CTNS-gene

The CTNS gene, also known as the cystinosin gene, is located on chromosome 17p 13.2 in humans and encodes the protein cystinosin, a receptor protein with seven transmembrane domains that is embedded in the lysosomal membrane of cells. Cystinosin is a transport protein.

Cystinosin acts as a symporter that actively transports protons and specifically the amino acid cystine out of the lysosome. This process is necessary to prevent cystine from accumulating in the lysosome, allowing the lysosome to continue to function. Cystinosin has also been discovered in melanosomes and is associated with the control and regulation of melanin.

Mutations in CTNS can lead to the clinical picture of cystinosis. Cystinosis, or cystine storage disease, is a form of lysosomal transport disorder, a subset of lysosomal storage diseases. A variation in the encoded cystinosin protein results in inhibition or loss of its ability to transport cystine from the lysosome. Cystine molecules accumulate and form crystals within the lysosome, impairing its function.

Cystinosis occurs in patients with a range of CTNS mutations; > 100 mutations have been identified to date. The most common mutation is a deletion of a large portion of the CTNS gene (sometimes referred to as a 57-kb deletion), resulting in complete loss of cystinosin. This deletion is responsible for about 50% of cystinosis cases in people of European ancestry. Other mutations result in the formation of an abnormally short protein that cannot perform its normal transport function. Mutations that alter very small regions of the CTNS gene may allow the transporter protein to retain some of its usual activity, resulting in a milder form of cystinosis. Infantile nephropathic cystinosis ( is the most severe form of the disease, most commonly associated with total loss of activity.

1. Anikster Y et al. (1999) CTNS mutations in patients with cystinosis. Hum Mutat 14:454-458.
2. Bendavid C et al (2004) FISH diagnosis of the common 57-kb deletion in CTNS causing cystinosis. Hum Genet 115:510-514.
3. Haq MR et al (2002) Immunolocalization of cystinosin, the protein defective in cystinosis. J Am Soc Nephrol 13:2046-2051.
4. Kalatzis V et al (2002) Cystinosis: from gene to disease. Nephrol Dial Transplant 17:1883-1886.
5. Servais A et alk. (2008) Late-onset nephropathic cystinosis: clinical presentation, outcome, and genotyping. Clin J Am Soc Nephrol 3:27-35.
6. Wamelink MM et al. (2008) Sedoheptulokinase deficiency due to a 57-kb deletion in cystinosis patients causes urinary accumulation of sedoheptulose: elucidation of the CARKL gene. Hum Mutat 29:532-536.