Griscelli syndrome At least two mutations in the MYO5A gene have been found in people with Griscelli syndrome. These mutations cause a form of the condition designated type 1, which is characterized by unusually light (hypopigmented) skin, silvery-gray hair, and neurological abnormalities resulting in delayed development, intellectual disability, and seizures. The known MYO5A gene mutations prevent the production of functional myosin Va. Because the nonfunctional protein cannot form a complex with the proteins made from the MLPH and RAB27A genes, melanosomes cannot be transported to the edges of melanocytes. Instead, these structures clump near the center of melanocytes, trapping melanin within these cells and preventing normal pigmentation of skin and hair. A loss of myosin Va in neurons disrupts the transport of proteins and other molecules within and out of these cells, which likely causes the neurological problems found in Griscelli syndrome type 1.

     The MYO5A gene provides instructions for making a protein called myosin Va, which is part of a group of proteins called unconventional myosins. These proteins, which have similar structures, each play a role in transporting molecules within cells. Myosins interact with actin, a protein that is important for cell movement and shape. Researchers believe that myosins use long filaments of actin as tracks along which to transport other molecules. Myosin Va is found in pigment-producing cells called melanocytes, where it helps transport structures called melanosomes. These structures produce a pigment called melanin, which is the substance that gives skin, hair, and eyes their color (pigmentation). Myosin Va interacts with proteins produced from the MLPH and RAB27A genes to form a complex that transports melanosomes to the outer edges of melanocytes. From there, the melanosomes are transferred to other types of cells, where they provide the pigment needed for normal hair, skin, and eye coloring. Myosin Va also plays an important role in nerve cells (neurons) in the brain. Studies suggest that myosin Va transports various proteins and other molecules within neurons. It is also involved in the release of certain substances from these cells (exocytosis). The movement of these materials appears to be critical for normal brain function.

The following transcription factors affect gene expression:

• Evi-1

Tissue specificity:

Detected in melanocytes.

Molecular Function:

• Atp Binding
• Calcium Ion Binding
• Microfilament Motor Activity
• Poly(A) Rna Binding
• Rab Gtpase Binding

Biological Processes:

• Actin Filament-Based Movement
• Cellular Response To Insulin Stimulus
• Chemical Synaptic Transmission
• Endoplasmic Reticulum Localization
• Exocytosis
• Insulin Secretion
• Locomotion Involved In Locomotory Behavior
• Long-Chain Fatty Acid Biosynthetic Process
• Melanin Biosynthetic Process
• Melanocyte Differentiation
• Melanosome Transport
• Myelination
• Odontogenesis
• Post-Golgi Vesicle-Mediated Transport
• Protein Localization To Plasma Membrane
• Regulation Of Inositol 1,4,5-Trisphosphate-Sensitive Calcium-Release Channel Activity
• Secretory Granule Localization
• Synapse Organization
• Transport
• Vesicle-Mediated Transport
• Vesicle Transport Along Actin Filament
• Visual Perception