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CSTB gene
URL of this page: https://medlineplus.gov/genetics/gene/cstb/

CSTB gene

cystatin B

Normal Function

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, which are compartments in the cell that digest and recycle different types of molecules. Cystatin B may help protect the cells' proteins from cathepsins that leak out of the lysosomes.

Cystatin B is also believed to play a role in the development, movement, and communication of nerve cells. In addition, cystatin B helps control the nervous system's immune response (inflammation) and protects cells from harm caused by unstable molecules in the body (oxidative stress). 


Health Conditions Related to Genetic Changes

Progressive myoclonic epilepsy type 1

Most variants (also called mutations) in the CSTB gene cause progressive myoclonic epilepsy type 1, a rare inherited form of epilepsy. One region of DNA that controls the activity of the CSTB gene has a particular repeating sequence of 12 DNA building blocks (nucleotides). This sequence is known as the dodecamer repeat. Normally, this sequence is repeated two or three times. However, in most people with progressive myoclonic epilepsy type 1, this sequence is repeated more than 30 times (called a repeat expansion). Most people with progressive myoclonic epilepsy type 1 have two copies of this variant.

A small number of people with progressive myoclonic epilepsy type 1 have one copy of the dodecamer repeat expansion and one copy of the CSTB gene with another type of variant. Some of these variants substitute one protein building block (amino acid) for another amino acid in the cystatin B protein. Other variants cause the protein to be pieced together incorrectly or lead to the production of a shortened protein that may not function properly. Researchers have suggested that people who carry one copy of the expanded repeat plus another type of variant may have more severe signs and symptoms than those with two copies of the expanded dodecamer repeat.

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. This change is believed to cause the signs and symptoms of progressive myoclonic epilepsy type 1, but the specific mechanism is unknown.


More About This Health Condition

Other Disorders

Rarely, some individuals have two variants in the CSTB gene that result in no cystatin B production. These individuals have more severe signs and symptoms, which may include a small head size (microcephaly), severe developmental delays, abnormal movements (dyskinesia), seizures, and encephalopathy (abnormal brain function). These symptoms resemble those seen in a group of severe epilepsies known as developmental and epileptic encephalopathies.


Other Names for This Gene

  • CPI-B
  • CST6
  • cystatin B (stefin B)
  • EPM1
  • EPM1A
  • PME
  • stefin B
  • STFB
  • ULD

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • 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. doi: 10.1016/s0378-1119(99)00550-8. Citation on PubMed
  • 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. doi: 10.1038/sj.ejhg.5201300. Citation on PubMed
  • 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. doi: 10.1016/j.mehy.2004.11.038. Citation on PubMed
  • Daura E, Tegelberg S, Yoshihara M, Jackson C, Simonetti F, Aksentjeff K, Ezer S, Hakala P, Katayama S, Kere J, Lehesjoki AE, Joensuu T. Cystatin B-deficiency triggers ectopic histone H3 tail cleavage during neurogenesis. Neurobiol Dis. 2021 Aug;156:105418. doi: 10.1016/j.nbd.2021.105418. Epub 2021 Jun 5. Citation on PubMed
  • 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. doi: 10.1002/neu.10253. Citation on PubMed
  • 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. doi: 10.1038/sj.ejhg.5201723. Epub 2006 Sep 27. Citation on PubMed
  • 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. doi: 10.1159/000072857. Citation on PubMed
  • Lehesjoki AE, Kalviainen R. Progressive Myoclonic Epilepsy Type 1. 2004 Jun 24 [updated 2020 Jul 2]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK1142/ Citation on PubMed
  • Lehesjoki AE. Molecular background of progressive myoclonus epilepsy. EMBO J. 2003 Jul 15;22(14):3473-8. doi: 10.1093/emboj/cdg338. Citation on PubMed or Free article on PubMed Central
  • Mancini GM, Schot R, de Wit MC, de Coo RF, Oostenbrink R, Bindels-de Heus K, Berger LP, Lequin MH, de Vries FA, Wilke M, van Slegtenhorst MA. CSTB null mutation associated with microcephaly, early developmental delay, and severe dyskinesia. Neurology. 2016 Mar 1;86(9):877-8. doi: 10.1212/WNL.0000000000002422. Epub 2016 Feb 3. No abstract available. Citation on PubMed
  • 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. doi: 10.1046/j.1528-1157.2003.03703.x. Citation on PubMed
  • Moulard B, Genton P, Grid D, Jeanpierre M, Ouazzani R, Mrabet A, Morris M, LeGuern E, Dravet C, Mauguiere F, Utermann B, Baldy-Moulinier M, Belaidi H, Bertran F, Biraben A, Ali Cherif 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. doi: 10.1007/s00439-002-0755-x. Epub 2002 Jul 23. Citation on PubMed
  • O'Brien A, Marshall CR, Blaser S, Ray PN, Yoon G. Severe neurodegeneration, progressive cerebral volume loss and diffuse hypomyelination associated with a homozygous frameshift mutation in CSTB. Eur J Hum Genet. 2017 Jun;25(6):775-778. doi: 10.1038/ejhg.2017.39. Epub 2017 Apr 5. Citation on PubMed
  • Okuneva O, Korber I, Li Z, Tian L, Joensuu T, Kopra O, Lehesjoki AE. Abnormal microglial activation in the Cstb(-/-) mouse, a model for progressive myoclonus epilepsy, EPM1. Glia. 2015 Mar;63(3):400-11. doi: 10.1002/glia.22760. Epub 2014 Oct 18. Citation on PubMed
  • Shahwan A, Farrell M, Delanty N. Progressive myoclonic epilepsies: a review of genetic and therapeutic aspects. Lancet Neurol. 2005 Apr;4(4):239-48. doi: 10.1016/S1474-4422(05)70043-0. Citation on PubMed
  • Susgun S, Yucesan E, Goncu B, Hasanoglu Sayin S, Kina UY, Ozgul C, Duzenli OF, Kocaturk O, Calik M, Ozbek U, Ugur Iseri SA. Two rare autosomal recessive neurological disorders identified by combined genetic approaches in a single consanguineous family with multiple offspring. Neurol Sci. 2024 May;45(5):2271-2277. doi: 10.1007/s10072-023-07211-y. Epub 2023 Nov 28. Citation on PubMed

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