Congenital myopathy

Gene: FOXK2

I don't know

Comment on list classification: As reviewed by Anna Sarkozy, there are five unrelated families and functional evidence from zebrafish and mice available in support of the association of FOXK2 with congenital myopathy. However all five reported variants are present in gnomAD 4.1.1 (one in >2,000 individuals). Hence, this gene should not be recommended for promotion to green rating with the current evidence.

Created: 17 Jun 2026, 4:36 p.m. | Last Modified: 17 Jun 2026, 4:36 p.m.

Panel Version: 7.67

PMID:40410591 (2025) reported the identification of five different heterozygous missense FOXK2 variants in five pedigrees with congenital myopathy and ptosis through whole exome sequencing and Sanger sequencing. Zebrafish with foxk2 deficiency exhibited underdeveloped skeletal muscles and reduced mobility, while mice with Foxk2 deletion in skeletal muscle stem cells showed generalised skeletal muscle abnormalities. FOXK2 deficiency impaired myogenic differentiation in C2C12 cells and disrupted mitochondrial homeostasis in both mouse muscle stem cells and C2C12 cells. All the five variants are present in heterozygous state in general population as reported in gnomAD v4.1.1, of which p.Arg544Gln variant is present in over 2000 individuals and with homozygous state in 24.

This gene is currently rated red in PanelApp Australia, while not yet associated with any phenotypes in OMIM or Gene2Phenotype.

Created: 17 Jun 2026, 4:31 p.m. | Last Modified: 17 Jun 2026, 4:31 p.m.

Panel Version: 7.63

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
congenital myopathy, MONDO:0019952

Publications

• 40410591

Green List (high evidence)

five pedigrees with congenital myopathy and ptosis

Created: 27 May 2026, 9:42 a.m. | Last Modified: 27 May 2026, 9:42 a.m.

Panel Version: 7.25

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Publications

• 40410591