ADGRA2

Summary

ADGRA2 (adhesion G protein-coupled receptor A2, HGNC:17849) is a protein-coding gene on chromosome 8p11.23, encoding Adhesion G protein-coupled receptor A2 (Q96PE1). Endothelial receptor which functions together with RECK to enable brain endothelial cells to selectively respond to Wnt7 signals (WNT7A or WNT7B).

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.

Source: NCBI Gene 25960 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 275 total — 1 pathogenic, 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_032777

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17849
Approved symbol	ADGRA2
Name	adhesion G protein-coupled receptor A2
Location	8p11.23
Locus type	gene with protein product
Status	Approved
Aliases	TEM5, DKFZp434C211, DKFZp434J0911, KIAA1531, FLJ14390
Ensembl gene	ENSG00000020181
Ensembl biotype	protein_coding
OMIM	606823
Entrez	25960

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000315215, ENST00000412232, ENST00000428068, ENST00000875442, ENST00000923347, ENST00000947409, ENST00000947410

RefSeq mRNA: 1 — MANE Select: NM_032777 NM_032777

CCDS: CCDS6097

Canonical transcript exons

ENST00000412232 — 19 exons

Exon	Start	End
ENSE00000911668	37829261	37829332
ENSE00000911671	37814896	37814967
ENSE00001234537	37828888	37828959
ENSE00001633765	37833010	37833208
ENSE00001662659	37833688	37833837
ENSE00001699072	37835174	37835398
ENSE00001715091	37831423	37831587
ENSE00001736957	37835554	37835770
ENSE00001747396	37829851	37830014
ENSE00001767688	37833967	37834128
ENSE00001778698	37840760	37840849
ENSE00001802540	37830710	37830923
ENSE00001804794	37837731	37837939
ENSE00001813601	37796883	37797534
ENSE00002059027	37829488	37829559
ENSE00002108593	37841086	37844896
ENSE00003230821	37840121	37840266
ENSE00003282446	37838956	37839083
ENSE00003303906	37839499	37839622

Expression profiles

Bgee: expression breadth ubiquitous, 226 present calls, max score 95.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.0773 / max 163.6586, expressed in 1298 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
88453	12.3860	1286
88455	0.6316	383
88457	0.3955	245
88454	0.3746	221
88456	0.2896	175

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	95.61	gold quality
seminal vesicle	UBERON:0000998	93.77	gold quality
endocervix	UBERON:0000458	93.17	gold quality
left uterine tube	UBERON:0001303	92.61	gold quality
saphenous vein	UBERON:0007318	92.18	gold quality
body of uterus	UBERON:0009853	91.36	gold quality
gall bladder	UBERON:0002110	90.73	gold quality
right ovary	UBERON:0002118	90.53	gold quality
cauda epididymis	UBERON:0004360	90.40	gold quality
superficial temporal artery	UBERON:0001614	90.19	gold quality
prostate gland	UBERON:0002367	90.12	gold quality
mammary duct	UBERON:0001765	90.03	gold quality
myometrium	UBERON:0001296	89.37	gold quality
ectocervix	UBERON:0012249	89.33	gold quality
smooth muscle tissue	UBERON:0001135	89.19	gold quality
urinary bladder	UBERON:0001255	88.80	gold quality
urethra	UBERON:0000057	88.54	gold quality
left ovary	UBERON:0002119	88.51	gold quality
epithelium of mammary gland	UBERON:0003244	87.72	gold quality
decidua	UBERON:0002450	87.69	gold quality
apex of heart	UBERON:0002098	87.44	gold quality
ovary	UBERON:0000992	87.23	gold quality
skin of hip	UBERON:0001554	86.84	gold quality
placenta	UBERON:0001987	86.80	gold quality
subcutaneous adipose tissue	UBERON:0002190	86.20	gold quality
cardiac muscle of right atrium	UBERON:0003379	86.03	silver quality
mucosa of paranasal sinus	UBERON:0005030	85.99	silver quality
adipose tissue	UBERON:0001013	85.98	gold quality
female reproductive system	UBERON:0000474	85.95	gold quality
caput epididymis	UBERON:0004358	85.71	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.10

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

116 targeting ADGRA2, 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-1277-5P	100.00	73.95	5056
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-450B-5P	99.92	71.48	3175

Literature-anchored findings (GeneRIF, showing 10)

• Proteolytically processed soluble tumor endothelial marker TEM5 mediates endothelial cell survival during angiogenesis by linking integrin alpha(v)beta3 to glycosaminoglycans (PMID:16982628)
• TEM5 expression during capillary morphogenesis is induced by the small GTPase Rac and mediates contact inhibition of proliferation in endothelial cells. (PMID:19853600)
• Thrombin-induced shedding of tumour endothelial marker 5 and exposure of its RGD motif are regulated by cell-surface protein disulfide-isomerase. (PMID:22013897)
• Observed an inverse correlation between the expression of miR-138-5p and GPR124 in lung adenocarcinoma specimens. Knockdown of GPR124 mimicked the effects of miR-138-5p on the sensitivity to gefitinib. (PMID:24582749)
• Data suggest that GPR124 promotes cell adhesion via interaction with Elmo1-Dock180 and intersectin 1/2; this constitutes a previously unrecognized heteromeric complex that is putatively involved in GPR124-dependent adhesive/angiogenic responses in vascular endothelial cells. (GPR124 = G-protein coupled receptor 124; Elmo1 = ELMO domain-containing protein 1; Dock180 = dedicator of cytokinesis protein 1 180 kDa) (PMID:28600358)
• Increases and decreases in GPR124 expression in glioblastoma cells reduce cell proliferation by differentially altering the duration mitotic progression. GPR124 interacts with ch-TOG, a known regulator of both microtubule (MT)-plus-end assembly and mitotic progression. Changes in GPR124 expression and ch-TOG similarly affect MT assembly. (PMID:31058365)
• Serum TEM5 and TEM7 concentrations correlate with clinicopathologic features and poor prognosis of colorectal cancer patients (PMID:31352222)
• Variants of WNT7A and GPR124 are associated with hemorrhagic transformation following intravenous thrombolysis in ischemic stroke. (PMID:32991049)
• An integrated model for Gpr124 function in Wnt7a/b signaling among vertebrates. (PMID:35649360)
• Down-regulated Wnt7a and GPR124 in early-onset preeclampsia placentas reduce invasion and migration of trophoblast cells. (PMID:37694534)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	adgra2	ENSDARG00000076994
mus_musculus	Adgra2	ENSMUSG00000031486
rattus_norvegicus	Adgra2	ENSRNOG00000012991

Paralogs (42): CALCR (ENSG00000004948), GIPR (ENSG00000010310), 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), ADGRB1 (ENSG00000181790), ADGRG3 (ENSG00000182885), ADGRA1 (ENSG00000197177)

Protein

Protein identifiers

Adhesion G protein-coupled receptor A2 — Q96PE1 (reviewed: Q96PE1)

Alternative names: G-protein coupled receptor 124, Tumor endothelial marker 5

All UniProt accessions (2): Q96PE1, H7C1L1

UniProt curated annotations — full annotation on UniProt →

Function. Endothelial receptor which functions together with RECK to enable brain endothelial cells to selectively respond to Wnt7 signals (WNT7A or WNT7B). Plays a key role in Wnt7-specific responses, such as endothelial cell sprouting and migration in the forebrain and neural tube, and establishment of the blood-brain barrier. Acts as a Wnt7-specific coactivator of canonical Wnt signaling: required to deliver RECK-bound Wnt7 to frizzled by assembling a higher-order RECK-ADGRA2-Fzd-LRP5-LRP6 complex. ADGRA2-tethering function does not rely on its G-protein coupled receptor (GPCR) structure but instead on its combined capacity to interact with RECK extracellularly and recruit the Dishevelled scaffolding protein intracellularly. Binds to the glycosaminoglycans heparin, heparin sulfate, chondroitin sulfate and dermatan sulfate.

