CSNK1A1

Chr 5

casein kinase 1 alpha 1

Also known as: CK1, CK1a, CKIa, HEL-S-77p, HLCDGP1, PRO2975

NCBI Gene: 1452ENSG00000113712UniProt: P48729

Enables protein serine/threonine kinase activity. Involved in several processes, including intermediate filament cytoskeleton organization; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; and regulation of signal transduction. Located in cytoskeleton and nucleus. Part of beta-catenin destruction complex. Biomarker of Alzheimer's disease and inclusion body myositis. [provided by Alliance of Genome Resources, Jul 2025]

19
ClinVar variants
11
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— CSNK1A1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 7 VUS of 19 total submissions

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.
0.21LOEUF
pLI 0.998
Z-score 4.15
OE 0.05 (0.01–0.21)
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.
4.30Z-score
OE missense 0.14 (0.10–0.19)
28 obs / 198.6 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.0.05 (0.01–0.21)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.14 (0.10–0.19)
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: 1 / 22.1Missense obs/exp: 28 / 198.6Syn Z: 0.30

ClinVar Variant Classifications

19 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
VUS7
Likely Benign1
11
Pathogenic
7
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
0
0
0
0
0
VUS
0
4
3
0
7
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total0415019

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

View in ClinVar →

Protein Context — Lollipop Plot

CSNK1A1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The gut microbiome switches mutant p53 from tumour-suppressive to oncogenic.
Kadosh E et al.·Nature
2020
TSPAN1 promotes autophagy flux and mediates cooperation between WNT-CTNNB1 signaling and autophagy via the MIR454-FAM83A-TSPAN1 axis in pancreatic cancer.
Zhou C et al.·Autophagy
2021
Rps14, Csnk1a1 and miRNA145/miRNA146a deficiency cooperate in the clinical phenotype and activation of the innate immune system in the 5q- syndrome.
Ribezzo F et al.·Leukemia
2019
The role of CSNK1A1 and its de novo mutations in infantile spasms syndrome.
Ren D et al.·Hum Mol Genet
2025Case report
CSNK1A1 mutations and isolated del(5q) abnormality in myelodysplastic syndrome: a retrospective mutational analysis.
Smith AE et al.·Lancet Haematol
2015
Treatment of Lymphoid and Myeloid Malignancies by Immunomodulatory Drugs.
Fuchs O·Cardiovasc Hematol Disord Drug Targets
2019Review
A precision medicine approach to the myelodysplastic syndrome with isolated deletion 5q, 50 years after its discovery.
Roncador M et al.·Blood
2025Review
Molecular pathogenesis of myelodysplastic syndromes with deletion 5q.
Lee JH et al.·Eur J Haematol
2019Review
The ubiquitin ligase HUWE1 enhances WNT signaling by antagonizing destruction complex-mediated β-catenin degradation and through a mechanism independent of changes in β-catenin abundance.
McKenna JK et al.·PLoS Genet
2025Functional
Pathophysiologic and clinical implications of molecular profiles resultant from deletion 5q.
Adema V et al.·EBioMedicine
2022
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools