GPR171

Summary

GPR171 (G protein-coupled receptor 171, HGNC:30057) is a protein-coding gene on chromosome 3q25.1, encoding G-protein coupled receptor 171 (O14626). G-protein coupled receptor for Big LEN, a 16-amino acid neuropeptide produced from the precursor protein, proSAAS (encoded by PCSK1N).

Predicted to enable G protein-coupled purinergic nucleotide receptor activity; neuropeptide binding activity; and neuropeptide receptor activity. Predicted to be involved in adenylate cyclase-modulating G protein-coupled receptor signaling pathway; regulation of feeding behavior; and regulation of sensory perception of pain. Predicted to act upstream of or within negative regulation of myeloid cell differentiation. Predicted to be located in membrane.

Source: NCBI Gene 29909 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 45 total
• Druggable target: yes
• MANE Select transcript: NM_013308

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30057
Approved symbol	GPR171
Name	G protein-coupled receptor 171
Location	3q25.1
Locus type	gene with protein product
Status	Approved
Aliases	H963
Ensembl gene	ENSG00000174946
Ensembl biotype	protein_coding
OMIM	618925
Entrez	29909

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000309180, ENST00000480322, ENST00000617554

RefSeq mRNA: 1 — MANE Select: NM_013308 NM_013308

CCDS: CCDS3155

Canonical transcript exons

ENST00000309180 — 3 exons

Exon	Start	End
ENSE00001208996	151197832	151199439
ENSE00001513450	151200909	151200997
ENSE00001908627	151203104	151203216

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 88.25.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.4532 / max 354.3158, expressed in 167 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45127	2.7898	149
45126	0.6635	94

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.25	gold quality
buccal mucosa cell	CL:0002336	86.55	gold quality
vermiform appendix	UBERON:0001154	85.43	gold quality
blood	UBERON:0000178	84.26	gold quality
lymph node	UBERON:0000029	82.99	gold quality
granulocyte	CL:0000094	82.05	gold quality
spleen	UBERON:0002106	80.72	gold quality
caecum	UBERON:0001153	79.89	gold quality
small intestine Peyer’s patch	UBERON:0003454	78.46	gold quality
superficial temporal artery	UBERON:0001614	75.90	gold quality
amniotic fluid	UBERON:0000173	75.64	gold quality
gall bladder	UBERON:0002110	75.52	gold quality
small intestine	UBERON:0002108	75.46	gold quality
rectum	UBERON:0001052	74.24	gold quality
adrenal tissue	UBERON:0018303	73.02	gold quality
visceral pleura	UBERON:0002401	72.20	gold quality
left uterine tube	UBERON:0001303	71.98	gold quality
upper lobe of left lung	UBERON:0008952	71.82	gold quality
right lung	UBERON:0002167	70.88	gold quality
omental fat pad	UBERON:0010414	70.86	gold quality
peritoneum	UBERON:0002358	70.78	gold quality
pleura	UBERON:0000977	70.71	gold quality
parietal pleura	UBERON:0002400	70.71	gold quality
epithelium of nasopharynx	UBERON:0001951	70.24	gold quality
nasopharynx	UBERON:0001728	70.23	gold quality
upper lobe of lung	UBERON:0008948	69.82	gold quality
body of stomach	UBERON:0001161	69.71	gold quality
adipose tissue of abdominal region	UBERON:0007808	69.62	gold quality
mucosa of transverse colon	UBERON:0004991	69.51	gold quality
palpebral conjunctiva	UBERON:0001812	69.06	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-97	yes	625.14
E-CURD-46	yes	62.17
E-CURD-88	yes	47.18
E-MTAB-8410	yes	14.21
E-ANND-3	yes	10.85
E-MTAB-4850	no	1013.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

40 targeting GPR171, 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-4673	100.00	66.64	1490
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-548N	99.98	71.94	4170
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-3940-5P	99.14	65.26	493
HSA-MIR-4507	99.14	65.27	515
HSA-MIR-3152-3P	99.10	66.35	678
HSA-MIR-219A-1-3P	98.91	67.87	639
HSA-MIR-487A-5P	98.85	69.37	993
HSA-MIR-487B-5P	98.85	69.48	987
HSA-MIR-4490	98.51	68.47	943

Literature-anchored findings (GeneRIF, showing 1)

• High GPR171 expression enhances proliferation and metastasis of lung cancer. (PMID:26760963)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr171	ENSDARG00000105008
mus_musculus	Gpr171	ENSMUSG00000050075
rattus_norvegicus	Gpr171	ENSRNOG00000025297

Paralogs (6): GPR87 (ENSG00000138271), P2RY12 (ENSG00000169313), PTAFR (ENSG00000169403), GPR34 (ENSG00000171659), P2RY14 (ENSG00000174944), P2RY13 (ENSG00000181631)

Protein

Protein identifiers

G-protein coupled receptor 171 — O14626 (reviewed: O14626)

Alternative names: G-protein coupled receptor H963

All UniProt accessions (2): O14626, C9JR91

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled receptor for Big LEN, a 16-amino acid neuropeptide produced from the precursor protein, proSAAS (encoded by PCSK1N). Acts through a G(i)-alpha-mediated pathway in response to Big LEN. Big LEN-GPR171 system plays an important role in regulating feeding and metabolism. Also plays a role in modulating fear and anxiety-like behaviors in the basolateral amygdala. Big LEN-GPR171 modulates the mu-type opioid receptor signaling and antinociception. Acts as a negative regulator T cell function.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in both T-cell subsets and natural killer cells, while it is undetectable in B cells or CD14(+) monocytes. Expressed in peripheral blood mononuclear cells (PBMC) and Jurkat cells (at protein level).

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

RefSeq proteins (1): NP_037440* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR048077	GPR171	Family

Pfam: PF00001

UniProt features (18 total): topological domain 8, transmembrane region 7, chain 1, glycosylation site 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14626-F1	87.72	0.57

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 (1): 3

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 260 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, MORF_ITGA2, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_G_PROTEIN_COUPLED_PURINERGIC_NUCLEOTIDE_RECEPTOR_SIGNALING_PATHWAY, GOBP_BEHAVIOR, CREBP1_Q2, RACCACAR_AML_Q6, MORF_RAD51L3, CAIRO_HEPATOBLASTOMA_CLASSES_DN, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_SENSORY_PERCEPTION_OF_PAIN, GOBP_REGULATION_OF_HEMOPOIESIS, GOBP_REGULATION_OF_BEHAVIOR, GOBP_REGULATION_OF_FEEDING_BEHAVIOR

GO Biological Process (8): G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), negative regulation of myeloid cell differentiation (GO:0045638), regulation of sensory perception of pain (GO:0051930), regulation of feeding behavior (GO:0060259), signal transduction (GO:0007165), neuropeptide signaling pathway (GO:0007218), G protein-coupled purinergic nucleotide receptor signaling pathway (GO:0035589)

GO Molecular Function (5): G protein-coupled receptor activity (GO:0004930), neuropeptide receptor activity (GO:0008188), G protein-coupled peptide receptor activity (GO:0008528), neuropeptide binding (GO:0042923), G protein-coupled purinergic nucleotide receptor activity (GO:0045028)

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	3
G protein-coupled receptor signaling pathway	3
signal transduction	1
adenylate cyclase activity	1
myeloid cell differentiation	1
negative regulation of cell differentiation	1
regulation of myeloid cell differentiation	1
sensory perception of pain	1
regulation of sensory perception	1
feeding behavior	1
regulation of behavior	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
purinergic nucleotide receptor signaling pathway	1
transmembrane signaling receptor activity	1
neuropeptide signaling pathway	1
G protein-coupled peptide receptor activity	1
neuropeptide binding	1
peptide receptor activity	1
peptide binding	1
purinergic nucleotide receptor activity	1
G protein-coupled purinergic nucleotide receptor signaling pathway	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

880 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR171	PCSK1N	Q9UHG2	862
GPR171	GPR83	Q9NYM4	727
GPR171	GPR152	Q8TDT2	578
GPR171	VIP	P01282	506
GPR171	GPR158	Q5T848	501
GPR171	GPR108	Q9NPR9	493
GPR171	FAM81A	Q8TBF8	463
GPR171	GPR142	Q7Z601	463
GPR171	OR56B4	Q8NH76	455
GPR171	OR56A3	Q8NH54	437
GPR171	GPR162	Q16538	436
GPR171	ALDH18A1	P54886	435
GPR171	OR52W1	Q6IF63	420
GPR171	PTGER1	P34995	412
GPR171	OR56A4	Q8NGH8	391

IntAct

11 interactions, top by confidence:

A	B	Type	Score
GPR171	DAZAP1	psi-mi:“MI:0915”(physical association)	0.400
GPR171	NME2P1	psi-mi:“MI:0915”(physical association)	0.400
GPR171	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	GPR171	psi-mi:“MI:0915”(physical association)	0.400
GPR171	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
GPR171	RAMP3	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (5): DAZAP1 (Proximity Label-MS), NME2P1 (Affinity Capture-MS), LARP6 (Cross-Linking-MS (XL-MS)), ACADVL (Cross-Linking-MS (XL-MS)), GPR171 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: B5X337, D4A4Q2, D4A7K7, O00398, O14626, O35881, P21556, P25105, P32249, P43657, P60019, Q15391, Q1RMI1, Q2NNR5, Q3SAG9, Q3SX17, Q3U507, Q3U6B2, Q3UJF0, Q3ZBK9, Q4G072, Q5ZI82, Q6XCF2, Q80Z39, Q8BFU7, Q8BG55, Q8BLG2, Q8BMC0, Q920A1, Q924T8, Q924T9, Q95KC3, Q95N02, Q95N03, Q99677, Q99JA4, Q99MT7, Q9BXC1, Q9BY21, Q9CPV9

Diamond homologs: D4A4Q2, O14626, O35881, P30992, P32250, Q15391, Q3SX17, Q3ZBK9, Q6GUG4, Q8BG55, Q95KC3, Q99MT7, Q9BE53, Q9BPV8, Q9BY21, Q9CPV9, Q9D8I2, Q9EPX4, Q9ESG6, Q9H244, O00254, P25105, Q28553, P60019, Q05394, Q3SAG9, Q6XCF2, Q9R1K6, Q9UPC5, O55197, Q2NNR5, Q99PE4, Q9Y271, P35366, Q58D85, O42179, P21556, P58825, Q62035, Q9XSD4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

477 predictions. Top by Δscore:

Variant	Effect	Δscore
3:151199438:CT:C	acceptor_gain	0.9900
3:151203099:CATA:C	donor_loss	0.9900
3:151203100:ATACC:A	donor_loss	0.9900
3:151203101:TACCT:T	donor_loss	0.9900
3:151203102:A:AC	donor_gain	0.9900
3:151203103:C:CC	donor_gain	0.9900
3:151201005:A:T	acceptor_gain	0.9800
3:151199440:C:CC	acceptor_gain	0.9500
3:151203102:AC:A	donor_gain	0.9500
3:151203103:CC:C	donor_gain	0.9500
3:151203103:CCTG:C	donor_gain	0.9400
3:151199071:C:CC	acceptor_gain	0.9300
3:151201015:G:GC	acceptor_gain	0.9300
3:151203103:CCT:C	donor_gain	0.9300
3:151203103:CCTGG:C	donor_gain	0.9300
3:151201003:TCA:T	acceptor_gain	0.9100
3:151201020:A:C	acceptor_gain	0.9000
3:151199068:ATGCT:A	acceptor_gain	0.8900
3:151199436:GACT:G	acceptor_gain	0.8900
3:151199437:ACTC:A	acceptor_loss	0.8800
3:151199439:TC:T	acceptor_loss	0.8800
3:151199440:CTGTA:C	acceptor_loss	0.8800
3:151199441:T:G	acceptor_loss	0.8800
3:151199452:C:CT	acceptor_loss	0.8800
3:151199453:A:T	acceptor_loss	0.8800
3:151199717:A:T	acceptor_gain	0.8800
3:151199554:GAACT:G	donor_loss	0.8700
3:151199555:AACT:A	donor_loss	0.8700
3:151199556:ACT:A	donor_loss	0.8700
3:151199557:C:G	donor_loss	0.8700

AlphaMissense

2099 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:151198659:C:G	R243P	0.997
3:151198972:A:G	W139R	0.996
3:151198972:A:T	W139R	0.996
3:151199060:G:C	S109R	0.996
3:151199060:G:T	S109R	0.996
3:151199062:T:G	S109R	0.996
3:151198679:A:C	F236L	0.995
3:151198679:A:T	F236L	0.995
3:151198681:A:G	F236L	0.995
3:151198587:T:A	K267I	0.994
3:151198893:C:G	C165S	0.994
3:151198894:A:T	C165S	0.994
3:151199127:C:G	C87S	0.994
3:151199128:A:T	C87S	0.994
3:151198674:G:C	P238R	0.993
3:151198674:G:T	P238H	0.992
3:151198552:A:G	C279R	0.991
3:151198684:A:G	C235R	0.991
3:151198880:T:A	K169N	0.991
3:151198880:T:G	K169N	0.991
3:151198894:A:G	C165R	0.991
3:151199305:C:G	G28R	0.991
3:151199305:C:T	G28R	0.991
3:151198575:A:G	L271P	0.990
3:151198823:A:C	F188L	0.990
3:151198823:A:T	F188L	0.990
3:151198825:A:G	F188L	0.990
3:151198861:A:G	W176R	0.990
3:151198861:A:T	W176R	0.990
3:151199126:G:C	C87W	0.990

dbSNP variants (sampled 300 via entrez): RS1000808796 (3:151202692 A>G,T), RS1001050057 (3:151200233 C>T), RS1001870958 (3:151199923 T>G), RS1002492520 (3:151199557 C>G), RS1002671193 (3:151204838 A>G), RS1002826513 (3:151200022 G>A), RS1002865935 (3:151204413 A>G), RS1002918593 (3:151204784 A>G), RS1003100663 (3:151197891 C>T), RS1003133347 (3:151205067 T>C), RS1003204434 (3:151202822 T>C), RS1003550302 (3:151198026 G>A), RS1005308325 (3:151200710 G>T), RS1005351295 (3:151201126 G>C), RS1005392317 (3:151202021 T>C)

Disease associations

OMIM: gene MIM:618925 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

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): CHEMBL4523860 (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

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression, increases expression	3
GSK-J4	decreases expression	1
TL8-506	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
Acetaminophen	increases expression	1
Air Pollutants, Occupational	decreases expression	1
Demecolcine	increases expression	1
Valproic Acid	decreases methylation	1
Antirheumatic Agents	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
CHEMBL4883430	Binding	PRESTO-Tango GPCRome screening (GPR171)	Data for DCP probe UCSF924

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KX46	PathHunter CHO-K1 GPR171 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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