GHRL

Summary

GHRL (ghrelin and obestatin prepropeptide, HGNC:18129) is a protein-coding gene on chromosome 3p25.3, encoding Appetite-regulating hormone (Q9UBU3). Precursor of the appetite-regulating peptide ghrelin, including ghrelin-27 and ghrelin-28.

This gene encodes the ghrelin-obestatin preproprotein that is cleaved to yield two peptides, ghrelin and obestatin. Ghrelin is a powerful appetite stimulant and plays an important role in energy homeostasis. Its secretion is initiated when the stomach is empty, whereupon it binds to the growth hormone secretagogue receptor in the hypothalamus which results in the secretion of growth hormone (somatotropin). Ghrelin is thought to regulate multiple activities, including hunger, reward perception via the mesolimbic pathway, gastric acid secretion, gastrointestinal motility, and pancreatic glucose-stimulated insulin secretion. It was initially proposed that obestatin plays an opposing role to ghrelin by promoting satiety and thus decreasing food intake, but this action is still debated. Recent reports suggest multiple metabolic roles for obestatin, including regulating adipocyte function and glucose metabolism. Alternative splicing results in multiple transcript variants. In addition, antisense transcripts for this gene have been identified and may potentially regulate ghrelin-obestatin preproprotein expression.

Source: NCBI Gene 51738 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 31 total
• Phenotypes (HPO): 6
• Druggable target: yes
• MANE Select transcript: NM_016362

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18129
Approved symbol	GHRL
Name	ghrelin and obestatin prepropeptide
Location	3p25.3
Locus type	gene with protein product
Status	Approved
Aliases	MTLRP, ghrelin, obestatin
Ensembl gene	ENSG00000157017
Ensembl biotype	protein_coding
OMIM	605353
Entrez	51738

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 15 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000287656, ENST00000335542, ENST00000422159, ENST00000425479, ENST00000429122, ENST00000430179, ENST00000437422, ENST00000439975, ENST00000446937, ENST00000449238, ENST00000457360, ENST00000475759, ENST00000476283, ENST00000481287, ENST00000491589, ENST00000910666, ENST00000910668, ENST00000910670, ENST00000910671

RefSeq mRNA: 10 — MANE Select: NM_016362 NM_001134941, NM_001134944, NM_001134945, NM_001134946, NM_001302821, NM_001302822, NM_001302823, NM_001302824, NM_001302825, NM_016362

CCDS: CCDS33700, CCDS46747, CCDS46748, CCDS46749, CCDS46750

Canonical transcript exons

ENST00000335542 — 6 exons

Exon	Start	End
ENSE00001386954	10290073	10290209
ENSE00001547498	10290716	10291451
ENSE00001812025	10285666	10285894
ENSE00002106906	10292842	10292947
ENSE00003542562	10289762	10289878
ENSE00003637018	10286704	10286812

Expression profiles

Bgee: expression breadth ubiquitous, 174 present calls, max score 98.31.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5417 / max 72.6116, expressed in 154 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41036	0.3812	117
41035	0.0985	30
41034	0.0621	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cardia of stomach	UBERON:0001162	98.31	gold quality
body of stomach	UBERON:0001161	92.22	gold quality
stomach	UBERON:0000945	91.85	gold quality
epithelial cell of pancreas	CL:0000083	90.06	silver quality
fundus of stomach	UBERON:0001160	89.13	gold quality
bone marrow cell	CL:0002092	88.54	gold quality
pancreatic ductal cell	CL:0002079	88.33	silver quality
islet of Langerhans	UBERON:0000006	88.07	gold quality
duodenum	UBERON:0002114	87.82	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.40	gold quality
mammary duct	UBERON:0001765	84.30	gold quality
epithelium of mammary gland	UBERON:0003244	84.15	gold quality
nasal cavity epithelium	UBERON:0005384	83.66	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	82.07	gold quality
pancreas	UBERON:0001264	81.32	gold quality
blood	UBERON:0000178	80.25	gold quality
granulocyte	CL:0000094	80.21	gold quality
sural nerve	UBERON:0015488	79.95	gold quality
pylorus	UBERON:0001166	79.85	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.01	gold quality
body of pancreas	UBERON:0001150	78.52	gold quality
lymph node	UBERON:0000029	78.07	gold quality
leukocyte	CL:0000738	77.48	gold quality
monocyte	CL:0000576	77.44	gold quality
myocardium	UBERON:0002349	77.29	gold quality
upper arm skin	UBERON:0004263	76.69	gold quality
bone marrow	UBERON:0002371	75.81	gold quality
vermiform appendix	UBERON:0001154	75.59	gold quality
sperm	CL:0000019	75.49	gold quality
jejunal mucosa	UBERON:0000399	75.49	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-31	yes	134187.85
E-MTAB-5061	no	43853.54
E-ANND-3	no	2.16

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ARX, ISL1, KLF4, NEUROD1, NKX2-2, POU1F1, USF1

miRNA regulators (miRDB)

5 targeting GHRL, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-1281	92.96	65.73	260

Literature-anchored findings (GeneRIF, showing 40)

