GFRA3

Summary

GFRA3 (GDNF family receptor alpha 3, HGNC:4245) is a protein-coding gene on chromosome 5q31.2, encoding GDNF family receptor alpha-3 (O60609). Receptor for artemin (ARTN), a growth factor that supports the survival of sensory and sympathetic peripheral neurons.

The protein encoded by this gene is a glycosylphosphatidylinositol(GPI)-linked cell surface receptor and a member of the GDNF receptor family. It forms a signaling receptor complex with RET tyrosine kinase receptor and binds the ligand, artemin.

Source: NCBI Gene 2676 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 54 total
• Druggable target: yes
• MANE Select transcript: NM_001496

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4245
Approved symbol	GFRA3
Name	GDNF family receptor alpha 3
Location	5q31.2
Locus type	gene with protein product
Status	Approved
Aliases	GFRa-3
Ensembl gene	ENSG00000146013
Ensembl biotype	protein_coding
OMIM	605710
Entrez	2676

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 nonsense_mediated_decay

ENST00000274721, ENST00000378362, ENST00000714689, ENST00000714690, ENST00000962296

RefSeq mRNA: 1 — MANE Select: NM_001496 NM_001496

CCDS: CCDS4201

Canonical transcript exons

ENST00000274721 — 8 exons

Exon	Start	End
ENSE00003991837	138253766	138253900
ENSE00003991841	138253287	138253375
ENSE00003991842	138259557	138259649
ENSE00003991843	138252380	138253057
ENSE00003991847	138274334	138274621
ENSE00003991851	138254057	138254160
ENSE00003991853	138264261	138264548
ENSE00004024870	138257639	138257951

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 92.77.

FANTOM5 (CAGE): breadth broad, TPM avg 0.8026 / max 539.9782, expressed in 205 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63684	0.2199	79
63678	0.2124	57
63683	0.0993	24
63681	0.0879	24
63679	0.0800	22
63680	0.0612	19
63682	0.0419	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
dorsal root ganglion	UBERON:0000044	92.77	gold quality
trigeminal ganglion	UBERON:0001675	90.11	gold quality
tibial nerve	UBERON:0001323	88.01	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.60	gold quality
sural nerve	UBERON:0015488	82.74	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.04	gold quality
lower esophagus muscularis layer	UBERON:0035833	79.11	gold quality
lower esophagus	UBERON:0013473	79.09	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	77.82	gold quality
muscle layer of sigmoid colon	UBERON:0035805	76.45	gold quality
vena cava	UBERON:0004087	75.26	silver quality
seminal vesicle	UBERON:0000998	72.96	gold quality
mucosa of transverse colon	UBERON:0004991	72.02	gold quality
body of stomach	UBERON:0001161	71.76	gold quality
apex of heart	UBERON:0002098	71.70	gold quality
rectum	UBERON:0001052	71.56	gold quality
fundus of stomach	UBERON:0001160	70.95	gold quality
cerebellar cortex	UBERON:0002129	70.61	gold quality
cerebellar hemisphere	UBERON:0002245	70.60	gold quality
right atrium auricular region	UBERON:0006631	70.46	gold quality
endocervix	UBERON:0000458	70.22	gold quality
pancreatic ductal cell	CL:0002079	70.19	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	70.15	gold quality
secondary oocyte	CL:0000655	70.03	silver quality
cerebellum	UBERON:0002037	70.02	gold quality
stomach	UBERON:0000945	69.78	gold quality
cardiac atrium	UBERON:0002081	69.78	gold quality
right hemisphere of cerebellum	UBERON:0014890	69.61	gold quality
esophagus	UBERON:0001043	69.25	gold quality
caecum	UBERON:0001153	69.02	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-ENAD-20	yes	1314.84
E-GEOD-124472	yes	801.89
E-HCAD-11	yes	32.65
E-MTAB-8410	yes	17.86
E-ANND-3	no	1.95

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting GFRA3, 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-652-5P	99.91	67.49	505
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-6880-5P	98.08	65.59	1282
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-376A-5P	97.70	65.61	863
HSA-MIR-6515-5P	97.08	65.48	1219
HSA-MIR-7847-3P	96.63	64.58	952
HSA-MIR-4515	95.70	65.73	716
HSA-MIR-12115	94.19	66.37	738

Literature-anchored findings (GeneRIF, showing 9)

• 1.92 A crystal structure of the complex formed between ARTN and its receptor GFRalpha3 was reported. (PMID:16765900)
• In the human digestive and reproductive systems, a subset of epithelial cells exhibited GFRalpha3- and RET-like staining, suggesting co-localization. (PMID:16773224)
• Artemin and GFRalpha3 expressions may play an important role in perineural invasion of pancreatic carcinoma. (PMID:19304517)
• This study found nominally-significant evidence for interactions between GFRA1, 2 and 3 associated with schizophrenia and clozapine response, consistent with the locations of these three genes within linkage regions for schizophrenia. (PMID:20116071)
• The lack of expression of the RET/GFRA system could be related to the cell mislocation and deregulated growth of craniopharyngiomas. (PMID:22031517)
• The expression of GFRalpha1 and/or GFRalpha3, especially when combined with ARTN expression, may be useful predictors of disease progression and outcome in specific subtypes of mammary carcinoma. (PMID:23351331)
• The GFRA3 promoter region showed marked hypermethylation in almost all tumors, and its correlation with survival and other clinicopathological parameters may have important prognostic significance. (PMID:26984265)
• Mir-34a directly regulates GFRA3 via its coding region.GFRA3 is crucial for breast cancer growth. (PMID:28356515)
• increased GFRalpha3 expression is significantly correlated with poor prognosis of patients with urothelial carcinoma (PMID:28651425)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gfra3	ENSDARG00000087704
mus_musculus	Gfra3	ENSMUSG00000024366
rattus_norvegicus	Gfra3	ENSRNOG00000020309
drosophila_melanogaster	Gfrl	FBGN0262869
caenorhabditis_elegans		WBGENE00022100

Paralogs (4): GFRA4 (ENSG00000125861), GFRA1 (ENSG00000151892), GFRA2 (ENSG00000168546), GFRAL (ENSG00000187871)

Protein

Protein identifiers

GDNF family receptor alpha-3 — O60609 (reviewed: O60609)

All UniProt accessions (4): A0AAQ5BI91, A0AAQ5BI95, O60609, K9J968

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for artemin (ARTN), a growth factor that supports the survival of sensory and sympathetic peripheral neurons. ARTN-binding leads to autophosphorylation and activation of the RET receptor.

Subunit / interactions. Interacts with ARTN ligand and RET: forms a 2:2:2 ternary complex composed of ARTN ligand, GFRA3 and RET receptor. Interacts with SORL1.

Subcellular location. Cell membrane.

Tissue specificity. Widely expressed in adult and fetus which exhibit a similar pattern. Essentially not expressed in the central nervous system, but highly expressed in several sensory and sympathetic ganglia of the peripheral nervous system. Moderate expression in many non-neuronal tissues, particularly those of the digestive and urogenital systems, but high expression in stomach and appendix. Several types of glandular tissues show low expression. Very low or no expression detected in the hematopoietic system.

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the GDNFR family.

Isoforms (2)

UniProt ID	Names	Canonical?
O60609-1	1	yes
O60609-2	2

RefSeq proteins (1): NP_001487* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003438	GDNF_rcpt	Family
IPR003505	GDNF_rcpt_A3	Family
IPR016017	GDNF/GAS1	Domain
IPR037193	GDNF_alpha	Homologous_superfamily

Pfam: PF02351

UniProt features (39 total): helix 12, disulfide bond 11, strand 5, glycosylation site 3, turn 2, signal peptide 1, chain 1, splice variant 1, sequence conflict 1, propeptide 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2GH0	X-RAY DIFFRACTION	1.92
6Q2S	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60609-F1	78.90	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.

Post-translational modifications (1): 374

Disulfide bonds (11): 186–196, 191–239, 220–227, 248–316, 255–261, 272–288, 281–340, 318–328, 51–57, 162–218, 169–175

Glycosylation sites (3): 95, 148, 309

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-8853659	RET signaling

MSigDB gene sets: 124 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, MODULE_64, GOCC_CELL_SURFACE, GOBP_NEUROGENESIS, TAL1ALPHAE47_01, RIZKI_TUMOR_INVASIVENESS_3D_DN, GATA6_01, IRF1_Q6, GOBP_SYMPATHETIC_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_NEURON_MIGRATION, GFI1_01, SABATES_COLORECTAL_ADENOMA_DN, P300_01, GOBP_AUTONOMIC_NERVOUS_SYSTEM_DEVELOPMENT, KANG_IMMORTALIZED_BY_TERT_DN

GO Biological Process (8): neuron migration (GO:0001764), signal transduction (GO:0007165), nervous system development (GO:0007399), peripheral nervous system development (GO:0007422), glial cell-derived neurotrophic factor receptor signaling pathway (GO:0035860), sympathetic nervous system development (GO:0048485), axon guidance (GO:0007411), neuron development (GO:0048666)

GO Molecular Function (5): signaling receptor binding (GO:0005102), axon guidance receptor activity (GO:0008046), glial cell-derived neurotrophic factor receptor activity (GO:0016167), signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (7): cytosol (GO:0005829), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), extrinsic component of membrane (GO:0019898), signaling receptor complex (GO:0043235), membrane (GO:0016020), side of membrane (GO:0098552)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
MAPK1/MAPK3 signaling	1
Axon guidance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
system development	3
membrane	3
cell migration	1
generation of neurons	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
nervous system development	1
cell surface receptor protein tyrosine kinase signaling pathway	1
autonomic nervous system development	1
axonogenesis	1
neuron projection guidance	1
neuron differentiation	1
cell development	1
protein binding	1
transmembrane signaling receptor activity	1
axon guidance	1
cytokine receptor activity	1
glial cell-derived neurotrophic factor receptor signaling pathway	1
molecular transducer activity	1
binding	1
cytoplasm	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
protein-containing complex	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

724 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GFRA3	ARTN	Q5T4W7	999
GFRA3	NRTN	Q99748	998
GFRA3	PSPN	O60542	997
GFRA3	RET	P07949	994
GFRA3	GDNF	P39905	990
GFRA3	NTRK1	P04629	726
GFRA3	NTF3	P20783	683
GFRA3	NGF	P01138	678
GFRA3	GFRA1	P56159	633
GFRA3	NTF4	P34130	613
GFRA3	NTRK2	Q16620	612
GFRA3	BDNF	P23560	606
GFRA3	TRPV1	Q8NER1	570
GFRA3	GFRA4	Q9GZZ7	552
GFRA3	GFRA2	O00451	512

IntAct

6 interactions, top by confidence:

A	B	Type	Score
ARTN	GFRA3	psi-mi:“MI:0407”(direct interaction)	0.650
GFRA3	B3GAT3	psi-mi:“MI:0914”(association)	0.350

BioGRID (14): GFRA3 (Synthetic Lethality), GFRA3 (Synthetic Lethality), GFRA3 (Reconstituted Complex), STK36 (Affinity Capture-MS), FCGRT (Affinity Capture-MS), SELT (Affinity Capture-MS), SLC12A7 (Affinity Capture-MS), B3GAT3 (Affinity Capture-MS), HLA-DRB1 (Affinity Capture-MS), ADAMTS2 (Affinity Capture-MS), CNNM1 (Affinity Capture-MS), B3GALNT2 (Affinity Capture-MS), GLRB (Affinity Capture-MS), JMJD8 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IKU3, A0A4Y5X186, B8JI67, D3ZB94, E9Q8Q8, F1M928, G7PWZ3, I6M4H4, O35118, O42493, O43278, O60609, O89103, O93512, P08833, P16042, P16229, P17668, P51653, P51882, Q07662, Q17QN8, Q29016, Q32L50, Q3TYX2, Q3UPR9, Q503V3, Q5EA85, Q5XHC5, Q60485, Q64716, Q6DFV8, Q6MG84, Q6PVW7, Q6SJE0, Q6UXV0, Q8BKV1, Q8CB67, Q8IVN8, Q8IZJ1

Diamond homologs: O00451, O08842, O13156, O13157, O35118, O60609, O93512, P56159, P97785, Q5E9X0, Q5RAD6, Q62997, Q9EPI2, Q9GZZ7, Q9JJT2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ARTN	up-regulates	GFRA3	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1231 predictions. Top by Δscore:

Variant	Effect	Δscore
5:138253373:CCG:C	acceptor_gain	1.0000
5:138253374:CGC:C	acceptor_gain	1.0000
5:138253764:A:AC	donor_gain	1.0000
5:138253765:C:CA	donor_gain	1.0000
5:138253795:T:TA	donor_gain	1.0000
5:138253898:TCCCT:T	acceptor_loss	1.0000
5:138253899:CC:C	acceptor_gain	1.0000
5:138253900:CC:C	acceptor_gain	1.0000
5:138253900:CCTGT:C	acceptor_loss	1.0000
5:138253901:C:CC	acceptor_gain	1.0000
5:138253901:CT:C	acceptor_loss	1.0000
5:138253902:T:C	acceptor_loss	1.0000
5:138257636:CA:C	donor_loss	1.0000
5:138257637:A:AG	donor_loss	1.0000
5:138257638:C:A	donor_loss	1.0000
5:138257947:TGAGT:T	acceptor_gain	1.0000
5:138257950:GT:G	acceptor_gain	1.0000
5:138257952:C:CC	acceptor_gain	1.0000
5:138257952:CTGGG:C	acceptor_loss	1.0000
5:138274329:CTCA:C	donor_loss	1.0000
5:138274331:CA:C	donor_loss	1.0000
5:138274332:A:AC	donor_gain	1.0000
5:138274333:C:CC	donor_gain	1.0000
5:138274333:C:CT	donor_loss	1.0000
5:138274333:CCGG:C	donor_gain	1.0000
5:138253054:CATT:C	acceptor_gain	0.9900
5:138253056:TT:T	acceptor_gain	0.9900
5:138253371:CTCCG:C	acceptor_gain	0.9900
5:138253372:TCCG:T	acceptor_gain	0.9900
5:138253373:CCGC:C	acceptor_gain	0.9900

AlphaMissense

2614 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:138254143:A:C	F268C	0.993
5:138257918:C:G	C169S	0.992
5:138257919:A:T	C169S	0.992
5:138257900:C:G	C175S	0.991
5:138257901:A:T	C175S	0.991
5:138257939:C:G	C162S	0.991
5:138257940:A:T	C162S	0.991
5:138253879:A:C	F304C	0.990
5:138257772:A:G	C218R	0.990
5:138257815:G:C	F203L	0.989
5:138257815:G:T	F203L	0.989
5:138257817:A:G	F203L	0.989
5:138257888:C:G	R179P	0.989
5:138257917:A:C	C169W	0.989
5:138253885:G:T	P302H	0.988
5:138254130:G:C	C272W	0.988
5:138254131:C:G	C272S	0.988
5:138254132:A:T	C272S	0.988
5:138257732:C:G	R231P	0.988
5:138257744:C:G	C227S	0.988
5:138257745:A:T	C227S	0.988
5:138257771:C:G	C218S	0.988
5:138257772:A:T	C218S	0.988
5:138257918:C:T	C169Y	0.988
5:138257919:A:G	C169R	0.988
5:138254057:C:A	G297W	0.987
5:138253807:C:G	C328S	0.986
5:138253808:A:T	C328S	0.986
5:138254131:C:T	C272Y	0.986
5:138254143:A:G	F268S	0.986

dbSNP variants (sampled 300 via entrez): RS1000225033 (5:138271165 T>C), RS1000243771 (5:138263428 T>C), RS1000403178 (5:138267164 C>G), RS1000414290 (5:138267540 C>A,T), RS1000423073 (5:138256352 C>T), RS1000473636 (5:138260191 G>C), RS1000687242 (5:138254509 G>A), RS1000736538 (5:138262063 A>G), RS1000753207 (5:138256157 G>GGAGGC), RS1000961357 (5:138269418 C>T), RS1000963969 (5:138254538 T>C), RS1001000362 (5:138274708 G>A,C), RS1001160221 (5:138254822 A>T), RS1001187123 (5:138252357 G>A), RS1001294481 (5:138260018 A>C,G)

