CSNK2B

Chr 6AD

casein kinase 2 beta

Also known as: CK II beta, CK2B, CK2N, CSK2B, Ckb1, Ckb2, G5A, POBINDS

NCBI Gene: 1460ENSG00000204435UniProt: P67870

This gene encodes the beta subunit of casein kinase II, a ubiquitous protein kinase which regulates metabolic pathways, signal transduction, transcription, translation, and replication. The enzyme is composed of three subunits, alpha, alpha prime and beta, which form a tetrameric holoenzyme. The alpha and alpha prime subunits are catalytic, while the beta subunit serves regulatory functions. The enzyme localizes to the endoplasmic reticulum and the Golgi apparatus. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

Primary Disease Associations & Inheritance

Poirier-Bienvenu neurodevelopmental syndromeMIM #618732
AD
190
ClinVar variants
108
Pathogenic / LP
0.92
pLI score· haploinsufficient
1
Active trials
Clinical Summary— CSNK2B
🧬
Gene-Disease Validity (ClinGen)
Poirier-Bienvenu neurodevelopmental syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.92). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
108 Pathogenic / Likely Pathogenic· 57 VUS of 190 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.38LOEUF
pLI 0.917
Z-score 3.00
OE 0.08 (0.03–0.38)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.13Z-score
OE missense 0.21 (0.16–0.30)
27 obs / 125.8 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.08 (0.03–0.38)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.21 (0.16–0.30)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.83
0≤1.21.6
LoF obs/exp: 1 / 12.4Missense obs/exp: 27 / 125.8Syn Z: 0.91

ClinVar Variant Classifications

190 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic56
Likely Pathogenic52
VUS57
Likely Benign11
Benign8
Conflicting6
56
Pathogenic
52
Likely Pathogenic
57
VUS
11
Likely Benign
8
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
25
9
22
0
56
Likely Pathogenic
19
18
15
0
52
VUS
4
40
12
1
57
Likely Benign
0
0
2
9
11
Benign
0
0
7
1
8
Conflicting
—6
Total48675811190

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CSNK2B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

CSNK2B-related Poirier-Bienvenu neurodevelopmental syndrome

definitive
ADLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. Disorders
G2P ↗
splice region variantframeshift variantstop gainedmissense variant

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Poirier-Bienvenu neurodevelopmental syndrome

MIM #618732

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — CSNK2B
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
CSNK2B: A broad spectrum of neurodevelopmental disability and epilepsy severity.
Ernst ME et al.·Epilepsia
2021
Refining of the electroclinical phenotype in familial and sporadic cases of CSNK2B-related Neurodevelopmental Syndrome.
Trivisano M et al.·Epilepsy Behav
2023Cohort
Genetic analysis and literature review of a Poirier-Bienvenu neurodevelopmental syndrome family line caused by a de novo frameshift variant in CSNK2B.
Li D et al.·Mol Genet Genomic Med
2024Review
Clinical and genetic analysis of six Chinese children with Poirier-Bienvenu neurodevelopmental syndrome caused by CSNK2B mutation.
Yang S et al.·Neurogenetics
2021
Characterization of 13 Novel Genetic Variants in Genes Associated with Epilepsy: Implications for Targeted Therapeutic Strategies.
Andjelkovic M et al.·Mol Diagn Ther
2024
Pathogenic missense variants of CSNK2B associated with Poirier-Bienvenu neurodevelopmental disorder impact differently on CK2 holoenzyme formation.
Kavaliova H et al.·Biol Chem
2025
Genetic analysis of four cases of Poirier Bienvenu neurodevelopmental syndrome associated with CSNK2B variant.
Yang L et al.·BMC Med Genomics
2025Cohort
CSNK2B Mutation: A Rare Cause of IGHD.
Aouchiche K et al.·Clin Endocrinol (Oxf)
2025Case report
Germline de novo variants in CSNK2B in Chinese patients with epilepsy.
Li J et al.·Sci Rep
2019Cohort
Expanding Phenotype of Poirier-Bienvenu Syndrome: New Evidence from an Italian Multicentrical Cohort of Patients.
Orsini A et al.·Genes (Basel)
2022Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10

External Resources

Links to major genomics databases and tools