ADGRA3

Summary

ADGRA3 (adhesion G protein-coupled receptor A3, HGNC:13839) is a protein-coding gene on chromosome 4p15.2, encoding Adhesion G protein-coupled receptor A3 (Q8IWK6). Orphan receptor that may have a role in planar cell polarity pathway.

This gene encodes a member of the G protein-coupled receptor superfamily. This membrane protein may play a role in tumor angiogenesis through its interaction with the human homolog of the Drosophila disc large tumor suppressor gene. This gene is mapped to a candidate region of chromosome 4 which may be associated with bipolar disorder and schizophrenia.

Source: NCBI Gene 166647 — RefSeq curated summary.

At a glance

• Gene–disease (curated): retinitis pigmentosa (Limited, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 1,151 total — 5 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes
• MANE Select transcript: NM_145290

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13839
Approved symbol	ADGRA3
Name	adhesion G protein-coupled receptor A3
Location	4p15.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ38547, PGR21
Ensembl gene	ENSG00000152990
Ensembl biotype	protein_coding
OMIM	612303
Entrez	166647

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 7 protein_coding_CDS_not_defined, 7 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000282943, ENST00000334304, ENST00000499527, ENST00000502482, ENST00000504617, ENST00000506133, ENST00000506155, ENST00000506346, ENST00000508133, ENST00000511051, ENST00000513385, ENST00000514129, ENST00000514749, ENST00000878434, ENST00000878435, ENST00000878436

RefSeq mRNA: 1 — MANE Select: NM_145290 NM_145290

CCDS: CCDS33964

Canonical transcript exons

ENST00000334304 — 19 exons

Exon	Start	End
ENSE00001305429	22515528	22516066
ENSE00001335095	22413601	22413814
ENSE00002073737	22387376	22388947
ENSE00003471461	22473772	22473843
ENSE00003482699	22392545	22392690
ENSE00003524049	22420886	22421089
ENSE00003537295	22402675	22402799
ENSE00003540831	22435311	22435466
ENSE00003547476	22461737	22461808
ENSE00003554779	22447440	22447511
ENSE00003559021	22389088	22389183
ENSE00003575725	22454866	22454937
ENSE00003576549	22442650	22442863
ENSE00003643125	22424191	22424352
ENSE00003650086	22436440	22436641
ENSE00003666320	22401431	22401554
ENSE00003675517	22438256	22438420
ENSE00003678317	22413182	22413390
ENSE00003689603	22444973	22445133

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 96.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.7995 / max 162.2208, expressed in 1469 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
51616	4.9745	1415
51615	1.3385	733
51614	0.2529	101
51611	0.2206	7
203118	0.0129	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	96.10	gold quality
ganglionic eminence	UBERON:0004023	94.82	gold quality
right lobe of liver	UBERON:0001114	94.54	gold quality
liver	UBERON:0002107	94.13	gold quality
buccal mucosa cell	CL:0002336	93.83	gold quality
right uterine tube	UBERON:0001302	93.61	gold quality
embryo	UBERON:0000922	93.43	gold quality
stromal cell of endometrium	CL:0002255	93.02	gold quality
mucosa of sigmoid colon	UBERON:0004993	92.76	gold quality
colonic mucosa	UBERON:0000317	92.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.57	gold quality
synovial joint	UBERON:0002217	91.53	gold quality
calcaneal tendon	UBERON:0003701	91.10	gold quality
rectum	UBERON:0001052	90.66	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.37	gold quality
biceps brachii	UBERON:0001507	89.70	gold quality
sigmoid colon	UBERON:0001159	89.58	gold quality
transverse colon	UBERON:0001157	89.56	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	89.51	gold quality
hair follicle	UBERON:0002073	89.49	silver quality
endometrium	UBERON:0001295	89.44	gold quality
secondary oocyte	CL:0000655	89.43	gold quality
large intestine	UBERON:0000059	89.27	gold quality
colon	UBERON:0001155	89.21	gold quality
corpus callosum	UBERON:0002336	89.21	gold quality
tibia	UBERON:0000979	89.17	gold quality
thyroid gland	UBERON:0002046	89.03	gold quality
vastus lateralis	UBERON:0001379	89.02	silver quality
body of pancreas	UBERON:0001150	89.01	gold quality
cartilage tissue	UBERON:0002418	88.95	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.37
E-MTAB-6142	no	138.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting ADGRA3, 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-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-4668-3P	100.00	68.74	2635
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-5100	99.11	67.52	1098
HSA-MIR-8066	99.05	68.66	1532
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-6738-3P	99.03	67.14	1326
HSA-MIR-6830-5P	99.01	68.73	1884

Literature-anchored findings (GeneRIF, showing 3)

• ID4 and GPR125 are expressed on partially overlapping spermatogonial populations and are more broadly expressed in normal adult human testis. ID4 and GPR125 could be used for identifying previously unrecognized human spermatogonial subpopulations (PMID:24902969)
• GPR125 overexpression inhibited the beta-catenin transcriptional activity, and down-regulated the expression levels of the Wnt downstream proteins-Axin2, c-Myc, cylinD1, and lef-1. (PMID:30231258)
• data support that the constitutive internalization of GPR125 contributes to its biological functions by controlling receptor surface expression and accessibility for ligands (PMID:31659746)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	adgra3	ENSDARG00000073673
mus_musculus	Adgra3	ENSMUSG00000029090
rattus_norvegicus	Adgra3	ENSRNOG00000004279

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), 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 A3 — Q8IWK6 (reviewed: Q8IWK6)

Alternative names: G-protein coupled receptor 125

All UniProt accessions (3): Q8IWK6, D6RDX4, D6RER4

UniProt curated annotations — full annotation on UniProt →

Function. Orphan receptor that may have a role in planar cell polarity pathway.

Subunit / interactions. Interacts (via PDZ-binding motif) with DLG1.

Subcellular location. Membrane.

Miscellaneous. Most adhesion GPCRs proteins undergo autoproteolysis at the GPS region of the GAIN-B domain. ADGRA3 is predicted non-cleavable because of the lack of a consensus catalytic triad sequence within GPS region.

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q8IWK6-1	1	yes
Q8IWK6-2	2
Q8IWK6-3	3
Q8IWK6-4	4

RefSeq proteins (1): NP_660333* (*=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
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR036179	Ig-like_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 (59 total): glycosylation site 13, topological domain 8, splice variant 8, transmembrane region 7, repeat 5, region of interest 5, domain 3, compositionally biased region 2, disulfide bond 2, sequence variant 2, signal peptide 1, chain 1, short sequence motif 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IWK6-F1	70.20	0.31

Functional residue map

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

Disulfide bonds (2): 264–324, 720–734

Glycosylation sites (13): 81, 98, 159, 206, 301, 332, 433, 453, 592, 652, 687, 728, 821

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 128 (showing top): GOCC_CELL_SURFACE, ONKEN_UVEAL_MELANOMA_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, CAIRO_HEPATOBLASTOMA_DN, ACATTCC_MIR1_MIR206, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, JAATINEN_HEMATOPOIETIC_STEM_CELL_UP, GOCC_SIDE_OF_MEMBRANE, NAKAYAMA_SOFT_TISSUE_TUMORS_PCA1_DN, chr4p15, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, RHEIN_ALL_GLUCOCORTICOID_THERAPY_DN, EPPERT_PROGENITOR, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_DN

GO Biological Process (3): cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), signal transduction (GO:0007165)

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

GO Cellular Component (3): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
G protein-coupled receptor activity	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
signaling receptor activity	1
binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1178 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADGRA3	ZBTB16	Q05516	681
ADGRA3	GFRA1	P56159	670
ADGRA3	ADGRF2P	Q8IZF7	632
ADGRA3	ADGRG5	Q8IZF4	580
ADGRA3	DDX4	Q9NQI0	561
ADGRA3	ADGRG3	Q86Y34	551
ADGRA3	ACR	P10323	546
ADGRA3	DAZL	Q92904	532
ADGRA3	UTF1	Q5T230	521
ADGRA3	UCHL1	P09936	518
ADGRA3	MAGEA4	P43358	517
ADGRA3	ADGRD2	Q7Z7M1	496
ADGRA3	ADGRV1	Q8WXG9	488
ADGRA3	ADGRG1	Q9Y653	480
ADGRA3	ADGRF4	Q8IZF3	476

IntAct

141 interactions, top by confidence:

A	B	Type	Score
DLG1	ADGRA3	psi-mi:“MI:0915”(physical association)	0.610
ADGRA3	DLG1	psi-mi:“MI:0407”(direct interaction)	0.610
DLG1	ADGRA3	psi-mi:“MI:0407”(direct interaction)	0.610
RYK	PCDH7	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
ADGRA3	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA3	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA3	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA3	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA3	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA3	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA3	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA3	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
TAX1BP3	ADGRA3	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA3	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA3	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA3	MAGI1	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA3	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
DLG2	ADGRA3	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA3	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRA3	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (26): GPR125 (Affinity Capture-RNA), GPR125 (Affinity Capture-RNA), GPR125 (Affinity Capture-MS), GPR125 (Affinity Capture-MS), GPR125 (Two-hybrid), GPR125 (Two-hybrid), GPR125 (Affinity Capture-MS), GPR125 (Affinity Capture-MS), GPR125 (Affinity Capture-MS), GPR125 (Affinity Capture-MS), GPR125 (Affinity Capture-MS), GPR125 (Affinity Capture-MS), GPR125 (Affinity Capture-MS), GPR125 (Affinity Capture-MS), GPR125 (Affinity Capture-MS)

ESM2 similar proteins: A6QLU6, A8WCC4, B8JK39, F1MLX5, J3S6Y1, O94955, P07224, P07225, P13612, P51810, P57097, P59822, P70259, P98118, Q12866, Q13797, Q14246, Q28520, Q2TBA3, Q3TDN0, Q3URE9, Q5M900, Q5R5V8, Q5Y4N8, Q60805, Q61549, Q61730, Q63621, Q6F3F9, Q6NRQ1, Q6QNK2, Q6R6I6, Q6R6I7, Q7L985, Q7TT36, Q7Z443, Q80T32, Q86SQ4, Q8IWK6, Q8NFZ0

Diamond homologs: E7FBY6, Q7TT36, Q86SQ6, Q8C4G9, Q8IWK6, Q91ZV8, Q96PE1, S4X0Q8, P48960, Q9BY15, A6QLU6, B7ZCC9, D4A3T6, G5ECX0, G5EDW2, O35161, O88917, O88923, O94910, O95490, O97817, O97827, O97831, Q14246, Q16983, Q2Q421, Q2Q426, Q2VWQ2, Q58Y75, Q59I63, Q5Y4N8, Q61549, Q62919, Q6F3F9, Q6QNK2, Q7SY09, Q80T32, Q80TR1, Q80TS3, Q86SQ3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 104 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
Dopamine Neurotransmitter Release Cycle	5	36.0×	2e-05
Assembly and cell surface presentation of NMDA receptors	9	33.1×	8e-10
Neurexins and neuroligins	11	31.4×	1e-11
Protein-protein interactions at synapses	7	26.9×	6e-07
RHOB GTPase cycle	5	11.2×	2e-03
RHOA GTPase cycle	6	6.5×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	9	52.8×	3e-11
protein localization to synapse	6	46.4×	5e-07
receptor clustering	6	37.8×	1e-06
regulation of postsynaptic membrane neurotransmitter receptor levels	7	35.0×	3e-07
protein-containing complex assembly	9	10.3×	2e-05
cell-cell adhesion	9	9.2×	5e-05
chemical synaptic transmission	8	6.2×	2e-03
cell adhesion	10	3.8×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1151 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	1
Uncertain significance	742
Likely benign	334
Benign	34

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
146534	GRCh38/hg38 4p15.32-15.1(chr4:16925022-32113076)x1	Pathogenic
1527077	GRCh37/hg19 4p15.31-14(chr4:19892850-37325128)	Pathogenic
625699	GRCh37/hg19 4p15.33-15.1(chr4:12778849-27760141)	Pathogenic
625782	GRCh37/hg19 4p15.31-15.2(chr4:19186845-24548281)	Pathogenic
814537	GRCh37/hg19 4p15.31-15.1(chr4:20406475-29134345)x1	Pathogenic
2685107	GRCh37/hg19 4p15.33-15.2(chr4:12238766-23083496)x1	Likely pathogenic

SpliceAI

3934 predictions. Top by Δscore:

Variant	Effect	Δscore
4:22388948:C:CC	acceptor_gain	1.0000
4:22389080:ATACT:A	donor_loss	1.0000
4:22389084:TCA:T	donor_loss	1.0000
4:22389085:CA:C	donor_loss	1.0000
4:22389086:A:AC	donor_gain	1.0000
4:22389087:C:CA	donor_gain	1.0000
4:22389087:CT:C	donor_gain	1.0000
4:22389087:CTA:C	donor_gain	1.0000
4:22389087:CTAG:C	donor_gain	1.0000
4:22389087:CTAGG:C	donor_gain	1.0000
4:22389179:AAAAT:A	acceptor_gain	1.0000
4:22389180:AAAT:A	acceptor_gain	1.0000
4:22389181:AAT:A	acceptor_gain	1.0000
4:22389181:AATCT:A	acceptor_loss	1.0000
4:22389182:AT:A	acceptor_gain	1.0000
4:22389182:ATCTA:A	acceptor_loss	1.0000
4:22389183:TCT:T	acceptor_loss	1.0000
4:22389184:C:CA	acceptor_loss	1.0000
4:22389184:C:CC	acceptor_gain	1.0000
4:22389185:T:A	acceptor_loss	1.0000
4:22401429:A:AC	donor_gain	1.0000
4:22401430:C:CC	donor_gain	1.0000
4:22401430:CTG:C	donor_gain	1.0000
4:22401551:CAAA:C	acceptor_gain	1.0000
4:22401555:C:CC	acceptor_gain	1.0000
4:22413261:T:C	donor_gain	1.0000
4:22413268:T:TA	donor_gain	1.0000
4:22414523:T:A	donor_gain	1.0000
4:22420701:AGGGC:A	donor_gain	1.0000
4:22421088:TA:T	acceptor_gain	1.0000

AlphaMissense

8623 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:22421026:A:G	C557R	1.000
4:22435432:G:T	A441D	1.000
4:22436486:C:G	C414S	1.000
4:22436487:A:G	C414R	1.000
4:22436487:A:T	C414S	1.000
4:22436509:C:A	W406C	1.000
4:22436509:C:G	W406C	1.000
4:22436511:A:G	W406R	1.000
4:22436511:A:T	W406R	1.000
4:22436527:A:C	C400W	1.000
4:22436528:C:G	C400S	1.000
4:22436528:C:T	C400Y	1.000
4:22436529:A:G	C400R	1.000
4:22436529:A:T	C400S	1.000
4:22436534:C:G	R398P	1.000
4:22436638:C:A	W363C	1.000
4:22436638:C:G	W363C	1.000
4:22436640:A:G	W363R	1.000
4:22436640:A:T	W363R	1.000
4:22438294:A:C	C349W	1.000
4:22438295:C:G	C349S	1.000
4:22438295:C:T	C349Y	1.000
4:22438296:A:G	C349R	1.000
4:22438296:A:T	C349S	1.000
4:22438369:A:C	C324W	1.000
4:22438370:C:G	C324S	1.000
4:22438370:C:T	C324Y	1.000
4:22438371:A:G	C324R	1.000
4:22438371:A:T	C324S	1.000
4:22438375:C:A	W322C	1.000

dbSNP variants (sampled 300 via entrez): RS1000012974 (4:22499825 C>T), RS1000034757 (4:22436221 G>A), RS1000053852 (4:22477762 T>A), RS1000057320 (4:22419455 T>C), RS1000071093 (4:22413754 T>C,G), RS1000088276 (4:22488878 G>T), RS1000157050 (4:22414897 G>A,C), RS1000172698 (4:22480035 A>G), RS1000234486 (4:22459669 A>G), RS1000270399 (4:22497580 C>T), RS1000282403 (4:22420869 T>C,G), RS10002842 (4:22412400 C>A,T), RS1000330928 (4:22448211 G>A), RS1000342813 (4:22512041 C>A,G), RS1000348058 (4:22419194 G>A)

Disease associations

OMIM: gene MIM:612303 | disease phenotypes: MIM:194190, MIM:268000

GenCC curated gene-disease

Disease	Classification	Inheritance
retinitis pigmentosa	Limited	Autosomal recessive

Mondo (4): inherited retinal dystrophy (MONDO:0019118), optic atrophy (MONDO:0003608), Wolf-Hirschhorn syndrome (MONDO:0008684), retinitis pigmentosa (MONDO:0019200)

Orphanet (3): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Wolf-Hirschhorn syndrome (Orphanet:280), Retinitis pigmentosa (Orphanet:791)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000556	Retinal dystrophy

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000917_7	Rheumatoid arthritis	7.000000e-06
GCST002932_8	Manganese levels	6.000000e-06
GCST010916_11	Proportion of activated microglia (inferior temporal cortex)	1.000000e-06

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
D054877	Wolf-Hirschhorn Syndrome	C16.131.077.944; C16.131.260.985; C16.320.180.985

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523887 (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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases methylation, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
bisphenol S	affects cotreatment, affects methylation	1
(+)-JQ1 compound	increases expression	1
Fulvestrant	affects cotreatment, increases methylation, affects methylation	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	decreases expression	1
Cadmium	increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects expression	1
Formaldehyde	decreases expression	1
Hydralazine	increases expression, affects cotreatment	1
Methyl Methanesulfonate	decreases expression	1
Phenobarbital	affects expression	1
Quercetin	decreases expression	1
Thiram	decreases expression	1
Valproic Acid	affects cotreatment, increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Raloxifene Hydrochloride	increases expression	1
Vitamin K 3	affects 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
CHEMBL4883406	Binding	PRESTO-Tango GPCRome screening (GPR125)	Data for DCP probe UCSF924

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT00063765	PHASE1	COMPLETED	Evaluation of Safety of Ciliary Neurotrophic Factor Implants in the Eye
NCT00065455	PHASE1	COMPLETED	Investigating the Effect of Vitamin A Supplementation on Retinitis Pigmentosa
NCT00458575	PHASE1	TERMINATED	A Study to Evaluate the Safety of CNTO 2476 in Patients With Advanced Retinitis Pigmentosa