MLC1

MKS1 (Meckel syndrome type 1) is a protein that in humans is encoded by the MKS1 gene. This gene is associated with Meckel syndrome, a rare, lethal, autosomal recessive disorder characterized by renal cystic dysplasia, central nervous system malformations, and polydactyly.

Function

The MKS1 protein is a component of the primary cilium, a microtubule-based organelle that protrudes from the surface of most vertebrate cells. Primary cilia are involved in various signaling pathways, including the Hedgehog signaling pathway, which is crucial for embryonic development. MKS1 is thought to play a role in the structure and function of the cilium, and mutations in this gene can disrupt ciliary function, leading to the phenotypic manifestations of Meckel syndrome.

Clinical Significance

Mutations in the MKS1 gene are one of the genetic causes of Meckel syndrome. This syndrome is characterized by a triad of symptoms: occipital encephalocele, polycystic kidneys, and postaxial polydactyly. The condition is usually diagnosed prenatally or at birth, and it is typically fatal in the neonatal period. Genetic testing can confirm the diagnosis by identifying mutations in the MKS1 gene.

Pathophysiology

The pathophysiology of Meckel syndrome involves defects in the formation and function of primary cilia. MKS1, along with other proteins such as TMEM67 and CC2D2A, forms a complex that is essential for ciliary function. Disruption of this complex due to mutations in the MKS1 gene leads to the clinical features observed in Meckel syndrome.

Research Directions

Current research is focused on understanding the precise molecular mechanisms by which MKS1 and its associated protein complex regulate ciliary function. Studies are also exploring potential therapeutic approaches to manage or treat the symptoms of Meckel syndrome, although no effective treatments are currently available.

Also see

• Meckel syndrome
• Primary cilium
• Hedgehog signaling pathway
• Ciliopathy