GPR157

Summary

GPR157 (G protein-coupled receptor 157, HGNC:23687) is a protein-coding gene on chromosome 1p36.22, encoding G-protein coupled receptor 157 (Q5UAW9). Orphan receptor that promotes neuronal differentiation of radial glial progenitors (RGPs).

Predicted to enable G protein-coupled receptor activity. Predicted to be involved in adenylate cyclase-activating G protein-coupled receptor signaling pathway; phospholipase C-activating G protein-coupled receptor signaling pathway; and radial glial cell differentiation. Predicted to be located in ciliary membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 80045 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 66 total
• Druggable target: yes
• MANE Select transcript: NM_024980

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23687
Approved symbol	GPR157
Name	G protein-coupled receptor 157
Location	1p36.22
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12132
Ensembl gene	ENSG00000180758
Ensembl biotype	protein_coding
OMIM	620860
Entrez	80045

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000377411, ENST00000465853, ENST00000466131, ENST00000961135

RefSeq mRNA: 1 — MANE Select: NM_024980 NM_024980

CCDS: CCDS100

Canonical transcript exons

ENST00000377411 — 4 exons

Exon	Start	End
ENSE00001773183	9105486	9105680
ENSE00001797549	9111276	9111489
ENSE00001905968	9128645	9129102
ENSE00001951864	9100305	9104634

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 96.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.4956 / max 154.8917, expressed in 999 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10204	2.0922	898
10206	0.3098	99
10205	0.0936	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	96.46	gold quality
vastus lateralis	UBERON:0001379	94.73	gold quality
upper arm skin	UBERON:0004263	94.72	gold quality
quadriceps femoris	UBERON:0001377	94.55	gold quality
gingiva	UBERON:0001828	93.98	gold quality
gingival epithelium	UBERON:0001949	93.91	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.94	gold quality
biceps brachii	UBERON:0001507	91.73	gold quality
lower esophagus mucosa	UBERON:0035834	91.50	gold quality
skeletal muscle tissue	UBERON:0001134	91.32	gold quality
oral cavity	UBERON:0000167	90.79	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.51	gold quality
upper leg skin	UBERON:0004262	89.27	gold quality
tibialis anterior	UBERON:0001385	89.01	silver quality
nasal cavity epithelium	UBERON:0005384	88.87	silver quality
esophagus mucosa	UBERON:0002469	88.23	gold quality
muscle tissue	UBERON:0002385	87.81	gold quality
muscle of leg	UBERON:0001383	87.67	gold quality
deltoid	UBERON:0001476	87.67	gold quality
gastrocnemius	UBERON:0001388	87.53	gold quality
ileal mucosa	UBERON:0000331	87.19	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.69	gold quality
placenta	UBERON:0001987	86.57	gold quality
pancreatic ductal cell	CL:0002079	85.96	silver quality
heart right ventricle	UBERON:0002080	85.95	gold quality
zone of skin	UBERON:0000014	84.42	gold quality
skin of leg	UBERON:0001511	84.35	gold quality
skin of abdomen	UBERON:0001416	83.65	gold quality
mammalian vulva	UBERON:0000997	82.78	gold quality
palpebral conjunctiva	UBERON:0001812	82.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	89.65
E-ANND-3	yes	7.53

Regulation

Is transcription factor: no

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr157	ENSDARG00000034975
mus_musculus	Gpr157	ENSMUSG00000047875
rattus_norvegicus	Gpr157	ENSRNOG00000017528

Paralogs (1): TMEM116 (ENSG00000198270)

Protein

Protein identifiers

G-protein coupled receptor 157 — Q5UAW9 (reviewed: Q5UAW9)

All UniProt accessions (2): Q5UAW9, K7ERQ3

UniProt curated annotations — full annotation on UniProt →

Function. Orphan receptor that promotes neuronal differentiation of radial glial progenitors (RGPs). The activity of this receptor is mediated by a G(q)-protein that activates a phosphatidylinositol-calcium second messenger.

Subcellular location. Cell projection. Cilium membrane.

Similarity. Belongs to the G-protein coupled receptor 2 family.

