CSNK2B

Chr 6AD

casein kinase 2 beta

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

NCBI Gene: 1460 ENSG00000204435 UniProt: P67870 OMIM: 115441

The beta subunit of casein kinase II serves regulatory functions within this tetrameric protein kinase that controls metabolic pathways, signal transduction, transcription, translation, and replication. Mutations cause Poirier-Bienvenu neurodevelopmental syndrome through an autosomal dominant inheritance pattern. The pathogenic mechanism involves loss of function, consistent with the protein's essential regulatory role in multiple cellular processes.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.381 OMIM phenotype

Clinical Summary— CSNK2B

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Gene-Disease Validity (ClinGen)

Poirier-Bienvenu neurodevelopmental syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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.

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ClinVar Variants

104 unique Pathogenic / Likely Pathogenic· 56 VUS of 198 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — CSNK2B

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

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?

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?

LoF OE?0.08 (0.03–0.38)

0≤0.351.4

Missense OE?0.21 (0.16–0.30)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 1 / 12.4Missense obs/exp: 27 / 125.8Syn Z: 0.91

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveCSNK2B-related Poirier-Bienvenu neurodevelopmental syndromeLOFAD

This gene — mechanism propensity

0.3594th %ile

GOF

0.3986th %ile

LOF

0.66top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 69% of P/LP variants are LoF · LOEUF 0.38

Literature Evidence

LOFOur results indicate that CSNK2B haploinsufficiency plays a crucial role in the development of the CSNK2B deficiency phenotype.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

1.PMID 33758130 ↗

ClinVar Variant Classifications

198 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic54

Likely Pathogenic50

VUS56

Likely Benign11

Benign8

Conflicting7

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	44	10	0	0	54
Likely Pathogenic	28	17	5	0	50
VUS	4	42	9	1	56
Likely Benign	0	0	2	9	11
Benign	0	0	7	1	8
Conflicting	—				7
Total	76	69	23	11	186

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap CSNK2B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →