MYF5

myogenic factor 5, the group of Myogenic regulatory family|Basic helix-loop-helix proteins

Basic information

Region (hg38): 12:80716911-80719671

Links

ENSG00000111049 ∙ NCBI:4617 ∙ OMIM:159990 ∙ HGNC:7565 ∙ Uniprot:P13349 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ophthalmoplegia, external, with rib and vertebral anomalies (Limited), mode of inheritance: AR
• ophthalmoplegia, external, with rib and vertebral anomalies (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ophthalmoplegia, external, with rib and vertebral anomalies	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; Ophthalmologic	29887215

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYF5 gene.

• Inborn genetic diseases (11 variants)
• not provided (1 variants)
• Ophthalmoplegia, external, with rib and vertebral anomalies (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYF5 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					1	1
missense			12			12
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	12	0	1

Variants in MYF5

This is a list of pathogenic ClinVar variants found in the MYF5 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-80717083-GCCAGTTCTCA-G		External ophthalmoplegia;Abnormal rib morphology;Scoliosis • Ophthalmoplegia, external, with rib and vertebral anomalies	Pathogenic (Oct 26, 2018)
12-80717114-C-G		Ophthalmoplegia, external, with rib and vertebral anomalies	Uncertain significance (Nov 14, 2019)
12-80717117-C-T		MYF5-related disorder	Likely benign (Jun 13, 2019)
12-80717143-A-G		not specified	Uncertain significance (Dec 14, 2021)
12-80717146-T-C		not specified	Uncertain significance (Feb 15, 2023)
12-80717170-T-A		not specified	Uncertain significance (Dec 20, 2021)
12-80717201-G-A		MYF5-related disorder	Benign (Jul 11, 2019)
12-80717206-G-A		not specified	Uncertain significance (Feb 27, 2024)
12-80717313-C-G		not specified	Uncertain significance (Oct 20, 2023)
12-80717346-C-T		External ophthalmoplegia;Abnormal rib morphology;Scoliosis • Ophthalmoplegia, external, with rib and vertebral anomalies	Pathogenic (Oct 26, 2018)
12-80717384-G-C		not specified	Uncertain significance (Dec 13, 2022)
12-80717403-C-A		not specified	Uncertain significance (Sep 06, 2022)
12-80717410-A-G		not specified	Uncertain significance (Mar 12, 2024)
12-80717491-A-G		not specified	Uncertain significance (Apr 18, 2023)
12-80717524-C-G		not specified	Uncertain significance (Dec 06, 2023)
12-80717526-G-C		not specified	Uncertain significance (Oct 12, 2021)
12-80718355-T-C		MYF5-related disorder	Likely benign (Jun 26, 2019)
12-80718386-G-T		not specified	Uncertain significance (Dec 14, 2023)
12-80718416-G-C		not specified	Uncertain significance (Jan 10, 2022)
12-80718424-G-A		not specified	Uncertain significance (Dec 01, 2022)
12-80718430-A-G		not specified	Uncertain significance (Jul 14, 2021)
12-80718907-C-A		MYF5-related disorder	Likely benign (May 20, 2019)
12-80719022-A-G		not specified	Uncertain significance (Feb 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYF5	protein_coding	protein_coding	ENST00000228644	3	2762

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000229	0.766	125727	0	21	125748	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.283	165	155	1.06	0.00000941	1663
Missense in Polyphen		67	67.123	0.99817		709
Synonymous	-0.317	69	65.7	1.05	0.00000426	512
Loss of Function	1.05	7	10.7	0.653	5.84e-7	116

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000370	0.000369
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000440	0.0000439
Middle Eastern	0.000163	0.000163
South Asian	0.000164	0.000163
Other	0.000163	0.000163

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 MYOG and MYOD1, co-occupies muscle-specific gene promoter core region during myogenesis. Induces fibroblasts to differentiate into myoblasts. Probable sequence specific DNA-binding protein.
• Pathway: Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);miRs in Muscle Cell Differentiation;Developmental Biology;CDO in myogenesis;Myogenesis;Regulation of nuclear beta catenin signaling and target gene transcription (Consensus)

Recessive Scores

• pRec: 0.304

Intolerance Scores

• loftool: 0.367
• rvis_EVS: -0.54
• rvis_percentile_EVS: 20.26

Haploinsufficiency Scores

• pHI: 0.980
• hipred: Y
• hipred_score: 0.524
• ghis: 0.468

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Myf5
• Phenotype: vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; immune system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; neoplasm; 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); normal phenotype; growth/size/body region phenotype; craniofacial phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism 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: myf5
• Affected structure: pharyngeal arch 6
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

• Biological process: cartilage condensation;ossification;somitogenesis;regulation of cell-matrix adhesion;regulation of transcription by RNA polymerase II;muscle organ development;skeletal muscle tissue development;extracellular matrix organization;skeletal muscle cell differentiation;muscle cell fate commitment;camera-type eye development;positive regulation of myoblast differentiation;positive regulation of transcription by RNA polymerase II;embryonic skeletal system morphogenesis;positive regulation of skeletal muscle fiber development;positive regulation of muscle cell differentiation;muscle tissue morphogenesis;positive regulation of myoblast fusion
• Cellular component: nucleus;nucleoplasm;RNA polymerase II transcription factor complex
• Molecular function: 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;protein binding;protein heterodimerization activity;E-box binding