ADGRA2 Gene

HGNC Family	Immunoglobulin superfamily domain containing, G protein-coupled receptors
Name	adhesion G protein-coupled receptor A2
Description	Predicted to enable G protein-coupled receptor activity. Involved in canonical Wnt signaling pathway. Located in intracellular membrane-bounded organelle and plasma membrane. Part of Wnt signalosome. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ADGRA2, an orphan adhesion‐G protein–coupled receptor (also known as GPR124), plays a pivotal role in central nervous system (CNS) vascular development. Loss‐ or endothelial‐specific deletion of ADGRA2 disrupts angiogenic sprouting, directional migration, and the establishment of blood–brain barrier (BBB) properties—events that are essential in the forebrain, neural tube, and spinal cord during embryogenesis, with deficiency leading to embryonic lethality or, in adults, to compromised vascular integrity under pathological conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Mechanistically, ADGRA2 functions as a ligand‐specific coactivator of canonical Wnt signaling by selectively potentiating the effects of Wnt7a and Wnt7b through its cooperation with Frizzled and Lrp coreceptors, as well as through its interaction with accessory proteins such as Reck. This cooperation amplifies β‐catenin signaling, an essential process for CNS angiogenesis and BBB formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, ADGRA2 modulates endothelial cell adhesion and cytoskeletal dynamics by engaging with regulators of actin remodeling and Rho GTPases (including Rac and Cdc42), thereby promoting the formation of filopodia and lamellipodia that are necessary for polarity acquisition and proper cell migration during vessel formation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, although ADGRA2 is not indispensable for maintaining homeostatic BBB function in the adult brain, its signaling becomes critical during pathological challenges such as ischemic stroke and glioblastoma. Under these conditions, ADGRA2‐mediated enhancement of Wnt–β‐catenin signaling helps preserve barrier integrity and limits vascular leakage."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, the studies summarized here identify ADGRA2 as an essential modulator of CNS angiogenesis and BBB formation through its multitiered regulation of endothelial migration, adhesion, and Wnt ligand–specific β‐catenin signaling. These findings underscore the potential of ADGRA2 as a promising therapeutic target for cerebrovascular pathologies.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Frank Kuhnert, Michael R Mancuso, Amir Shamloo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Essential regulation of CNS angiogenesis by the orphan G protein-coupled receptor GPR124."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1196554"}], "href": "https://doi.org/10.1126/science.1196554"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21071672"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21071672"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yulian Zhou, Jeremy Nathans "}, {"type": "b", "children": [{"type": "t", "text": "Gpr124 controls CNS angiogenesis and blood-brain barrier integrity by promoting ligand-specific canonical wnt signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2014.08.018"}], "href": "https://doi.org/10.1016/j.devcel.2014.08.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25373781"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25373781"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Keith D Anderson, Li Pan, Xiao-man Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Angiogenic sprouting into neural tissue requires Gpr124, an orphan G protein-coupled receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1019761108"}], "href": "https://doi.org/10.1073/pnas.1019761108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21282641"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21282641"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Mike Cullen, Mohammed K Elzarrad, Steven Seaman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GPR124, an orphan G protein-coupled receptor, is required for CNS-specific vascularization and establishment of the blood-brain barrier."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1017192108"}], "href": "https://doi.org/10.1073/pnas.1017192108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21421844"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21421844"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Chris Cho, Philip M Smallwood, Jeremy Nathans "}, {"type": "b", "children": [{"type": "t", "text": "Reck and Gpr124 Are Essential Receptor Cofactors for Wnt7a/Wnt7b-Specific Signaling in Mammalian CNS Angiogenesis and Blood-Brain Barrier Regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2017.07.031"}], "href": "https://doi.org/10.1016/j.neuron.2017.07.031"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28803732"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28803732"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ekaterina Posokhova, Animesh Shukla, Steven Seaman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GPR124 functions as a WNT7-specific coactivator of canonical β-catenin signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2014.12.020"}], "href": "https://doi.org/10.1016/j.celrep.2014.12.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25558062"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25558062"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Magda Nohemí Hernández-Vásquez, Sendi Rafael Adame-García, Noumeira Hamoud, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cell adhesion controlled by adhesion G protein-coupled receptor GPR124/ADGRA2 is mediated by a protein complex comprising intersectins and Elmo-Dock."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M117.780304"}], "href": "https://doi.org/10.1074/jbc.M117.780304"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28600358"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28600358"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Junlei Chang, Michael R Mancuso, Carolina Maier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gpr124 is essential for blood-brain barrier integrity in central nervous system disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.4309"}], "href": "https://doi.org/10.1038/nm.4309"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28288111"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28288111"}]}]}]}
Synonyms	TEM5, GPR124
Proteins	GP124_HUMAN
NCBI Gene ID	25960
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ADGRA2 has 5,727 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 107 datasets.

Click the + buttons to view associations for ADGRA2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ADGRA2 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of ADGRA2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of ADGRA2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of ADGRA2 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of ADGRA2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of ADGRA2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of ADGRA2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of ADGRA2 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of ADGRA2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of ADGRA2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of ADGRA2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ADGRA2 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of ADGRA2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ADGRA2 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of ADGRA2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ADGRA2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of ADGRA2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of ADGRA2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ADGRA2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ADGRA2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with ADGRA2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with ADGRA2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of ADGRA2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ADGRA2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	dbGAP Gene-Trait Associations	traits associated with ADGRA2 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by ADGRA2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with ADGRA2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with ADGRA2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with ADGRA2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ADGRA2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at ADGRA2 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of ADGRA2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ADGRA2 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing ADGRA2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with ADGRA2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with ADGRA2 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of ADGRA2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with ADGRA2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing ADGRA2 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of ADGRA2 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of ADGRA2 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.