Reviewed June 2008
What is the official name of the CSTB gene?
The official name of this gene is “cystatin B (stefin B).”
CSTB is the gene's official symbol. The CSTB gene is also known by other names, listed below.
What is the normal function of the CSTB gene?
The CSTB gene provides instructions for making a protein called cystatin B. This protein reduces the activity of (inhibits) enzymes called cathepsins. Cathepsins help break down certain proteins in the lysosomes (compartments in the cell that digest and recycle materials). While the specific function of cystatin B is unclear, it may help protect the cells' proteins from cathepsins that leak out of the lysosomes.
One region of the CSTB gene has a particular repeating sequence of 12 DNA building blocks (nucleotides) written as CCCCG-CCCCG-CG. This sequence, called a dodecamer repeat, is usually repeated two or three times within a part of the gene that helps regulate cystatin B protein production.
How are changes in the CSTB gene related to health conditions?
- Unverricht-Lundborg disease - caused by mutations in the CSTB gene
In almost all affected individuals, Unverricht-Lundborg disease is caused by an increased number of copies (expansion) of the dodecamer repeat in the CSTB gene. Most people with this disorder have more than 30 repeats of the dodecamer sequence in both copies of the CSTB gene.
In a small number of individuals, one copy of the CSTB gene has the expanded dodecamer repeat while the second copy carries one of nine other identified mutations. Some of these mutations substitute one protein building block (amino acid) for another amino acid in the cystatin B protein. Others result in a shortened protein that may function improperly or not at all, or cause the protein to be pieced together incorrectly. Only one individual with Unverricht-Lundborg disease has been reported to have mutations other than the dodecamer repeat expansion in both copies of the gene in each cell.
The expanded dodecamer repeat in the CSTB gene seems to interfere with the production of cystatin B protein. Levels of cystatin B in affected individuals are only 5 to 10 percent of normal, and cathepsin levels are significantly increased. These changes are believed to cause the signs and symptoms of Unverricht-Lundborg disease, but the specific mechanism is unknown.
Where is the CSTB gene located?
Cytogenetic Location: 21q22.3
Molecular Location on chromosome 21: base pairs 45,193,545 to 45,196,255
The CSTB gene is located on the long (q) arm of chromosome 21 at position 22.3.
More precisely, the CSTB gene is located from base pair 45,193,545 to base pair 45,196,255 on chromosome 21.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about CSTB?
You and your healthcare professional may find the following resources about CSTB helpful.
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1142/)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for CSTB (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=1476%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((CSTB%5BTIAB%5D)%20OR%20(cystatin%20B%5BTIAB%5D))%20OR%20((EPM1%5BTIAB%5D)%20OR%20(STFB%5BTIAB%5D)%20OR%20(cystatin%20B%5BTIAB%5D)%20OR%20(CPI-B%5BTIAB%5D)%20OR%20(stefin%20B%5BTIAB%5D)%20OR%20(liver%20thiol%20proteinase%20inhibitor%5BTIAB%5D))%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201440%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/601145)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_CSTB.html)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=1476)
- HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=2482)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/1476)
What other names do people use for the CSTB gene or gene products?
- cystatin B
- liver thiol proteinase inhibitor
- stefin B
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding CSTB?
amino acid ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Alakurtti K, Virtaneva K, Joensuu T, Palvimo JJ, Lehesjoki AE. Characterization of the cystatin B gene promoter harboring the dodecamer repeat expanded in progressive myoclonus epilepsy, EPM1. Gene. 2000 Jan 25;242(1-2):65-73. (http://www.ncbi.nlm.nih.gov/pubmed/10721698?dopt=Abstract)
- Alakurtti K, Weber E, Rinne R, Theil G, de Haan GJ, Lindhout D, Salmikangas P, Saukko P, Lahtinen U, Lehesjoki AE. Loss of lysosomal association of cystatin B proteins representing progressive myoclonus epilepsy, EPM1, mutations. Eur J Hum Genet. 2005 Feb;13(2):208-15. Erratum in: Eur J Hum Genet. 2005 Feb;13(2):264. (http://www.ncbi.nlm.nih.gov/pubmed/15483648?dopt=Abstract)
- Ceru S, Rabzelj S, Kopitar-Jerala N, Turk V, Zerovnik E. Protein aggregation as a possible cause for pathology in a subset of familial Unverricht-Lundborg disease. Med Hypotheses. 2005;64(5):955-9. (http://www.ncbi.nlm.nih.gov/pubmed/15780491?dopt=Abstract)
- Houseweart MK, Pennacchio LA, Vilaythong A, Peters C, Noebels JL, Myers RM. Cathepsin B but not cathepsins L or S contributes to the pathogenesis of Unverricht-Lundborg progressive myoclonus epilepsy (EPM1). J Neurobiol. 2003 Sep 15;56(4):315-27. (http://www.ncbi.nlm.nih.gov/pubmed/12918016?dopt=Abstract)
- Joensuu T, Kuronen M, Alakurtti K, Tegelberg S, Hakala P, Aalto A, Huopaniemi L, Aula N, Michellucci R, Eriksson K, Lehesjoki AE. Cystatin B: mutation detection, alternative splicing and expression in progressive myclonus epilepsy of Unverricht-Lundborg type (EPM1) patients. Eur J Hum Genet. 2007 Feb;15(2):185-93. Epub 2006 Sep 27. (http://www.ncbi.nlm.nih.gov/pubmed/17003839?dopt=Abstract)
- Lalioti MD, Antonarakis SE, Scott HS. The epilepsy, the protease inhibitor and the dodecamer: progressive myoclonus epilepsy, cystatin b and a 12-mer repeat expansion. Cytogenet Genome Res. 2003;100(1-4):213-23. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14526183?dopt=Abstract)
- Lehesjoki AE. Molecular background of progressive myoclonus epilepsy. EMBO J. 2003 Jul 15;22(14):3473-8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12853462?dopt=Abstract)
- Moulard B, Darcel F, Mignard D, Jeanpierre M, Genton P, Cartault F, Yaouanq J, Roubertie A, Biraben A, Buresi C, Malafosse A. FOunder effect in patients with Unverricht-Lundborg disease on reunion island. Epilepsia. 2003 Oct;44(10):1357-60. (http://www.ncbi.nlm.nih.gov/pubmed/14510831?dopt=Abstract)
- Moulard B, Genton P, Grid D, Jeanpierre M, Ouazzani R, Mrabet A, Morris M, LeGuern E, Dravet C, Mauguière F, Utermann B, Baldy-Moulinier M, Belaidi H, Bertran F, Biraben A, Ali Chérif A, Chkili T, Crespel A, Darcel F, Dulac O, Geny C, Humbert-Claude V, Kassiotis P, Buresi C, Malafosse A. Haplotype study of West European and North African Unverricht-Lundborg chromosomes: evidence for a few founder mutations. Hum Genet. 2002 Sep;111(3):255-62. Epub 2002 Jul 23. (http://www.ncbi.nlm.nih.gov/pubmed/12215838?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/1476)
- OMIM: CYSTATIN B (http://omim.org/entry/601145)
- Shahwan A, Farrell M, Delanty N. Progressive myoclonic epilepsies: a review of genetic and therapeutic aspects. Lancet Neurol. 2005 Apr;4(4):239-48. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15778103?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.