ADGRB2

protein-coding

adhesion G protein-coupled receptor B2, the group of Adhesion G protein-coupled receptors, subfamily B|MicroRNA protein coding host genes

Gene summary

This gene encodes a a seven-span transmembrane protein that is thought to be a member of the secretin receptor family. The encoded protein is a brain-specific inhibitor of angiogenesis. The mature peptide may be further cleaved into additional products (PMID:20367554). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

Previous symbols:

BAI2

MANE transcript

NM_001364857.2

Inheritance

—

ClinVar variants

P:1U:239B:116

Top phenotype

Progressive spastic paraparesis

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr1:31,727,117-31,764,893

External References & Databases

Ensembl (ENSG00000121753)

Transcript & Mutation Effects

hg38 • Region Span ~37.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ADGRB2 variants in ClinVar

4 Conditions Cataloged

not providedTotal: 282

not specifiedTotal: 150

Progressive spastic paraparesisTotal: 1

Hereditary spastic paraplegiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001364857.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	76 clinvar	20 clinvar	99
missense		1 clinvar	227 clinvar	13 clinvar	7 clinvar	248
nonsense			3 clinvar			3
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	1	239	89	27	356

Highest pathogenic variant AF is 0.000003717767

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 44 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001364857.2	RefSeq	NP_001351786.1	31	MANE Select
ENST00000373658.8	Ensembl	ENSP00000362762.3	31	MANE Select
NM_001294335.2	RefSeq	NP_001281264.1	31	Standard
NM_001294336.2	RefSeq	NP_001281265.1	30	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cell surface receptor signaling pathway
G protein-coupled receptor signaling pathway
adenylate cyclase-activating G protein-coupled receptor signaling pathway
peripheral nervous system development
negative regulation of angiogenesis

Molecular Function

G protein-coupled receptor activity
protein binding

Cellular Component

centrosome
plasma membrane
integral component of plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373658
Coding exons: 31
Length: 37777
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125747
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	4.49	567	958	0.592	0.0000635	10021
Missense (PolyPhen)		218	451.94	0.48237		4820
Synonymous	1.23	384	416	0.923	0.0000285	3315
Loss of Function	6.73	11	73.1	0.151	0.00000359	809

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000075	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000065	0.000062	rare
South Asian	0.000076	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Orphan G-protein coupled receptor involved in cell adhesion and probably in cell-cell interactions. Activates NFAT- signaling pathway, a transcription factor, via the G-protein GNAZ (PubMed:20367554, PubMed:28891236). Involved in angiogenesis inhibition (By similarity). {ECO:0000250|UniProtKB:Q8CGM1, ECO:0000269|PubMed:20367554, ECO:0000269|PubMed:28891236}.;

Recessive Scores

pRec: 0.106

Intolerance Scores

RVIS EVS: -1.52
RVIS percentile EVS: 3.47

Essentials

Essential (gene trap): N