CAMK4

Chr 5

calcium/calmodulin dependent protein kinase IV

Also known as: CaMK IV, CaMK-GR, CaMKIV, caMK

NCBI Gene: 814ENSG00000152495UniProt: Q16566

The product of this gene belongs to the serine/threonine protein kinase family, and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. This enzyme is a multifunctional serine/threonine protein kinase with limited tissue distribution, that has been implicated in transcriptional regulation in lymphocytes, neurons and male germ cells. [provided by RefSeq, Jul 2008]

137
ClinVar variants
27
Pathogenic / LP
0.51
pLI score
0
Active trials
Clinical Summary— CAMK4
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.51) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 94 VUS of 137 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.47LOEUF
pLI 0.510
Z-score 3.23
OE 0.21 (0.10–0.47)
Moderately 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.
1.81Z-score
OE missense 0.68 (0.60–0.77)
177 obs / 259.0 exp
Tolerant

Mild missense constraint

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.0.21 (0.10–0.47)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.68 (0.60–0.77)
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 / 19.3Missense obs/exp: 177 / 259.0Syn Z: 0.39

ClinVar Variant Classifications

137 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
VUS94
Likely Benign5
Benign5
27
Pathogenic
94
VUS
5
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
25
0
27
Likely Pathogenic
0
0
0
0
0
VUS
5
68
21
0
94
Likely Benign
0
3
1
1
5
Benign
0
2
2
1
5
Total674492131

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

View in ClinVar →

Protein Context — Lollipop Plot

CAMK4 · 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
SPP1(high) macrophage-induced T-cell stress promotes colon cancer liver metastasis through SPP1/CD44/PI3K/AKT signaling.
Ding D et al.·J Immunother Cancer
2025
Impaired CAMK4 Activity Limits Atherosclerosis and Reprograms Myelopoiesis.
Gonzalez AL et al.·Arterioscler Thromb Vasc Biol
2025
Convergence on CaMK4: A Key Modulator of Autism-Associated Signaling Pathways in Neurons.
Kaiser J et al.·Biol Psychiatry
2025Review
Recent genetic advances in early-onset dystonia.
Steel D et al.·Curr Opin Neurol
2020Review
CaMK4, a key target for treating pathogenesis of depression?
Yang Y et al.·Biochem Pharmacol
2025Review
New therapeutics in systemic lupus erythematosus.
Paz Z et al.·Curr Opin Rheumatol
2013Review
Understanding the pathogenic significance of altered calcium-calmodulin signaling in T cells in autoimmune diseases.
Koga T·Clin Immunol
2024Review
A unique de novo gain-of-function variant in CAMK4 associated with intellectual disability and hyperkinetic movement disorder.
Zech M et al.·Cold Spring Harb Mol Case Stud
2018Case report
Identifying changes in immune cells and constructing prognostic models using immune-related genes in post-burn immunosuppression.
Wang P et al.·PeerJ
2022Functional
Integrated Transcriptome Analyses Revealed Key Target Genes in Mouse Models of Autism.
Duan W et al.·Autism Res
2020Functional
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