MYF5 (myogenic factor 5; HGNC:7565, NCBI Gene ID 4617) is a human locus mapped to chromosome band 12q21.31 that encodes basic helix-loop-helix (bHLH) transcription factor Myf-5 (255 aa). MYF5 acts in earliest epaxial somitic myoblast determination, satellite cell self-renewal & shared Myf5+ brown adipocyte progenitor specification, together with MYF6 (Linked MRF4 Paralog at 12q21.31), MYOD1 (Myogenic Differentiation 1 Gene), and MYOG (Myogenin Gene). Encodes Myf-5, the earliest-expressed myogenic regulatory factor specifying embryonic somitic myoblasts and marking the shared progenitor lineage of skeletal muscle and brown adipose tissue.
Biallelic LoF mutations cause Congenital External Ophthalmoplegia with Rib and Vertebral Anomalies
Gene Structure & Expression
Genomic Organization & Cytogenetic Locus: 3-exon gene on chromosome 12q21.31 situated just 8.5 kb downstream of its linked paralog MYF6 (MRF4), regulated by a complex array of long-range enhancers distributed across >140 kb that respond to neural-tube Wnt1/3a, notochord Sonic Hedgehog (SHH), and PAX3/PAX7.
Cellular & Tissue Expression Profile: The very first myogenic regulatory factor expressed in vertebrate embryogenesis (appearing at day 8 in the dorsomedial dermomyotome to specify epaxial paraspinal and intercostal muscles and extraocular muscles), and continuously expressed in ~90% of adult quiescent and self-renewing PAX7+ skeletal muscle satellite stem cells.
Molecular Function & Pathways
Biochemical & Physiological Mechanism: Establishes permissive chromatin accessibility at muscle loci without immediately forcing terminal cell-cycle exit, enabling Myf5-expressing myoblasts and adult satellite cells to proliferate extensively before MYOD1 and MYOG induction; lineage-tracing studies also revealed that classical UCP1-positive interscapular brown adipocytes (unlike white adipocytes) arise from MYF5-expressing dermomyotomal progenitors when PRDM16 and EBF2 divert them from myogenesis.
Clinical & Therapeutic Significance
Human Genetic Variants & Disease Phenotypes: Biallelic loss-of-function mutations in human MYF5 cause an autosomal recessive syndrome of congenital external ophthalmoplegia, ptosis, scoliosis, and rib/vertebral anomalies—reflecting the non-redundant requirement for MYF5 in extraocular and epaxial rib-cage myogenesis prior to MYOD1 expression.
Therapeutic & Clinical Pharmacology: Modulating the asymmetric division of PAX7+/MYF5- quiescent satellite stem cells versus PAX7+/MYF5+ committed myogenic progenitors (regulated by p38-alpha/beta MAPK and Carm1 arginine methyltransferase) is a key strategy for rejuvenating aged or dystrophic muscle stem cell pools.