Subunit / interactions. Interacts with RECK; the interaction is direct. Interacts (via PDZ-binding motif) with DLG1 (via PDZ domains). The cleaved extracellular subunit interacts with the integrin heterodimer ITGAV:ITGB3.

Subcellular location. Cell membrane. Cell projection. Filopodium.

Tissue specificity. Expressed in endothelial cells (at protein level). Abundantly expressed in heart, placenta, ovary, small intestine, and colon.

Post-translational modifications. Glycosylated. Proteolytically cleaved into two subunits, an extracellular subunit and a seven-transmembrane subunit. Cleaved by thrombin (F2) and MMP1. Also cleaved by MMP9, with lower efficiency. Presence of the protein disulfide-isomerase P4HB at the cell surface is additionally required for shedding of the extracellular subunit, suggesting that the subunits are linked by disulfide bonds. Shedding is enhanced by the growth factor FGF2 and may promote cell survival during angiogenesis.

Domain organisation. The leucine-rich repeats (LRRs) are important for potentiation of Wnt7 signaling. The RGD motif is involved in integrin ITGAV:ITGB3 binding.

Similarity. Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96PE1-1	1	yes
Q96PE1-2	2
Q96PE1-3	3

RefSeq proteins (1): NP_116166* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000203	GPS	Conserved_site
IPR000483	Cys-rich_flank_reg_C	Domain
IPR000832	GPCR_2_secretin-like	Family
IPR001611	Leu-rich_rpt	Repeat
IPR001879	GPCR_2_extracellular_dom	Domain
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR017981	GPCR_2-like_7TM	Domain
IPR017983	GPCR_2_secretin-like_CS	Conserved_site
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR036445	GPCR_2_extracell_dom_sf	Homologous_superfamily
IPR046338	GAIN_dom_sf	Homologous_superfamily
IPR051963	Adhesion_GPCR_A	Family
IPR057244	GAIN_B	Domain
IPR058808	GAIN_ADGRA2/3	Domain

Pfam: PF00002, PF01825, PF13855, PF26588

UniProt features (61 total): topological domain 8, compositionally biased region 8, transmembrane region 7, glycosylation site 7, region of interest 6, repeat 4, domain 3, mutagenesis site 3, short sequence motif 2, site 2, disulfide bond 2, splice variant 2, sequence variant 2, sequence conflict 2, signal peptide 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96PE1-F1	70.47	0.33

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 (2): 369–370 (cleavage; by thrombin); 398–399 (cleavage; by thrombin)

Post-translational modifications (1): 1107

Disulfide bonds (2): 268–328, 729–743

Glycosylation sites (7): 84, 101, 162, 207, 275, 602, 690

Mutagenesis-validated functional residues (3):

Position	Phenotype
369	minimal effect on thrombin cleavage. abolishes thrombin cleavage; when associated with g-398.
398	minimal effect on thrombin cleavage. abolishes thrombin cleavage; when associated with a-369.
1335–1338	fails to interact with dlg1.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 185 (showing top): GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, BENPORATH_ES_WITH_H3K27ME3, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_SIGNALING_PATHWAY, GOCC_CELL_SURFACE, AREB6_01, TGACCTY_ERR1_Q2, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, CTATGCA_MIR153, COUP_01, GOBP_POSITIVE_REGULATION_OF_ENDOTHELIAL_CELL_MIGRATION, GOBP_TAXIS, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_SPROUTING_ANGIOGENESIS, GOBP_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_REGULATION_OF_ENDOTHELIAL_CELL_MIGRATION

GO Biological Process (15): sprouting angiogenesis (GO:0002040), cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), central nervous system development (GO:0007417), positive regulation of endothelial cell migration (GO:0010595), endothelial cell migration (GO:0043542), regulation of angiogenesis (GO:0045765), regulation of chemotaxis (GO:0050920), canonical Wnt signaling pathway (GO:0060070), regulation of establishment of blood-brain barrier (GO:0090210), positive regulation of canonical Wnt signaling pathway (GO:0090263), negative regulation of vascular endothelial growth factor signaling pathway (GO:1900747), angiogenesis (GO:0001525), signal transduction (GO:0007165), Wnt signaling pathway (GO:0016055)

