TMEM216

Overview

TMEM216 (Transmembrane Protein 216) is a protein that in humans is encoded by the TMEM216 gene. This protein is a component of the ciliary transition zone, which is crucial for the proper functioning of cilia. Cilia are hair-like structures that protrude from the surface of many eukaryotic cells and are involved in movement and signaling pathways.

Function

TMEM216 is part of the transition zone complex, which acts as a gatekeeper to regulate the entry and exit of proteins and other molecules into the cilia. This regulation is essential for maintaining the unique composition and function of the ciliary membrane. TMEM216 interacts with other proteins such as TMEM67, CEP290, and NPHP1, forming a complex that is critical for ciliary function and structure.

Clinical Significance

Mutations in the TMEM216 gene have been associated with several ciliopathies, including Joubert syndrome and Meckel-Gruber syndrome. These are rare genetic disorders characterized by developmental abnormalities, particularly affecting the brain, kidneys, and liver. Patients with TMEM216 mutations often present with neurological symptoms, such as hypotonia, ataxia, and developmental delay.

Joubert Syndrome

Joubert syndrome is a rare genetic disorder that affects the cerebellum, an area of the brain that controls balance and coordination. TMEM216 mutations can lead to the "molar tooth sign," a distinctive brain malformation seen on MRI scans of affected individuals.

Meckel-Gruber Syndrome

Meckel-Gruber syndrome is a lethal condition characterized by renal cystic dysplasia, occipital encephalocele, and polydactyly. TMEM216 mutations disrupt normal ciliary function, contributing to the development of these severe phenotypes.

Genetic Information

The TMEM216 gene is located on chromosome 11 in humans. It consists of several exons and encodes a protein that is approximately 200 amino acids in length. The gene is expressed in various tissues, with high expression levels in the brain and kidneys, which correlates with the phenotypic manifestations of its associated disorders.

Research and Studies

Ongoing research is focused on understanding the precise molecular mechanisms by which TMEM216 and its associated protein complexes regulate ciliary function. Studies using model organisms, such as zebrafish and mice, have provided insights into the role of TMEM216 in development and disease.

Also see

• Ciliopathy
• Cilia
• Joubert syndrome
• Meckel-Gruber syndrome
• TMEM67
• CEP290