quality
Ammon’s horn	UBERON:0001954	84.12	gold quality
temporal lobe	UBERON:0001871	83.71	gold quality
substantia nigra	UBERON:0002038	83.17	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	83.10	gold quality
cerebellum	UBERON:0002037	82.97	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.24

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MBD2, TP53

miRNA regulators (miRDB)

29 targeting ADGRB1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-6529-3P	98.68	66.76	1020
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-1914-5P	97.83	66.21	807
HSA-MIR-4308	97.56	67.13	1385
HSA-MIR-6748-3P	97.20	65.66	836
HSA-MIR-1291	96.28	65.89	1224
HSA-MIR-6775-3P	95.76	65.91	982
HSA-MIR-339-3P	94.34	67.96	97

Literature-anchored findings (GeneRIF, showing 19)

• brain-specific angiogenesis inhibitor 1 over-expression suppresses tumour angiogenesis (PMID:11875720)
• BAI1 was expressed in cerebral neurons but not astrocytes. It was localized in the cytoplasm and cell membrane. BAI1 protein may play an important role in synapse formation and signal transduction (PMID:12074842)
• BAI1 was widely expressed in normal brain but was absent in 28 glioma cell lines and in the majority of human glioblastoma investigated. BAI1 expression did not correlate with TP53 status (PMID:12507886)
• MBD2 overexpression during gliomagenesis may drive tumor growth by suppressing the antiangiogenic activity of a key tumor BAI1. (PMID:21724586)
• Proprotein convertases, primarily furin, activate latent matrix metalloproteinase-14, which then directly cleaves BAI1 to release the bioactive fragment. (PMID:22330140)
• The results of this study indicated that BAI1 plays an important role in synaptogenesis that is mechanistically distinct from its role in phagocytosis. (PMID:23595754)
• findings demonstrate that BAI1 is a synaptic receptor that can activate both the Rho and ERK pathways, with the N-terminal and C-terminal regions of the receptor playing key roles in the regulation of BAI1 signaling activity (PMID:23782696)
• recognition of apoptotic cells by BAI1 contributes to their clearance in the human gastric mucosa and this is associated with anti-inflammatory effects (PMID:24509909)
• Results show that lower BAI1 expression correlates with poorer patient survival, and high Nestin expression is associated with an increased probability of metastases in breast cancer patients. (PMID:25376607)
• BAI1 may be involved in the negative regulation of bladder transitional cell carcinoma microvascular proliferation, and its expression may be associated with a reduction in p53 mutations. (PMID:26129954)
• Data suggest agonist-induced signal transduction via either BAI1/ADGRB1 or GPR56/ADGRG1 does not require conserved membrane-proximal stalk region; thus, it appears GAIN domain cleavage via autoproteolysis is not necessary for receptor activation. (PMID:26710850)
• We have uncovered a new role for BAI1 in facilitating macrophage anti-viral responses. We show that arming oHSV with antiangiogenic Vstat120 also shields them from inflammatory macrophage antiviral response, without reducing safety (PMID:27852701)
• Brain-specific angiogenesis inhibitor 1 (BAI1) prevents proto-oncogene Protein c-mdm2 (Mdm2)-mediated tumor supressor p53 (p53) polyubiquitination, and its loss substantially reduces p53 levels. (PMID:29894688)
• EZH2 targeting reduces medulloblastoma growth through epigenetic reactivation of the BAI1/p53 tumor suppressor pathway. (PMID:31582835)
• BAI1 acts as a tumor suppressor in lung cancer A549 cells by inducing metabolic reprogramming via the SCD1/HMGCR module. (PMID:32255478)
• Brain-specific angiogenesis inhibitor 1 is expressed in the Myo/Nog cell lineage. (PMID:32614850)
• BAI1 nuclear expression reflects the survival of nonsmoking non-small cell lung cancer patients. (PMID:33934543)
• BAI1 as a Prognostic Marker of Clear Cell Renal Cell Carcinoma (ccRCC). (PMID:34475070)
• Maternal exposure to atmospheric PM2.5 and fetal brain development: Associations with BAI1 methylation and thyroid hormones. (PMID:35738517)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	adgrb1a	ENSDARG00000075133
danio_rerio	adgrb1b	ENSDARG00000078529
mus_musculus	Adgrb1	ENSMUSG00000034730
rattus_norvegicus	AABR07058422.1	ENSRNOG00000029450