GO Molecular Function (3): G protein-coupled receptor activity (GO:0004930), transmembrane signaling receptor activity (GO:0004888), protein binding (GO:0005515)

GO Cellular Component (6): plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), filopodium (GO:0030175), Wnt signalosome (GO:1990909), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
angiogenesis	2
signal transduction	2
G protein-coupled receptor activity	1
nervous system development	1
system development	1
regulation of endothelial cell migration	1
positive regulation of cell migration	1
endothelial cell migration	1
cell migration	1
regulation of anatomical structure morphogenesis	1
regulation of vasculature development	1
chemotaxis	1
regulation of response to external stimulus	1
regulation of locomotion	1
Wnt signaling pathway	1
regulation of cell development	1
establishment of blood-brain barrier	1
positive regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
negative regulation of signal transduction	1
vascular endothelial growth factor signaling pathway	1
regulation of vascular endothelial growth factor signaling pathway	1
negative regulation of cellular response to vascular endothelial growth factor stimulus	1
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell surface receptor signaling pathway	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
signaling receptor activity	1
binding	1
membrane	1
cell periphery	1
actin-based cell projection	1

Protein interactions and networks

STRING

1212 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADGRA2	FZD4	Q9ULV1	786
ADGRA2	NDP	Q00604	763
ADGRA2	WNT7A	O00755	747
ADGRA2	ITSN2	Q9NZM3	685
ADGRA2	WNT7B	P56706	684
ADGRA2	LRP5	O75197	683
ADGRA2	TSPAN12	O95859	680
ADGRA2	PLXDC1	Q8IUK5	661
ADGRA2	DLG1	Q12959	660
ADGRA2	ADGRF2P	Q8IZF7	580
ADGRA2	ADGRF1	Q5T601	579
ADGRA2	RECK	O95980	562
ADGRA2	PLPBP	O94903	546
ADGRA2	ITSN1	Q15811	510
ADGRA2	CD248	Q9HCU0	505

IntAct

123 interactions, top by confidence:

A	B	Type	Score
DLG1	ADGRA2	psi-mi:“MI:0915”(physical association)	0.700
ADGRA2	DLG1	psi-mi:“MI:0407”(direct interaction)	0.700
DLG1	ADGRA2	psi-mi:“MI:0407”(direct interaction)	0.700
RYK	PCDH7	psi-mi:“MI:0914”(association)	0.530
ADGRA2	DLG1	psi-mi:“MI:0915”(physical association)	0.520
DLG1	ADGRA2	psi-mi:“MI:0915”(physical association)	0.520
ADGRA2	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.440
SNX27	ADGRA2	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA2	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA2	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA2	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA2	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA2	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA2	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA2	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA2	MAGI1	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA2	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA2	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA2	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA2	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA2	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
DLG3	ADGRA2	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA2	SNTA1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (10): GPR124 (Two-hybrid), DLG1 (Affinity Capture-Western), GPR124 (Reconstituted Complex), GPR124 (Protein-RNA), CCNDBP1 (Two-hybrid), GPR124 (Affinity Capture-MS), GPR124 (Affinity Capture-RNA), CCT3 (Cross-Linking-MS (XL-MS)), GPR124 (Affinity Capture-MS), GPR124 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LHF2, A0EQL2, D3YZF7, D7PDD4, O15533, O55237, O70394, O70540, O95866, P04278, P05111, P07994, P08689, P0C6B3, P0DP72, P15196, P17490, P18627, P40238, P55101, P60882, P97497, Q00657, Q08351, Q14393, Q14773, Q16671, Q3SWY4, Q5BK54, Q5NKT8, Q5TJE4, Q61790, Q61826, Q62588, Q6PZD2, Q6UVK1, Q6UWB1, Q7Z7M0, Q7Z7M1, Q86VR7

Diamond homologs: E7FBY6, Q7TT36, Q86SQ6, Q8C4G9, Q8IWK6, Q91ZV8, Q96PE1, S4X0Q8, P48960, Q9BY15, G5EFX6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
hsa-miR-138-5p	“down-regulates quantity by repression”	ADGRA2	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 82 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Assembly and cell surface presentation of NMDA receptors	8	37.6×	3e-09
Neurexins and neuroligins	10	36.5×	2e-11
Protein-protein interactions at synapses	6	29.5×	3e-06
RHOB GTPase cycle	5	14.3×	4e-04
RHOA GTPase cycle	6	8.3×	1e-03
Neuronal System	6	4.9×	9e-03
Signaling by Rho GTPases	7	4.4×	7e-03
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	7	4.3×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	9	67.9×	2e-12
protein localization to synapse	6	59.7×	1e-07
receptor clustering	6	48.6×	2e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	6	38.6×	9e-07
cell-cell adhesion	9	11.9×	4e-06
protein-containing complex assembly	8	11.8×	2e-05
regulation of small GTPase mediated signal transduction	5	9.3×	4e-03
protein localization to plasma membrane	5	7.1×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	240
Likely benign	7
Benign	5

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1807790	GRCh37/hg19 8p21.2-11.22(chr8:26808969-38346383)x1	Pathogenic
1527425	GRCh37/hg19 8p11.23-11.22(chr8:37566388-38802788)	Likely pathogenic

SpliceAI

3300 predictions. Top by Δscore:

Variant	Effect	Δscore
8:37797535:G:GG	donor_gain	1.0000
8:37814965:GCT:G	donor_gain	1.0000
8:37814968:G:GG	donor_gain	1.0000
8:37828960:G:GG	donor_gain	1.0000
8:37829259:A:AG	acceptor_gain	1.0000
8:37829260:G:GG	acceptor_gain	1.0000
8:37829260:GA:G	acceptor_gain	1.0000
8:37829329:GACT:G	donor_gain	1.0000
8:37829330:ACT:A	donor_gain	1.0000
8:37829332:TGT:T	donor_loss	1.0000
8:37829333:G:GG	donor_gain	1.0000
8:37829555:GTTGT:G	donor_gain	1.0000
8:37829560:G:GG	donor_gain	1.0000
8:37830704:CCACA:C	acceptor_loss	1.0000
8:37830708:A:AG	acceptor_gain	1.0000
8:37830708:A:AT	acceptor_loss	1.0000
8:37830708:AGAG:A	acceptor_gain	1.0000
8:37830708:AGAGG:A	acceptor_gain	1.0000
8:37830709:G:GA	acceptor_gain	1.0000
8:37830709:GA:G	acceptor_gain	1.0000
8:37830709:GAGG:G	acceptor_gain	1.0000
8:37830709:GAGGG:G	acceptor_gain	1.0000
8:37830921:CAGGT:C	donor_loss	1.0000
8:37830924:G:GG	donor_gain	1.0000
8:37830924:GTATG:G	donor_loss	1.0000
8:37833679:A:AG	acceptor_gain	1.0000
8:37833680:A:G	acceptor_gain	1.0000
8:37833681:T:G	acceptor_gain	1.0000
8:37833683:CCCA:C	acceptor_loss	1.0000
8:37833684:CCAG:C	acceptor_loss	1.0000

