CSTB

Chr 21AR

cystatin B

Also known as: CPI-B, CST6, EPM1, EPM1A, PME, STFB, ULD

NCBI Gene: 1476 ENSG00000160213 UniProt: P04080 OMIM: 601145

CSTB encodes cystatin B, an intracellular thiol protease inhibitor that reversibly inhibits cathepsins L, H, and B, protecting cells against proteases that leak from lysosomes. Mutations cause Unverricht-Lundborg disease (progressive myoclonic epilepsy type 1A), a childhood-onset progressive myoclonic epilepsy inherited in an autosomal recessive pattern. The gene shows low constraint against loss-of-function variants (pLI 0.007, LOEUF 1.85), consistent with its recessive inheritance pattern.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and kininogens. This gene encodes a stefin that functions as an intracellular thiol protease inhibitor. The protein is able to form a dimer stabilized by noncovalent forces, inhibiting papain and cathepsins l, h and b. The protein is thought to play a role in protecting against the proteases leaking from lysosomes. Evidence indicates that mutations in this gene are responsible for the primary defects in patients with progressive myoclonic epilepsy (EPM1). One type of mutation responsible for EPM1 is the expansion in the promoter region of this gene of a CCCCGCCCCGCG repeat from 2-3 copies to 30-78 copies. [provided by RefSeq, Jul 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg)MIM #254800

Clinical highlights

Gene-disease validity (ClinGen)

Unverricht-Lundborg syndrome · ARDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.85

LOEUF

LOF

Mechanism· G2P

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GeneReview available — CSTB