MSTN

Summary

MSTN (myostatin, HGNC:4223) is a protein-coding gene on chromosome 2q32.2, encoding Growth/differentiation factor 8 (O14793). Acts specifically as a negative regulator of skeletal muscle growth.

This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein negatively regulates skeletal muscle cell proliferation and differentiation. Mutations in this gene are associated with increased skeletal muscle mass in humans and other mammals.

Source: NCBI Gene 2660 — RefSeq curated summary.

At a glance

• Gene–disease (curated): myostatin-related muscle hypertrophy (Supportive, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 7 total
• Phenotypes (HPO): 3
• Druggable target: yes
• MANE Select transcript: NM_005259

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4223
Approved symbol	MSTN
Name	myostatin
Location	2q32.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000138379
Ensembl biotype	protein_coding
OMIM	601788
Entrez	2660

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000260950

RefSeq mRNA: 1 — MANE Select: NM_005259 NM_005259

CCDS: CCDS2303

Canonical transcript exons

ENST00000260950 — 3 exons

Exon	Start	End
ENSE00000783895	190060062	190060435
ENSE00001001150	190062224	190062729
ENSE00001001151	190055700	190057638

Expression profiles

Bgee: expression breadth ubiquitous, 158 present calls, max score 88.31.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7614 / max 769.3640, expressed in 102 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
32884	0.6100	93
32883	0.1515	28

Top tissues by expression

285 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	88.31	gold quality
vastus lateralis	UBERON:0001379	77.71	gold quality
quadriceps femoris	UBERON:0001377	75.84	gold quality
biceps brachii	UBERON:0001507	74.73	silver quality
hindlimb stylopod muscle	UBERON:0004252	74.68	gold quality
muscle organ	UBERON:0001630	69.86	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	69.74	silver quality
ventricular zone	UBERON:0003053	69.21	gold quality
muscle of leg	UBERON:0001383	68.67	gold quality
skeletal muscle tissue	UBERON:0001134	68.20	gold quality
gastrocnemius	UBERON:0001388	67.24	gold quality
muscle tissue	UBERON:0002385	65.97	gold quality
deltoid	UBERON:0001476	65.13	silver quality
right adrenal gland cortex	UBERON:0035827	64.66	gold quality
diaphragm	UBERON:0001103	63.85	gold quality
right adrenal gland	UBERON:0001233	62.37	gold quality
left adrenal gland	UBERON:0001234	61.27	gold quality
endocervix	UBERON:0000458	60.78	gold quality
left adrenal gland cortex	UBERON:0035825	60.58	gold quality
adrenal cortex	UBERON:0001235	59.95	gold quality
calcaneal tendon	UBERON:0003701	59.63	gold quality
adrenal gland	UBERON:0002369	59.08	gold quality
descending thoracic aorta	UBERON:0002345	58.89	gold quality
thoracic aorta	UBERON:0001515	58.80	gold quality
ascending aorta	UBERON:0001496	58.75	gold quality
adrenal tissue	UBERON:0018303	58.25	gold quality
ectocervix	UBERON:0012249	56.64	gold quality
stromal cell of endometrium	CL:0002255	56.28	gold quality
tibialis anterior	UBERON:0001385	56.12	silver quality
ganglionic eminence	UBERON:0004023	55.93	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.10

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CEBPB, CEBPD, CREB1, FOXO1, FOXO3, MEF2A, MEF2C, MYOD1, MYOG, NFKB, NR4A3, PAX7, POU4F2, PPARGC1A, RELA, SMAD2, SMAD3, SMAD4, SMAD7, SP1, TCF3, ZNF699

miRNA regulators (miRDB)

193 targeting MSTN, 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-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-432-3P	100.00	67.86	705
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883

Literature-anchored findings (GeneRIF, showing 40)

• Deficiency of this protein in mice affects skeletal muscle and bone weight and development. (PMID:12060865)
• Insulin-like growth factor-1 and myostatin mRNA expression in muscle: comparison between 62-77 and 21-31 yr old men (PMID:12175483)
• negative regulation in vivo by myostatin propeptide and follistatin-related gene (PMID:12194980)
• myostatin might represent an important regulator of skeletal muscle size also in conditions of food restriction in obese subjects. (PMID:15181048)
• Loss-of-function mutation in myostatin gene caused muscle hypertrophy; provides strong evidence myostatin plays important role in regulation of muscle mass in humans. (PMID:15215484)
• GDF-8 functions as a negative regulator of muscle growth (PMID:15567067)
• An early, high-level postnatal expression of myostatin transgene is identified as being responsible for a highly muscled phenotype in myostatin transgenic mice. (PMID:16437538)
• myostatin is synthesized, released, and acts within the human placenta (PMID:16464946)
• GDF8 is a weight-loss-responsive gene in skeletal muscle. Its observed transcriptional modulation may increase muscle mass, with weight loss. (PMID:16849634)
• positive natural selection has acted on human nucleotide variation at GDF8 (PMID:17186467)
• We conclude that smoking impairs the muscle protein synthesis process and increases the expression of genes associated with impaired muscle maintenance; smoking therefore likely increases the risk of sarcopenia. (PMID:17609255)
• No compelling evidence that myostatin is differentially regulated in humans demonstrating robust resistance training-mediated myofiber hypertrophy vs. those more resistant to growth. (PMID:17673556)
• results suggest the genetic polymorphisms in myostatin likely play a role in attainment of peak BMD in Chinese women. (PMID:17703271)
• Myostatin specifically inhibits glucose uptake in BeWo cells. (PMID:17711997)
• Myostatin mRNA was decreased after bouts of acute exercise. (PMID:17823296)
• extracellular pro-myostatin constitutes the major pool of latent myostatin in muscle (PMID:18175804)
• myostatin enhanced nuclear translocation of beta-catenin and formation of the Smad3-beta-catenin-TCF4 complex, together with the altered expression of a number of Wnt/beta-catenin pathway genes in hMSCs (PMID:18203713)
• Human sarcopenia reveals an increase in SOCS-3 and myostatin and a reduced efficiency of Akt phosphorylation. (PMID:18240972)
• results disclosed a wide range in serum myostatin concentrations in Duchenne muscular dystrophy patients; no significant difference found in serum myostatin concentration between patients with mutation in the 5’ and 3’ regions of the dystrophin gene (PMID:18284920)
• Myostatin might play a role in the pathogenic cascade of Type-II muscle fibre atrophy. (PMID:18335407)
• Differential antagonism of activin, myostatin and growth and differentiation factor 11 by wild-type and mutant follistatin. (PMID:18535106)
• A retrovirus-based system to stably silence GDF-8 expression and enhance myogenic differentiation in rhabdomyosarcoma cells is reported. (PMID:18563849)
• myostatin mRNA showed no significant regulation…6 months after orthognathic surgery (PMID:18567511)
• Both WFIKKN1 and WFIKKN2 have high affinity for growth and differentiation factors 8 and 11. (PMID:18596030)
• Findings show that increased expression of myostatin in skeletal muscle with obesity and insulin resistance results in elevated circulating myostatin. (PMID:18835929)
• The state of the current literature on myostatin is discussed in this overview of key metabolic and molecular processes regulating muscle size in adult humans, with a focus on skeletal muscle protein synthesis and muscle satellite cell recruitment. (PMID:19147968)
• Except in the youngest patient, clinical severity was higher in myostatin K153R carriers than in their K/K(2) controls (aged 33, 40 and 46 years). Peak cardiorespiratory capacity was very low (< or = 13 mLO(2)/kg/min) in all K153R carriers. (PMID:19232494)
• We found statistical significance for the ACE ID and II genotypes in soccer players than in endurance runners; Statistical significance was also reached for AMPD1, but not for GDF-8 K153R (PMID:19277943)
• Resistance exercise rapidly increases mTOR signaling and may decrease myostatin protein expression in muscle. (PMID:19299575)
• MSTN 2379 A > G and FST -5003 A > T were associated with baseline muscle strength and size among African Americans only. (PMID:19346981)
• This study demenostrated that the myostatin is reduced in skeletal muscle of chronic spinal cord-injured patients. (PMID:19533653)
• myostatin plays a positive role in tendon maintenance and that exogenous protein administration stimulates proliferation and growth of early repair tissue (PMID:19591015)
• Myostatin or 20 ng/mL BMP-11 maintain the colony and cellular morphology of undifferentiated hESC, maintain POU5f1, NANOG, TRA-1-60, and SSEA4 expression, and display increased SMAD2/3 phosphorylation (PMID:19751112)
• Myostatin gene expression is enhanced by essential amino acid ingestion. (PMID:19828686)
• in 2 families with myotonia congenita, no variants in MSTN gene were found; results show that the hypermusculature associated with myotonia in these families could not be attributed to modulation of muscle growth by variation in myostatin expression (PMID:19918890)
• Creatine supplementation in conjunction with resistance training lead to greater decreases in serum myostatin (p<0.05), but had not additional effect on GASP-1 (p>0.05). (PMID:20026378)
• Results show that the myostatin precursor protein is capable of forming amyloid structures in vitro with implications for a role in sIBM pathogenesis. (PMID:20161792)
• data suggest that myostatin is a pro-fibrogenic factor that enhances cellular proliferation and extracellular matrix synthesis by ACL fibroblasts. (PMID:20186835)
• Common variants of MSTN and CKM genes don’t play a role in attaining high level endurance performance in Caucasians. (PMID:20536908)
• heterozygosity for the GDF8 K153R polymorphism does not seem to exert a negative influence on the muscle phenotypes (PMID:20640547)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mstn	ENSMUSG00000026100
rattus_norvegicus	Mstn	ENSRNOG00000021294

Paralogs (31): TGFB2 (ENSG00000092969), BMP7 (ENSG00000101144), TGFB1 (ENSG00000105329), BMP5 (ENSG00000112175), BMP8B (ENSG00000116985), TGFB3 (ENSG00000119699), INHBA (ENSG00000122641), INHA (ENSG00000123999), BMP4 (ENSG00000125378), BMP2 (ENSG00000125845), GDF5 (ENSG00000125965), GDF1 (ENSG00000130283), BMP15 (ENSG00000130385), GDF15 (ENSG00000130513), GDF11 (ENSG00000135414), INHBE (ENSG00000139269), LEFTY2 (ENSG00000143768), GDF7 (ENSG00000143869), BMP3 (ENSG00000152785), BMP6 (ENSG00000153162), GDF6 (ENSG00000156466), NODAL (ENSG00000156574), INHBB (ENSG00000163083), BMP10 (ENSG00000163217), GDF9 (ENSG00000164404), INHBC (ENSG00000175189), BMP8A (ENSG00000183682), GDF3 (ENSG00000184344), LEFTY1 (ENSG00000243709), GDF2 (ENSG00000263761), GDF10 (ENSG00000266524)

Protein

Protein identifiers

Growth/differentiation factor 8 — O14793 (reviewed: O14793)

Alternative names: Myostatin

All UniProt accessions (2): O14793, Q53S46

UniProt curated annotations — full annotation on UniProt →

Function. Acts specifically as a negative regulator of skeletal muscle growth.

Subunit / interactions. Homodimer; disulfide-linked. Interacts with WFIKKN2, leading to inhibit its activity. Interacts with FST3.

Subcellular location. Secreted.

Post-translational modifications. Synthesized as large precursor molecule that undergoes proteolytic cleavage to generate an N-terminal propeptide and a disulfide linked C-terminal dimer, which is the biologically active molecule. The circulating form consists of a latent complex of the C-terminal dimer and other proteins, including its propeptide, which maintain the C-terminal dimer in a latent, inactive state. Ligand activation requires additional cleavage of the prodomain by a tolloid-like metalloproteinase.

Disease relevance. Muscle hypertrophy (MSLHP) [MIM:614160] A condition characterized by increased muscle bulk and strength. Affected individuals are exceptionally strong. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TGF-beta family.

RefSeq proteins (1): NP_005250* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001111	TGF-b_propeptide	Domain
IPR001839	TGF-b_C	Domain
IPR015615	TGF-beta-like	Family
IPR017948	TGFb_CS	Conserved_site
IPR029034	Cystine-knot_cytokine	Homologous_superfamily

Pfam: PF00019, PF00688

UniProt features (51 total): strand 18, mutagenesis site 10, helix 8, disulfide bond 5, sequence variant 4, signal peptide 1, propeptide 1, chain 1, site 1, turn 1, glycosylation site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
5F3B	X-RAY DIFFRACTION	1.76
5NTU	X-RAY DIFFRACTION	2.58
5F3H	X-RAY DIFFRACTION	2.7
6UMX	X-RAY DIFFRACTION	2.79
5NXS	X-RAY DIFFRACTION	4.19

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14793-F1	78.84	0.36

Antibody-complex structures (SAbDab): 3 — 5F3B, 5F3H, 6UMX

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 98–99 (cleavage)

Disulfide bonds (5): 272–282, 281–340, 309–372, 313–374, 339

Glycosylation sites (1): 71

Mutagenesis-validated functional residues (10):

Position	Phenotype
267	decreases smad3 protein signal transduction; when associated with l-268.
268	decreases smad3 protein signal transduction; when associated with n-267.
312	slightly decreased smad3 protein signal transduction.
315	increases smad3 protein signal transduction; when associated with m-316 and m-318.
316	increases smad3 protein signal transduction; when associated with y-315 and m-318.
318	increases smad3 protein signal transduction; when associated with y-315 and m-316.
328	increases smad3 protein signal transduction.
355	increases smad3 protein signal transduction; when associated with q-357.
357	increases smad3 protein signal transduction; when associated with d-355.
366	increases smad3 protein signal transduction.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9617828	FOXO-mediated transcription of cell cycle genes

MSigDB gene sets: 296 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_SKELETAL_MUSCLE_TISSUE_REGENERATION, HNF3ALPHA_Q6, GOBP_RESPONSE_TO_ELECTRICAL_STIMULUS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_REGULATION_OF_SKELETAL_MUSCLE_CELL_DIFFERENTIATION, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_RESPONSE_TO_CORTICOSTEROID, GOBP_SKELETAL_MUSCLE_ADAPTATION, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GOBP_GROWTH

