STXBP1

STXBP1-related disorders are rare neurodevelopmental conditions caused by mutations in the STXBP1 gene, a key regulator of brain signaling. They are a leading cause of early-onset epilepsy and often involve developmental delay, movement disorders, and behavioral challenges. Symptoms and severity vary widely across individuals.

Biological Function

The STXBP1 gene encodes a protein which is critical for communication by neurons in the brain.

STXBP1 haploinsufficiency leads to epileptic encephalopathy. Seizures are very common and additional potential symptoms include, but are not limited to: delays, movement disorders, hypotonia, and behavioral issues.

Incidence

The estimated incidence of STXBP1-related disorders is approximately 1 in 30,000 births, based on updated analysis of clinical and genetic data.

Research at Northwestern

Research at Northwestern is primarily aimed at resolving variants of uncertain significance (VUS) which confound achieving a precise genetic diagnosis of STXBP1-related DEE. We developed EpiPred, a gene-specific machine learning classifier that predicts the pathogenicity of STXBP1 missense variants.

Key publications include:

A gene-specific machine learning approach for STXBP1 variant pathogenicity prediction.
Jeffrey D Calhoun, Chengbing Wang, Carina Biar, Jonathan R Gunti, John Lee, Aaron M Geller, Jung H Hong, Santiago Schnell, Louis T Dang, Yu Wang, Jack Parent, Lori L. Isom, Michael D Uhler, Heather C. Mefford, M. Elizabeth Ross, Vanessa Aguiar-Pulido, Gemma L Carvill.
bioRxiv. 2025 Aug 9. doi: 10.1101/2025.08.09.669488
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Patient advocacy organizations

The STXBP1 Disorders Foundation is a nonprofit organization that supports individuals and families affected by STXBP1-related disorders. It provides community support, educational resources, and advocates for research and awareness globally.