GFRAL

Summary

GFRAL (GDNF family receptor alpha like, HGNC:32789) is a protein-coding gene on chromosome 6p12.1, encoding GDNF family receptor alpha-like (Q6UXV0). Brainstem-restricted receptor for GDF15 hormone, which triggers an aversive response, characterized by nausea, vomiting, and/or loss of appetite in response to various stresses.

Enables glial cell-derived neurotrophic factor receptor activity and receptor tyrosine kinase binding activity. Involved in GDF15-GFRAL signaling pathway; positive regulation of MAPK cascade; and positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction. Located in several cellular components, including actin cytoskeleton; focal adhesion; and nucleoplasm.

Source: NCBI Gene 389400 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 71 total
• Druggable target: yes
• MANE Select transcript: NM_207410

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32789
Approved symbol	GFRAL
Name	GDNF family receptor alpha like
Location	6p12.1
Locus type	gene with protein product
Status	Approved
Aliases	GRAL, UNQ9356, bA360D14.1
Ensembl gene	ENSG00000187871
Ensembl biotype	protein_coding
OMIM	617837
Entrez	389400

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000340465

RefSeq mRNA: 1 — MANE Select: NM_207410 NM_207410

CCDS: CCDS4957

Canonical transcript exons

ENST00000340465 — 9 exons

Exon	Start	End
ENSE00001364263	55351253	55351583
ENSE00001366975	55333786	55333944
ENSE00001367614	55350092	55350145
ENSE00001370803	55358888	55359138
ENSE00001371826	55331715	55331849
ENSE00001376151	55399180	55399275
ENSE00001376296	55401790	55402493
ENSE00001376437	55399369	55399441
ENSE00001421523	55327469	55327576

Expression profiles

Bgee: expression breadth tissue_specific, 10 present calls, max score 77.17.

Top tissues by expression

112 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	77.17	silver quality
sural nerve	UBERON:0015488	54.95	silver quality
right lobe of liver	UBERON:0001114	51.40	gold quality
liver	UBERON:0002107	48.40	gold quality
subcutaneous adipose tissue	UBERON:0002190	43.62	gold quality
ventricular zone	UBERON:0003053	40.18	gold quality
stromal cell of endometrium	CL:0002255	39.73	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
calcaneal tendon	UBERON:0003701	37.16	gold quality
adipose tissue	UBERON:0001013	36.91	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
primary visual cortex	UBERON:0002436	36.04	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
body of pancreas	UBERON:0001150	34.00	silver quality
endometrium	UBERON:0001295	33.99	gold quality
mucosa of stomach	UBERON:0001199	33.86	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
bone marrow	UBERON:0002371	32.90	gold quality
pancreas	UBERON:0001264	32.80	silver quality
thoracic mammary gland	UBERON:0005200	32.38	silver quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
muscle tissue	UBERON:0002385	32.11	gold quality
cerebellar cortex	UBERON:0002129	31.77	gold quality
cerebellar hemisphere	UBERON:0002245	31.69	gold quality
cerebellum	UBERON:0002037	31.66	gold quality
lymph node	UBERON:0000029	30.87	silver quality
urinary bladder	UBERON:0001255	30.76	gold quality
prefrontal cortex	UBERON:0000451	30.33	gold quality
monocyte	CL:0000576	30.19	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.92

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

53 targeting GFRAL, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-185-5P	99.35	68.60	2497

Literature-anchored findings (GeneRIF, showing 4)

• Antibody-mediated inhibition of GDF15-GFRAL activity reverses cancer cachexia in mice. (PMID:32661391)
• Upregulated GDF-15 expression facilitates pancreatic ductal adenocarcinoma progression through orphan receptor GFRAL. (PMID:33201838)
• Genome-wide association and transcriptome analysis suggests total serum ghrelin to be linked with GFRAL. (PMID:33852427)
• GDF-15 Inhibits ADP-Induced Human Platelet Aggregation through the GFRAL/RET Signaling Complex. (PMID:38254638)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gfral	ENSDARG00000089709
mus_musculus	Gfral	ENSMUSG00000059383
rattus_norvegicus	Gfral	ENSRNOG00000032063
drosophila_melanogaster	Gfrl	FBGN0262869
caenorhabditis_elegans		WBGENE00022100

Paralogs (4): GFRA4 (ENSG00000125861), GFRA3 (ENSG00000146013), GFRA1 (ENSG00000151892), GFRA2 (ENSG00000168546)

Protein

Protein identifiers

GDNF family receptor alpha-like — Q6UXV0 (reviewed: Q6UXV0)