Paralogs (42): CALCR (ENSG00000004948), GIPR (ENSG00000010310), ADGRA2 (ENSG00000020181), CALCRL (ENSG00000064989), GLP2R (ENSG00000065325), ADGRF5 (ENSG00000069122), ADGRL1 (ENSG00000072071), ADCYAP1R1 (ENSG00000078549), SCTR (ENSG00000080293), VIPR2 (ENSG00000106018), CRHR2 (ENSG00000106113), GHRHR (ENSG00000106128), ADGRD1 (ENSG00000111452), GLP1R (ENSG00000112164), ADGRG6 (ENSG00000112414), VIPR1 (ENSG00000114812), ADGRL2 (ENSG00000117114), CRHR1 (ENSG00000120088), ADGRB2 (ENSG00000121753), ADGRE5 (ENSG00000123146), ADGRE2 (ENSG00000127507), ADGRE3 (ENSG00000131355), ADGRB3 (ENSG00000135298), PTH2R (ENSG00000144407), ADGRG7 (ENSG00000144820), ADGRL3 (ENSG00000150471), ADGRA3 (ENSG00000152990), ADGRF1 (ENSG00000153292), ADGRF4 (ENSG00000153294), ADGRG4 (ENSG00000156920), ADGRG5 (ENSG00000159618), PTH1R (ENSG00000160801), ADGRL4 (ENSG00000162618), EVA1C (ENSG00000166979), ADGRF3 (ENSG00000173567), ADGRG2 (ENSG00000173698), ADGRE1 (ENSG00000174837), ADGRD2 (ENSG00000180264), ADGRG3 (ENSG00000182885), ADGRA1 (ENSG00000197177)

Protein

Protein identifiers

Adhesion G protein-coupled receptor B1 — O14514 (reviewed: O14514)

Alternative names: Brain-specific angiogenesis inhibitor 1

All UniProt accessions (3): A0A2R8Y5M7, E5RG74, O14514

UniProt curated annotations — full annotation on UniProt →

Function. Phosphatidylserine receptor which enhances the engulfment of apoptotic cells. Also mediates the binding and engulfment of Gram-negative bacteria. Stimulates production of reactive oxygen species by macrophages in response to Gram-negative bacteria, resulting in enhanced microbicidal macrophage activity. In the gastric mucosa, required for recognition and engulfment of apoptotic gastric epithelial cells. Promotes myoblast fusion. Activates the Rho pathway in a G-protein-dependent manner. Inhibits MDM2-mediated ubiquitination and degradation of DLG4/PSD95, promoting DLG4 stability and regulating synaptic plasticity. Required for the formation of dendritic spines by ensuring the correct localization of PARD3 and TIAM1. Potent inhibitor of angiogenesis in brain and may play a significant role as a mediator of the p53/TP53 signal in suppression of glioblastoma. Inhibits angiogenesis in a CD36-dependent manner. Inhibits angiogenesis.

Subunit / interactions. Interacts with ELMO1 and DOCK. When bound to ELMO1 and DOCK1, acts as a module to promote apoptotic cell engulfment. Interacts with MDM2; the interaction results in inhibition of MDM2-mediated ubiquitination and degradation of DLG4/PSD95. Interacts with PARD3 and TIAM1; the interaction is required for correct dendritic. localization of PARD3 and TIAM1 and for dendritic spine formation. Interacts with MAGI1. Interacts with MAGI3. Interacts with BAIAP2. Interacts with PHYHIP. Interacts with DLG4 (via PDZ domain). Vasculostatin-120: Interacts with CD36. Vasculostatin-120: Interacts with ARRB2. Interacts with BAIAP3; this interaction is direct.