RefSeq proteins (1): NP_079256* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000832	GPCR_2_secretin-like	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR017981	GPCR_2-like_7TM	Domain
IPR022343	GCR1-cAMP_receptor	Family

Pfam: PF00002

UniProt features (19 total): topological domain 8, transmembrane region 7, chain 1, region of interest 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5UAW9-F1	81.86	0.50

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 82 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GOBP_CIRCADIAN_RHYTHM, GOBP_BEHAVIOR, GOBP_NEUROGENESIS, TGACCTY_ERR1_Q2, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, TGCTGAY_UNKNOWN, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, GOBP_RHYTHMIC_BEHAVIOR, GOBP_GLIAL_CELL_DIFFERENTIATION, GOBP_PHOSPHOLIPASE_C_ACTIVATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, CTAWWWATA_RSRFC4_Q2, HOXA4_Q2, GOCC_CELL_PROJECTION_MEMBRANE

GO Biological Process (8): cell surface receptor signaling pathway (GO:0007166), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), circadian behavior (GO:0048512), radial glial cell differentiation (GO:0060019), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), cell differentiation (GO:0030154)

GO Molecular Function (2): G protein-coupled receptor activity (GO:0004930), transmembrane signaling receptor activity (GO:0004888)

GO Cellular Component (4): plasma membrane (GO:0005886), ciliary membrane (GO:0060170), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
G protein-coupled receptor signaling pathway	2
cellular anatomical structure	2
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
phospholipase C activator activity	1
rhythmic behavior	1
circadian rhythm	1
glial cell differentiation	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
cellular developmental process	1
transmembrane signaling receptor activity	1
signaling receptor activity	1
membrane	1
cell periphery	1
cilium	1
cell projection membrane	1
bounding membrane of organelle	1

Protein interactions and networks

STRING

748 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR157	LZIC	Q8WZA0	655
GPR157	GPR137C	Q8N3F9	558
GPR157	GPR83	Q9NYM4	498
GPR157	GPR107	Q5VW38	483
GPR157	TEX44	Q53QW1	478
GPR157	TIMM17B	O60830	474
GPR157	ADGRD1	Q6QNK2	461
GPR157	SLC25A33	Q9BSK2	455
GPR157	TPRA1	Q86W33	449
GPR157	QRFP	P83859	448
GPR157	NMUR1	Q9HB89	418
GPR157	TULP3	O75386	413
GPR157	GPR108	Q9NPR9	412
GPR157	SLC45A1	Q9Y2W3	412
GPR157	TMEM185A	Q8NFB2	411

IntAct

0 interactions, top by confidence:

BioGRID (2): GPR157 (Affinity Capture-RNA), GPR157 (Affinity Capture-RNA)

ESM2 similar proteins: A0A2Z2U4G9, O35659, O46502, O95838, P23811, P25107, P25117, P25961, P30082, P30083, P30988, P32082, P32214, P32215, P32241, P32301, P34999, P35000, P41587, P41588, P41593, P43218, P43219, P43220, P47871, P47872, P48546, P49190, P50133, P51839, P70555, P79222, P97751, Q02643, Q02644, Q03431, Q0P543, Q1LZF7, Q28992, Q29627

Diamond homologs: O42602, O62772, P25107, P30650, P32241, P34998, P35347, P35353, P35464, Q03431, Q0P4Y4, Q5UAW9, Q68EK2, Q76LL8, Q8AXU4, Q9TU31, Q5FVG1, Q8C206

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1170 predictions. Top by Δscore:

