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MIM.604312 20p11.2

Monday 29 November 2004


Definition: Cystatin C belongs to the type II cystatin gene family. It is the most abundant extracellular inhibitor of cysteine proteases.

It is a 13-kD protein constitutively secreted shortly after its synthesis.

Cystatin C or cystatin 3 (formerly gamma trace, post-gamma-globulin, or neuroendocrine basic polypeptide), a protein encoded by the CST3 gene, is mainly used as a biomarker of kidney function.

Recently, it has been studied for its role in predicting new-onset or deteriorating cardiovascular disease.

It also seems to play a role in brain disorders involving amyloid (a specific type of protein deposition), such as Alzheimer’s disease. In humans, all cells with a nucleus (cell core containing the DNA) produce cystatin C as a chain of 120 amino acids. It is found in virtually all tissues and body fluids.

It is a potent inhibitor of lysosomal proteinases (enzymes from a special subunit of the cell that break down proteins) and probably one of the most important extracellular inhibitors of cysteine proteases (it prevents the breakdown of proteins outside the cell by a specific type of protein degrading enzymes).

Cystatin C belongs to the type 2 cystatin gene family.


cystatins }

The cystatins / CSTs are a family of cysteine protease inhibitors which share a sequence homology and a common tertiary structure of an alpha helix lying on top of an anti-parallel beta sheet. The family is subdivided as described below.

Cystatins show similarity to fetuins, kininogens, histidine-rich glycoproteins and cystatin-related proteins.

Cystatins mainly inhibit peptidase enzymes (another term for proteases) belonging to peptidase families C1 (papain family) and C13 (legumain family). They are known to mis-fold to form amyloid deposits and are implicated in several diseases.


CST1, CST2, CST3 (cystatin C, a marker of kidney function), CST4, CST5, CST6, CST7, CST8, CST9, CST11, CSTA (cystatin A), CSTB (cystatin B)


- cystatin C-associated amyloidosis
- glassy appearance of Brunner cells


- amyloidosis type 6 (icelandic type cerebroarterial amyloidosis or amyloidosis VI) (MIM.105150)