GPR161

Summary

GPR161 (G protein-coupled receptor 161, HGNC:23694) is a protein-coding gene on chromosome 1q24.2, encoding G-protein coupled receptor 161 (Q8N6U8). Key negative regulator of Shh signaling, which promotes the processing of GLI3 into GLI3R during neural tube development.

The protein encoded by this gene is an orphan G protein-coupled receptor whose ligand is unknown. This gene is overexpressed in triple-negative breast cancer, and disruption of this gene slows the proliferation of basal breast cancer cells. Therefore, this gene is a potential drug target for triple-negative breast cancer.

Source: NCBI Gene 23432 — RefSeq curated summary.

At a glance

• Gene–disease (curated): medulloblastoma (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 184 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 22
• Druggable target: yes
• MANE Select transcript: NM_001375883

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23694
Approved symbol	GPR161
Name	G protein-coupled receptor 161
Location	1q24.2
Locus type	gene with protein product
Status	Approved
Aliases	RE2
Ensembl gene	ENSG00000143147
Ensembl biotype	protein_coding
OMIM	612250
Entrez	23432

Gene structure

Transcript identifiers

Ensembl transcripts: 58 — 55 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000271357, ENST00000367835, ENST00000367836, ENST00000367838, ENST00000478868, ENST00000485232, ENST00000493800, ENST00000537209, ENST00000539777, ENST00000546300, ENST00000682931, ENST00000867324, ENST00000867325, ENST00000867326, ENST00000867327, ENST00000867328, ENST00000867329, ENST00000867330, ENST00000867331, ENST00000867332, ENST00000867333, ENST00000867334, ENST00000867335, ENST00000867336, ENST00000867337, ENST00000867338, ENST00000867339, ENST00000867340, ENST00000867341, ENST00000867342, ENST00000867343, ENST00000867344, ENST00000867345, ENST00000928798, ENST00000928799, ENST00000928800, ENST00000928801, ENST00000928802, ENST00000928803, ENST00000928804, ENST00000928805, ENST00000928806, ENST00000928807, ENST00000928808, ENST00000928809, ENST00000928810, ENST00000928811, ENST00000952413, ENST00000952414, ENST00000952415, ENST00000952416, ENST00000952417, ENST00000952418, ENST00000952419, ENST00000952420, ENST00000952421, ENST00000952422, ENST00000952423

RefSeq mRNA: 15 — MANE Select: NM_001375883 NM_001267609, NM_001267610, NM_001267611, NM_001267612, NM_001267613, NM_001267614, NM_001349632, NM_001349633, NM_001349634, NM_001349635, NM_001375883, NM_001375884, NM_001375885, NM_001381909, NM_153832

CCDS: CCDS1268, CCDS58042, CCDS58043, CCDS58044, CCDS58045, CCDS72978

Canonical transcript exons

ENST00000682931 — 6 exons

Exon	Start	End
ENSE00001193896	168090564	168090668
ENSE00001264313	168087585	168087704
ENSE00003657610	168104477	168104894
ENSE00003674159	168096508	168097232
ENSE00003916179	168079542	168085796
ENSE00003919383	168136739	168136930

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 94.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1.7885 / max 26.7028, expressed in 991 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15814	0.9941	628
15813	0.4787	240
15812	0.2245	84
15815	0.0913	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	94.42	gold quality
ganglionic eminence	UBERON:0004023	92.76	gold quality
myometrium	UBERON:0001296	91.28	gold quality
buccal mucosa cell	CL:0002336	91.17	gold quality
ventricular zone	UBERON:0003053	90.85	gold quality
cauda epididymis	UBERON:0004360	89.47	gold quality
body of uterus	UBERON:0009853	89.25	gold quality
substantia nigra pars reticulata	UBERON:0001966	89.09	gold quality
embryo	UBERON:0000922	88.69	gold quality
stromal cell of endometrium	CL:0002255	88.25	gold quality
dorsal root ganglion	UBERON:0000044	87.72	gold quality
cervix squamous epithelium	UBERON:0006922	87.62	silver quality
substantia nigra pars compacta	UBERON:0001965	86.48	gold quality
smooth muscle tissue	UBERON:0001135	86.14	gold quality
left uterine tube	UBERON:0001303	84.71	gold quality
tendon of biceps brachii	UBERON:0008188	84.37	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.20	gold quality
trigeminal ganglion	UBERON:0001675	84.17	gold quality
seminal vesicle	UBERON:0000998	83.98	gold quality
uterus	UBERON:0000995	83.48	gold quality
nipple	UBERON:0002030	83.10	gold quality
Brodmann (1909) area 23	UBERON:0013554	82.97	gold quality
saphenous vein	UBERON:0007318	82.32	gold quality
decidua	UBERON:0002450	81.82	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	81.70	silver quality
primary visual cortex	UBERON:0002436	81.01	gold quality
lower esophagus	UBERON:0013473	80.91	gold quality
lower esophagus muscularis layer	UBERON:0035833	80.91	gold quality
visceral pleura	UBERON:0002401	80.73	gold quality
lateral nuclear group of thalamus	UBERON:0002736	80.45	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	4.91
E-ANND-3	no	5.80