• ghrelin inhibited Akt kinase activity as well as up-regulated gluconeogenesis. These findings raise the possibility that ghrelin modulates insulin activities in humans (PMID:11724768)
• identification of missense variants and a frameshift mutation in extremely obese children and adolescents and healthy normal weight students (PMID:12050239)
• Elevated plasma levels in Prader Willi syndrome (PMID:12091883)
• Characterisation of gastric ghrelin cells in man and other mammals in adult and fetal tissues (PMID:12107501)
• expression of ghrelin in endocrine growths of the stomach and endocrine tumours of the pancreas, intestine and lung (PMID:12107502)
• patients with active acromegaly show low levels of circulating ghrelin that are not further reduced by oral glucose tolerance test (PMID:12153739)
• A variation in the ghrelin gene increases weight and decreases insulin secretion in tall, obese children. (PMID:12161552)
• ghrelin levels are decreased in polycystic ovary syndrome women and are highly correlated to the degree of insulin resistance (PMID:12364442)
• study shows that somatostatin and cortistatin strongly inhibit ghrelin secretion and inhibition persists even after stopping the infusion of SRIF or CST (PMID:12364482)
• Data suggest that the stomach is the major source of circulating ghrelin and that other tissues compensate for the loss of ghrelin production after gastrectomy. (PMID:12414809)
• plasma ghrelin and growth hormone levels are both reciprocally related with body mass index, but no causative relationship could be demonstrated between low ghrelin levels and the hyposomatropism in human obesity (PMID:12429880)
• ghrelin is increased in anorexia nervosa and constitutionally thin subjects who display very low BMI but different eating behaviors, suggesting that not only is ghrelin dependent on body fat mass, but it is also influenced by nutritional status (PMID:12519838)
• ghrelin levels in children with Prader-Willi syndrome are significantly elevated compared with BMI-matched obese controls; elevated levels may play a role as an orexigenic factor driving the insatiable appetite and obesity found in PWS (PMID:12519848)
• Ghrelin can bind to a species of high density lipoprotein associated with paraoxonase (PMID:12531885)
• Expressed in fetal thyroid tissue: expression affects thyroid tumor growth. (PMID:12547722)
• human ghrelin levels decrease by almost 50% under hyperinsulinemic euglycemic clamp conditions but constant lipid infusion failed to change plasma ghrelin (PMID:12553549)
• ghrelin-induced growth hormone secretion was severely blunted in patients with active Cushing’s syndrome, in addition to a remarkable hyper-response in ACTH and cortisol secretion (PMID:12566947)
• plasma levels are increased in lung cancer cachexia; increased ghrelin may represent a compensatory mechanism under catabolic-anabolic imbalance in cachectic patients with lung cancer (PMID:12576449)
• Helicobacter pylori has no effect on plasma ghrelin concentration (PMID:12656662)
• fat restriction avoids the increase in ghrelin levels caused by dietary energy restriction (PMID:12679442)
• plasma ghrelin increases after gastric bypass surgery in patients experiencing active weight loss (PMID:12679444)
• acute plasma ghrelin response to food intake, which in healthy individuals is independent of meal caloric value, is impaired in women with anorexia nervosa (PMID:12679456)
• lowered serum levels of ghrelin in active acromegaly rise with postsurgery normalization of growth hormone and insulin-like growth factor-I and improved insulin resistance but long-acting octreotide therapy persistently suppressed serum ghrelin levels (PMID:12727951)
• study showed that 1) ghrelin secretion is sexually dimorphic in humans with women in the late follicular stage having higher levels than men; 2) ghrelin secretion is suppressed by somatostatin; and 3) growth hormone has no influence over ghrelin secretion (PMID:12727973)
• ghrelin is a novel paracrine/autocrine factor that is involved in cross-talk between the endometrium and embryo during embryonal implantation (PMID:12727993)
• Cloning and characterization of the 5(’)-flanking region of the ghrelin gene. (PMID:12732215)
• hyperghrelinemia in anorectic patients is caused at least partly by increased secretion of active ghrelin and that glucose ingestion suppresses active ghrelin release in these patients. (PMID:12824869)
• insulin reduces plasma ghrelin in nondiabetic patients and, to a lesser extent, in type 2 diabetic patients before insulin therapy;findings indicate an indirect effect of insulin via ghrelin on the suppression of hunger sensation and appetite (PMID:12829648)
• the involvement of ghrelin in the autocrine-paracrine regulation of human adrenal growth (PMID:12851720)
• results suggest that both body mass index and the presence of binge-eating/purging may have some influence on fasting plasma ghrelin levels in patients with anorexia nervosa (PMID:12892652)
• ghrelin receptor is highly constitutively active and that this activity could be of physiological importance in its role as a regulator of both GH secretion and appetite control (PMID:12907757)
• Umbilical cord concentrations of ghrelin are similar in Caucasian and Asian newborns, suggesting that ghrelin does not cause differences in body composition and growth hormone metabolism in these neonates. (PMID:12931038)
• Low ghrelin associated with type 2 diabetes, insulin concentration, insulin resistance, and hypertension. Might have role in etiology of type 2 diabetes and regulation of blood pressure. The ghrelin Arg51Gln mutation associated with low plasma ghrelin. (PMID:14514639)
• Circulating levels of C-terminal pro-ghrelin peptides are altered in patients with cadiovascular diseases. (PMID:14521948)
• Reduced ghrelin, impaired growth hormone(GH) response to GHRH by excess FFA, and increased somatostatin tone contribute to reduced GH secretion in patients with HIV-lipodystrophy. (PMID:14559725)
• a low-dose i.v. glucose bolus reduces ghrelin both in controls and in type II diabetes mellitus subjects and therefore that early insulin response does not affect plasma ghrelin. (PMID:14585085)
• ghrelin may contribute to fetal and neonatal growth. (PMID:14602792)
• Plasma ghrelin changes were significantly associated with hunger changes so circulating ghrelin is differently suppressed by diet manipulations. (PMID:14602798)
• Type 1 diabetes is associted with abnormal ghrelin secretion (PMID:14614562)
• Insulin resistance is a major factor controlling ghrelin levels in subjects with and without nonalcoholic fatty liver disease. (PMID:14671152)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ghrl	ENSMUSG00000064177
rattus_norvegicus	Ghrl	ENSRNOG00000010349

