GPR45

Summary

GPR45 (G protein-coupled receptor 45, HGNC:4503) is a protein-coding gene on chromosome 2q12.1, encoding Probable G-protein coupled receptor 45 (Q9Y5Y3). Orphan receptor.

This intronless gene encodes a member of the G protein-coupled receptor (GPCR) family. Members of this protein family contain seven putative transmembrane domains and may mediate signaling processes to the interior of the cell via activation of heterotrimeric G proteins. This protein may function in the central nervous system.

Source: NCBI Gene 11250 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cone-rod dystrophy (Limited, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 225 total
• Druggable target: yes
• MANE Select transcript: NM_007227

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4503
Approved symbol	GPR45
Name	G protein-coupled receptor 45
Location	2q12.1
Locus type	gene with protein product
Status	Approved
Aliases	PSP24, PSP24A
Ensembl gene	ENSG00000135973
Ensembl biotype	protein_coding
OMIM	604838
Entrez	11250

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000258456

RefSeq mRNA: 1 — MANE Select: NM_007227 NM_007227

CCDS: CCDS2066

Canonical transcript exons

ENST00000258456 — 1 exons

Exon	Start	End
ENSE00000921874	105241743	105243467

Expression profiles

Bgee: expression breadth broad, 50 present calls, max score 73.24.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of urinary bladder	UBERON:0001259	73.24	gold quality
diaphragm	UBERON:0001103	73.02	gold quality
endometrium epithelium	UBERON:0004811	68.95	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	67.37	gold quality
frontal pole	UBERON:0002795	65.76	gold quality
cortical plate	UBERON:0005343	65.11	gold quality
paraflocculus	UBERON:0005351	64.60	gold quality
middle frontal gyrus	UBERON:0002702	64.59	gold quality
epithelial cell of pancreas	CL:0000083	64.37	gold quality
upper arm skin	UBERON:0004263	64.31	gold quality
sperm	CL:0000019	63.57	gold quality
prefrontal cortex	UBERON:0000451	62.71	gold quality
male germ cell	CL:0000015	62.63	gold quality
orbitofrontal cortex	UBERON:0004167	62.35	gold quality
endothelial cell	CL:0000115	62.12	gold quality
cervix epithelium	UBERON:0004801	60.43	gold quality
oviduct epithelium	UBERON:0004804	60.15	gold quality
jejunal mucosa	UBERON:0000399	58.99	gold quality
frontal cortex	UBERON:0001870	58.41	gold quality
vastus lateralis	UBERON:0001379	58.31	gold quality
secondary oocyte	CL:0000655	57.82	gold quality
quadriceps femoris	UBERON:0001377	57.56	gold quality
neocortex	UBERON:0001950	57.39	gold quality
cartilage tissue	UBERON:0002418	57.15	gold quality
right frontal lobe	UBERON:0002810	56.71	gold quality
cerebellar vermis	UBERON:0004720	56.49	gold quality
Brodmann (1909) area 9	UBERON:0013540	56.49	gold quality
Brodmann (1909) area 46	UBERON:0006483	55.85	gold quality
cingulate cortex	UBERON:0003027	55.69	gold quality
anterior cingulate cortex	UBERON:0009835	55.41	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting GPR45, 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-5193	100.00	67.26	1744
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-1228-3P	99.00	66.53	857
HSA-MIR-1911-5P	98.92	67.53	325
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-3928-5P	98.50	67.48	980
HSA-MIR-6806-3P	98.50	67.31	980
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-3920	97.75	69.02	1168
HSA-MIR-6782-3P	97.60	67.75	931
HSA-MIR-3189-5P	97.55	66.71	655
HSA-MIR-4771	97.43	67.69	596
HSA-MIR-134-5P	97.11	66.52	976
HSA-MIR-3118	97.11	66.58	984
HSA-MIR-1913	97.07	66.20	1417

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr45	ENSDARG00000063357
mus_musculus	Gpr45	ENSMUSG00000041907
rattus_norvegicus	Gpr45	ENSRNOG00000016446

Paralogs (3): GPR63 (ENSG00000112218), GPR26 (ENSG00000154478), GPR78 (ENSG00000155269)

Protein

Protein identifiers

Probable G-protein coupled receptor 45 — Q9Y5Y3 (reviewed: Q9Y5Y3)

Alternative names: PSP24-1, PSP24-alpha

All UniProt accessions (2): B5B0C1, Q9Y5Y3

UniProt curated annotations — full annotation on UniProt →

Function. Orphan receptor. May play a role in brain function.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in brain; detected in the basal forebrain, frontal cortex, and caudate, but not in thalamus, hippocampus, or putamen.

Similarity. Belongs to the G-protein coupled receptor 1 family.

RefSeq proteins (1): NP_009158* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR051880	GPC_Orphan_Receptors	Family

Pfam: PF00001

UniProt features (22 total): topological domain 8, transmembrane region 7, glycosylation site 3, sequence variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y5Y3-F1	83.48	0.52

Functional residue map

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

Glycosylation sites (3): 4, 17, 20

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-418555	G alpha (s) signalling events

MSigDB gene sets: 51 (showing top): chr2q12, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, JAZAG_TGFB1_SIGNALING_VIA_SMAD4_UP, ULE_SPLICING_VIA_NOVA2, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, MEISSNER_NPC_HCP_WITH_H3K4ME3_AND_H3K27ME3, MIKKELSEN_NPC_HCP_WITH_H3K4ME3_AND_H3K27ME3, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, JNK_DN.V1_UP, DCA_UP.V1_UP, ALK_DN.V1_DN, KRAS.LUNG_UP.V1_DN, MIR218_5P, MIR4660

GO Biological Process (2): G protein-coupled receptor signaling pathway (GO:0007186), signal transduction (GO:0007165)

GO Molecular Function (2): G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor activity	1
signal transduction	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
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

562 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR45	LPAR2	Q9HBW0	639
GPR45	GPR87	Q9BY21	513
GPR45	GPR62	Q9BZJ7	468
GPR45	GPR61	Q9BZJ8	445
GPR45	GPR22	Q99680	432
GPR45	GPR65	Q8IYL9	413
GPR45	C16orf96	A6NNT2	397
GPR45	GPR176	Q14439	389
GPR45	GPR82	Q96P67	388
GPR45	GPR4	P46093	384
GPR45	GPR85	P60893	384
GPR45	FAM194C	Q8ND61	379
GPR45	GPR88	Q9GZN0	373
GPR45	ZNF514	Q96K75	367
GPR45	GPR52	Q9Y2T5	367

IntAct

14 interactions, top by confidence:

A	B	Type	Score
OTX2	GPR45	psi-mi:“MI:0915”(physical association)	0.560
ABL1	GPR45	psi-mi:“MI:0915”(physical association)	0.400
GPR45	FYN	psi-mi:“MI:0915”(physical association)	0.400
GRB2	GPR45	psi-mi:“MI:0915”(physical association)	0.400
GPR45	NCK1	psi-mi:“MI:0915”(physical association)	0.400
GPR45	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	GPR45	psi-mi:“MI:0915”(physical association)	0.400
GPR45	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	GPR45	psi-mi:“MI:0915”(physical association)	0.400
GPR45	VWA8	psi-mi:“MI:0914”(association)	0.350
GPR45	OTX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (299): OTX2 (Two-hybrid), CECR5 (Affinity Capture-MS), GEMIN4 (Affinity Capture-MS), NTPCR (Affinity Capture-MS), MMP14 (Affinity Capture-MS), SLC5A3 (Affinity Capture-MS), MTOR (Affinity Capture-MS), RAB29 (Affinity Capture-MS), IPO13 (Affinity Capture-MS), RARS2 (Affinity Capture-MS), COQ5 (Affinity Capture-MS), SPG11 (Affinity Capture-MS), PLEKHB1 (Affinity Capture-MS), STAT1 (Affinity Capture-MS), MMP15 (Affinity Capture-MS)

ESM2 similar proteins: C8YUV0, O19037, O77616, P31392, P43142, P55167, P56442, P56445, P56447, P56448, Q01726, Q29154, Q2AC31, Q5NUL3, Q6A155, Q7TMA4, Q7TQP3, Q80SS9, Q864F4, Q864F6, Q864F7, Q864F8, Q864H5, Q864H7, Q864H8, Q864H9, Q864I4, Q864I6, Q864I7, Q864J1, Q864J2, Q864J3, Q864J4, Q864J5, Q864J7, Q864J8, Q864J9, Q864K0, Q864K2, Q864K3

Diamond homologs: A5A4K9, A5A4L1, C3ZQF9, O08725, O17239, O42179, O43193, O55040, O88319, P19020, P20789, P20905, P21917, P24628, P30728, P30989, P58826, Q09388, Q28553, Q58CW4, Q5QD24, Q8BZ39, Q8ITC7, Q90WY4, Q923Y8, Q92847, Q93126, Q95254, Q99P50, Q9ESQ4, Q9GZQ4, Q9HB89, Q9JJI5, Q9VML9, Q9Y5Y3, A0A287A2K5, O42574, O43613, O62709, O62729

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	165
Likely benign	50
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

156 predictions. Top by Δscore:

Variant	Effect	Δscore
2:105242519:AC:A	acceptor_gain	0.6800
2:105242696:T:A	acceptor_gain	0.6600
2:105242516:AACAC:A	acceptor_gain	0.6300
2:105242520:C:CA	acceptor_gain	0.6000
2:105242616:AACAG:A	donor_loss	0.6000
2:105242617:ACAG:A	donor_loss	0.6000
2:105242618:CAG:C	donor_loss	0.6000
2:105242619:AGGT:A	donor_loss	0.6000
2:105242620:G:GA	donor_loss	0.6000
2:105242621:GTCA:G	donor_loss	0.6000
2:105242622:T:G	donor_loss	0.6000
2:105242735:AGC:A	acceptor_gain	0.5900
2:105242482:T:TA	acceptor_gain	0.5800
2:105242790:GGCTC:G	donor_gain	0.5800
2:105242516:A:AG	acceptor_gain	0.5700
2:105242520:C:G	acceptor_gain	0.5600
2:105242615:CAACA:C	donor_loss	0.5600
2:105242454:T:TA	acceptor_gain	0.5500
2:105242806:G:GG	donor_gain	0.5500
2:105242519:A:AG	acceptor_gain	0.5400
2:105242727:C:A	donor_gain	0.5400
2:105242805:A:AG	donor_gain	0.5300
2:105242797:T:G	donor_gain	0.5200
2:105242457:T:TA	acceptor_gain	0.5100
2:105242767:C:CA	acceptor_gain	0.5000
2:105242458:G:GA	donor_gain	0.4900
2:105242678:G:GG	donor_gain	0.4900
2:105242625:G:C	donor_loss	0.4800
2:105242677:C:CG	donor_gain	0.4800
2:105242791:GC:G	donor_gain	0.4800

AlphaMissense

2405 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:105242243:A:C	S129R	0.999
2:105242245:C:A	S129R	0.999
2:105242245:C:G	S129R	0.999
2:105242014:C:A	N52K	0.996
2:105242014:C:G	N52K	0.996
2:105242253:G:C	R132P	0.996
2:105242849:T:C	F331L	0.996
2:105242851:C:A	F331L	0.996
2:105242851:C:G	F331L	0.996
2:105242000:G:A	G48R	0.995
2:105242000:G:C	G48R	0.995
2:105242024:T:C	C56R	0.995
2:105242097:A:T	D80V	0.995
2:105242324:T:A	W156R	0.995
2:105242324:T:C	W156R	0.995
2:105242068:C:A	N70K	0.994
2:105242068:C:G	N70K	0.994
2:105242097:A:C	D80A	0.994
2:105242158:G:C	W100C	0.994
2:105242158:G:T	W100C	0.994
2:105242644:G:C	K262N	0.994
2:105242644:G:T	K262N	0.994
2:105242826:T:A	V323D	0.994
2:105242009:G:C	G51R	0.992
2:105242076:T:A	L73Q	0.992
2:105242219:G:C	G121R	0.992
2:105242250:A:C	D131A	0.992
2:105242639:T:C	F261L	0.992
2:105242641:C:A	F261L	0.992
2:105242641:C:G	F261L	0.992

dbSNP variants (sampled 300 via entrez): RS1000431061 (2:105241815 G>A,C,T), RS1000864987 (2:105243547 C>A), RS1000872948 (2:105240616 C>A,T), RS1000925099 (2:105240999 G>A,T), RS1001150403 (2:105243276 G>A), RS1001916710 (2:105243604 G>A,T), RS1003360149 (2:105243295 G>C), RS1003479730 (2:105242906 C>T), RS1005154660 (2:105241334 T>A), RS1005354962 (2:105242768 G>A,T), RS1005659249 (2:105243872 G>A), RS1008407408 (2:105241614 A>C,G), RS1009008319 (2:105241032 G>C,T), RS1009842147 (2:105243570 G>A), RS1011524564 (2:105239816 T>C)

Disease associations

OMIM: gene MIM:604838 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
cone-rod dystrophy	Limited	Autosomal recessive

Mondo (1): cone-rod dystrophy (MONDO:0015993)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002541_39	Menarche (age at onset)	7.000000e-13
GCST003993_33	Menarche (age at onset)	2.000000e-11
GCST005951_42	Body mass index	1.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0004340	body mass index

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523928 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Class A Orphans with no pharmacology

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
aristolochic acid I	increases expression	1
bisphenol A	decreases methylation	1
terbufos	increases methylation	1
ferrous chloride	decreases expression	1
abrine	decreases expression	1
Fonofos	increases methylation	1
Parathion	increases methylation	1
Valproic Acid	increases methylation	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
CHEMBL4883454	Binding	PRESTO-Tango GPCRome screening (GPR45)	Data for DCP probe UCSF924

Cellosaurus cell lines

2 cell lines: 1 spontaneously immortalized cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_KX64	PathHunter CHO-K1 GPR45 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_KZ56	PathHunter HEK 293 GPR45 beta-arrestin	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT06467344	PHASE1/PHASE2	RECRUITING	Study to Evaluate ACDN-01 in ABCA4-related Stargardt Retinopathy (STELLAR)
NCT06789445	PHASE1/PHASE2	RECRUITING	A Study to Investigate the Safety of OpCT-001 in Adults Who Have Primary Photoreceptor Disease (CLARICO)
NCT00427180	Not specified	UNKNOWN	IRIS PILOT - Extended Pilot Study With a Retinal Implant System
NCT01864486	Not specified	COMPLETED	Restoring Vision With the Intelligent Retinal Implant System (IRIS V1)in Patients With Retinal Dystrophy
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT02670980	Not specified	COMPLETED	Compensation for Blindness With the Intelligent Retinal Implant System (IRIS V2) in Patients With Retinal Dystrophy
NCT04658251	Not specified	TERMINATED	Study of New Mutations in Cone Disorders
NCT05355415	Not specified	RECRUITING	Adaptive Optics Imaging of Outer Retinal Diseases
NCT06445322	Not specified	RECRUITING	Prescreening Study to Identify Potential Stargardt Participants for ACDN-01 Clinical Trials (STARPATH)
NCT07548944	Not specified	RECRUITING	Observational Study to Investigate the Short-term Effects of Transcorneal Electrical Stimulation on Visual Performance