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 8)

• False positive non-synonymous polymorphisms of G-protein coupled receptor genes. (PMID:11959142)
• G-protein-coupled receptor GPR161 is overexpressed in breast cancer and is a promoter of cell proliferation and invasion. (PMID:24599592)
• Smoothened determines beta-arrestin-mediated removal of the G protein-coupled receptor Gpr161 from the primary cilium. (PMID:27002170)
• Gpr161 is an A-kinase anchoring protein and the cAMP-sensing Gpr161:PKA complex acts as cilium-compartmentalized signalosome (PMID:27357676)
• Gpr161 is a critical factor in the basal suppression machinery of Shh signaling, neural tube morphogenesis and closure. (Review) (PMID:27731925)
• Gpr161 restricts cerebellar granule cell progenitor production by preventing premature and sonic hedgehog-dependent pathway activity, highlighting the importance of basal pathway suppression in tumorigenesis (PMID:29386106)
• rare variants of GPR161 from Spina bifida infants and determination of their functional relevance in the Shh and Wnt signaling pathways (PMID:30256984)
• Authors describe a novel brain tumor predisposition syndrome that is caused by germline GPR161 mutations and characterized by MBSHH in infants. (PMID:31609649)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr161b	ENSDARG00000055659
danio_rerio	gpr161a	ENSDARG00000058903
mus_musculus	Gpr161	ENSMUSG00000040836
rattus_norvegicus	Gpr161	ENSRNOG00000003073

Paralogs (25): DRD4 (ENSG00000069696), HRH3 (ENSG00000101180), HRH2 (ENSG00000113749), CHRM3 (ENSG00000133019), HRH4 (ENSG00000134489), TAAR5 (ENSG00000135569), GPR84 (ENSG00000139572), TAAR2 (ENSG00000146378), TAAR6 (ENSG00000146383), TAAR8 (ENSG00000146385), TAAR1 (ENSG00000146399), DRD3 (ENSG00000151577), HTR4 (ENSG00000164270), CHRM1 (ENSG00000168539), DRD5 (ENSG00000169676), HTR1A (ENSG00000178394), HTR1D (ENSG00000179546), CHRM4 (ENSG00000180720), CHRM2 (ENSG00000181072), DRD1 (ENSG00000184845), CHRM5 (ENSG00000184984), GPR21 (ENSG00000188394), HRH1 (ENSG00000196639), GPR52 (ENSG00000203737), TAAR9 (ENSG00000237110)

Protein

Protein identifiers

G-protein coupled receptor 161 — Q8N6U8 (reviewed: Q8N6U8)

Alternative names: G-protein coupled receptor RE2

All UniProt accessions (2): Q8N6U8, A0A0A0MQW8

UniProt curated annotations — full annotation on UniProt →

Function. Key negative regulator of Shh signaling, which promotes the processing of GLI3 into GLI3R during neural tube development. Recruited by TULP3 and the IFT-A complex to primary cilia and acts as a regulator of the PKA-dependent basal repression machinery in Shh signaling by increasing cAMP levels, leading to promote the PKA-dependent processing of GLI3 into GLI3R and repress the Shh signaling. In presence of SHH, it is removed from primary cilia and is internalized into recycling endosomes, preventing its activity and allowing activation of the Shh signaling. Its ligand is unknown.

Subcellular location. Cell projection. Cilium membrane. Cell membrane.