Subcellular location. Cell membrane. Cell projection. Phagocytic cup. Cell junction. Focal adhesion. Dendritic spine. Postsynaptic density Secreted Secreted.

Tissue specificity. Expressed in brain (at protein level). Expressed on mononuclear phagocytes and monocyte-derived macrophages in the gastric mucosa (at protein level). Expressed in normal pancreatic tissue but not in pancreatic tumor tissue. Reduced or no expression is observed in some glioblastomas.

Post-translational modifications. Proteolytically cleaved to produce vasculostatin-40 and vasculostatin-120. Vasculostatin-40 is the major form and is produced through proteolytic cleavage by MMP14 between residues 321 and 329 with cleavage likely to be between Ser-326 and Leu-327. Ubiquitinated.

Domain organisation. The TSP type-1 repeats in the extracellular domain mediate binding to phosphatidylserine. They are also required for bacterial recognition and binding to bacterial outer membrane lipopolysaccharide.

Induction. By p53/TP53.

Similarity. Belongs to the G-protein coupled receptor 2 family. LN-TM7 subfamily.

RefSeq proteins (3): NP_001378914, NP_001378915, NP_001693* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000203	GPS	Conserved_site
IPR000832	GPCR_2_secretin-like	Family
IPR000884	TSP1_rpt	Repeat
IPR001879	GPCR_2_extracellular_dom	Domain
IPR008077	GPCR_2_brain_angio_inhib	Family
IPR017981	GPCR_2-like_7TM	Domain
IPR032471	AGRL2-4_GAIN_subdom_A	Domain
IPR036383	TSP1_rpt_sf	Homologous_superfamily
IPR036445	GPCR_2_extracell_dom_sf	Homologous_superfamily
IPR043838	AGRB_N	Domain
IPR046338	GAIN_dom_sf	Homologous_superfamily
IPR057244	GAIN_B	Domain

Pfam: PF00002, PF00090, PF01825, PF02793, PF16489, PF19188

UniProt features (71 total): disulfide bond 19, topological domain 8, region of interest 8, transmembrane region 7, glycosylation site 7, domain 6, compositionally biased region 4, mutagenesis site 4, chain 3, modified residue 2, signal peptide 1, site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14514-F1	62.83	0.06

Functional residue map

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

Catalytic / active sites (1): 926–927 (cleavage)

Post-translational modifications (2): 609, 1469

Disulfide bonds (19): 273–309, 277–314, 288–299, 366–400, 370–406, 381–390, 421–456, 425–461, 436–446, 479–514, 483–519, 494–504, 534–569, 538–574, 549–559, 581–616, 604–634, 884–921, 909–923

Glycosylation sites (7): 64, 401, 607, 692, 844, 877, 881

Mutagenesis-validated functional residues (4):

Position	Phenotype
323–325	abolishes processing of vasculostatin-40.
326–328	does not affect processing of vasculostatin-40.
927	abolishes cleavage and production of vasculostatin-120.
927	increased levels of vasculostatin-120 and decreased levels of vasculostatin-40.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 201 (showing top): GGGACCA_MIR133A_MIR133B, E2F_Q4_01, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_SYNAPSE_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_BIOSYNTHETIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_SYNAPSE_ASSEMBLY, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_APOPTOTIC_CELL_CLEARANCE, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT

GO Biological Process (25): phagocytosis, recognition (GO:0006910), cell adhesion (GO:0007155), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), axonogenesis (GO:0007409), peripheral nervous system development (GO:0007422), muscle organ development (GO:0007517), negative regulation of cell population proliferation (GO:0008285), negative regulation of endothelial cell migration (GO:0010596), negative regulation of angiogenesis (GO:0016525), negative regulation of protein ubiquitination (GO:0031397), negative regulation of protein catabolic process (GO:0042177), apoptotic cell clearance (GO:0043277), engulfment of apoptotic cell (GO:0043652), innate immune response (GO:0045087), regulation of synaptic plasticity (GO:0048167), defense response to Gram-negative bacterium (GO:0050829), positive regulation of synapse assembly (GO:0051965), positive regulation of myoblast fusion (GO:1901741), positive regulation of reactive oxygen species biosynthetic process (GO:1903428), immune system process (GO:0002376), phagocytosis (GO:0006909), phagocytosis, engulfment (GO:0006911), nervous system development (GO:0007399)

GO Molecular Function (6): lipopolysaccharide binding (GO:0001530), phosphatidylserine binding (GO:0001786), G protein-coupled receptor activity (GO:0004930), PDZ domain binding (GO:0030165), transmembrane signaling receptor activity (GO:0004888), protein binding (GO:0005515)

GO Cellular Component (15): phagocytic cup (GO:0001891), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), focal adhesion (GO:0005925), postsynaptic density (GO:0014069), membrane (GO:0016020), dendrite (GO:0030425), dendritic spine (GO:0043197), perinuclear region of cytoplasm (GO:0048471), extracellular region (GO:0005576), cell junction (GO:0030054), cell projection (GO:0042995), synapse (GO:0045202), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
phagocytosis	2
cellular process	2
signal transduction	2
cell junction	2
cell recognition	1
cargo receptor activity	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
nervous system development	1
system development	1
animal organ development	1
muscle structure development	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
regulation of endothelial cell migration	1
negative regulation of cell migration	1
endothelial cell migration	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
protein ubiquitination	1
regulation of protein ubiquitination	1
negative regulation of protein modification by small protein conjugation or removal	1
negative regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
negative regulation of protein metabolic process	1
phagocytosis, engulfment	1
apoptotic cell clearance	1
immune response	1
defense response to symbiont	1
modulation of chemical synaptic transmission	1

Protein interactions and networks

STRING

1666 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADGRB1	BAIAP2	Q9UQB8	974
ADGRB1	DOCK1	Q14185	959
ADGRB1	ELMO2	Q96JJ3	881
ADGRB1	ELMO1	Q92556	871
ADGRB1	STAB2	Q8WWQ8	862
ADGRB1	TIMD4	Q96H15	852
ADGRB1	BAIAP3	O94812	815
ADGRB1	IFT122	Q9HBG6	762
ADGRB1	CRK	P46108	735
ADGRB1	GULP1	Q9UBP9	717
ADGRB1	MAGI1	Q96QZ7	708
ADGRB1	TIAM1	Q13009	690
ADGRB1	ELMO3	Q96BJ8	689
ADGRB1	SCARB1	Q8WTV0	678
ADGRB1	SCARB2	Q14108	678
ADGRB1	CD36	P16671	678

IntAct

16 interactions, top by confidence:

A	B	Type	Score
SLC30A2	ESYT2	psi-mi:“MI:0914”(association)	0.530
ADGRB1	MAGI3	psi-mi:“MI:0915”(physical association)	0.490
MAGI3	ADGRB1	psi-mi:“MI:0915”(physical association)	0.490
ADGRB1	BAIAP3	psi-mi:“MI:0915”(physical association)	0.480
ADGRB1	BAIAP3	psi-mi:“MI:0914”(association)	0.480
ELMO1	ADGRB1	psi-mi:“MI:0915”(physical association)	0.400
ADGRB1	ELMO1	psi-mi:“MI:0915”(physical association)	0.400
ADGRB1	Dlg4	psi-mi:“MI:0915”(physical association)	0.400
ADGRB1	DRD2	psi-mi:“MI:0915”(physical association)	0.370
ADGRB1	GPR35	psi-mi:“MI:0915”(physical association)	0.370
ADGRB1	GPR37	psi-mi:“MI:0915”(physical association)	0.370
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
EIF3H		psi-mi:“MI:0914”(association)	0.350
ADGRB1	RAB3B	psi-mi:“MI:0914”(association)	0.350
SYP	TMEM223	psi-mi:“MI:0914”(association)	0.350

BioGRID (47): BAI1 (Reconstituted Complex), BAI1 (Two-hybrid), BAI1 (Two-hybrid), BAIAP2 (Two-hybrid), BAIAP2 (Reconstituted Complex), BAI1 (Affinity Capture-MS), BAI1 (Proximity Label-MS), BAI1 (Proximity Label-MS), BAI1 (Affinity Capture-MS), BAI1 (Two-hybrid), BAI1 (Two-hybrid), BAI1 (Two-hybrid), BAI1 (Two-hybrid), BAI1 (Affinity Capture-MS), RAB9A (Affinity Capture-MS)

ESM2 similar proteins: A0JNA2, A4FUY1, C0HL12, O14514, O19131, O60241, O75325, P0C5H6, P15151, P32506, P32507, P70225, P98095, Q05BQ1, Q13477, Q14626, Q14CZ8, Q29RN8, Q3UHD1, Q4V9Z5, Q53EL9, Q5DRQ8, Q5R7Y0, Q5RF19, Q5STE3, Q63148, Q64385, Q6AX42, Q6BAA4, Q6MZW2, Q6UWL2, Q6UWL6, Q6UXD5, Q6WN34, Q7TSK2, Q7TSU7, Q8BHA1, Q8BQC3, Q8CGM1, Q8IVU1

Diamond homologs: A2VEC9, A6QNY1, B3EWZ3, B3EWZ8, C0HL12, C5IAW9, D3YXG0, D3ZTD8, F1LW30, O08721, O08722, O08747, O14514, O15072, O55225, O60241, O60242, O75173, O88783, O95185, O95450, P04275, P07358, P07996, P27918, P35441, P35442, P35448, P55314, P57110, P58397, P58459, P59384, P79331, P80012, P97857, P98088, P98092, P98160, P98164

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	0
Uncertain significance	209
Likely benign	6
Benign	7

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
146735	GRCh38/hg38 8q24.3(chr8:142201468-144002730)x1	Pathogenic
152355	GRCh38/hg38 8q24.3(chr8:141738068-144140607)x1	Pathogenic
3063013	GRCh37/hg19 8p23.3-q24.3(chr8:158048-146295771)x3	Pathogenic
4682717	GRCh37/hg19 8q24.3(chr8:142893048-144990940)x1	Pathogenic
57129	GRCh38/hg38 8q24.3(chr8:142201425-142550407)x1	Pathogenic
815173	GRCh37/hg19 8q24.3(chr8:142132678-145569441)x1	Pathogenic

SpliceAI

6562 predictions. Top by Δscore:

Variant	Effect	Δscore
8:142450103:AGGTA:A	donor_loss	1.0000
8:142450104:GGTA:G	donor_loss	1.0000
8:142476691:GACCG:G	donor_gain	1.0000
8:142478184:C:A	acceptor_gain	1.0000
8:142479691:A:AG	acceptor_gain	1.0000
8:142479692:G:GG	acceptor_gain	1.0000
8:142481250:CCAGG:C	acceptor_loss	1.0000
8:142481251:CAG:C	acceptor_loss	1.0000
8:142481252:A:AG	acceptor_gain	1.0000
8:142481252:A:T	acceptor_loss	1.0000
8:142481252:AG:A	acceptor_gain	1.0000
8:142481253:G:GG	acceptor_gain	1.0000
8:142481253:G:GT	acceptor_loss	1.0000
8:142481253:GG:G	acceptor_gain	1.0000
8:142481253:GGACT:G	acceptor_gain	1.0000
8:142481513:GCAGA:G	acceptor_loss	1.0000
8:142481514:CAGAC:C	acceptor_loss	1.0000
8:142481515:A:AG	acceptor_gain	1.0000
8:142481516:G:GG	acceptor_gain	1.0000
8:142481516:GACCC:G	acceptor_gain	1.0000
8:142481676:A:T	donor_gain	1.0000
8:142481703:G:GT	donor_gain	1.0000
8:142481703:G:T	donor_gain	1.0000
8:142481708:ACAGG:A	donor_loss	1.0000
8:142481709:CAGGT:C	donor_loss	1.0000
8:142484654:AGGC:A	acceptor_gain	1.0000
8:142484655:GGCG:G	acceptor_gain	1.0000
8:142484763:GG:G	donor_gain	1.0000
8:142484764:GG:G	donor_gain	1.0000
8:142484765:G:GG	donor_gain	1.0000

