KCNB1
Pathogenic variants in KCNB1 have been associated with developmental encephalopathy. Individuals with KCNB1 encephalopathy have global developmental delay beginning in infancy or early childhood. Most patients develop seizures that can be challenging to treat with available medications. However, some patients have infrequent or no seizures but still have abnormal patterns on EEG. While mutations in KCNB1 are rare, the Center for Autism and Neurodevelopment is actively recruiting individuals with KCNB1 variants and determining how those variants affect Kv2.1 channel function.
Biological Function
KCNB1 encodes the Kv2.1 voltage-gated potassium channel that is widely expressed in neurons. Kv2.1 channels transport potassium ions out of neurons during periods of neuronal excitation. Proper Kv2.1 function is critical for regulating neuronal activity and supporting communication between cells.
Mutations
The Kearney lab has identified numerous variants in KCNB1 that reduce its activity in neurons and are linked to developmental encephalopathy.
Learn more in published research by Torkamani (2014), Calhoun (2017), and Kang (2019).
Incidence
Over 50 pathogenic and 55 likely pathogenic variants in the KCNB1 gene have been identified and annotated in ClinVar, a public database of genetic variants.
Additionally, 15 variants are currently listed in the DECIPHER database, which connects clinical data to genetic information to support diagnosis and research.
As access to genetic testing expands, the number of identified KCNB1 variants is expected to grow, helping researchers and clinicians better understand this condition.
Associated Conditions
Variants in KCNB1 have also been associated with later-onset neuropsychiatric disorders, including bipolar disorder and schizophrenia. Outside of the nervous system, KCNB1 has been implicated in risk for type 2 diabetes and is a prognostic biomarker for various cancers.
Research at Northwestern
Ongoing research projects at the Center for Autism and Neurodevelopment (CAN) — particularly in the Kearney Lab — are investigating how pathogenic variants in the KCNB1 gene contribute to neurodevelopmental disorders. These efforts include the development of mouse models of KCNB1-related encephalopathy, which are critical for testing and advancing potential new therapies.
Featured Publications from the CAN Network
Explore key findings from recent KCNB1 studies published by researchers in the CAN network:Kang SK, Vanoye CG, Misra SN, Echevarria DM, Calhoun JD, O’Connor JB, et al.
Spectrum of KV2.1 Dysfunction in KCNB1-Associated Neurodevelopmental Disorders.
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Torkamani A, Bersell K, Jorge BS, Bjork RL Jr, Friedman JR, Bloss CS, et al.
De novo KCNB1 mutations in epileptic encephalopathy.
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Calhoun JD, Vanoye CG, Kok F, George AL Jr, Kearney JA.
Characterization of a KCNB1 variant associated with autism, intellectual disability, and epilepsy.
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Hawkins NA, Misra SN, Jurado M, Kang SK, Vierra NC, Nguyen K, et al.
Epilepsy and neurobehavioral abnormalities in mice with a dominant-negative KCNB1 pathogenic variant.
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Kang SK, Hawkins NA, Echevarria-Cooper DM, Baker EM, Dixon CJ, Speakes N, et al.
Altered neurological and neurobehavioral phenotypes in a mouse model of the recurrent KCNB1-p.R306C voltage-sensor variant.
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Important publications form other laboratories
Bar C, Kuchenbuch M, Barcia G, Schneider A, Jennesson M, Le Guyader G, et al.
Developmental and epilepsy spectrum of KCNB1 encephalopathy with long-term outcome.
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Bar C, Barcia G, Jennesson M, Le Guyader G, Schneider A, Mignot C, et al.
Expanding the genetic and phenotypic relevance of KCNB1 variants in developmental and epileptic encephalopathies: 27 new patients and overview of the literature.
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Saitsu H, Akita T, Tohyama J, Goldberg-Stern H, Kobayashi Y, Cohen R, et al.
De novo KCNB1 mutations in infantile epilepsy inhibit repetitive neuronal firing.
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Thiffault I, Speca DJ, Austin DC, Cobb MM, Eum KS, Safina NP, et al.
A novel epileptic encephalopathy mutation in KCNB1 disrupts Kv2.1 ion selectivity, expression, and localization.
Read more
Genetic Testing
Currently KCNB1 variants are detected by whole genome/exome sequencing. KCNB1 is included on genetic testing panels for epilepsy and developmental delay/disorder.
Clinical Trials
While there are currently no clinical trials specifically for KCNB1-associated mutations, there are clinical trials for Developmental and Epileptic Encephalopathies.
Patient advocacy organizations
Several organizations offer support, advocacy, and information for families and individuals affected by KCNB1-related conditions:
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KCNB1.org
A global community providing resources, patient stories, research updates, and connections for families navigating KCNB1-related diagnoses.
Visit kcnb1.org -
KCNB1 France Association
A French-based nonprofit supporting families, raising awareness, and promoting collaboration with clinicians and researchers.
Visit kcnb1-france.org