ADGRB1

Chr 8

adhesion G protein-coupled receptor B1

Also known as: BAI1, GDAIF

NCBI Gene: 575 ENSG00000181790 UniProt: O14514

ADGRB1 encodes a phosphatidylserine receptor that functions in apoptotic cell clearance, synaptic plasticity regulation, dendritic spine formation, and angiogenesis inhibition in the brain. Mutations cause autosomal recessive developmental and epileptic encephalopathy with movement abnormalities. This gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.14), indicating that haploinsufficiency is likely not tolerated.

ResearchSummary from RefSeq, UniProt

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 [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.14

Clinical Summary— ADGRB1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

208 VUS of 239 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.14LOEUF

pLI 1.000

Z-score 7.03

OE 0.06 (0.03–0.14)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

4.48Z-score

OE missense 0.58 (0.54–0.62)

515 obs / 891.5 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.06 (0.03–0.14)

0≤0.351.4

Missense OE?0.58 (0.54–0.62)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 4 / 65.4Missense obs/exp: 515 / 891.5Syn Z: -0.78

This gene — mechanism propensity

0.3892th %ile

GOF

0.5955th %ile

LOF

0.69top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.14

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

239 submitted variants in ClinVar

ClinVar

Classification Summary

VUS208

Likely Benign6

Benign7

208

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	2	206	0	0	208
Likely Benign	0	4	0	2	6
Benign	0	1	1	5	7
Total	2	211	1	7	221

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

59 pathogenic / likely-pathogenic (of 64) ClinVar copy-number / structural variants overlap ADGRB1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →