GPR153

Summary

GPR153 (G protein-coupled receptor 153, HGNC:23618) is a protein-coding gene on chromosome 1p36.31, encoding Probable G-protein coupled receptor 153 (Q6NV75). Orphan receptor.

This gene encodes an integral membrane protein that belongs to the Class A rhodopsin superfamily of G protein coupled receptors. The encoded protein is expressed primarily in the central nervous system. A knockdown of the orthologous gene in rat is associated with a significant reduction in food intake and impaired decision making ability. Mutations in this gene are associated with schizophrenia, autism, and other neuropsychiatric disorders. The expression of this gene is activated by the glioma-associated oncogene homolog 1 transcription factor which, in turn, is activated by sonic hedgehog in normal and tumorigenic cells.

Source: NCBI Gene 387509 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 150 total — 2 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_207370

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23618
Approved symbol	GPR153
Name	G protein-coupled receptor 153
Location	1p36.31
Locus type	gene with protein product
Status	Approved
Aliases	PGR1
Ensembl gene	ENSG00000158292
Ensembl biotype	protein_coding
OMIM	614269
Entrez	387509

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000377893, ENST00000937749, ENST00000937750, ENST00000957092

RefSeq mRNA: 1 — MANE Select: NM_207370 NM_207370

CCDS: CCDS64

Canonical transcript exons

ENST00000377893 — 6 exons

Exon	Start	End
ENSE00001038216	6253718	6254147
ENSE00001064734	6251338	6251530
ENSE00001373369	6254550	6255014
ENSE00001404850	6250440	6250624
ENSE00001410775	6260825	6261098
ENSE00001475432	6247353	6250003

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 92.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.9471 / max 65.1138, expressed in 1328 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10005	4.6490	1319
10004	0.2982	166

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	92.18	gold quality
lateral nuclear group of thalamus	UBERON:0002736	91.50	gold quality
triceps brachii	UBERON:0001509	90.20	gold quality
gluteal muscle	UBERON:0002000	88.72	gold quality
pancreatic ductal cell	CL:0002079	88.12	silver quality
cortical plate	UBERON:0005343	87.99	gold quality
buccal mucosa cell	CL:0002336	87.54	gold quality
cerebellar vermis	UBERON:0004720	87.25	silver quality
endothelial cell	CL:0000115	87.22	gold quality
cervix squamous epithelium	UBERON:0006922	86.94	gold quality
dorsal plus ventral thalamus	UBERON:0001897	86.40	gold quality
olfactory bulb	UBERON:0002264	85.99	gold quality
diaphragm	UBERON:0001103	85.63	gold quality
ganglionic eminence	UBERON:0004023	84.82	gold quality
mammalian vulva	UBERON:0000997	84.14	gold quality
type B pancreatic cell	CL:0000169	84.08	gold quality
cervix epithelium	UBERON:0004801	83.74	gold quality
gingival epithelium	UBERON:0001949	83.59	gold quality
periodontal ligament	UBERON:0008266	83.31	gold quality
apex of heart	UBERON:0002098	83.17	gold quality
layer of synovial tissue	UBERON:0007616	83.11	gold quality
small intestine Peyer’s patch	UBERON:0003454	82.97	gold quality
male germ cell	CL:0000015	82.90	gold quality
upper arm skin	UBERON:0004263	82.82	gold quality
substantia nigra pars reticulata	UBERON:0001966	82.79	silver quality
heart right ventricle	UBERON:0002080	82.78	gold quality
sperm	CL:0000019	82.66	gold quality
hair follicle	UBERON:0002073	82.39	gold quality
nasal cavity epithelium	UBERON:0005384	82.37	gold quality
substantia nigra pars compacta	UBERON:0001965	82.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

94 targeting GPR153, 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-4455	100.00	65.48	1587
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-4492	99.87	68.25	3611
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6785-5P	99.82	68.68	4428

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr153	ENSDARG00000087601
mus_musculus	Gpr153	ENSMUSG00000042804
rattus_norvegicus	Gpr153	ENSRNOG00000010718

Paralogs (1): GPR162 (ENSG00000250510)

Protein

Protein identifiers

Probable G-protein coupled receptor 153 — Q6NV75 (reviewed: Q6NV75)

Alternative names: G-protein coupled receptor PGR1

All UniProt accessions (2): Q6NV75, A0A0I9QQ03

UniProt curated annotations — full annotation on UniProt →

Function. Orphan receptor.

Subcellular location. Cell membrane.

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

RefSeq proteins (1): NP_997253* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR022335	GPR153	Family
IPR022347	GCR_153/162	Family

Pfam: PF00001

UniProt features (23 total): topological domain 8, transmembrane region 7, compositionally biased region 4, region of interest 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NV75-F1	65.60	0.34

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 90 (showing top): WHITE_NEUROBLASTOMA_WITH_1P36.3_DELETION, MEF2_02, AMIT_EGF_RESPONSE_480_MCF10A, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, CTAWWWATA_RSRFC4_Q2, PARENT_MTOR_SIGNALING_UP, STAT5A_01, GAUSSMANN_MLL_AF4_FUSION_TARGETS_D_UP, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GAZDA_DIAMOND_BLACKFAN_ANEMIA_ERYTHROID_DN, MMEF2_Q6, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, chr1p36, MEISSNER_NPC_HCP_WITH_H3K4ME2, KOYAMA_SEMA3B_TARGETS_DN

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

GO Molecular Function (1): G protein-coupled receptor activity (GO:0004930)

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

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

2090 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR153	GPR176	Q14439	570
GPR153	GPR68	Q15743	558
GPR153	GPR161	Q8N6U8	524
GPR153	ZNF764	Q96H86	499
GPR153	TTLL2	Q9BWV7	474
GPR153	GPR139	Q6DWJ6	473
GPR153	GPR146	Q96CH1	472
GPR153	COX7B2	Q8TF08	459
GPR153	RNF207	Q6ZRF8	447
GPR153	BEST2	Q8NFU1	445
GPR153	GPR149	Q86SP6	444
GPR153	DMXL1	Q9Y485	443
GPR153	ADGRA3	Q8IWK6	442
GPR153	CLCN7	P51798	437
GPR153	GINM1	Q9NU53	436

IntAct

0 interactions, top by confidence:

BioGRID (2): GPR153 (Positive Genetic), GPR153 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: F2Z333, O00155, O43193, O54897, O60755, O77808, O88626, O88721, O88853, O95977, P21917, P30518, P32307, P34995, P35375, P46095, P48044, P50406, P51436, P51651, P70597, Q00788, Q5E9H8, Q5IS65, Q684M3, Q6NV75, Q6PI62, Q6TLJ0, Q6YNI2, Q7TQN7, Q7TQP2, Q80UC6, Q862A8, Q862A9, Q8BGE9, Q8HYC3, Q8IZ08, Q91X56, Q96P69, Q9BGL8

Diamond homologs: Q16538, Q3UN16, Q6NV75, Q8K0Z9, P31389, P70174, P31390

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	125
Likely benign	10
Benign	3

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
208391	NM_207370.4(GPR153):c.217C>T (p.Arg73Cys)	Likely pathogenic
976729	GRCh37/hg19 1p36.33-36.23(chr1:762080-7309686)	Likely pathogenic

SpliceAI

1175 predictions. Top by Δscore:

Variant	Effect	Δscore
1:6250623:CT:C	acceptor_gain	1.0000
1:6250625:C:CC	acceptor_gain	1.0000
1:6250632:G:C	acceptor_gain	1.0000
1:6253716:A:AC	donor_gain	1.0000
1:6253717:C:CC	donor_gain	1.0000
1:6253717:CCAG:C	donor_gain	1.0000
1:6260823:AC:A	donor_gain	1.0000
1:6260824:CC:C	donor_gain	1.0000
1:6260824:CCCTG:C	donor_gain	1.0000
1:6250620:GGTCT:G	acceptor_gain	0.9900
1:6250621:GTCT:G	acceptor_gain	0.9900
1:6250622:TCT:T	acceptor_gain	0.9900
1:6250622:TCTC:T	acceptor_loss	0.9900
1:6250623:CTC:C	acceptor_gain	0.9900
1:6250624:TC:T	acceptor_loss	0.9900
1:6250624:TCT:T	acceptor_gain	0.9900
1:6250625:C:CG	acceptor_loss	0.9900
1:6250625:C:G	acceptor_gain	0.9900
1:6250627:G:C	acceptor_gain	0.9900
1:6250632:G:GC	acceptor_gain	0.9900
1:6250639:G:C	acceptor_gain	0.9900
1:6250639:G:GC	acceptor_gain	0.9900
1:6251331:T:TA	donor_gain	0.9900
1:6251332:CCTCA:C	donor_loss	0.9900
1:6251333:CTCAC:C	donor_loss	0.9900
1:6251335:CA:C	donor_loss	0.9900
1:6251336:A:AC	donor_gain	0.9900
1:6251336:A:C	donor_loss	0.9900
1:6251337:C:CC	donor_gain	0.9900
1:6251337:CCAT:C	donor_gain	0.9900

AlphaMissense

3876 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:6253955:G:C	S183R	0.993
1:6253955:G:T	S183R	0.993
1:6253957:T:G	S183R	0.993
1:6253988:A:C	F172L	0.993
1:6253988:A:T	F172L	0.993
1:6253990:A:G	F172L	0.993
1:6251522:G:C	S265R	0.991
1:6251522:G:T	S265R	0.991
1:6251524:T:G	S265R	0.991
1:6254658:C:T	C83Y	0.990
1:6254672:C:A	W78C	0.990
1:6254672:C:G	W78C	0.990
1:6254101:A:G	W135R	0.988
1:6254101:A:T	W135R	0.988
1:6254657:G:C	C83W	0.987
1:6254658:C:G	C83S	0.987
1:6254659:A:T	C83S	0.987
1:6254022:C:G	C161S	0.986
1:6254023:A:T	C161S	0.986
1:6254583:C:G	R108P	0.986
1:6254015:G:C	F163L	0.985
1:6254015:G:T	F163L	0.985
1:6254016:A:G	F163S	0.985
1:6254017:A:G	F163L	0.985
1:6254057:C:A	W149C	0.985
1:6254057:C:G	W149C	0.985
1:6254831:A:C	N25K	0.985
1:6254831:A:T	N25K	0.985
1:6254036:G:C	F156L	0.984
1:6254036:G:T	F156L	0.984

dbSNP variants (sampled 300 via entrez): RS1000203967 (1:6251936 C>G,T), RS1000808703 (1:6247569 C>T), RS1000849658 (1:6261145 C>T), RS1000919038 (1:6260260 C>A,T), RS1001285317 (1:6252946 C>T), RS1001328397 (1:6261018 C>T), RS1001362090 (1:6262778 C>A,T), RS1001371026 (1:6256665 T>C), RS1001604635 (1:6251746 T>C), RS1001612161 (1:6253244 A>G), RS1001675479 (1:6258352 C>G,T), RS1001985916 (1:6252712 T>A,G), RS1002056809 (1:6251477 G>A), RS1002105041 (1:6247602 C>G,T), RS1002336937 (1:6252945 C>A,T)

Disease associations

OMIM: gene MIM:614269 | disease phenotypes: MIM:617183

GenCC curated gene-disease

Mondo (2): childhood-onset schizophrenia (MONDO:0957430), Harel-Yoon syndrome (MONDO:0014958)

Orphanet (2): Childhood-onset schizophrenia (Orphanet:641496), Ocular anomalies-axonal neuropathy-developmental delay syndrome (Orphanet:496790)

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523876 (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

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation, affects cotreatment, decreases expression, affects expression	5
trichostatin A	affects cotreatment, decreases expression	3
mercuric bromide	decreases expression, affects cotreatment	2
Benzo(a)pyrene	decreases expression, increases methylation, affects methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
methyleugenol	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
sulforaphane	decreases expression	1
sodium arsenite	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Calcitriol	increases expression, affects cotreatment	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
DEET	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Niclosamide	increases expression	1
Smoke	decreases expression	1
Testosterone	increases expression, affects cotreatment	1
Tetrachlorodibenzodioxin	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	decreases expression	1
Okadaic Acid	decreases 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
CHEMBL4883422	Binding	PRESTO-Tango GPCRome screening (GPR153)	Data for DCP probe UCSF924

Clinical trials (associated diseases)

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