All UniProt accessions (1): Q6UXV0

UniProt curated annotations — full annotation on UniProt →

Function. Brainstem-restricted receptor for GDF15 hormone, which triggers an aversive response, characterized by nausea, vomiting, and/or loss of appetite in response to various stresses. The aversive response is both required to reduce continuing exposure to those stresses at the time of exposure and to promote avoidance behavior in the future. The GDF15-GFRAL aversive response is triggered by stresses, such as anticancer drugs (camptothecin or cisplatin), cancers or drugs such as metformin. Upon interaction with its ligand, GDF15, mediates the GDF15-induced autophosphorylation and activation of the RET tyrosine kinase receptor, leading to activation of MAPK- and AKT- signaling pathways. Ligand-binding activates GFRAL-expressing neurons localized in the area postrema and nucleus tractus solitarius of the brainstem. The GDF15-GFRAL signal induces expression of genes involved in metabolism, such as lipid metabolism in adipose tissues.

Subunit / interactions. Interacts (via the extracellular domain) with GDF15 and RET; receptor of GDF15, mediates cellular signaling through interaction with RET after GDF15-binding. Interaction with RET requires previous GDF15-binding.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in the brainstem, restricted to cells in the area postrema and the immediately adjacent region of the nucleus tractus solitarius (at protein level). Detected at low levels in testis and adipose tissue.

Post-translational modifications. Cleaved and inactivated by MMP14, inhibiting the GDF15-GFRAL aversive response.

Activity regulation. Specifically inhibited by 3P10 monoclonal antibody. Strongly activated by LY3463251, a long-acting and stable agonist composed of GDF15 conjugated monomeric human IgG4 Fc.

Similarity. Belongs to the GDNFR family.

RefSeq proteins (1): NP_997293* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF02351

UniProt features (45 total): helix 14, disulfide bond 11, glycosylation site 6, sequence variant 3, turn 3, topological domain 2, signal peptide 1, chain 1, mutagenesis site 1, strand 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
9HYT	X-RAY DIFFRACTION	1.9
5VZ4	X-RAY DIFFRACTION	2.2
6WMW	X-RAY DIFFRACTION	2.91
6Q2J	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UXV0-F1	76.73	0.41

Antibody-complex structures (SAbDab): 1 — 6WMW

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 (11): 131–189, 138–144, 155–167, 162–210, 191–198, 220–291, 227–233, 244–275, 252–258, 269–316, 293–304

Glycosylation sites (6): 103, 116, 23, 50, 62, 67

Mutagenesis-validated functional residues (1):

Position	Phenotype
261	abolished formation of a ternary complex with gdf15 and ret.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 76 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_BEHAVIOR, GOBP_RESPONSE_TO_DIETARY_EXCESS, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOCC_CELL_SURFACE, GOBP_RESPONSE_TO_FOOD, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_EATING_BEHAVIOR, chr6p12, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_REGULATION_OF_RESPONSE_TO_FOOD, GOBP_PHOSPHATIDYLINOSITOL_3_KINASE_PROTEIN_KINASE_B_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY

GO Biological Process (10): reduction of food intake in response to dietary excess (GO:0002023), nervous system development (GO:0007399), stress-activated protein kinase signaling cascade (GO:0031098), negative regulation of appetite (GO:0032099), positive regulation of MAPK cascade (GO:0043410), negative regulation of neuron apoptotic process (GO:0043524), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), GDF15-GFRAL signaling pathway (GO:0160144), response to metformin (GO:1901558), negative regulation of extrinsic apoptotic signaling pathway in absence of ligand (GO:2001240)

GO Molecular Function (5): hormone activity (GO:0005179), glial cell-derived neurotrophic factor receptor activity (GO:0016167), receptor tyrosine kinase binding (GO:0030971), signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (7): nucleoplasm (GO:0005654), plasma membrane (GO:0005886), focal adhesion (GO:0005925), external side of plasma membrane (GO:0009897), actin cytoskeleton (GO:0015629), signaling receptor complex (GO:0043235), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular response to stress	2
positive regulation of intracellular signal transduction	2
glial cell-derived neurotrophic factor receptor signaling pathway	2
cellular anatomical structure	2
response to dietary excess	1
eating behavior	1
system development	1
intracellular signal transduction	1
negative regulation of response to food	1
regulation of appetite	1
MAPK cascade	1
regulation of MAPK cascade	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
response to nitrogen compound	1
extrinsic apoptotic signaling pathway in absence of ligand	1
negative regulation of signal transduction in absence of ligand	1
negative regulation of extrinsic apoptotic signaling pathway	1
regulation of extrinsic apoptotic signaling pathway in absence of ligand	1
receptor ligand activity	1
cytokine receptor activity	1
signaling receptor binding	1
protein tyrosine kinase binding	1
molecular transducer activity	1
binding	1
nuclear lumen	1
membrane	1
cell periphery	1
cell-substrate junction	1
plasma membrane	1
cell surface	1
side of membrane	1
cytoskeleton	1
protein-containing complex	1