Protein

Protein identifiers

Appetite-regulating hormone — Q9UBU3 (reviewed: Q9UBU3)

Alternative names: Growth hormone secretagogue, Growth hormone-releasing peptide, Motilin-related peptide, Protein M46

All UniProt accessions (3): Q9UBU3, A8DN24, E7ESW0

UniProt curated annotations — full annotation on UniProt →

Function. Precursor of the appetite-regulating peptide ghrelin, including ghrelin-27 and ghrelin-28. Ghrelin is the ligand for growth hormone secretagogue receptor type 1 (GHSR). Induces the release of growth hormone from the pituitary. Has an appetite-stimulating effect, induces adiposity and stimulates gastric acid secretion. Involved in growth regulation. Ghrelin is the ligand for growth hormone secretagogue receptor type 1 (GHSR). Octanoylated ghrelin-28 is the most commonly found ghrelin and octanoylation is essential for the activation of the growth hormone secretagogue receptor type 1 (GHSR). Induces the release of growth hormone from the pituitary. Has an appetite-stimulating effect, induces adiposity and stimulates gastric acid secretion. Involved in growth regulation. May be the ligand for GPR39. May have an appetite-reducing effect resulting in decreased food intake. May reduce gastric emptying activity and jejunal motility.

Subcellular location. Secreted.

Tissue specificity. Highest level in stomach. All forms are found in serum as well. Other tissues compensate for the loss of ghrelin synthesis in the stomach following gastrectomy.

Post-translational modifications. O-octanoylated by GOAT/MBOAT4. O-octanoylation or O-decanoylation is essential for ghrelin activity. The O-decanoylated forms Ghrelin-27-C10 and Ghrelin-28-C10 differ in the length of the carbon backbone of the carboxylic acid bound to Ser-26. A small fraction of ghrelin, ghrelin-28-C10:1, may be modified with a singly unsaturated carboxylic acid. Also O-acetylated and O-butyrylated on Ser-26 to minor levels. Amidation of Leu-98 is essential for obestatin activity.

Similarity. Belongs to the motilin family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9UBU3-1	1, Ghrelin	yes
Q9UBU3-2	2, des-Gln14-ghrelin
Q9UBU3-3	3
Q9UBU3-4	4
Q9UBU3-5	5
Q9UBU3-6	6

RefSeq proteins (10): NP_001128413, NP_001128416, NP_001128417, NP_001128418, NP_001289750, NP_001289751, NP_001289752, NP_001289753, NP_001289754, NP_057446* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005441	Preproghrelin	Family
IPR006737	Motilin_assoc	Domain
IPR006738	Motilin_ghrelin	Domain

Pfam: PF04643, PF04644

UniProt features (19 total): splice variant 4, peptide 3, lipid moiety-binding region 3, sequence variant 2, propeptide 2, signal peptide 1, helix 1, region of interest 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7NA7	ELECTRON MICROSCOPY	2.7
7W2Z	ELECTRON MICROSCOPY	2.8
7F9Y	ELECTRON MICROSCOPY	2.9
6H3E	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBU3-F1	64.12	0.00

Antibody-complex structures (SAbDab): 3 — 7F9Y, 7NA7, 7W2Z

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 (4): 26, 26, 98, 26

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-416476	G alpha (q) signalling events
R-HSA-422085	Synthesis, secretion, and deacylation of Ghrelin

MSigDB gene sets: 366 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_DENDRITE_DEVELOPMENT, GOBP_DIGESTION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_ACID_SECRETION, GOBP_BEHAVIOR, GOBP_RESPONSE_TO_ELECTRICAL_STIMULUS, GOBP_CARTILAGE_DEVELOPMENT, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_NEGATIVE_REGULATION_OF_INTERLEUKIN_1_PRODUCTION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_INFLAMMATORY_RESPONSE, GOBP_SYNAPSE_ASSEMBLY, GOCC_SECRETORY_GRANULE

GO Biological Process (61): gastric acid secretion (GO:0001696), negative regulation of endothelial cell proliferation (GO:0001937), glucose metabolic process (GO:0006006), G protein-coupled receptor signaling pathway (GO:0007186), positive regulation of cytosolic calcium ion concentration (GO:0007204), synapse assembly (GO:0007416), actin polymerization or depolymerization (GO:0008154), adult feeding behavior (GO:0008343), response to hormone (GO:0009725), hormone-mediated signaling pathway (GO:0009755), dendrite development (GO:0016358), negative regulation of angiogenesis (GO:0016525), growth hormone secretion (GO:0030252), positive regulation of insulin secretion (GO:0032024), regulation of response to food (GO:0032095), positive regulation of appetite (GO:0032100), negative regulation of interleukin-1 beta production (GO:0032691), negative regulation of interleukin-6 production (GO:0032715), negative regulation of tumor necrosis factor production (GO:0032720), positive regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0035774), positive regulation of growth rate (GO:0040010), negative regulation of locomotion (GO:0040013), positive regulation of multicellular organism growth (GO:0040018), regulation of cell population proliferation (GO:0042127), negative regulation of circadian sleep/wake cycle, REM sleep (GO:0042322), negative regulation of apoptotic process (GO:0043066), cortisol secretion (GO:0043400), positive regulation of MAPK cascade (GO:0043410), response to estrogen (GO:0043627), positive regulation of circadian sleep/wake cycle, non-REM sleep (GO:0046010), negative regulation of insulin secretion (GO:0046676), decidualization (GO:0046697), negative regulation of inflammatory response (GO:0050728), cartilage development (GO:0051216), positive regulation of corticotropin secretion (GO:0051461), positive regulation of cortisol secretion (GO:0051464), response to electrical stimulus (GO:0051602), positive regulation of synapse assembly (GO:0051965), regulation of transmission of nerve impulse (GO:0051969), excitatory postsynaptic potential (GO:0060079)

GO Molecular Function (6): G protein-coupled receptor binding (GO:0001664), growth hormone-releasing hormone activity (GO:0016608), protein tyrosine kinase activator activity (GO:0030296), ghrelin receptor binding (GO:0031768), hormone activity (GO:0005179), protein binding (GO:0005515)

GO Cellular Component (10): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), axon (GO:0030424), secretory granule lumen (GO:0034774), Schaffer collateral - CA1 synapse (GO:0098685), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), neuronal dense core vesicle lumen (GO:0099013), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1
Peptide hormone metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
synapse	3
signal transduction	2
digestive system process	1
acid secretion	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
negative regulation of epithelial cell proliferation	1
hexose metabolic process	1
G protein-coupled receptor activity	1
regulation of biological quality	1
nervous system development	1
cell junction assembly	1
synapse organization	1
actin filament organization	1
feeding behavior	1
adult behavior	1
response to endogenous stimulus	1
response to chemical	1
cellular response to hormone stimulus	1
neuron projection development	1
anatomical structure development	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
peptide hormone secretion	1
insulin secretion	1
positive regulation of protein secretion	1
regulation of insulin secretion	1
positive regulation of peptide hormone secretion	1
response to food	1
regulation of response to nutrient levels	1
positive regulation of response to food	1
regulation of appetite	1
interleukin-1 beta production	1
regulation of interleukin-1 beta production	1
negative regulation of interleukin-1 production	1
negative regulation of cytokine production	1
interleukin-6 production	1
regulation of interleukin-6 production	1

Protein interactions and networks

STRING

1922 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GHRL	GHSR	Q92847	999
GHRL	GPR39	O43194	983
GHRL	NPY	P01303	983
GHRL	LEP	P41159	978
GHRL	AGRP	O00253	977
GHRL	MBOAT4	Q96T53	968
GHRL	PYY	P10082	959
GHRL	INS	P01308	936
GHRL	POMC	P01189	933
GHRL	CCK	P06307	933
GHRL	GHRH	P01286	931
GHRL	SST	P01166	926
GHRL	PPY	P01298	903
GHRL	GCG	P01275	897
GHRL	MC4R	P32245	884

IntAct

14 interactions, top by confidence:

A	B	Type	Score
UBQLN1	GHRL	psi-mi:“MI:0915”(physical association)	0.560
GHRL	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
GHRL	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
GHRL	GNPAT	psi-mi:“MI:0914”(association)	0.350
BRK1	KIF5C	psi-mi:“MI:0914”(association)	0.350
FARSB	HSBP1	psi-mi:“MI:0914”(association)	0.350
DNAJC19	CORO7	psi-mi:“MI:0914”(association)	0.350
GHRL	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (22): GHRL (Two-hybrid), GHRL (Reconstituted Complex), UBQLN2 (Two-hybrid), GPD2 (Affinity Capture-MS), GHRL (Affinity Capture-MS), SIRT5 (Affinity Capture-MS), C2orf44 (Affinity Capture-MS), GHRL (Affinity Capture-MS), GNPAT (Affinity Capture-MS), GHRL (Affinity Capture-MS), NECAP2 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), UTP6 (Affinity Capture-MS), GHRL (Cross-Linking-MS (XL-MS)), GHRL (FRET)

ESM2 similar proteins: A0MLS4, A2BD09, A2D4U1, A2D670, A2T6K4, O14669, P01257, P01286, P02818, P02820, P02822, P27916, P41547, P51693, P63292, P70160, P84348, P84349, P84350, Q03157, Q0VCT2, Q2NL23, Q3KNT9, Q3TYX2, Q5HZE8, Q5T124, Q60549, Q64375, Q6AYE5, Q6BEG6, Q6BEG7, Q71SY6, Q76IQ4, Q7M742, Q7TNI2, Q86UD1, Q8JFY4, Q8K2B0, Q8QZR4, Q8R182

Diamond homologs: A0MLS4, Q6BEG6, Q6BEG7, Q76IQ4, Q8JFY4, Q9BDJ6, Q9BEF8, Q9EQX0, Q9GKY5, Q9QYH7, Q9UBU3, Q8AUU1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GHRL	up-regulates	GHSR	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	16
Likely benign	1
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

1072 predictions. Top by Δscore:

Variant	Effect	Δscore
3:10289769:T:TA	donor_gain	1.0000
3:10286697:GACTC:G	donor_loss	0.9900
3:10286698:ACTCA:A	donor_loss	0.9900
3:10286699:CTCA:C	donor_loss	0.9900
3:10286700:TCACC:T	donor_loss	0.9900
3:10286701:CACCT:C	donor_loss	0.9900
3:10286813:C:CC	acceptor_gain	0.9900
3:10289758:CGA:C	donor_loss	0.9900
3:10289759:GA:G	donor_loss	0.9900
3:10289760:A:AG	donor_loss	0.9900
3:10289760:AC:A	donor_gain	0.9900
3:10289761:CC:C	donor_gain	0.9900
3:10289770:C:A	donor_gain	0.9900
3:10289796:TG:T	donor_gain	0.9900
3:10289874:CTCTG:C	acceptor_gain	0.9900
3:10289875:TCTG:T	acceptor_loss	0.9900
3:10289876:CTG:C	acceptor_gain	0.9900
3:10289876:CTGC:C	acceptor_loss	0.9900
3:10289878:GC:G	acceptor_loss	0.9900
3:10289879:C:CA	acceptor_loss	0.9900
3:10289879:C:CC	acceptor_gain	0.9900
3:10289880:T:G	acceptor_loss	0.9900
3:10292837:CTTA:C	donor_loss	0.9900
3:10292838:TTA:T	donor_loss	0.9900
3:10292839:TA:T	donor_loss	0.9900
3:10285893:CT:C	acceptor_gain	0.9800
3:10285895:C:CC	acceptor_gain	0.9800
3:10286808:TTGAA:T	acceptor_gain	0.9800
3:10286809:TGAA:T	acceptor_gain	0.9800
3:10289760:A:AC	donor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000183653 (3:10288125 C>T), RS1000408195 (3:10291645 G>A), RS1000466170 (3:10288950 G>A), RS1000796435 (3:10293265 G>C,T), RS1001102122 (3:10289038 G>A), RS1001143811 (3:10293047 C>T), RS1001245968 (3:10291993 T>C), RS1001470480 (3:10288119 A>G), RS1001533674 (3:10289225 C>T), RS1001782502 (3:10288619 A>G), RS1001839466 (3:10287879 A>G), RS1001959162 (3:10291040 T>C), RS1002067066 (3:10289328 C>A,T), RS1003109466 (3:10286206 T>G), RS1003326045 (3:10293357 G>A)

Disease associations

OMIM: gene MIM:605353 | disease phenotypes: MIM:601665

GenCC curated gene-disease

Mondo (2): obesity disorder (MONDO:0011122), inherited obesity (MONDO:0019182)

Orphanet (3): Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), Genetic obesity (Orphanet:77828), NON RARE IN EUROPE: Non rare obesity (Orphanet:521399)

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0001513	Obesity
HP:0010982	Polygenic inheritance
HP:0012340	Decreased resting energy expenditure
HP:0031819	Increased waist to hip ratio

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004521_106	Autism spectrum disorder or schizophrenia	2.000000e-08
GCST012316_3	ghrelin levels	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0600001	ghrelin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1921664 (SINGLE PROTEIN)

