CTSC Gene

The CTSC gene (CTSC is the acronym for Cathepsin C) is a protein coding gene located on chromosome 11q14.2.

Diseases associated with CTSC include:

• Keratosis palmoplantaris diffusa with mutations in cathepsin C (Papillon-Lefevre syndrome: diffuse pressure point-associated palmoplantar keratosis with premature tooth loss; OMIM: 245000).
• Keratosis palmoplantaris, periodontopathy,onychogryposis with mutation in CTSC gene (see also the comments on Haim-Munk syndrome; OMIM: 245010)
• Juvenile periodontitis 1 (OMIM: 602365)

An important paralog of this gene is CTSB.

This gene encodes a member of the C1 family of peptidases and a lysosomal cysteine proteinase that appears to be a central coordinator for the activation of many serine proteinases in cells of the immune system. Alternative splicing results in multiple transcript variants, at least one of which encodes a preprotein that is proteolytically processed to form heavy and light chains that form a disulfide-linked dimer. A portion of the propeptide acts as an intramolecular chaperone for folding and stabilization of the mature enzyme. This enzyme requires chloride ions for its activity and can degrade glucagon. Defects in the encoded protein have been shown to cause Papillon-Lefevre syndrome, an autosomal recessive disorder characterized by palmoplantar keratosis and periodontitis.

Cathepsin C functions as a key enzyme in the activation of granular serine peptidases in inflammatory cells, such as elastase and cathepsin G in neutrophils and chymase and tryptase in mast cells. In many inflammatory diseases such as rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), inflammatory bowel disease, asthma, sepsis, and cystic fibrosis, a significant part of the pathogenesis is due to increased activity of some of these inflammatory proteases. Once activated by cathepsin C, these proteases can degrade various extracellular matrix components, leading to tissue damage and chronic inflammation.

Related metabolic pathways include transport to the Golgi and subsequent modification and metabolism of proteins. Gene Ontology (GO) annotations for this gene include identical protein binding and cysteine-type peptidase activity.

1. Giannetti L et al (2020) Papillon-Lefèvre syndrome: oral aspects and treatment. Dermatol Ther 33:e13336.
2. Hacham-Zadeh S et al (1978) A genetic analysis of the Papillon-Lefevre syndrome in a Jewish family from Cochin. Am J Med Genet 2: 153-157.
3. Haim S, Munk J (1965) Keratosis palmo-plantaris congenita, with periodontosis, arachnodactyly and peculiar deformity of the terminal phalanges. Brit J Derm 77: 42-54.
4. Hart TC et al (2001) Haim-Munk syndrome and Papillon-Lefevre syndrome are allelic mutations in cathepsin C. J Med Genet 37: 88-94.
5. Hart TC et al (1997) Genetic studies of syndromes with severe periodontitis and palmoplantar hyperkeratosis. J Periodont Res 32: 81-89.
6. Puliyel JM et al (1986) A syndrome of keratosis palmo-plantaris congenita, pes planus, onychogryphosis, periodontosis, arachnodactyly and a peculiar acro-osteolysis. Brit J Derm 115: 243-248.
7. Smith P et al (1967) Seven cases of Papillon-Lefevre syndrome. Periodontics 5: 42-46.