Disease relevance. Medulloblastoma (MDB) [MIM:155255] Malignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

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

Isoforms (6)

UniProt ID	Names	Canonical?
Q8N6U8-1	1	yes
Q8N6U8-2	2
Q8N6U8-3	3
Q8N6U8-4	4
Q8N6U8-5	5
Q8N6U8-6	6

RefSeq proteins (15): NP_001254538, NP_001254539, NP_001254540, NP_001254541, NP_001254542, NP_001254543, NP_001336561, NP_001336562, NP_001336563, NP_001336564, NP_001362812, NP_001362813, NP_001362814, NP_001368838, NP_722561 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (52 total): helix 15, topological domain 8, transmembrane region 7, splice variant 7, sequence conflict 5, turn 4, glycosylation site 2, strand 2, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8SMV	ELECTRON MICROSCOPY	2.74
8KH4	ELECTRON MICROSCOPY	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N6U8-F1	69.30	0.33

Antibody-complex structures (SAbDab): 2 — 8KH4, 8SMV

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): 100–178

Glycosylation sites (2): 4, 15

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5610787	Hedgehog ‘off’ state
R-HSA-5632684	Hedgehog ‘on’ state

MSigDB gene sets: 206 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, RORA1_01, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_NEURAL_TUBE_DEVELOPMENT, MODULE_16, GOBP_DORSAL_VENTRAL_PATTERN_FORMATION, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_SMOOTHENED_SIGNALING_PATHWAY, GOBP_DORSAL_VENTRAL_NEURAL_TUBE_PATTERNING, GOBP_REGULATION_OF_SMOOTHENED_SIGNALING_PATHWAY, MORF_PML, GOBP_SMOOTHENED_SIGNALING_PATHWAY, MORF_PDPK1

GO Biological Process (4): G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning (GO:1901621), signal transduction (GO:0007165)

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

GO Cellular Component (7): cilium (GO:0005929), endocytic vesicle membrane (GO:0030666), recycling endosome (GO:0055037), ciliary membrane (GO:0060170), plasma membrane (GO:0005886), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by Hedgehog	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
bounding membrane of organelle	2
cellular anatomical structure	2
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
negative regulation of smoothened signaling pathway	1
smoothened signaling pathway involved in dorsal/ventral neural tube patterning	1
regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning	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
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
endocytic vesicle	1
cytoplasmic vesicle membrane	1
endosome	1
cilium	1
cell projection membrane	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1060 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR161	FOXE3	Q13461	957
GPR161	TULP3	O75386	843
GPR161	SMO	Q99835	742
GPR161	ARL13B	Q3SXY8	733
GPR161	GLI1	P08151	705
GPR161	SUFU	Q9UMX1	687
GPR161	ARRB2	P32121	649
GPR161	IFT88	Q13099	624
GPR161	PTCH1	Q13635	615
GPR161	GNAS	Q5JWF2	611
GPR161	RAP2A	P10114	609
GPR161	GLI3	P10071	604
GPR161	EVC2	Q86UK5	592
GPR161	GLI2	P10070	585
GPR161	HBS1L	Q9Y450	582

IntAct

32 interactions, top by confidence:

A	B	Type	Score
PRKACB	PRKAR1A	psi-mi:“MI:0914”(association)	0.790
PRKACA	VAPB	psi-mi:“MI:0914”(association)	0.730
EFNA5	GPR161	psi-mi:“MI:0915”(physical association)	0.560
CLDN19	GPR161	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	GPR161	psi-mi:“MI:0915”(physical association)	0.560
GPR161	SLC30A2	psi-mi:“MI:0915”(physical association)	0.560
COMT	GPR161	psi-mi:“MI:0915”(physical association)	0.560
PRKACB	PRKAR1A	psi-mi:“MI:0914”(association)	0.550
GPR161	USP12	psi-mi:“MI:0914”(association)	0.530
PRKAR1A	AKAP3	psi-mi:“MI:0914”(association)	0.530
GPR161	PRKAR1A	psi-mi:“MI:0914”(association)	0.530
GPR161	CCR2	psi-mi:“MI:0915”(physical association)	0.370
GPR161	GPR35	psi-mi:“MI:0915”(physical association)	0.370
GPR161	PRKAR1A	psi-mi:“MI:0915”(physical association)	0.370
PRKACB	MYL1	psi-mi:“MI:0914”(association)	0.350
PRKAR1B	ZNF749	psi-mi:“MI:0914”(association)	0.350
PRKAR1B	DNAJC13	psi-mi:“MI:0914”(association)	0.350
SLC6A7	ABCB1	psi-mi:“MI:0914”(association)	0.350
EFNA5	GPR161	psi-mi:“MI:0915”(physical association)	0.000
CLDN19	GPR161	psi-mi:“MI:0915”(physical association)	0.000
UPK1B	GPR161	psi-mi:“MI:0915”(physical association)	0.000
SLC30A2	GPR161	psi-mi:“MI:0915”(physical association)	0.000
COMT	GPR161	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (49): GPR161 (Affinity Capture-RNA), GPR161 (Affinity Capture-MS), GPR161 (Affinity Capture-MS), GPR161 (Affinity Capture-MS), PRKAR1B (Affinity Capture-MS), BTRC (Affinity Capture-MS), PRKACG (Affinity Capture-MS), FBXW11 (Affinity Capture-MS), UBE2Q1 (Affinity Capture-MS), PRKACA (Affinity Capture-MS), USP12 (Affinity Capture-MS), GOLGA5 (Affinity Capture-MS), RTN4 (Affinity Capture-MS), LMBR1 (Affinity Capture-MS), GNB4 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R9YJI3, B2ZHY2, B3DM66, B4XF06, D4A3U0, O02777, O43194, O46635, P08909, P08911, P0C0W8, P14842, P18599, P20272, P21554, P28223, P28335, P32240, P34311, P34968, P35363, P47746, P50128, P50129, P56971, P70259, Q09502, Q333S9, Q5IS53, Q5IS66, Q5IS73, Q5IS98, Q5R4Q6, Q5U431, Q60F97, Q6DWJ6, Q71SP5, Q75Z89, Q801M1, Q80UC8

Diamond homologs: B2RPY5, B3DM66, O02664, O02836, O35210, O42384, O77408, O77590, O77621, P08908, P16395, P19327, P21917, P22270, P25095, P25104, P29754, P30555, P30556, P32250, P34969, P34976, P43240, P49019, P49146, P49220, P79113, P97295, Q0EAB6, Q0GBZ5, Q24563, Q25321, Q25322, Q25414, Q2YDN1, Q58CW4, Q5IS62, Q64264, Q6XXX9, Q6XXY0

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
GPR161	“up-regulates activity”	GNAS	binding
SMO	“down-regulates activity”	GPR161	relocalization
TULP3	“up-regulates activity”	GPR161	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 19 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
GPCR downstream signalling	5	12.8×	1e-04
Signaling by GPCR	5	11.8×	2e-04
G alpha (i) signalling events	5	11.5×	2e-04
Transport of small molecules	6	8.9×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	117
Likely benign	28
Benign	19

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1710300	NM_001375883.1(GPR161):c.487_488del (p.Leu163fs)	Pathogenic
4759295	NM_001375883.1(GPR161):c.585G>A (p.Trp195Ter)	Likely pathogenic

SpliceAI

1710 predictions. Top by Δscore:

Variant	Effect	Δscore
1:168085680:C:CA	donor_gain	0.9900
1:168085681:C:A	donor_gain	0.9900
1:168085794:CTT:C	acceptor_gain	0.9900
1:168085796:TCTGA:T	acceptor_loss	0.9900
1:168085797:C:CC	acceptor_gain	0.9900
1:168085797:CTGAG:C	acceptor_loss	0.9900
1:168085798:T:C	acceptor_loss	0.9900
1:168087579:GCCAA:G	donor_loss	0.9900
1:168087580:CCAA:C	donor_loss	0.9900
1:168087581:CAA:C	donor_loss	0.9900
1:168087582:AACCT:A	donor_loss	0.9900
1:168087584:C:CT	donor_loss	0.9900
1:168087602:T:TA	donor_gain	0.9900
1:168090558:GGTTA:G	donor_loss	0.9900
1:168090559:GTTA:G	donor_loss	0.9900
1:168090560:TTAC:T	donor_loss	0.9900
1:168090561:TA:T	donor_loss	0.9900
1:168090562:ACCT:A	donor_loss	0.9900
1:168090563:CCT:C	donor_loss	0.9900
1:168090669:C:CC	acceptor_gain	0.9900
1:168104915:C:CT	acceptor_gain	0.9900
1:168085659:AGACC:A	donor_gain	0.9800
1:168085676:T:TA	donor_gain	0.9800
1:168085738:A:C	donor_gain	0.9800
1:168085792:AGCTT:A	acceptor_gain	0.9800
1:168085795:TT:T	acceptor_gain	0.9800
1:168087585:C:G	donor_loss	0.9800
1:168087605:T:TA	donor_gain	0.9800
1:168087705:CTAA:C	acceptor_loss	0.9800
1:168090668:TCTGA:T	acceptor_loss	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000085009 (1:168102994 T>G), RS1000105416 (1:168094870 T>C), RS1000133741 (1:168104113 G>A), RS1000166827 (1:168126957 C>A,G), RS1000269202 (1:168100967 G>A), RS1000274100 (1:168086044 A>G), RS1000342131 (1:168106550 G>A), RS1000343332 (1:168131975 A>C,G), RS1000360942 (1:168114175 T>C), RS1000386384 (1:168126674 A>T), RS1000439154 (1:168091579 G>C), RS1000469724 (1:168138394 A>G), RS1000488505 (1:168133629 G>A), RS1000495947 (1:168088722 C>A,G), RS1000564848 (1:168114669 T>A,C,G)

Disease associations

OMIM: gene MIM:612250 | disease phenotypes: MIM:155255

GenCC curated gene-disease

Disease	Classification	Inheritance
medulloblastoma	Strong	Autosomal dominant
pituitary stalk interruption syndrome	Supportive	Autosomal dominant

Mondo (2): medulloblastoma (MONDO:0007959), pituitary stalk interruption syndrome (MONDO:0019828)

Orphanet (2): Medulloblastoma (Orphanet:616), Pituitary stalk interruption syndrome (Orphanet:95496)

HPO phenotypes

22 total (22 of 22 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000786	Primary amenorrhea
HP:0000821	Hypothyroidism
HP:0000823	Delayed puberty
HP:0000835	Adrenal hypoplasia
HP:0000864	Abnormality of the hypothalamus-pituitary axis
HP:0000873	Diabetes insipidus
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001442	Typified by somatic mosaicism
HP:0001508	Failure to thrive
HP:0001522	Death in infancy
HP:0001943	Hypoglycemia
HP:0002885	Medulloblastoma
HP:0003829	Typified by incomplete penetrance
HP:0004322	Short stature
HP:0008736	Hypoplasia of penis
HP:0011755	Ectopic posterior pituitary
HP:0100842	Septo-optic dysplasia

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004621_38	Red cell distribution width	3.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008527	Medulloblastoma	C04.557.465.625.600.380.515; C04.557.465.625.600.590.500; C04.557.470.670.380.515; C04.557.470.670.590.500; C04.557.580.625.600.380.515; C04.557.580.625.600.590.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523894 (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

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression, increases expression	3
bisphenol A	decreases expression, decreases methylation	2
entinostat	decreases expression, affects cotreatment	2
Benzo(a)pyrene	increases expression, increases methylation	2
Estradiol	affects expression, affects cotreatment, increases expression	2
Valproic Acid	decreases expression, increases expression	2
FR900359	decreases phosphorylation	1
lasiocarpine	increases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
methylselenic acid	increases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression, increases abundance	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Cadmium	decreases expression	1
Copper	affects binding, decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	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
CHEMBL4883427	Binding	PRESTO-Tango GPCRome screening (GPR161)	Data for DCP probe UCSF924