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

ChEMBL bioactivities

67 potent at pChembl≥5 of 67 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.03	IC50	0.9333	nM	CHEMBL5177247
9.00	EC50	1	nM	CHEMBL5177247
8.86	EC50	1.38	nM	CHEMBL5180468
8.84	IC50	1.45	nM	CHEMBL5177247
8.84	IC50	1.445	nM	CHEMBL5177247
8.82	EC50	1.51	nM	CHEMBL5177624
8.82	EC50	1.514	nM	CHEMBL5177624
8.80	IC50	1.585	nM	CHEMBL5180468
8.80	EC50	1.58	nM	CHEMBL5174499
8.80	EC50	1.585	nM	CHEMBL5174499
8.79	EC50	1.62	nM	CHEMBL5193962
8.79	EC50	1.622	nM	CHEMBL5193962
8.78	IC50	1.66	nM	CHEMBL5177624
8.72	IC50	1.905	nM	CHEMBL5174499
8.71	EC50	1.95	nM	CHEMBL425281
8.66	IC50	2.19	nM	CHEMBL425281
8.66	IC50	2.188	nM	CHEMBL425281
8.66	IC50	2.19	nM	CHEMBL5177624
8.66	IC50	2.188	nM	CHEMBL5177624
8.65	IC50	2.239	nM	CHEMBL5193962
8.63	EC50	2.344	nM	CHEMBL5185223
8.62	EC50	2.4	nM	CHEMBL5185223
8.60	IC50	2.512	nM	CHEMBL5185223
8.57	IC50	2.69	nM	CHEMBL5180468
8.57	IC50	2.692	nM	CHEMBL5180468
8.49	IC50	3.24	nM	CHEMBL5174499
8.49	IC50	3.236	nM	CHEMBL5174499
8.48	EC50	3.31	nM	CHEMBL5171639
8.48	EC50	3.311	nM	CHEMBL5171639
8.45	IC50	3.55	nM	CHEMBL425281
8.45	IC50	3.548	nM	CHEMBL425281
8.42	IC50	3.802	nM	CHEMBL5171639
8.37	IC50	4.27	nM	CHEMBL5185223
8.37	IC50	4.266	nM	CHEMBL5185223
8.34	IC50	4.57	nM	CHEMBL5193962
8.34	IC50	4.571	nM	CHEMBL5193962
8.22	IC50	6.026	nM	CHEMBL5200946
8.18	EC50	6.61	nM	CHEMBL5200946
8.18	EC50	6.607	nM	CHEMBL5200946
8.17	EC50	6.76	nM	CHEMBL5183670
8.17	EC50	6.761	nM	CHEMBL5183670
8.07	IC50	8.51	nM	CHEMBL5171639
8.07	IC50	8.511	nM	CHEMBL5171639
8.00	IC50	10	nM	CHEMBL5200946
7.98	IC50	10.5	nM	CHEMBL5177247
7.98	IC50	10.47	nM	CHEMBL5177247
7.94	IC50	11.48	nM	CHEMBL5183670
7.93	IC50	11.7	nM	CHEMBL425281
7.93	IC50	11.75	nM	CHEMBL425281
7.92	IC50	12	nM	CHEMBL5180468