Variant	Effect	Δscore
1:9105484:A:AC	donor_gain	1.0000
1:9105485:C:CC	donor_gain	1.0000
1:9105485:CATG:C	donor_gain	1.0000
1:9105494:C:CT	donor_gain	1.0000
1:9111272:CTA:C	donor_loss	1.0000
1:9111273:TACCG:T	donor_loss	1.0000
1:9111274:A:AC	donor_gain	1.0000
1:9111274:A:C	donor_loss	1.0000
1:9111275:C:A	donor_loss	1.0000
1:9111275:C:CC	donor_gain	1.0000
1:9111275:CCG:C	donor_gain	1.0000
1:9111275:CCGCT:C	donor_gain	1.0000
1:9111293:T:TA	donor_gain	1.0000
1:9111293:TCCGG:T	donor_gain	1.0000
1:9111350:T:TA	donor_gain	1.0000
1:9111485:CCCAG:C	acceptor_gain	1.0000
1:9111486:CCAG:C	acceptor_gain	1.0000
1:9111486:CCAGC:C	acceptor_gain	1.0000
1:9111487:CAG:C	acceptor_gain	1.0000
1:9111487:CAGC:C	acceptor_gain	1.0000
1:9111490:C:CC	acceptor_gain	1.0000
1:9104456:T:TA	donor_gain	0.9900
1:9105495:C:CT	donor_gain	0.9900
1:9105679:TG:T	acceptor_gain	0.9900
1:9105681:C:CC	acceptor_gain	0.9900
1:9105683:G:C	acceptor_gain	0.9900
1:9111329:ATG:A	donor_gain	0.9900
1:9111351:C:A	donor_gain	0.9900
1:9111488:AG:A	acceptor_gain	0.9900
1:9111489:GC:G	acceptor_loss	0.9900

AlphaMissense

2108 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:9111407:A:G	W156R	0.997
1:9111407:A:T	W156R	0.997
1:9105555:G:C	S241R	0.996
1:9105555:G:T	S241R	0.996
1:9105557:T:G	S241R	0.996
1:9111403:C:G	C157S	0.996
1:9111404:A:T	C157S	0.996
1:9111405:C:A	W156C	0.996
1:9111405:C:G	W156C	0.996
1:9128752:G:C	S92R	0.996
1:9128752:G:T	S92R	0.996
1:9128754:T:G	S92R	0.996
1:9104590:G:C	F279L	0.994
1:9104590:G:T	F279L	0.994
1:9104592:A:G	F279L	0.994
1:9105560:A:G	W240R	0.994
1:9105560:A:T	W240R	0.994
1:9111344:A:G	W177R	0.994
1:9111344:A:T	W177R	0.994
1:9128742:A:G	W96R	0.994
1:9128742:A:T	W96R	0.994
1:9104623:G:C	N268K	0.993
1:9104623:G:T	N268K	0.993
1:9104627:C:T	G267E	0.993
1:9111399:C:A	W158C	0.993
1:9111399:C:G	W158C	0.993
1:9111488:A:G	W129R	0.993
1:9111488:A:T	W129R	0.993
1:9111402:G:C	C157W	0.991
1:9111403:C:T	C157Y	0.991

dbSNP variants (sampled 300 via entrez): RS1000009881 (1:9119599 G>A), RS1000099860 (1:9112864 A>G), RS1000127255 (1:9110206 T>G), RS1000235922 (1:9118586 G>A,C,T), RS1000431049 (1:9112296 G>A), RS1000506930 (1:9107156 C>A,T), RS1000539098 (1:9106923 C>A), RS1000713050 (1:9102279 C>T), RS1000787113 (1:9103495 C>G,T), RS1000802031 (1:9112440 A>C), RS1001070693 (1:9114016 G>A), RS1001178414 (1:9109684 G>A), RS1001203417 (1:9104231 T>C), RS1001286493 (1:9125547 C>A,T), RS1001318702 (1:9108526 C>G)

Disease associations

OMIM: gene MIM:620860 | 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): CHEMBL4523875 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Other non-GPCR 7TM proteins

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation	4
Acetaminophen	increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
trichostatin A	increases expression	1
afimoxifene	decreases expression, decreases reaction	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
1,1,2,2-tetrabromoethane	affects response to substance	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
entinostat	increases expression	1
abrine	decreases expression	1
jinfukang	decreases expression	1
Bortezomib	decreases expression	1
Vorinostat	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Estrogens	decreases expression, decreases reaction	1
Lipopolysaccharides	increases expression, decreases reaction	1
Methapyrilene	increases methylation	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Triclosan	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	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
CHEMBL4883424	Binding	PRESTO-Tango GPCRome screening (GPR157)	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_KX43	PathHunter CHO-K1 GPR157 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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