AlphaMissense

8586 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:37833011:T:A	W367R	1.000
8:37833011:T:C	W367R	1.000
8:37833013:G:C	W367C	1.000
8:37833013:G:T	W367C	1.000
8:37833139:G:C	W409C	1.000
8:37833139:G:T	W409C	1.000
8:37830766:T:C	F259L	0.999
8:37830767:T:G	F259C	0.999
8:37830768:C:A	F259L	0.999
8:37830768:C:G	F259L	0.999
8:37831468:G:C	W326C	0.999
8:37831468:G:T	W326C	0.999
8:37831547:T:A	C353S	0.999
8:37831547:T:C	C353R	0.999
8:37831548:G:A	C353Y	0.999
8:37831548:G:C	C353S	0.999
8:37831549:C:G	C353W	0.999
8:37831584:T:C	F365S	0.999
8:37831584:T:G	F365C	0.999
8:37833012:G:C	W367S	0.999
8:37833119:T:A	C403S	0.999
8:37833119:T:C	C403R	0.999
8:37833120:G:C	C403S	0.999
8:37833137:T:A	W409R	0.999
8:37833137:T:C	W409R	0.999
8:37833161:T:A	C417S	0.999
8:37833161:T:C	C417R	0.999
8:37833162:G:A	C417Y	0.999
8:37833162:G:C	C417S	0.999
8:37833163:T:G	C417W	0.999

dbSNP variants (sampled 300 via entrez): RS1000044150 (8:37832214 A>G), RS1000048165 (8:37837693 C>G), RS1000110508 (8:37795077 T>C), RS1000124614 (8:37823320 C>T), RS1000240904 (8:37816910 T>C), RS1000255051 (8:37799684 C>A), RS1000257753 (8:37816583 C>G,T), RS1000269443 (8:37828706 T>C), RS1000375337 (8:37805514 A>G,T), RS1000481920 (8:37812143 A>G), RS1000530765 (8:37811094 A>G), RS1000554554 (8:37810009 G>C), RS1000575361 (8:37815690 C>T), RS1000640594 (8:37843382 A>G), RS1000707159 (8:37804114 C>G)

Disease associations

OMIM: gene MIM:606823 | disease phenotypes: MIM:101600, MIM:147950, MIM:615033

GenCC curated gene-disease

Mondo (4): Pfeiffer syndrome (MONDO:0007043), hypogonadotropic hypogonadism 2 with or without anosmia (MONDO:0007844), hereditary spastic paraplegia 54 (MONDO:0014018), ependymoma (MONDO:0016698)

Orphanet (4): Autosomal recessive spastic paraplegia type 54 (Orphanet:320380), Kallmann syndrome (Orphanet:478), Pfeiffer syndrome (Orphanet:710), Ependymoma (Orphanet:251636)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002115_11	Axial length	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005318	axial length measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D004806	Ependymoma	C04.557.465.625.600.380.290; C04.557.470.670.380.290; C04.557.580.625.600.380.290

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523909 (SINGLE PROTEIN)

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
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	6
sodium arsenite	affects cotreatment, increases abundance, decreases expression	4
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	3
bisphenol A	decreases expression, decreases methylation, increases expression	2
entinostat	increases expression, affects cotreatment	2
Estradiol	affects expression, affects cotreatment, increases expression	2
Tretinoin	decreases expression	2
aristolochic acid I	decreases expression	1
propionaldehyde	increases expression	1
sulforaphane	decreases expression	1
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
pentanal	increases expression	1
3-nitrobenzanthrone	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Aldehydes	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Methapyrilene	decreases methylation	1
Methyl Methanesulfonate	increases expression	1
Nickel	decreases expression	1
Isotretinoin	increases expression	1
Aflatoxin B1	affects methylation	1
Antirheumatic Agents	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4883405	Binding	PRESTO-Tango GPCRome screening (GPR124)	Data for DCP probe UCSF924