Disease associations

OMIM: gene MIM:605710 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001537_2	Immune reponse to smallpox (secreted IL-12p40)	6.000000e-08
GCST002500_53	QT interval	5.000000e-11
GCST002539_60	Schizophrenia	5.000000e-09
GCST004521_66	Autism spectrum disorder or schizophrenia	1.000000e-08
GCST90000025_16	Appendicular lean mass	7.000000e-20

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0004682	QT interval
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066221 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — GDNF Family Receptor (GFR)

ChEMBL bioactivities

8 potent at pChembl≥5 of 10 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.70	IC50	200	nM	CHEMBL5596770
6.16	IC50	700	nM	CHEMBL5591042
5.96	IC50	1100	nM	CHEMBL5597875
5.55	IC50	2800	nM	CHEMBL5596389
5.27	IC50	5400	nM	CHEMBL5597536
5.13	IC50	7400	nM	CHEMBL5597522
5.06	IC50	8800	nM	CHEMBL5596703
5.04	IC50	9100	nM	CHEMBL5598111

PubChem BioAssay actives

8 with measured affinity, of 32 total; 8 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2R)-2-[[2-[3-[[(2R)-5-(2-anilinopyrimidin-5-yl)-2,3-dihydro-1H-inden-2-yl]oxy]phenyl]acetyl]amino]-2-cyclohexyl-N-methylacetamide	2120389: Inhibition of GFRalpha3 (unknown origin)	ic50	0.2000	uM
(2R)-2-[[2-[3-[[(1S)-5-(2-anilinopyrimidin-5-yl)-2,3-dihydro-1H-inden-1-yl]oxy]phenyl]acetyl]amino]-2-cyclohexyl-N-methylacetamide	2120389: Inhibition of GFRalpha3 (unknown origin)	ic50	0.7000	uM
(2R)-2-[[2-[3-[[(1S)-5-(5-anilinopyrimidin-2-yl)-2,3-dihydro-1H-inden-1-yl]oxy]phenyl]acetyl]amino]-2-cyclohexylacetamide	2120389: Inhibition of GFRalpha3 (unknown origin)	ic50	1.1000	uM
2-[3-[[(1S)-5-(2-anilinopyrimidin-5-yl)-2,3-dihydro-1H-inden-1-yl]oxy]phenyl]acetic acid	2120389: Inhibition of GFRalpha3 (unknown origin)	ic50	2.8000	uM
(2S)-2-[[2-[3-[[(1S)-5-(2-anilinopyrimidin-5-yl)-2,3-dihydro-1H-inden-1-yl]oxy]phenyl]acetyl]amino]-3-(1H-imidazol-5-yl)-N-methylpropanamide	2120389: Inhibition of GFRalpha3 (unknown origin)	ic50	5.4000	uM
methyl (2S)-3-(1H-imidazol-5-yl)-2-[[2-[3-[[(1S)-5-(5-phenoxy-3-pyridinyl)-2,3-dihydro-1H-inden-1-yl]oxy]phenyl]acetyl]amino]propanoate	2120389: Inhibition of GFRalpha3 (unknown origin)	ic50	7.4000	uM
(1S)-5-(2-anilinopyrimidin-5-yl)-2,3-dihydro-1H-inden-1-ol	2120389: Inhibition of GFRalpha3 (unknown origin)	ic50	8.8000	uM
(2R)-2-cyclohexyl-2-[[2-[3-[[(1S)-2,3-dihydro-1H-inden-1-yl]oxy]phenyl]acetyl]amino]-N-methylacetamide	2120389: Inhibition of GFRalpha3 (unknown origin)	ic50	9.1000	uM

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	4
trichostatin A	affects cotreatment, increases expression	3
Nickel	decreases expression	2
aristolochic acid I	increases expression	1
bisphenol A	increases expression	1
beta-lapachone	decreases expression, increases expression	1
sodium arsenite	increases expression	1
beta-methylcholine	affects expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	increases expression	1
Amphotericin B	increases expression	1
Aspirin	increases expression	1
Benzo(a)pyrene	increases methylation	1
Hydralazine	affects cotreatment, increases expression	1
Aflatoxin B1	decreases methylation	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
CHEMBL5585988	Binding	Inhibition of GFRalpha3 (unknown origin)	Discovery of the first selective, small-molecule GFRα2/3 inhibitors through DNA-encoded library technology. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer