SPG21

The protein encoded by this gene was identified by a two-hybrid screen using CD4 as the bait. It binds to the hydrophobic C-terminal amino acids of CD4 which are involved in repression of T cell activation. The interaction with CD4 is mediated by the noncatalytic alpha/beta hydrolase fold domain of this protein. It is thus proposed that this gene product modulates the stimulatory activity of CD4. At least three different transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq]

spastic paraplegia 21 (autosomal recessive, Mast syndrome)

May play a role as a negative regulatory factor in CD4-dependent T-cell activation.

Antigen receptor-mediated signaling pathway

Cytoplasm, cytosol
Membrane
Endosome membrane
Golgi apparatus, trans-Golgi network membrane
Partially localized in the cytosol but also accumulated on an intracellular vesicular compartment. Colocalizes with CD4 on endosomal/trans-Golgi network.

Spastic paraplegia 21, autosomal recessive (SPG21):
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG21 is associated with dementia and other central nervous system abnormalities. Subtle childhood abnormalities may be present, but the main features develop in early adulthood. The disease is slowly progressive, and cerebellar and extrapyramidal signs are also found in patients with advanced disease. Patients have a thin corpus callosum and white-matter abnormalities.