AlphaMissense

10232 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:142464719:T:C	L174P	1.000
8:142464774:G:C	W192C	1.000
8:142464774:G:T	W192C	1.000
8:142475490:G:C	W267C	1.000
8:142475490:G:T	W267C	1.000
8:142477134:T:A	W360R	1.000
8:142477134:T:C	W360R	1.000
8:142477136:G:C	W360C	1.000
8:142477136:G:T	W360C	1.000
8:142477143:T:A	W363R	1.000
8:142477143:T:C	W363R	1.000
8:142477145:G:C	W363C	1.000
8:142477145:G:T	W363C	1.000
8:142477152:T:C	C366R	1.000
8:142477185:C:A	R377S	1.000
8:142477186:G:C	R377P	1.000
8:142477197:T:C	C381R	1.000
8:142477198:G:A	C381Y	1.000
8:142477224:T:A	C390S	1.000
8:142477224:T:C	C390R	1.000
8:142477225:G:C	C390S	1.000
8:142477254:T:A	C400S	1.000
8:142477255:G:C	C400S	1.000
8:142477398:G:C	W412C	1.000
8:142477398:G:T	W412C	1.000
8:142477405:T:A	W415R	1.000
8:142477405:T:C	W415R	1.000
8:142477407:G:C	W415C	1.000
8:142477407:G:T	W415C	1.000
8:142477414:T:A	W418R	1.000

dbSNP variants (sampled 300 via entrez): RS1000032621 (8:142506458 G>A,T), RS1000036960 (8:142526324 G>A,C), RS1000047385 (8:142491235 G>A), RS1000061678 (8:142478528 G>A), RS1000073848 (8:142515236 C>T), RS1000086972 (8:142510799 C>A,T), RS1000101577 (8:142457735 G>C), RS1000110325 (8:142457995 A>C), RS1000133286 (8:142472667 TCA>T), RS1000141369 (8:142462026 A>C), RS1000164799 (8:142465142 G>A), RS1000203112 (8:142520995 G>C), RS1000211916 (8:142462680 G>A), RS1000252938 (8:142530026 G>A), RS1000286988 (8:142490520 C>T)

Disease associations

OMIM: gene MIM:602682 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009440_6	Age-related cognitive decline (attention/processing speed) (slope of z-scores)	2.000000e-06
GCST012307_4	Bipolar disorder x sex interaction	4.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007710	cognitive decline measurement
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Adhesion Class GPCRs

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	2
aristolochic acid I	increases expression	1
naringenin	affects cotreatment, increases expression	1
propionaldehyde	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
quercitrin	decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
manganese chloride	decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
pentanal	increases expression	1
9,10-methylenehexadecanoic acid	affects binding, increases activity	1
calfactant	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Aldehydes	increases expression	1
Arsenic	affects methylation	1
Lead	affects expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Manganese	decreases expression, increases abundance	1
Methapyrilene	increases methylation	1
Quercetin	affects cotreatment, increases expression	1
Selenium	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1
Valproic Acid	increases methylation	1
Vitamin E	increases expression	1
Acrylamide	decreases expression	1
Nanotubes, Carbon	affects cotreatment, decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KW37	PathHunter CHO-K1 BAI1 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.