PubChem BioAssay actives

67 with measured affinity, of 67 total; 12 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
(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-hydroxypropanoyl]amino]-3-(2-methyloctylsulfanyl)propanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[(2S)-2-[(2S)-2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-5-amino-1-[(2S)-2-[[(1S)-4-carbamimidamido-1-carboxybutyl]carbamoyl]pyrrolidin-1-yl]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1865461: Displacement of C-terminal Cys-tagged SmBiT tracer from C-terminal Cys-tagged human Ghrelin expressed in HEK293T cells by microplate reader based NanoBiT-binding assay	ic50	0.0009	uM
(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-hydroxypropanoyl]amino]-3-(2-methylheptylsulfanyl)propanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[(2S)-2-[(2S)-2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-5-amino-1-[(2S)-2-[[(1S)-4-carbamimidamido-1-carboxybutyl]carbamoyl]pyrrolidin-1-yl]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1865463: Displacement of C-terminal Cys-tagged NanoLuc luciferase from C-terminal Cys-tagged human Ghrelin expressed in HEK293T cells by microplate reader based NanoBiT-binding assay	ec50	0.0014	uM
(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-hydroxypropanoyl]amino]-3-(2,6-dimethylheptylsulfanyl)propanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[(2S)-2-[(2S)-2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-5-amino-1-[(2S)-2-[[(1S)-4-carbamimidamido-1-carboxybutyl]carbamoyl]pyrrolidin-1-yl]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1865463: Displacement of C-terminal Cys-tagged NanoLuc luciferase from C-terminal Cys-tagged human Ghrelin expressed in HEK293T cells by microplate reader based NanoBiT-binding assay	ec50	0.0015	uM
(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-hydroxypropanoyl]amino]-3-nonylsulfanylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[(2S)-2-[(2S)-2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-5-amino-1-[(2S)-2-[[(1S)-4-carbamimidamido-1-carboxybutyl]carbamoyl]pyrrolidin-1-yl]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1865463: Displacement of C-terminal Cys-tagged NanoLuc luciferase from C-terminal Cys-tagged human Ghrelin expressed in HEK293T cells by microplate reader based NanoBiT-binding assay	ec50	0.0016	uM
(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-hydroxypropanoyl]amino]-3-decylsulfanylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[(2S)-2-[(2S)-2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-5-amino-1-[(2S)-2-[[(1S)-4-carbamimidamido-1-carboxybutyl]carbamoyl]pyrrolidin-1-yl]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1865463: Displacement of C-terminal Cys-tagged NanoLuc luciferase from C-terminal Cys-tagged human Ghrelin expressed in HEK293T cells by microplate reader based NanoBiT-binding assay	ec50	0.0016	uM
(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-hydroxypropanoyl]amino]-3-octanoyloxypropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[(2S)-2-[(2S)-2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-5-amino-1-[(2S)-2-[[(1S)-4-carbamimidamido-1-carboxybutyl]carbamoyl]pyrrolidin-1-yl]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1865463: Displacement of C-terminal Cys-tagged NanoLuc luciferase from C-terminal Cys-tagged human Ghrelin expressed in HEK293T cells by microplate reader based NanoBiT-binding assay	ec50	0.0019	uM
(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-hydroxypropanoyl]amino]-3-octylsulfanylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[(2S)-2-[(2S)-2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-5-amino-1-[(2S)-2-[[(1S)-4-carbamimidamido-1-carboxybutyl]carbamoyl]pyrrolidin-1-yl]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1865463: Displacement of C-terminal Cys-tagged NanoLuc luciferase from C-terminal Cys-tagged human Ghrelin expressed in HEK293T cells by microplate reader based NanoBiT-binding assay	ec50	0.0023	uM
(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-hydroxypropanoyl]amino]-3-heptylsulfanylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[(2S)-2-[(2S)-2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-5-amino-1-[(2S)-2-[[(1S)-4-carbamimidamido-1-carboxybutyl]carbamoyl]pyrrolidin-1-yl]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1865463: Displacement of C-terminal Cys-tagged NanoLuc luciferase from C-terminal Cys-tagged human Ghrelin expressed in HEK293T cells by microplate reader based NanoBiT-binding assay	ec50	0.0033	uM
(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-hydroxypropanoyl]amino]-3-(4-phenylbutylsulfanyl)propanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[(2S)-2-[(2S)-2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-5-amino-1-[(2S)-2-[[(1S)-4-carbamimidamido-1-carboxybutyl]carbamoyl]pyrrolidin-1-yl]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1865461: Displacement of C-terminal Cys-tagged SmBiT tracer from C-terminal Cys-tagged human Ghrelin expressed in HEK293T cells by microplate reader based NanoBiT-binding assay	ic50	0.0060	uM
(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-hydroxypropanoyl]amino]-3-hexylsulfanylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[(2S)-2-[(2S)-2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-5-amino-1-[(2S)-2-[[(1S)-4-carbamimidamido-1-carboxybutyl]carbamoyl]pyrrolidin-1-yl]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1865463: Displacement of C-terminal Cys-tagged NanoLuc luciferase from C-terminal Cys-tagged human Ghrelin expressed in HEK293T cells by microplate reader based NanoBiT-binding assay	ec50	0.0068	uM
(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-hydroxypropanoyl]amino]-3-pentylsulfanylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[(2S)-2-[(2S)-2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-5-amino-1-[(2S)-2-[[(1S)-4-carbamimidamido-1-carboxybutyl]carbamoyl]pyrrolidin-1-yl]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1865463: Displacement of C-terminal Cys-tagged NanoLuc luciferase from C-terminal Cys-tagged human Ghrelin expressed in HEK293T cells by microplate reader based NanoBiT-binding assay	ec50	0.0138	uM
(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-hydroxypropanoyl]amino]-3-(3-phenylmethoxypropylsulfanyl)propanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[(2S)-2-[(2S)-2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-5-amino-1-[(2S)-2-[[(1S)-4-carbamimidamido-1-carboxybutyl]carbamoyl]pyrrolidin-1-yl]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1865463: Displacement of C-terminal Cys-tagged NanoLuc luciferase from C-terminal Cys-tagged human Ghrelin expressed in HEK293T cells by microplate reader based NanoBiT-binding assay	ec50	0.0174	uM