Protein interactions and networks

STRING

264 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GFRAL	GDF15	P78360	997
GFRAL	RET	P07949	988
GFRAL	PSPN	O60542	797
GFRAL	GDNF	P39905	786
GFRAL	NRTN	Q99748	644
GFRAL	ARTN	Q5T4W7	618
GFRAL	TMED1	Q13445	461
GFRAL	SACK1B	Q5T0W9	391
GFRAL	GADD45GIP1	Q8TAE8	367
GFRAL	FGF21	Q9NSA1	358
GFRAL	HMGCLL1	Q8TB92	347
GFRAL	FNBP1L	Q5T0N5	327
GFRAL	GLP1R	P43220	306
GFRAL	GFRA2	O00451	292
GFRAL	PAEP	P09466	288

IntAct

3 interactions, top by confidence:

A	B	Type	Score
GDF15	GFRAL	psi-mi:“MI:0407”(direct interaction)	0.560

BioGRID (2): GFRAL (Affinity Capture-MS), GFRAL (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8QHQ6, A0A8M9PDM1, B4IXJ2, B5DFM7, D3ZB94, E9Q9F6, O35118, O35251, O43915, O77726, O88393, P0DP43, P13385, P20239, P20826, P26342, P51864, P51865, P79169, P79368, P97946, Q03167, Q06220, Q09322, Q0VCB1, Q13129, Q29030, Q3V140, Q5RCM7, Q5SY80, Q62959, Q6DFV8, Q6P7N7, Q6SJE0, Q6UXV0, Q6X782, Q6X784, Q6X786, Q86XM0, Q8N2E2

Diamond homologs: D3ZB94, Q6SJE0, Q6UXV0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1782 predictions. Top by Δscore:

Variant	Effect	Δscore
6:55358998:G:GT	donor_gain	1.0000
6:55399174:TTTCA:T	acceptor_loss	1.0000
6:55399175:TTCA:T	acceptor_loss	1.0000
6:55399176:TCAG:T	acceptor_loss	1.0000
6:55399177:CA:C	acceptor_loss	1.0000
6:55399178:A:C	acceptor_loss	1.0000
6:55399179:GATT:G	acceptor_gain	1.0000
6:55399281:T:G	donor_gain	1.0000
6:55327575:GG:G	donor_gain	0.9900
6:55327576:GG:G	donor_gain	0.9900
6:55327576:GGTA:G	donor_loss	0.9900
6:55327577:G:C	donor_loss	0.9900
6:55327577:G:GG	donor_gain	0.9900
6:55327578:TAAG:T	donor_loss	0.9900
6:55333782:T:TA	acceptor_gain	0.9900
6:55350086:TTCTA:T	acceptor_loss	0.9900
6:55350087:TCTA:T	acceptor_loss	0.9900
6:55350088:CTAGA:C	acceptor_loss	0.9900
6:55350089:TA:T	acceptor_loss	0.9900
6:55350090:A:AG	acceptor_gain	0.9900
6:55350090:A:AT	acceptor_loss	0.9900
6:55350091:G:C	acceptor_loss	0.9900
6:55350091:G:GG	acceptor_gain	0.9900
6:55358887:GGA:G	acceptor_gain	0.9900
6:55359082:G:GG	donor_gain	0.9900
6:55359139:G:GG	donor_gain	0.9900
6:55399178:A:AG	acceptor_gain	0.9900
6:55399179:G:GG	acceptor_gain	0.9900
6:55399179:GA:G	acceptor_gain	0.9900
6:55399271:CAATG:C	donor_loss	0.9900

AlphaMissense

2635 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:55351312:T:A	C144S	0.980
6:55351313:G:C	C144S	0.980
6:55351474:T:A	C198S	0.977
6:55351475:G:C	C198S	0.977
6:55358905:T:G	F240C	0.977
6:55359096:T:A	C304S	0.974
6:55359097:G:C	C304S	0.974
6:55351542:C:G	C220W	0.972
6:55358916:T:A	C244S	0.972
6:55358917:G:C	C244S	0.972
6:55358921:G:C	W245C	0.972
6:55358921:G:T	W245C	0.972
6:55351540:T:C	C220R	0.969
6:55351476:T:G	C198W	0.967
6:55351561:T:A	C227S	0.967
6:55351562:G:C	C227S	0.967
6:55359011:C:G	C275W	0.967
6:55351563:C:G	C227W	0.966
6:55359036:G:T	G284W	0.966
6:55359057:T:A	C291S	0.966
6:55359058:G:C	C291S	0.966
6:55351312:T:C	C144R	0.965
6:55359009:T:A	C275S	0.965
6:55359010:G:C	C275S	0.965
6:55359098:T:G	C304W	0.965
6:55351448:G:A	C189Y	0.963
6:55351474:T:C	C198R	0.963
6:55358916:T:C	C244R	0.963
6:55359057:T:C	C291R	0.963
6:55351313:G:A	C144Y	0.962