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 1 transformed cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7QV	Ubigene A-549 GPR161 KO	Cancer cell line	Male
CVCL_D8M1	Ubigene HCT 116 GPR161 KO	Cancer cell line	Male
CVCL_D9FS	Ubigene HEK293 GPR161 KO	Transformed cell line	Female
CVCL_E0E2	Ubigene HeLa GPR161 KO	Cancer cell line	Female
CVCL_KX44	PathHunter CHO-K1 GPR161 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02875314	PHASE4	ACTIVE_NOT_RECRUITING	HeadStart4: Newly Diagnosed Children (<10 y/o) With Medulloblastoma and Other CNS Embryonal Tumors
NCT04081701	PHASE4	RECRUITING	68-Ga DOTATATE PET/MRI in the Diagnosis and Management of Somatostatin Receptor Positive CNS Tumors.
NCT06760546	PHASE3	RECRUITING	A Trial of Setmelanotide in Patients With Congenital Hypothalamic Obesity (Sub-study of NCT05774756)
NCT00085735	PHASE3	COMPLETED	Comparison of Radiation Therapy Regimens in Combination With Chemotherapy in Treating Young Patients With Newly Diagnosed Standard-Risk Medulloblastoma
NCT00336024	PHASE3	COMPLETED	Combination Chemotherapy Followed By Peripheral Stem Cell Transplant in Treating Young Patients With Newly Diagnosed Supratentorial Primitive Neuroectodermal Tumors or High-Risk Medulloblastoma
NCT00392327	PHASE3	ACTIVE_NOT_RECRUITING	Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed, Previously Untreated, High-Risk Medulloblastoma/PNET
NCT01351870	PHASE3	COMPLETED	Hyperfractionated Versus Conventionally Fractionated Radiotherapy in Standard Risk Medulloblastoma (PNET4)
NCT07291102	PHASE3	NOT_YET_RECRUITING	Comparison of Neurocognitive Outcome in Two Standard Regimen for Treatment of Low-risk Medulloblastoma
NCT00031590	PHASE2	TERMINATED	Low-Dose Radiation and Combination Chemotherapy Following Surgery in Children With Newly Diagnosed Medulloblastoma
NCT00180791	PHASE2	UNKNOWN	High Risk Primitive Neuroectodermal (PNET) Brain Tumors in Childhood
NCT00180947	PHASE2	UNKNOWN	Study of Vinorelbine and Cyclofosfamide Among Patients With Refractory Tumours or in Relapse
NCT00404495	PHASE2	COMPLETED	Combination of Irinotecan and Temozolomide in Children With Brain Tumors.
NCT00407433	PHASE2	COMPLETED	Clinical Studies of Gemcitabine-Oxaliplatin
NCT00520936	PHASE2	COMPLETED	A Study of Pemetrexed in Children With Recurrent Cancer
NCT00601003	PHASE2	COMPLETED	Study of Nifurtimox to Treat Refractory or Relapsed Neuroblastoma or Medulloblastoma
NCT00840047	PHASE2	ACTIVE_NOT_RECRUITING	Methionine PET/CT Studies In Patients With Cancer
NCT01217437	PHASE2	COMPLETED	Temozolomide and Irinotecan Hydrochloride With or Without Bevacizumab in Treating Young Patients With Recurrent or Refractory Medulloblastoma or CNS Primitive Neuroectodermal Tumors
NCT01326104	PHASE2	COMPLETED	Vaccine Immunotherapy for Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor
NCT01356290	PHASE2	RECRUITING	Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma, ATRT and Rare CNS Tumors
NCT01542736	PHASE2	COMPLETED	Concurrent Carboplatin and Reduced Dose Craniospinal Radiation for Medulloblastoma and Primitive Neuroectodermal Tumor (PNET)
NCT01708174	PHASE2	COMPLETED	A Phase II Study of Oral LDE225 in Patients With Hedge-Hog (Hh)-Pathway Activated Relapsed Medulloblastoma (MB)
NCT01857453	PHASE2	UNKNOWN	Interest of a Dose Decrease for Radiotherapy Associated With Chemotherapy for Treatment of Standard Risk Adult Medulloblastomas
NCT01878617	PHASE2	ACTIVE_NOT_RECRUITING	A Clinical and Molecular Risk-Directed Therapy for Newly Diagnosed Medulloblastoma
NCT02017964	PHASE2	COMPLETED	Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed, Non-metastatic Desmoplastic Medulloblastoma
NCT02441062	PHASE2	COMPLETED	Impact of Ga-68 DOTATOC PET-CT Imaging in Management of Neuroendocrine Tumors
NCT02624388	PHASE2	TERMINATED	Study of Genistein in Pediatric Oncology Patients (UVA-Gen001)
NCT02681705	PHASE2	UNKNOWN	Radiation Therapy and Combination Chemotherapy for Medulloblastoma
NCT02689336	PHASE2	WITHDRAWN	Erlotinib in Combination With Temozolomide in Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors
NCT02724579	PHASE2	ACTIVE_NOT_RECRUITING	Reduced Craniospinal Radiation Therapy and Chemotherapy in Treating Younger Patients With Newly Diagnosed WNT-Driven Medulloblastoma
NCT03013387	PHASE2	WITHDRAWN	Dosimetry Guided PRRT With 90Y-DOTATOC
NCT03155620	PHASE2	ACTIVE_NOT_RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
NCT03173950	PHASE2	COMPLETED	Immune Checkpoint Inhibitor Nivolumab in People With Recurrent Select Rare CNS Cancers
NCT03210714	PHASE2	ACTIVE_NOT_RECRUITING	Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213652	PHASE2	ACTIVE_NOT_RECRUITING	Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
NCT03213665	PHASE2	COMPLETED	Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)
NCT03213678	PHASE2	COMPLETED	Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213704	PHASE2	ACTIVE_NOT_RECRUITING	Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)
NCT03233204	PHASE2	COMPLETED	Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)
NCT03257631	PHASE2	COMPLETED	A Study of Pomalidomide Monotherapy for Children and Young Adults With Recurrent or Progressive Primary Brain Tumors
NCT03273712	PHASE2	COMPLETED	Dosimetry-Guided, Peptide Receptor Radiotherapy (PRRT) With 90Y-DOTA- tyr3-Octreotide (90Y-DOTATOC)