GO Biological Process (30): transforming growth factor beta receptor signaling pathway (GO:0007179), muscle organ development (GO:0007517), skeletal muscle tissue development (GO:0007519), response to gravity (GO:0009629), positive regulation of lamellipodium assembly (GO:0010592), positive regulation of macrophage chemotaxis (GO:0010759), skeletal muscle atrophy (GO:0014732), negative regulation of muscle hypertrophy (GO:0014741), skeletal muscle satellite cell differentiation (GO:0014816), myoblast migration involved in skeletal muscle regeneration (GO:0014839), response to muscle activity (GO:0014850), ovulation cycle process (GO:0022602), response to testosterone (GO:0033574), response to estrogen (GO:0043627), response to ethanol (GO:0045471), negative regulation of myoblast differentiation (GO:0045662), positive regulation of DNA-templated transcription (GO:0045893), negative regulation of insulin receptor signaling pathway (GO:0046627), muscle cell cellular homeostasis (GO:0046716), negative regulation of skeletal muscle tissue growth (GO:0048632), response to electrical stimulus (GO:0051602), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), trophoblast cell migration (GO:0061450), cellular response to hypoxia (GO:0071456), cellular response to dexamethasone stimulus (GO:0071549), negative regulation of skeletal muscle satellite cell proliferation (GO:1902723), negative regulation of satellite cell differentiation (GO:1902725), negative regulation of myoblast proliferation (GO:2000818), skeletal muscle tissue regeneration (GO:0043403), response to glucocorticoid (GO:0051384)

GO Molecular Function (8): signaling receptor binding (GO:0005102), cytokine activity (GO:0005125), growth factor activity (GO:0008083), heparin binding (GO:0008201), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein binding (GO:0005515), protein serine/threonine kinase activator activity (GO:0043539)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
FOXO-mediated transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
receptor ligand activity	2
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
animal organ development	1
muscle structure development	1
striated muscle tissue development	1
skeletal muscle organ development	1
response to abiotic stimulus	1
regulation of lamellipodium assembly	1
lamellipodium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
positive regulation of lamellipodium organization	1
positive regulation of leukocyte chemotaxis	1
regulation of macrophage chemotaxis	1
macrophage chemotaxis	1
regulation of granulocyte chemotaxis	1
positive regulation of macrophage migration	1
striated muscle atrophy	1
skeletal muscle adaptation	1
regulation of muscle hypertrophy	1
muscle hypertrophy	1
negative regulation of multicellular organismal process	1
skeletal muscle cell differentiation	1
skeletal muscle tissue regeneration	1
myoblast migration	1
response to activity	1
reproductive process	1
ovulation cycle	1
rhythmic process	1
response to lipid	1
response to ketone	1
response to hormone	1
response to alcohol	1
myoblast differentiation	1
negative regulation of cell differentiation	1
regulation of myoblast differentiation	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1

Protein interactions and networks

STRING

2180 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MSTN	ACVR2B	Q13705	999
MSTN	ACVR2A	P27037	998
MSTN	FST	P19883	997
MSTN	ACVR1B	P36896	995
MSTN	TGFBR1	P36897	991
MSTN	FSTL3	O95633	988
MSTN	WFIKKN2	Q8TEU8	919
MSTN	DCN	P07585	888
MSTN	FBXO32	Q969P5	873
MSTN	LTBP3	Q9NS15	860
MSTN	SMAD2	Q15796	856
MSTN	MYF5	P13349	855
MSTN	LTBP2	Q14767	855
MSTN	HSPG2	P98160	849
MSTN	TGFBR2	P37173	831

IntAct

21 interactions, top by confidence:

A	B	Type	Score
MSTN	MSTN	psi-mi:“MI:0407”(direct interaction)	0.760
MSTN	MSTN	psi-mi:“MI:0195”(covalent binding)	0.760
BMP1	MSTN	psi-mi:“MI:0194”(cleavage reaction)	0.710
MSTN	BMP1	psi-mi:“MI:0194”(cleavage reaction)	0.710
FURIN	MSTN	psi-mi:“MI:0194”(cleavage reaction)	0.620
WFIKKN1	MSTN	psi-mi:“MI:0407”(direct interaction)	0.560
MSTN	WFIKKN1	psi-mi:“MI:0407”(direct interaction)	0.560
MSTN	ACVR2B	psi-mi:“MI:0407”(direct interaction)	0.540
ACVR2B	MSTN	psi-mi:“MI:0407”(direct interaction)	0.540
ACVR2B	MSTN	psi-mi:“MI:0915”(physical association)	0.540
MSTN	GDF11	psi-mi:“MI:0914”(association)	0.350