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00517959	PHASE3	UNKNOWN	SCRT Versus Conventional RT in Children and Young Adults With Low Grade and Benign Brain Tumors
NCT01096368	PHASE3	COMPLETED	Maintenance Chemotherapy or Observation Following Induction Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Ependymoma
NCT00003479	PHASE2	TERMINATED	Antineoplaston Therapy in Treating Patients With Ependymoma
NCT00520936	PHASE2	COMPLETED	A Study of Pemetrexed in Children With Recurrent Cancer
NCT00840047	PHASE2	ACTIVE_NOT_RECRUITING	Methionine PET/CT Studies In Patients With Cancer
NCT01088035	PHASE2	TERMINATED	Carboplatin as a Radiosensitizer in Treating Childhood Ependymoma
NCT01247922	PHASE2	TERMINATED	Single-agent Erlotinib in Patients Previously Treated With Oral Etoposide in Protocol OSI-774-205
NCT01288235	PHASE2	COMPLETED	Proton Radiotherapy for Pediatric Brain Tumors Requiring Partial Brain Irradiation
NCT01295944	PHASE2	COMPLETED	Carboplatin and Bevacizumab for Recurrent Ependymoma
NCT01356290	PHASE2	RECRUITING	Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma, ATRT and Rare CNS Tumors
NCT01836549	PHASE2	TERMINATED	Imetelstat Sodium in Treating Younger Patients With Recurrent or Refractory Brain Tumors
NCT02125786	PHASE2	ACTIVE_NOT_RECRUITING	A Trial of Surgery and Fractionated Re-Irradiation for Recurrent Ependymoma
NCT02689336	PHASE2	WITHDRAWN	Erlotinib in Combination With Temozolomide in Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors
NCT03095248	PHASE2	TERMINATED	Trial of Selumetinib in Patients With Neurofibromatosis Type II Related Tumors
NCT03155620	PHASE2	ACTIVE_NOT_RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
NCT03173950	PHASE2	COMPLETED	Immune Checkpoint Inhibitor Nivolumab in People With Recurrent Select Rare CNS Cancers
NCT03194906	PHASE2	COMPLETED	Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors
NCT03210714	PHASE2	ACTIVE_NOT_RECRUITING	Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213652	PHASE2	ACTIVE_NOT_RECRUITING	Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
NCT03213665	PHASE2	COMPLETED	Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)
NCT03213678	PHASE2	COMPLETED	Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213704	PHASE2	ACTIVE_NOT_RECRUITING	Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)
NCT03220035	PHASE2	COMPLETED	Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)
NCT03233204	PHASE2	COMPLETED	Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)
NCT03526250	PHASE2	COMPLETED	Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)
NCT03698994	PHASE2	ACTIVE_NOT_RECRUITING	Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
NCT03727841	PHASE2	TERMINATED	Marizomib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial, and Spinal Cord Ependymoma
NCT04049669	PHASE2	ACTIVE_NOT_RECRUITING	Pediatric Trial of Indoximod With Chemotherapy and Radiation for Relapsed Brain Tumors or Newly Diagnosed DIPG
NCT04195555	PHASE2	ACTIVE_NOT_RECRUITING	Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)
NCT04284774	PHASE2	ACTIVE_NOT_RECRUITING	Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04320888	PHASE2	ACTIVE_NOT_RECRUITING	Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04374305	PHASE2	RECRUITING	Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2)
NCT04743661	PHASE2	ACTIVE_NOT_RECRUITING	131I-Omburtamab, in Recurrent Medulloblastoma and Ependymoma
NCT06804655	PHASE2	NOT_YET_RECRUITING	Pharmacoscopy for Patients With Refractory Primary Brain Tumors
NCT07424092	PHASE2	RECRUITING	Intratumoral DNX-2401 for High Grade Pediatric Brain Tumors
NCT00634231	PHASE1	COMPLETED	A Phase I Study of AdV-tk + Prodrug Therapy in Combination With Radiation Therapy for Pediatric Brain Tumors
NCT00994071	PHASE1	COMPLETED	A Phase I Study of ABT-888, an Oral Inhibitor of Poly(ADP-ribose) Polymerase and Temozolomide in Children With Recurrent/Refractory CNS Tumors
NCT01171469	PHASE1	COMPLETED	Vaccination With Dendritic Cells Loaded With Brain Tumor Stem Cells for Progressive Malignant Brain Tumor
NCT01331135	PHASE1	COMPLETED	Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors
NCT01498783	PHASE1	COMPLETED	Phase I Study of 5-Fluorouracil in Children and Young Adults With Recurrent Ependymoma