MSTN

myostatin, the group of Transforming growth factor beta superfamily

Basic information

Region (hg38): 2:190055699-190062729

Previous symbols: [ "GDF8" ]

Links

ENSG00000138379 ∙ NCBI:2660 ∙ OMIM:601788 ∙ HGNC:4223 ∙ Uniprot:O14793 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• myostatin-related muscle hypertrophy (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Muscle hypertrophy	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal	15215484

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MSTN gene.

• Myostatin-related muscle hypertrophy (51 variants)
• not provided (14 variants)
• Inborn genetic diseases (10 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MSTN gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	3	2	10
missense			13	5	3	21
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	1	2
non coding			13	4	17	34
Total	0	0	31	12	22

Variants in MSTN

This is a list of pathogenic ClinVar variants found in the MSTN region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-190055744-G-C		Myostatin-related muscle hypertrophy	Benign (Jan 13, 2018)
2-190055808-A-G		Myostatin-related muscle hypertrophy	Benign (Jan 13, 2018)
2-190055896-T-C		Myostatin-related muscle hypertrophy	Benign (Jan 13, 2018)
2-190055926-T-C		Myostatin-related muscle hypertrophy	Benign (Jan 13, 2018)
2-190055942-G-C		Myostatin-related muscle hypertrophy	Uncertain significance (Jan 12, 2018)
2-190055985-G-A		Myostatin-related muscle hypertrophy	Uncertain significance (Jan 12, 2018)
2-190056055-C-G		Myostatin-related muscle hypertrophy	Benign (Jan 13, 2018)
2-190056112-AT-A		Myostatin-related muscle hypertrophy	Likely benign (Jun 14, 2016)
2-190056185-C-A		Myostatin-related muscle hypertrophy	Uncertain significance (Jan 13, 2018)
2-190056195-T-C		Myostatin-related muscle hypertrophy	Uncertain significance (Jan 12, 2018)
2-190056335-A-G		Myostatin-related muscle hypertrophy	Uncertain significance (Jan 13, 2018)
2-190056474-C-T		Myostatin-related muscle hypertrophy	Uncertain significance (Jan 12, 2018)
2-190056516-G-A		Myostatin-related muscle hypertrophy	Benign (Jan 13, 2018)
2-190056561-A-G		Myostatin-related muscle hypertrophy	Uncertain significance (Jan 12, 2018)
2-190056563-T-G		Myostatin-related muscle hypertrophy	Uncertain significance (Jan 13, 2018)
2-190056684-C-T		Myostatin-related muscle hypertrophy	Likely benign (Apr 27, 2017)
2-190056765-C-T		Myostatin-related muscle hypertrophy	Benign (Jan 13, 2018)
2-190056863-T-G		Myostatin-related muscle hypertrophy	Benign (Jan 13, 2018)
2-190056922-G-T		Myostatin-related muscle hypertrophy	Uncertain significance (Jan 12, 2018)
2-190056968-G-A		Myostatin-related muscle hypertrophy	Benign (Jan 12, 2018)
2-190056985-G-C		Myostatin-related muscle hypertrophy	Benign (Jan 13, 2018)
2-190056999-T-C		Myostatin-related muscle hypertrophy	Uncertain significance (Jan 12, 2018)
2-190057123-C-T		Myostatin-related muscle hypertrophy	Benign (Apr 27, 2017)
2-190057131-A-G		Myostatin-related muscle hypertrophy	Uncertain significance (Jan 12, 2018)
2-190057137-T-C		Myostatin-related muscle hypertrophy	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MSTN	protein_coding	protein_coding	ENST00000260950	3	7033

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.505	0.494	125683	0	16	125699	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.778	170	201	0.846	0.0000101	2465
Missense in Polyphen		21	43.247	0.48558		510
Synonymous	-1.21	85	72.0	1.18	0.00000389	710
Loss of Function	2.85	3	14.8	0.202	8.13e-7	181

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000509	0.000508
European (Non-Finnish)	0.0000267	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts specifically as a negative regulator of skeletal muscle growth. {ECO:0000250|UniProtKB:O08689}.
• Disease: DISEASE: Muscle hypertrophy (MSLHP) [MIM:614160]: A condition characterized by increased muscle bulk and strength. Affected individuals are exceptionally strong. {ECO:0000269|PubMed:15215484}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Factors and pathways affecting insulin-like growth factor (IGF1)-Akt signaling;Hypertrophy Model;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;TGF-beta super family signaling pathway canonical;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;GPCR signaling-G alpha i;BMP2 signaling TGF-beta MV;BMP signaling Dro (Consensus)

Recessive Scores

• pRec: 0.744

Intolerance Scores

• loftool: 0.236
• rvis_EVS: 0.66
• rvis_percentile_EVS: 84.55

Haploinsufficiency Scores

• pHI: 0.839
• hipred: Y
• hipred_score: 0.776
• ghis: 0.403

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.772

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mstn
• Phenotype: immune system phenotype; skeleton phenotype; renal/urinary system phenotype; limbs/digits/tail phenotype; digestive/alimentary phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; craniofacial phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: mstnb
• Affected structure: skeletal muscle cell
• Phenotype tag: abnormal
• Phenotype quality: increased amount

Gene ontology

• Biological process: transforming growth factor beta receptor signaling pathway;muscle organ development;response to heat;response to gravity;regulation of signaling receptor activity;positive regulation of lamellipodium assembly;positive regulation of macrophage chemotaxis;positive regulation of pathway-restricted SMAD protein phosphorylation;skeletal muscle atrophy;negative regulation of muscle hypertrophy;myoblast migration involved in skeletal muscle regeneration;response to muscle activity;ovulation cycle process;response to testosterone;negative regulation of kinase activity;regulation of apoptotic process;regulation of MAPK cascade;response to estrogen;response to ethanol;negative regulation of myoblast differentiation;positive regulation of transcription, DNA-templated;negative regulation of insulin receptor signaling pathway;muscle cell cellular homeostasis;cell development;negative regulation of skeletal muscle tissue growth;response to electrical stimulus;negative regulation of protein kinase B signaling;SMAD protein signal transduction;cellular response to dexamethasone stimulus;negative regulation of skeletal muscle satellite cell proliferation;negative regulation of satellite cell differentiation;negative regulation of myoblast proliferation
• Cellular component: extracellular space;cytoplasm
• Molecular function: signaling receptor binding;cytokine activity;transforming growth factor beta receptor binding;protein binding;growth factor activity;heparin binding;identical protein binding;protein homodimerization activity