BioGRID (31): FSTL3 (Affinity Capture-MS), FSTL3 (Affinity Capture-Western), FSTL3 (Reconstituted Complex), MSTN (Affinity Capture-Western), APPBP2 (Affinity Capture-MS), OXSR1 (Affinity Capture-MS), ZNF24 (Affinity Capture-MS), ADAMTS2 (Affinity Capture-MS), PRTG (Affinity Capture-MS), DIEXF (Affinity Capture-MS), KLHL42 (Affinity Capture-MS), GDF11 (Affinity Capture-MS), BMP1 (Affinity Capture-MS), VWDE (Affinity Capture-MS), GAS6 (Affinity Capture-MS)

ESM2 similar proteins: A1C2U3, A1C2U6, A1C2U7, A1C2V0, A1C2V5, F1QWZ4, O08689, O14793, O18828, O18830, O18831, O18836, O35312, O42220, O42221, O42222, O95393, P27091, P30885, P34822, P48970, P54631, P85857, P92172, Q24735, Q26974, Q4AEG6, Q5I3Q2, Q5RZV4, Q5USV5, Q5USV6, Q5USV7, Q5USV8, Q5USV9, Q5USW0, Q5USW1, Q6DTL9, Q6J1J2, Q6T5B8, Q6UKZ8

Diamond homologs: A1C2U3, A1C2U6, A1C2U7, A1C2V0, A1C2V5, A8E7N9, G5EEL5, O08689, O14793, O18828, O18830, O18831, O18836, O35312, O42220, O42221, O42222, O46576, O61643, O95390, O95393, P09534, P12644, P12645, P17491, P18075, P20722, P20863, P22003, P22004, P22444, P23359, P27091, P27539, P35621, P43026, P43027, P43028, P43029, P48970

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
TDGF1	down-regulates	MSTN
FSTL3	down-regulates	MSTN	binding
MSTN	“down-regulates activity”	AKT
FST	“down-regulates activity”	MSTN	binding
MSTN	“up-regulates activity”	ACVR2B	binding
CEBPD	“up-regulates quantity by expression”	MSTN	“transcriptional regulation”
PPARGC1A	“down-regulates quantity by repression”	MSTN	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	2
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

474 predictions. Top by Δscore:

Variant	Effect	Δscore
2:190062221:TA:T	donor_loss	1.0000
2:190062222:A:AC	donor_gain	1.0000
2:190062222:A:T	donor_loss	1.0000
2:190062222:ACACT:A	donor_gain	1.0000
2:190062223:C:CC	donor_gain	1.0000
2:190062223:CA:C	donor_gain	1.0000
2:190062223:CACT:C	donor_gain	1.0000
2:190062223:CACTC:C	donor_gain	1.0000
2:190057637:TT:T	acceptor_gain	0.9900
2:190060055:CACTT:C	donor_loss	0.9900
2:190060056:ACTTA:A	donor_loss	0.9900
2:190060057:CTT:C	donor_loss	0.9900
2:190060058:TTA:T	donor_loss	0.9900
2:190060059:TACCA:T	donor_loss	0.9900
2:190060060:A:T	donor_loss	0.9900
2:190060061:C:CT	donor_loss	0.9900
2:190060433:CAG:C	acceptor_gain	0.9900
2:190061303:G:A	donor_gain	0.9900
2:190062216:CTACT:C	donor_loss	0.9900
2:190062217:TACTT:T	donor_loss	0.9900
2:190062218:ACTTA:A	donor_loss	0.9900
2:190057638:TC:T	acceptor_loss	0.9800
2:190057639:C:CC	acceptor_gain	0.9800
2:190057639:C:CG	acceptor_loss	0.9800
2:190057640:T:C	acceptor_loss	0.9800
2:190060060:A:AC	donor_gain	0.9800
2:190060060:ACCAG:A	donor_gain	0.9800
2:190060061:C:CC	donor_gain	0.9800
2:190060061:CCAGC:C	donor_gain	0.9800
2:190062220:TTA:T	donor_gain	0.9800

AlphaMissense

2481 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:190057264:G:C	C374W	1.000
2:190057265:C:G	C374S	1.000
2:190057265:C:T	C374Y	1.000
2:190057266:A:G	C374R	1.000
2:190057266:A:T	C374S	1.000
2:190057270:A:C	C372W	1.000
2:190057271:C:A	C372F	1.000
2:190057271:C:G	C372S	1.000
2:190057271:C:T	C372Y	1.000
2:190057272:A:G	C372R	1.000
2:190057272:A:T	C372S	1.000
2:190057334:A:G	L351P	1.000
2:190057366:A:C	C340W	1.000
2:190057367:C:A	C340F	1.000
2:190057367:C:G	C340S	1.000
2:190057367:C:T	C340Y	1.000
2:190057368:A:G	C340R	1.000
2:190057368:A:T	C340S	1.000
2:190057369:G:C	C339W	1.000
2:190057370:C:T	C339Y	1.000
2:190057447:A:C	C313W	1.000
2:190057448:C:A	C313F	1.000
2:190057448:C:G	C313S	1.000
2:190057448:C:T	C313Y	1.000
2:190057449:A:G	C313R	1.000
2:190057449:A:T	C313S	1.000
2:190057454:C:A	G311V	1.000
2:190057454:C:T	G311E	1.000
2:190057455:C:G	G311R	1.000
2:190057455:C:T	G311R	1.000

dbSNP variants (sampled 300 via entrez): RS1000771191 (2:190058901 G>A,T), RS1001682608 (2:190058603 C>A), RS1001712094 (2:190058375 T>G), RS1001953878 (2:190064399 A>C), RS1002324844 (2:190061882 C>A), RS1003205777 (2:190057109 C>A,T), RS1003325096 (2:190063717 C>A,G), RS1003356142 (2:190064018 A>G), RS1003731314 (2:190056807 A>G), RS1004110267 (2:190055543 C>A), RS1004267865 (2:190061804 C>T), RS1004409822 (2:190061430 C>T), RS1005115590 (2:190057049 T>A), RS1005221857 (2:190056310 A>G), RS1005231840 (2:190056783 A>G)

Disease associations

OMIM: gene MIM:601788 | disease phenotypes: MIM:614160

GenCC curated gene-disease

Disease	Classification	Inheritance
myostatin-related muscle hypertrophy	Supportive	Autosomal recessive

Mondo (1): myostatin-related muscle hypertrophy (MONDO:0013598)

Orphanet (1): OBSOLETE: Myostatin-related muscle hypertrophy (Orphanet:275534)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001348	Brisk reflexes
HP:0003712	Skeletal muscle hypertrophy

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003518_96	Daytime sleep phenotypes	5.000000e-06
GCST012309_7	Schizophrenia	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536106	Myostatin-related muscle hypertrophy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3407325 (SINGLE PROTEIN)

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

ChEMBL bioactivities

21 potent at pChembl≥5 of 21 total, top 20 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.05	IC50	0.89	nM	CHEMBL5268044
8.68	IC50	2.1	nM	CHEMBL5285634
7.53	Kd	29.7	nM	CHEMBL3410232
7.45	Kd	35.9	nM	CHEMBL3410227
6.93	Kd	117	nM	CHEMBL3410234
6.89	IC50	130	nM	CHEMBL4448117
6.89	IC50	130	nM	CHEMBL4648474
6.72	IC50	190	nM	CHEMBL5078185
6.58	IC50	260	nM	CHEMBL4516740
6.58	IC50	260	nM	CHEMBL4448117
6.54	IC50	290	nM	CHEMBL4061416
6.52	IC50	300	nM	CHEMBL5092917
6.50	IC50	320	nM	CHEMBL4061416
6.44	IC50	360	nM	CHEMBL4061416
5.92	IC50	1200	nM	CHEMBL3892004
5.92	IC50	1190	nM	CHEMBL3892004
5.45	IC50	3560	nM	CHEMBL3410232
5.45	IC50	3560	nM	CHEMBL4448117
5.39	IC50	4100	nM	CHEMBL3410227
5.21	IC50	6200	nM	CHEMBL4646947

PubChem BioAssay actives

21 with measured affinity, of 196 total; 13 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)-6-amino-N-[(2R)-1-[[(2R)-1-[[(2R,3R)-1-[[(2R)-1-[[(1R)-2-[[(2R)-6-amino-1-[[(2R,3R)-1-[[(2R)-1-[[(2R)-1-[[(2R,3R)-1-[[(2R)-1-[[(2R)-1-amino-1-oxo-4-phenylbutan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxo-4-phenylbutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-cyclohexyl-2-oxoethyl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]-2-[[(2R)-2-[[(2R)-2-[[(2R)-2-[3-[1-[2-[6-[(E)-2-[6-[(E)-2-(1-azatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-7-yl)ethenyl]-5-bromo-2-fluoro-2-(trifluoromethyl)-3-oxa-1-oxonia-2-boranuidacyclohexa-4,6-dien-4-yl]ethenyl]-3,4-dihydro-2H-quinolin-1-yl]ethyl]triazol-4-yl]propanoylamino]-4-methylpentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-2-cyclohexylacetyl]amino]hexanamide	1929935: Photo-oxygenation mediated inactivation of human recombinant Myostatin expressed in Escherichia coli cells photoirradiated for 30 mins using LED followed by incubation with luciferase reporter transfected HEK293 cells for 4 hrs by luciferase reporter gene assay	ic50	0.0009	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-6-amino-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-4-amino-2-[[(2S)-5-amino-2-[[(2S)-5-carbamimidamido-2-(3,3-diphenylpropanoylamino)pentanoyl]amino]-5-oxopentanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylpentanoyl]amino]-4-carboxybutanoyl]amino]propanoyl]amino]-3-methylpentanoyl]amino]hexanoyl]amino]-3-methylpentanoyl]amino]-3-[1-[2-[6-[(E)-2-[6-[(E)-2-(1-azatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-7-yl)ethenyl]-5-bromo-2-fluoro-2-(trifluoromethyl)-3-oxa-1-oxonia-2-boranuidacyclohexa-4,6-dien-4-yl]ethenyl]-3,4-dihydro-2H-quinolin-1-yl]ethyl]triazol-4-yl]propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-methylpentanoic acid	1929935: Photo-oxygenation mediated inactivation of human recombinant Myostatin expressed in Escherichia coli cells photoirradiated for 30 mins using LED followed by incubation with luciferase reporter transfected HEK293 cells for 4 hrs by luciferase reporter gene assay	ic50	0.0021	uM
(4S)-5-[[(2S)-1-[[(2S,3S)-1-[[(2S)-6-amino-1-[[(2S,3S)-1-[[(2S)-5-amino-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-4-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-amino-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylpentanoyl]amino]-5-oxopentanoic acid	1196661: Binding affinity to recombinant myostatin (unknown origin) by surface plasmon resonance assay	kd	0.0297	uM
(4S)-5-[[(2S)-1-[[(2S,3S)-1-[[(2S)-6-amino-1-[[(2S,3S)-1-[[(2S)-5-amino-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-4-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylpentanoyl]amino]-5-oxopentanoic acid	1196661: Binding affinity to recombinant myostatin (unknown origin) by surface plasmon resonance assay	kd	0.0359	uM
(4S)-5-[[(2S)-1-[[(2S,3S)-1-[[(2S)-6-amino-1-[[(2S,3S)-1-[[(2S)-5-amino-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-4-amino-2-[[(2S)-5-amino-2-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylpentanoyl]amino]-5-oxopentanoic acid	1196661: Binding affinity to recombinant myostatin (unknown origin) by surface plasmon resonance assay	kd	0.1170	uM
(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-amino-3-(1H-indol-3-yl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-methylpentanoyl]amino]hexanoyl]amino]-2-cyclohexylacetyl]amino]-N-[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(1S)-2-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-cyclohexyl-2-oxoethyl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]pentanediamide	1599851: Inhibition of myostatin (unknown origin) expressed in HEK293 cells incubated for 4 hrs by dual luciferase reporter gene assay	ic50	0.1300	uM
(4S)-5-[[(2S)-1-[[(2S,3S)-1-[[(2S)-6-amino-1-[[(2S,3S)-1-[[(2S)-5-amino-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-amino-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-4-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-amino-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylpentanoyl]amino]-5-oxopentanoic acid	1650846: Inhibition of myostatin (unknown origin) expressed in HEK293 cells incubated for 4 hrs by dual luciferase reporter gene assay	ic50	0.1300	uM
(2R)-6-amino-N-[(2R)-1-[[(2R)-1-[[(2R,3R)-1-[[(2R)-1-[[(1R)-2-[[(2R)-6-amino-1-[[(2R,3R)-1-[[(2R)-1-[[(2R)-1-[[(2R,3R)-1-[[(2R)-1-[[(2R)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-cyclohexyl-2-oxoethyl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]-2-[[(2R)-2-[[(2R)-2-[[(2R)-2-amino-4-methylpentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-2-cyclohexylacetyl]amino]hexanamide	1823377: Inhibition of myostatin (unknown origin) expressed in HEK293 cells transfected with Smad2/3 responsive reporter plasmid incubated for 4 hrs by dual luciferase reporter gene based assay	ic50	0.1900	uM
(4S)-5-[[(2S)-1-[[(2S,3S)-1-[[(2S)-6-amino-1-[[(2S,3S)-1-[[(2S)-5-amino-1-[[(2S,3S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-[[(2S,3S)-2-[[(2S)-2-[[(3S,6S,9S,12S,15S)-15-[[(2S)-5-amino-2-[[(2S)-5-carbamimidamido-2-[(2-naphthalen-2-yloxyacetyl)amino]pentanoyl]amino]-5-oxopentanoyl]amino]-9-(3-carbamimidamidopropyl)-12-[(1R)-1-hydroxyethyl]-6-[(4-hydroxyphenyl)methyl]-5,8,11,14,18,22-hexaoxo-1,17-dioxa-4,7,10,13-tetrazacyclodocosane-3-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylpentanoyl]amino]-5-oxopentanoic acid	1638879: Inhibition of myostatin (unknown origin) expressed in HEK293 cells after 4 hrs by dual luciferase reporter gene assay	ic50	0.2600	uM
(4S)-5-[[(2S)-1-[[(2S,3S)-1-[[(2S)-6-amino-1-[[(2S,3S)-1-[[(2S)-5-amino-1-[[(2S,3S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-4-amino-2-[[(2S)-5-amino-2-[[(2S)-5-carbamimidamido-2-[(2-naphthalen-2-yloxyacetyl)amino]pentanoyl]amino]-5-oxopentanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylpentanoyl]amino]-5-oxopentanoic acid	1599851: Inhibition of myostatin (unknown origin) expressed in HEK293 cells incubated for 4 hrs by dual luciferase reporter gene assay	ic50	0.2900	uM
(2R)-6-amino-N-[(2R)-1-[[(2R)-1-[[(2R,3R)-1-[[(2R)-1-[[(1S)-2-[[(2R)-6-amino-1-[[(2R,3R)-1-[[(2R)-1-[[(2S)-1-[[(2R,3R)-1-[[(2R)-1-[[(2R)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-cyclohexyl-2-oxoethyl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]-2-[[(2R)-2-[[(2R)-2-amino-5-carbamimidamidopentanoyl]amino]-2-cyclohexylacetyl]amino]hexanamide	1823377: Inhibition of myostatin (unknown origin) expressed in HEK293 cells transfected with Smad2/3 responsive reporter plasmid incubated for 4 hrs by dual luciferase reporter gene based assay	ic50	0.3000	uM
(4S)-5-[[(2S)-1-[[(2S,3S)-1-[[(2S)-6-amino-1-[[(2S,3S)-1-[[(2S)-5-amino-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-4-amino-2-[[(2S)-5-amino-2-[[(2S)-5-carbamimidamido-2-[(2-naphthalen-2-yloxyacetyl)amino]pentanoyl]amino]-5-oxopentanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylpentanoyl]amino]-5-oxopentanoic acid	1454593: Inhibition of recombinant myostatin (unknown origin) expressed in HEK293 cells after 4 hrs by dual-luciferase reporter gene assay	ic50	1.1900	uM
(3S)-4-[[(2S)-4-amino-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-4-amino-1-[(2-amino-2-oxoethyl)amino]-1,4-dioxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-[[(2S)-4-amino-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-4-oxobutanoyl]amino]-4-oxobutanoic acid	1650846: Inhibition of myostatin (unknown origin) expressed in HEK293 cells incubated for 4 hrs by dual luciferase reporter gene assay	ic50	6.2000	uM

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects expression, increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Estradiol	decreases expression	2
methyleugenol	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression	1
incobotulinumtoxinA	decreases expression	1
Vorinostat	increases expression	1
Arsenic	affects expression	1
Valproic Acid	affects expression	1
Okadaic Acid	decreases expression	1
S-Nitrosoglutathione	increases expression	1

ChEMBL screening assays

39 unique, capped per target: 39 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3413636	Binding	Inhibition of human recombinant myostatin pre-incubated with 5 uM compound for 1 hr before addition to human HepG2 cells assessed as reduction in myostatin-mediated downstream transcriptional response by myostatin-responsive (CAGA)12-lucife	Identification of the minimum peptide from mouse myostatin prodomain for human myostatin inhibition. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03991117	Not specified	COMPLETED	Lower and Higher Load Resistance Exercise Protocols: Acute Muscle Activation and Skeletal Muscle Hypertrophy
NCT03993483	Not specified	COMPLETED	Upper Versus Lower Limb Responses to Higher Versus Lower Load Resistance Training in Young Men
NCT04000750	Not specified	COMPLETED	Time-Restricted Eating and Muscle Hypertrophy
NCT06666127	Not specified	ENROLLING_BY_INVITATION	The Effect of Peak Force At Long and Short Muscle Lengths and the Impact on Muscle Growth and Strength
NCT06698055	Not specified	COMPLETED	Muscle Adaptations in Children and Adults Following Twelve Weeks of Flywheel or Weight Stack Resistance Exercise
NCT06718712	Not specified	COMPLETED	Resistance Exercise Volume and Hypertrophic Response Variability in Elderly
NCT06760663	Not specified	COMPLETED	The Load-velocity Relationship: Neuromuscular Adaptations to Resistance Training
NCT06912867	Not specified	COMPLETED	Effects of BFR Training on Muscle Strength, Thickness, and Motivation in National Adolescent Male Canoe Athletes
NCT07171411	Not specified	COMPLETED	Combined Whey Protein and Collagen Supplementation in Resistance-Trained Men
NCT07360236	Not specified	NOT_YET_RECRUITING	Determining the Effect of Shoulder Flexion Angle on Latissimus Dorsi and Forearm Flexor Hypertrophy
NCT07412600	Not specified	COMPLETED	High- and Low-Load Resistance Training
NCT07561281	Not specified	COMPLETED	Low-Load BFR vs. High-Load Training on Biceps Hypertrophy
NCT07600138	Not specified	COMPLETED	Effects of Carbohydrates Versus Carbohydrates + Protein on Resistance Training Outcomes