GPR173

Summary

GPR173 (G protein-coupled receptor 173, HGNC:18186) is a protein-coding gene on chromosome Xp11.22, encoding Probable G-protein coupled receptor 173 (Q9NS66). Is a receptor for the SMIM20 derived peptides Phoenixin-14 and Phoenixin-20.

This gene encodes a member of the G-protein coupled receptor 1 family. This protein contains 7 transmembrane domains and conserved cysteine residues.

Source: NCBI Gene 54328 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 37 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_018969

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18186
Approved symbol	GPR173
Name	G protein-coupled receptor 173
Location	Xp11.22
Locus type	gene with protein product
Status	Approved
Aliases	SREB3
Ensembl gene	ENSG00000184194
Ensembl biotype	protein_coding
OMIM	300253
Entrez	54328

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000332582, ENST00000375466, ENST00000895512

RefSeq mRNA: 1 — MANE Select: NM_018969 NM_018969

CCDS: CCDS14349

Canonical transcript exons

ENST00000332582 — 2 exons

Exon	Start	End
ENSE00002443867	53048789	53049484
ENSE00002508942	53076525	53080615

Expression profiles

Bgee: expression breadth ubiquitous, 169 present calls, max score 91.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.4263 / max 86.3152, expressed in 950 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196398	3.0822	935
196401	0.3441	160

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	91.21	gold quality
ganglionic eminence	UBERON:0004023	89.42	gold quality
adenohypophysis	UBERON:0002196	85.11	gold quality
pituitary gland	UBERON:0000007	84.14	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.10	gold quality
cerebellar hemisphere	UBERON:0002245	83.87	gold quality
cerebellar cortex	UBERON:0002129	83.81	gold quality
ventricular zone	UBERON:0003053	82.89	gold quality
tibial nerve	UBERON:0001323	82.11	gold quality
cerebellum	UBERON:0002037	82.08	gold quality
right ovary	UBERON:0002118	81.68	gold quality
left ovary	UBERON:0002119	81.23	gold quality
right frontal lobe	UBERON:0002810	79.85	gold quality
nucleus accumbens	UBERON:0001882	78.49	gold quality
anterior cingulate cortex	UBERON:0009835	78.26	gold quality
cingulate cortex	UBERON:0003027	78.15	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.06	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	77.93	gold quality
amygdala	UBERON:0001876	77.75	gold quality
prefrontal cortex	UBERON:0000451	77.68	gold quality
mucosa of stomach	UBERON:0001199	77.48	gold quality
ovary	UBERON:0000992	77.31	gold quality
stromal cell of endometrium	CL:0002255	77.06	gold quality
caudate nucleus	UBERON:0001873	77.05	gold quality
left uterine tube	UBERON:0001303	76.81	gold quality
Brodmann (1909) area 9	UBERON:0013540	76.34	gold quality
neocortex	UBERON:0001950	76.19	gold quality
putamen	UBERON:0001874	75.96	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	75.96	gold quality
spinal cord	UBERON:0002240	75.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

129 targeting GPR173, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4271	99.88	68.32	2244

Literature-anchored findings (GeneRIF, showing 3)

• a molecular model of GPR173 was constructed using the screening results. The combination of computational and biological methods will provide a unique approach to ligand identification for orphan GPCRs and brain research. (PMID:27184081)
• Single-nucleotide polymorphism rs13440883 in GPR173 was found to be significantly associated with systemic lupus erythematous (PMID:29724251)
• GPR173 agonist phoenixin 20 promotes osteoblastic differentiation of MC3T3-E1 cells. (PMID:33196456)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr173	ENSDARG00000042922
mus_musculus	Gpr173	ENSMUSG00000056679
rattus_norvegicus	AABR07037489.1	ENSRNOG00000060137

Paralogs (2): GPR85 (ENSG00000164604), GPR27 (ENSG00000170837)

Protein

Protein identifiers

Probable G-protein coupled receptor 173 — Q9NS66 (reviewed: Q9NS66)

Alternative names: Super conserved receptor expressed in brain 3

All UniProt accessions (2): Q9NS66, J3KPD1

UniProt curated annotations — full annotation on UniProt →

Function. Is a receptor for the SMIM20 derived peptides Phoenixin-14 and Phoenixin-20. It mediates the Phoenixin-14 and Phoenixin-20 augmentation of gonadotropin-releasing hormone (GNRH) signaling in the hypothalamus and pituitary gland. In the ovary, it mediates the effects of Phoenixin-14 and Phoenixin-20 induced granulosa cell proliferation during follicular growth.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in the ovary, specifically in granulosa cells of follicles that have passed the primary stage and in oocytes (at protein level). Expressed at high levels in brain. Lower levels in small intestine. In brain regions, detected in all regions tested. Highest levels in the cerebellum and cerebral cortex.

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

RefSeq proteins (1): NP_061842* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR051509	GPCR_Orphan/Phoenixin	Family

Pfam: PF00001

UniProt features (19 total): topological domain 8, transmembrane region 7, glycosylation site 2, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NS66-F1	81.94	0.58

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 (1): 96–174

Glycosylation sites (2): 3, 184

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 101 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GCANCTGNY_MYOD_Q6, GOBP_NEUROGENESIS, TAL1ALPHAE47_01, GGGTGGRR_PAX4_03, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, MYOD_01, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, NF1_Q6_01, TGCTGAY_UNKNOWN, GOBP_REGULATION_OF_NEURON_MIGRATION, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_NEURON_MIGRATION, GOBP_CELLULAR_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_HORMONE

GO Biological Process (4): signal transduction (GO:0007165), negative regulation of neuron migration (GO:2001223), G protein-coupled receptor signaling pathway (GO:0007186), cellular response to gonadotropin-releasing hormone (GO:0097211)

GO Molecular Function (3): G protein-coupled receptor activity (GO:0004930), gonadotropin-releasing hormone receptor activity (GO:0004968), protein binding (GO:0005515)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor activity	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
neuron migration	1
negative regulation of cell migration	1
regulation of neuron migration	1
signal transduction	1
cellular response to peptide hormone stimulus	1
response to gonadotropin-releasing hormone	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
protein-hormone receptor activity	1
gonadotropin-releasing hormone binding	1
cellular response to gonadotropin-releasing hormone	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

472 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR173	SMIM20	Q8N5G0	883
GPR173	ALDH18A1	P54886	685
GPR173	GNRHR	P30968	551
GPR173	KISS1	Q15726	523
GPR173	GNRH1	P01148	448
GPR173	GPR160	Q9UJ42	442
GPR173	THOP1	P52888	403
GPR173	GPR142	Q7Z601	371
GPR173	ALG1L2	C9J202	360
GPR173	GPR174	Q9BXC1	350
GPR173	OR2F1	Q13607	349
GPR173	NUCB2	P80303	348
GPR173	DCUN1D3	Q8IWE4	344
GPR173	GPR25	O00155	343
GPR173	KISS1R	Q969F8	324

IntAct

10 interactions, top by confidence:

A	B	Type	Score
GPR173	CBX6	psi-mi:“MI:0915”(physical association)	0.560
GPR173	CBX6	psi-mi:“MI:0914”(association)	0.560
RAMP2	GPR173	psi-mi:“MI:0915”(physical association)	0.400
GPR173	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	GPR173	psi-mi:“MI:0915”(physical association)	0.400
GPR173	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
GPR173	CDIPT	psi-mi:“MI:0914”(association)	0.350

BioGRID (51): CBX6 (Affinity Capture-MS), CBX6 (Affinity Capture-MS), CBX6 (Affinity Capture-MS), RBKS (Affinity Capture-MS), GPRC5C (Affinity Capture-MS), CELSR2 (Affinity Capture-MS), CDIPT (Affinity Capture-MS), GOLGA5 (Affinity Capture-MS), YIPF3 (Affinity Capture-MS), ERMP1 (Affinity Capture-MS), TMEM259 (Affinity Capture-MS), SLC39A10 (Affinity Capture-MS), CIB1 (Affinity Capture-MS), MAOB (Affinity Capture-MS), VKORC1L1 (Affinity Capture-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: O54897, P60893, P60894, P60895, Q5E9H8, Q5RBG7, Q6PI62, Q9I918, Q9I919, Q9JJH2, Q9JJH3, Q9NS66, Q9NS67, A0A287A2K5, C3ZQF9, E7EM37, O02769, O02781, O08786, O15973, O19012, O19091, O43613, O77408, O77621, O77721, O88495, O97661, O97772, P08913, P18825, P18871, P21917, P21918, P22270, P22909, P28286, P30551, P30552, P30729

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	24
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
547105	GRCh37/hg19 Xp11.22(chrX:53094819-53414375)x1	Likely pathogenic

SpliceAI

236 predictions. Top by Δscore:

Variant	Effect	Δscore
X:53049481:CAAGG:C	donor_loss	0.9800
X:53049484:GGT:G	donor_loss	0.9800
X:53049485:GTAA:G	donor_loss	0.9800
X:53049486:T:A	donor_loss	0.9800
X:53075967:G:A	acceptor_gain	0.9800
X:53076758:T:A	acceptor_gain	0.9800
X:53075966:T:TA	acceptor_gain	0.9700
X:53049485:G:GG	donor_gain	0.9600
X:53049483:AG:A	donor_gain	0.9500
X:53049484:GG:G	donor_gain	0.9500
X:53075964:T:A	acceptor_gain	0.9400
X:53076521:GCA:G	acceptor_loss	0.9400
X:53076522:CAGGT:C	acceptor_loss	0.9400
X:53076523:A:T	acceptor_loss	0.9400
X:53050436:A:T	donor_gain	0.9300
X:53076523:AGGT:A	acceptor_gain	0.9300
X:53076524:GGTG:G	acceptor_gain	0.9300
X:53076524:GGTGC:G	acceptor_gain	0.9200
X:53050509:G:GT	donor_gain	0.9100
X:53076524:GGT:G	acceptor_gain	0.9100
X:53076517:A:AG	acceptor_gain	0.9000
X:53076523:AG:A	acceptor_gain	0.9000
X:53076524:GG:G	acceptor_gain	0.9000
X:53076511:A:AG	acceptor_gain	0.8900
X:53071064:TTC:T	donor_gain	0.8700
X:53076523:A:AG	acceptor_gain	0.8700
X:53076524:G:GC	acceptor_gain	0.8700
X:53050168:G:GT	donor_gain	0.8600
X:53050472:G:T	donor_gain	0.8600
X:53076512:T:G	acceptor_gain	0.8600

AlphaMissense

2432 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:53076727:A:C	S36R	0.999
X:53076729:C:A	S36R	0.999
X:53076729:C:G	S36R	0.999
X:53076973:A:C	S118R	0.999
X:53076975:C:A	S118R	0.999
X:53076975:C:G	S118R	0.999
X:53077120:T:C	F167L	0.999
X:53077122:T:A	F167L	0.999
X:53077122:T:G	F167L	0.999
X:53077141:T:A	C174S	0.999
X:53077141:T:C	C174R	0.999
X:53077142:G:C	C174S	0.999
X:53077143:C:G	C174W	0.999
X:53077311:G:C	W230C	0.999
X:53077311:G:T	W230C	0.999
X:53077315:T:C	F232L	0.999
X:53077317:C:A	F232L	0.999
X:53077317:C:G	F232L	0.999
X:53076908:G:A	C96Y	0.998
X:53077063:T:A	W148R	0.998
X:53077063:T:C	W148R	0.998
X:53077097:T:A	V159D	0.998
X:53077142:G:A	C174Y	0.998
X:53077300:A:C	S227R	0.998
X:53077302:C:A	S227R	0.998
X:53077302:C:G	S227R	0.998
X:53077309:T:A	W230R	0.998
X:53077309:T:C	W230R	0.998
X:53077316:T:C	F232S	0.998
X:53077353:C:A	N244K	0.998

dbSNP variants (sampled 300 via entrez): RS1000930862 (X:53056985 C>T), RS1001065346 (X:53056315 G>A), RS1001482393 (X:53050565 C>T), RS1001493701 (X:53050887 T>G), RS1001797191 (X:53070847 T>G), RS1001877964 (X:53048560 T>G), RS1002068683 (X:53058972 G>A,C), RS1002134789 (X:53068092 T>C), RS1002531126 (X:53053225 C>T), RS1002639362 (X:53067713 A>G), RS1003148171 (X:53062712 C>T), RS1003331743 (X:53080256 A>G), RS1003669451 (X:53079827 G>A,C), RS1004424808 (X:53048130 C>T), RS1004777871 (X:53047790 T>C)

Disease associations

OMIM: gene MIM:300253 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): congenital portosystemic shunt (MONDO:0018811)

Orphanet (1): Congenital portosystemic shunt (Orphanet:480531)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90000047_269	Age at first sexual intercourse	2.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009749	age at first sexual intercourse measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523922 (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 emerging pharmacology

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	2
entinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Arsenic	increases expression, affects cotreatment, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
propionaldehyde	decreases expression	1
quercitrin	increases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	increases expression, affects cotreatment	1
Lead	decreases expression	1
Lipopolysaccharides	decreases reaction, increases expression, increases reaction, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases expression	1
Aflatoxin B1	increases 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
CHEMBL4883431	Binding	PRESTO-Tango GPCRome screening (GPR173)	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_KX47	PathHunter CHO-K1 GPR173 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_KZ54	PathHunter HEK 293 GPR173 beta-arrestin	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06041906	Not specified	ENROLLING_BY_INVITATION	International Registry of Congenital Portosystemic Shunt (IRCPSS)
NCT07314814	Not specified	NOT_YET_RECRUITING	Genetic Hallmarks of Patients With Congenital Portosystemic Shunts and Portopulmonary Hypertension