dbSNP variants (sampled 300 via entrez): RS1000011174 (6:55340718 G>C), RS1000039854 (6:55361615 T>A), RS1000059498 (6:55392943 G>T), RS1000118749 (6:55372464 G>A,T), RS1000127334 (6:55334399 T>C), RS1000171837 (6:55342493 T>C,G), RS1000203191 (6:55342247 G>C), RS1000207367 (6:55380667 A>T), RS1000234484 (6:55370666 T>C,G), RS1000237272 (6:55331217 A>G), RS1000248756 (6:55331028 A>C,G), RS1000287418 (6:55337113 G>A), RS1000296306 (6:55377607 G>T), RS1000389150 (6:55387711 G>C), RS1000403653 (6:55398880 C>A,T)

Disease associations

OMIM: gene MIM:617837 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST005929_6	Severity of nausea and vomiting of pregnancy	6.000000e-09
GCST006288_451	Heel bone mineral density	1.000000e-08
GCST006288_547	Heel bone mineral density	5.000000e-10
GCST006585_256	Blood protein levels	2.000000e-14
GCST006979_287	Heel bone mineral density	2.000000e-26
GCST007565_162	Morning person	8.000000e-16
GCST007876_26	Estimated glomerular filtration rate	3.000000e-10
GCST008129_18	Body mass index	1.000000e-09
GCST010989_105	Body size at age 10	2.000000e-23
GCST90002409_40	Childhood body mass index	7.000000e-07

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0009265	nausea and vomiting of pregnancy severity measurement
EFO:0009270	heel bone mineral density
EFO:0008328	chronotype measurement
EFO:0004340	body mass index
EFO:0009819	comparative body size at age 10, self-reported

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465268 (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)

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
growth differentiation factor 15	Agonist	7.6	pKd
LY3463251	Agonist	7.26	pEC50
GRASP	Antagonist	7.13	pKd

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.05	Kd	8.98	nM	CHEMBL5406737
7.13	Kd	74.1	nM	CHEMBL5423661

PubChem BioAssay actives

2 with measured affinity, of 3 total; 2 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
1-[6-[[4-[3-[3-[[(2S,3R)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-5-amino-1-[[(2S)-6-amino-1-[[(2S,3R)-1-[[(2S)-1-[[(2S,3R)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1,2-dicarboxyethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-carboxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]propyl]-3,4,5,13-tetrazatetracyclo[13.4.0.02,6.07,12]nonadeca-1(19),2(6),4,7,9,11,15,17-octaen-13-yl]-4-oxobutyl]amino]-6-oxohexyl]-3,3-dimethyl-2-[(1E,3E,5E)-5-(1,3,3-trimethyl-5-sulfoindol-2-ylidene)penta-1,3-dienyl]indol-1-ium-5-sulfonate	2010594: Binding affinity to C-terminal polyhis-tagged recombinant human GFRAL (19 to 351 residues) expressed in HEK293 cells assessed as dissociation constant by flow cytometric analysis	kd	0.0090	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-hydroxybutanoyl]amino]-6-aminohexanoyl]amino]-4-carboxybutanoyl]amino]-4-carboxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]propanoyl]amino]-3-carboxypropanoyl]pyrrolidine-2-carbonyl]amino]-4-methylsulfanylbutanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]-5-amino-5-oxopentanoyl]amino]-6-aminohexanoyl]amino]-3-hydroxybutanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-5-amino-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]butanedioic acid	2010593: Binding affinity to C-terminal polyhis-tagged recombinant human GFRAL (19 to 351 residues) expressed in HEK293 cells assessed as dissociation constant with increasing enzyme concentration by SPR analysis	kd	0.0741	uM

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
acetochlor	affects response to substance	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	increases methylation	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5364160	Binding	Binding affinity to C-terminal polyhis-tagged recombinant human GFRAL (19 to 351 residues) expressed in HEK293 cells assessed as dissociation constant by SPR analysis	Creation of a Peptide Antagonist of the GFRAL-RET Receptor Complex for the Treatment of GDF15-Induced Malaise. — J Med Chem

Clinical trials (associated diseases)

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