PAM16

The PAM16 gene is located on the p arm of chromosome 16 at position 13.3 and it spans 11,150 base pairs.^[5] The PAM16 gene produces a 15.1 kDa protein composed of 137 amino acids.^[8][9] The structure has been found to contain a 21-residue mitochondrial targeting leader sequence.^[10]

The PAM16 gene encodes for a mitochondrial protein with multiple functions. It is responsible for the regulation of ATP-dependent protein translocation into the mitochondrial matrix, inhibition of DNAJC19 stimulation of HSPA9/Mortalin ATPase activity, and granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling. Furthermore, PAM16 plays a role in the import of nuclear-encoded mitochondrial proteins into the mitochondrial matrix and may be important in reactive oxygen species (ROS) homeostasis.^[7][6][5]

Mutations in the PAM16 gene has been shown to cause mitochondrial deficiencies and associated disorders. It is mainly associated with Megarbane-Dagher-Melike type spondylometaphyseal dysplasia, which is an autosomal recessive disease characterized by pre- and postnatal short stature, developmental delay, dysmorphic facial appearance, narrow chest, prominent abdomen, platyspondyly, short limbs, and other abnormalities of the skeleton.^{[6] [7][5]}