CSNK2B

Inheritance Pattern: AD

Disease ID:MONDO:0032889

Submitter: ClinGen

The CSNK2B gene is located on chromosome 6 at 6p21.33 and encodes the casein kinase 2 beta protein, the regulatory subunit of casein kinase 2 (CK2). The CK-beta subunits form homodimers at the core of the CK2 enzyme and are thought to contribute to the stability of the holoenzyme complex, regulating the catalytic activity and substrate recognition. CK2 is a ubiquitously expressed serine threonine kinase and plays a role in many cellular processes. CSNK2B was first reported in relation to autosomal dominant Poirier-Bienvenu neurodevelopmental syndrome in 2017 (Poirier et al., PMID: 28585349). This disorder is characterized by mild to profound intellectual disability, with or without epilepsy. The epilepsy is often early-onset occurring before three years of age, often intractable with the most common seizure type being generalized tonic-clonic seizures (Nakashima et al., 2019, PMID: 30655572; Li et al., 2019, PMID: 31784560; Ernst et al., 2021, PMID: 34041744). The presentation is variable. Other phenotypes commonly seen in patients include global developmental delays with mild to severe delayed psychomotor development, speech and language delay, facial dysmorphic features and growth abnormalities (PMID: 28585349; Sakaguchi et al., 2017, PMID: 28762608; PMIDs: 30655572, 31784560; Selvam et al., 2021, PMID: 33166063). Some affected individuals also exhibit autistic features, hypotonia, dystonia, and cerebral atrophy (PMID: 34041744). Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least ten unrelated individuals in five publications. At least ten unique variants have been reported and include a spectrum of missense, splice site, frameshift, and nonsense variants. Variants typically occur de novo. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. This gene-disease relationship is also supported by a temporal and spatial expression pattern of CK2 which is consistent with disease and studies reducing expression levels of Csnk2b mouse in neural stem cells and primary hippocampal neurons support a role for CSNK2B in the regulation of neuronal proliferation and differentiation as well as the modulation of synaptic transmission (Blanquet 2000, PMID: 10658642; Yang et al., 2018, PMID: 29483533). Furthermore, the CSNK2A gene which also encodes a subunit of CK2 holoenzyme, is associated with Okur-Chung neurodevelopmental syndrome and a similar phenotypic spectrum of disease (Okur et al., 2016; PMID: 27048600). In summary, CSNK2B is definitively associated with autosomal dominant Poirier-Bienvenu neurodevelopmental syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This classification was approved by the ClinGen Syndromic Disorders Gene Curation Expert Panel on the meeting date 01.21.2022 (SOP Version 8).

Inheritance Pattern: AD

Disease ID:MONDO:0032889

Submitter: Labcorp Genetics (formerly Invitae)

Inheritance Pattern: AD

Disease ID:MONDO:0032889

Submitter: Illumina

Inheritance Pattern: AD

Disease ID:MONDO:0032889

Submitter: G2P

Inheritance Pattern: AD

Disease ID:MONDO:0032889

Submitter: Ambry Genetics

Inheritance Pattern: AD

Disease ID:MONDO:0015802

Submitter: Orphanet