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Orlistat	decreases expression, decreases reaction, decreases secretion	2
Glucose	decreases reaction, increases expression, increases reaction, affects cotreatment, increases secretion	2
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
osteum	decreases expression, decreases reaction	1
sodium arsenite	decreases expression	1
arctigenin	increases expression, increases reaction, decreases reaction	1
dexloxiglumide	decreases reaction, decreases expression	1
homoeriodictyol	increases secretion, affects cotreatment	1
6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide	decreases reaction, increases expression	1
Olive Oil	decreases expression, decreases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	affects methylation	1
Dust	increases expression	1
Paraquat	decreases reaction, increases activity	1
Plant Extracts	affects cotreatment, decreases expression	1
Polychlorinated Biphenyls	affects expression	1
Prostaglandins E	increases secretion	1
Prostaglandins F	increases secretion	1
Tretinoin	increases expression	1
Triglycerides	decreases reaction, decreases secretion	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5120531	Binding	Displacement of C-terminal Cys-tagged SmBiT tracer from C-terminal Cys-tagged human Ghrelin expressed in HEK293T cells by microplate reader based NanoBiT-binding assay	Development of Esterase-Resistant and Highly Active Ghrelin Analogs via Thiol-Ene Click Chemistry. — ACS Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00076362	PHASE4	COMPLETED	Pediatric Hypothalamic Obesity
NCT00079547	PHASE4	COMPLETED	The Safety and Effectiveness of Low and High Carbohydrate Diets
NCT00115063	PHASE4	TERMINATED	LOSS- Louisiana Obese Subjects Study
NCT00134303	PHASE4	COMPLETED	Trial Comparing Metformin Versus Placebo in Non Alcoholic Steatohepatitis (NASH) Patients Receiving Bariatric Surgery for Obesity
NCT00143936	PHASE4	COMPLETED	The Safety and Efficacy of Low and High Carbohydrate Diets
NCT00143962	PHASE4	COMPLETED	Comparison of Two Approaches to Weight Loss Follow-Up Study
NCT00152360	PHASE4	COMPLETED	The Effect of Xenical on Weight and Risk Factors
NCT00176306	PHASE4	COMPLETED	Levofloxacin Pharmacokinetics (PK) in the Severely Obese
NCT00203450	PHASE4	COMPLETED	Zonegran for the Treatment of Weight Gain Associated With Psychotropic Medication Use: A Placebo-Controlled Trial
NCT00205504	PHASE4	COMPLETED	Oral Contraceptives in the Metabolic Syndrome
NCT00229229	PHASE4	TERMINATED	Comparison of 4 Diets in the Management of Overweight Patients With Vascular Disease
NCT00234988	PHASE4	COMPLETED	A Phase IV, Multi-Center, Open-Label Trial of Sibutramine in Combination With a Hypocaloric Diet in Obese and Overweight Thai Subjects.
NCT00264589	PHASE4	COMPLETED	Exercise Training and Cardiovascular Function in Obesity and in Type 2 Diabetes
NCT00288873	PHASE4	COMPLETED	Characterization of Hyperparathyroidism and Vitamin D Deficiency in Obesity
NCT00298857	PHASE4	TERMINATED	A Pharmacokinetic Study to Compare the Dosing of Valproic Acid in Subjects With Different Body Weights
NCT00315146	PHASE4	COMPLETED	Optimizing Body Composition for Function in Older Adults
NCT00319202	PHASE4	TERMINATED	Clinical Trial to Assess the Effects of Candesartan on the Carbohydrate Metabolism of Obese Subjects
NCT00327912	PHASE4	UNKNOWN	Laparoscopic Roux-en-Y Gastric Bypass Versus Laparoscopic Biliopancreatic Diversion (BPD)- Duodenal Switch for Superobesity
NCT00352287	PHASE4	COMPLETED	Study to Determine the Effects of Human Growth Hormone and Pioglitazone in Overweight, Prediabetic Adults
NCT00353054	PHASE4	COMPLETED	Effect of Calcium/Vitamin D Supplementation on Body Weight and Fat Loss.
NCT00390637	PHASE4	COMPLETED	Diet, Obesity and Genes (DiOGenes)
NCT00415688	PHASE4	COMPLETED	Lifestyle Modification for Obesity-Related Type 2 Diabetes
NCT00433641	PHASE4	COMPLETED	Weight Loss in Response to Sibutramine (MERIDIA) is Influenced by the Inherited Genes
NCT00440375	PHASE4	COMPLETED	Effects of Rosiglitazone on Bone in Postmenopausal Diabetic Women
NCT00453557	PHASE4	COMPLETED	Mechanism of Growth Hormone Effects on Adipose Tissue
NCT00456885	PHASE4	COMPLETED	The Effect of Exenatide on Weight and Hunger in Obese, Healthy Women
NCT00463112	PHASE4	COMPLETED	Effect of Diet Plus Sibutramine on Hormonal and Metabolic Features in Overweight and Obese Women With PCOS
NCT00512187	PHASE4	COMPLETED	Moderate Weight Loss Makes Obese Patients With Severe Chronic Plaque Psoriasis Responsive to Sub-Optimal Dose of Cyclosporine: an Investigator Blinded, Controlled, Randomized Clinical Trial
NCT00516919	PHASE4	COMPLETED	Study of Behavioral Weight Loss Therapy for Obesity and Binge Eating in Monolingual Hispanic Persons
NCT00522470	PHASE4	COMPLETED	Effects of Rosiglitazone on Serum Ghrelin and Peptide YY Levels
NCT00537810	PHASE4	COMPLETED	Treatment of Binge Eating in Obese Patients in Primary Care
NCT00538486	PHASE4	COMPLETED	A Randomized, Double-Blind, Active Control Trial Comparing Effects of Telmisartan, Candesartan and Amlodipine, Alone or Plus Metformin, on Non-Diabetic, Obese Hypertensive Patients
NCT00584389	PHASE4	TERMINATED	The Effect of Rimonabant on Energy Expenditure, Fat Metabolism and Body Composition
NCT00585182	PHASE4	COMPLETED	Study to Evaluate Weight-based Enoxaparin Dosing in Obese Medical Patients at Risk for DVT
NCT00632840	PHASE4	COMPLETED	Pharmacological Regulation of Fat Transport in Metabolic Syndrome
NCT00636142	PHASE4	COMPLETED	Effects of Infliximab on Insulin Sensitivity and Beta Cell Function in Insulin Resistant Human Obesity
NCT00675987	PHASE4	COMPLETED	A Randomized Clinical Trial To Study Losartan On Endothelial Dysfunction and Insulin Resistance In Obese Patients
NCT00694811	PHASE4	COMPLETED	Effects of Re-Feeding Duration on Weight Maintenance After Weight Loss With Very-Low-Energy Diets (VLEDs)
NCT00699413	PHASE4	TERMINATED	Supplements for Controlling Resistance to Insulin
NCT00729963	PHASE4	COMPLETED	Sibutramine Versus Continuous Positive Airway Pressure (CPAP)in Obstructive Sleep Apnea (OSA) Patients