CSNK2A1

Chr 20AD

casein kinase 2 alpha 1

Also known as: CK2A1, CKII, Cka1, Cka2, OCNDS

NCBI Gene: 1457ENSG00000101266UniProt: P68400

Casein kinase II is a serine/threonine protein kinase that phosphorylates acidic proteins such as casein. It is involved in various cellular processes, including cell cycle control, apoptosis, and circadian rhythm. The kinase exists as a tetramer and is composed of an alpha, an alpha-prime, and two beta subunits. The alpha subunits contain the catalytic activity while the beta subunits undergo autophosphorylation. The protein encoded by this gene represents the alpha subunit. Multiple transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Apr 2018]

Primary Disease Associations & Inheritance

Okur-Chung neurodevelopmental syndromeMIM #617062
AD
323
ClinVar variants
128
Pathogenic / LP
0.99
pLI score· haploinsufficient
1
Active trials
Clinical Summary— CSNK2A1
🧬
Gene-Disease Validity (ClinGen)
syndromic intellectual disability · 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 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
128 Pathogenic / Likely Pathogenic· 111 VUS of 323 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.
0.30LOEUF
pLI 0.987
Z-score 4.47
OE 0.13 (0.06–0.30)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
3.71Z-score
OE missense 0.30 (0.24–0.37)
66 obs / 221.5 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.0.13 (0.06–0.30)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.30 (0.24–0.37)
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.0.95
0≤1.21.6
LoF obs/exp: 4 / 30.8Missense obs/exp: 66 / 221.5Syn Z: 0.34

ClinVar Variant Classifications

323 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic73
Likely Pathogenic55
VUS111
Likely Benign56
Benign24
Conflicting4
73
Pathogenic
55
Likely Pathogenic
111
VUS
56
Likely Benign
24
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
17
47
0
73
Likely Pathogenic
7
27
21
0
55
VUS
2
63
46
0
111
Likely Benign
0
11
35
10
56
Benign
0
0
23
1
24
Conflicting
—4
Total1811817211323

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

View in ClinVar →

Protein Context — Lollipop Plot

CSNK2A1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CSNK2A1-related neurodevelopmental disorder (Okur-Chung syndrome)

definitive
ADGain Of FunctionAltered Gene Product Structure
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Okur-Chung neurodevelopmental syndrome

MIM #617062

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — CSNK2A1
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
Proteogenomic network analysis reveals dysregulated mechanisms and potential mediators in Parkinson's disease.
Doostparast Torshizi A et al.·Nat Commun
2024Functional
Multi-omics characterization of esophageal squamous cell carcinoma identifies molecular subtypes and therapeutic targets.
Zhao D et al.·JCI Insight
2024
CSNK2A1 confers gemcitabine resistance to pancreatic ductal adenocarcinoma via inducing autophagy.
Liu ZD et al.·Cancer Lett
2024
A Case of CSNK2A1 Gene Variant Causing Okur-Chung Syndrome and Analysis of the Clinical Phenotypic Spectrum.
Li X et al.·Mol Genet Genomic Med
2025Case report
Identification of novel CSNK2A1 variants and the genotype-phenotype relationship in patients with Okur-Chung neurodevelopmental syndrome: a case report and systematic literature review.
Wu RH et al.·J Int Med Res
2021Case report
Oncogenic cholesterol rewires lipid metabolism in hepatocellular carcinoma via the CSNK2A1-IGF2R Ser2484 axis.
Su RY et al.·J Adv Res
2025
Clinical and molecular results in 15 Turkish patients with Wiedemann-Steiner syndrome: identification of eight novel KMT2A variants and a case of dual molecular diagnosis in the CSNK2A1.
Yeter B et al.·Eur J Pediatr
2025Cohort
Extending the phenotype associated with the CSNK2A1-related Okur-Chung syndrome-A clinical study of 11 individuals.
Owen CI et al.·Am J Med Genet A
2018
[A case of Okur-Chung syndrome caused by CSNK2A1 gene variation and review of literature].
Duan HL et al.·Zhonghua Er Ke Za Zhi
2019Review
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