MYOD1

myogenic differentiation 1, the group of Basic helix-loop-helix proteins|Myogenic regulatory family

Basic information

Region (hg38): 11:17719571-17722136

Previous symbols: [ "MYF3" ]

Links

ENSG00000129152 ∙ NCBI:4654 ∙ OMIM:159970 ∙ HGNC:7611 ∙ Uniprot:P15172 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies (Limited), mode of inheritance: AR
• fetal akinesia deformation sequence 1 (Supportive), mode of inheritance: AR
• myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital myopathy 17	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	Craniofacial; Musculoskeletal; Pulmonary; Renal	26733463; 30403323; 31260566

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYOD1 gene.

• Myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies (2 variants)
• not provided (1 variants)
• Autosomal dominant centronuclear myopathy;Arthrogryposis multiplex congenita (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYOD1 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	2	7
missense			33	5	1	39
nonsense	1	1				2
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	2	1	33	10	3

Variants in MYOD1

This is a list of pathogenic ClinVar variants found in the MYOD1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-17719796-C-T		not specified	Uncertain significance (Oct 01, 2024)
11-17719800-A-G			Benign (Dec 31, 2019)
11-17719801-C-A		not specified	Uncertain significance (Oct 16, 2024)
11-17719818-C-A		not specified	Uncertain significance (Nov 07, 2022)
11-17719842-C-G			Likely benign (Nov 01, 2024)
11-17719845-C-T			Likely benign (Mar 02, 2018)
11-17719860-G-A		MYOD1-related disorder	Likely benign (Jan 27, 2021)
11-17719898-A-G		not specified	Uncertain significance (Jan 23, 2024)
11-17719904-G-T			Likely benign (Apr 01, 2022)
11-17719924-C-A			Likely benign (May 11, 2018)
11-17719948-C-T		not specified	Uncertain significance (Jun 19, 2024)
11-17719970-C-A		Myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies	Pathogenic (Mar 17, 2020)
11-17719976-T-A		not specified	Uncertain significance (Feb 16, 2023)
11-17719978-C-T		not specified	Uncertain significance (Dec 16, 2024)
11-17720001-G-A		MYOD1-related disorder	Likely benign (Jan 01, 2023)
11-17720007-A-C		MYOD1-related disorder	Likely benign (Mar 20, 2019)
11-17720017-G-A		not specified	Uncertain significance (Feb 13, 2024)
11-17720030-C-A		not specified	Uncertain significance (Jan 19, 2025)
11-17720045-A-G			Likely benign (Jul 21, 2018)
11-17720109-C-A		not specified	Uncertain significance (May 02, 2024)
11-17720134-G-T		Myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies	Likely pathogenic (Nov 01, 2024)
11-17720250-T-A		Myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies	Likely pathogenic (May 20, 2023)
11-17720266-G-A		not specified	Uncertain significance (Aug 28, 2021)
11-17720284-G-A		not specified	Uncertain significance (May 23, 2023)
11-17720285-A-G		not specified	Uncertain significance (Jan 18, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYOD1	protein_coding	protein_coding	ENST00000250003	3	2564

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.152	0.783	125369	0	5	125374	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.394	201	186	1.08	0.00000876	2032
Missense in Polyphen		70	72.04	0.97168		852
Synonymous	-0.421	90	85.1	1.06	0.00000426	684
Loss of Function	1.51	2	5.99	0.334	2.53e-7	83

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000365	0.0000353
Middle Eastern	0.00	0.00
South Asian	0.0000343	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation. Together with MYF5 and MYOG, co-occupies muscle-specific gene promoter core region during myogenesis. Induces fibroblasts to differentiate into myoblasts. Interacts with and is inhibited by the twist protein. This interaction probably involves the basic domains of both proteins (By similarity). {ECO:0000250}.
• Pathway: miRs in Muscle Cell Differentiation;Cell Differentiation - Index expanded;Cell Differentiation - Index;ID signaling pathway;Developmental Biology;signal dependent regulation of myogenesis by corepressor mitr;CDO in myogenesis;Myogenesis;control of skeletal myogenesis by hdac and calcium/calmodulin-dependent kinase (camk);C-MYB transcription factor network;ID;Notch-mediated HES/HEY network;Signaling events mediated by HDAC Class III;Regulation of retinoblastoma protein;Regulation of nuclear SMAD2/3 signaling (Consensus)

Recessive Scores

• pRec: 0.820

Intolerance Scores

• loftool: 0.264
• rvis_EVS: -0.14
• rvis_percentile_EVS: 43.29

Haploinsufficiency Scores

• pHI: 0.985
• hipred: Y
• hipred_score: 0.584
• ghis: 0.556

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Myod1
• Phenotype: skeleton phenotype; neoplasm; 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); normal 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); reproductive system phenotype; respiratory system phenotype; homeostasis/metabolism phenotype; muscle phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype

Zebrafish Information Network

• Gene name: myod1
• Affected structure: fast muscle cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: regulation of alternative mRNA splicing, via spliceosome;regulation of transcription by RNA polymerase II;protein phosphorylation;muscle organ development;myoblast fate determination;skeletal muscle tissue development;myoblast fusion;cellular response to starvation;myotube cell development;myotube differentiation involved in skeletal muscle regeneration;skeletal muscle cell differentiation;muscle cell fate commitment;positive regulation of skeletal muscle tissue regeneration;regulation of RNA splicing;skeletal muscle fiber adaptation;histone H3 acetylation;histone H4 acetylation;positive regulation of myoblast differentiation;positive regulation of transcription by RNA polymerase II;skeletal muscle fiber development;positive regulation of skeletal muscle fiber development;positive regulation of muscle cell differentiation;cellular response to tumor necrosis factor;cellular response to glucocorticoid stimulus;cellular response to estradiol stimulus;cellular response to oxygen levels;positive regulation of myoblast fusion;positive regulation of snRNA transcription by RNA polymerase II;negative regulation of myoblast proliferation
• Cellular component: nuclear chromatin;nucleus;nucleoplasm;transcription factor complex;cytosol;nuclear body;myofibril
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;chromatin binding;transcription coactivator activity;protein binding;chromatin DNA binding;ubiquitin protein ligase binding;nuclear hormone receptor binding;protein heterodimerization activity;E-box binding;promoter-specific chromatin binding