CAMK2B

Chr 7AD

calcium/calmodulin dependent protein kinase II beta

Also known as: CAM2, CAMK2, CAMKB, CaMKIIbeta, MRD54

NCBI Gene: 816ENSG00000058404UniProt: Q13554

The product of this gene belongs to the serine/threonine protein kinase family and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. In mammalian cells, the enzyme is composed of four different chains: alpha, beta, gamma, and delta. The product of this gene is a beta chain. It is possible that distinct isoforms of this chain have different cellular localizations and interact differently with calmodulin. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal dominant 54MIM #617799
AD
588
ClinVar variants
6
Pathogenic / LP
0.74
pLI score
1
Active trials
Clinical Summary— CAMK2B
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.74) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 258 VUS of 588 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
Missense constrained — critical functional residues
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.
0.36LOEUF
pLI 0.739
Z-score 4.65
OE 0.20 (0.12–0.36)
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.
4.07Z-score
OE missense 0.42 (0.37–0.48)
166 obs / 393.1 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.0.20 (0.12–0.36)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.42 (0.37–0.48)
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.0.98
0≤1.21.6
LoF obs/exp: 8 / 39.6Missense obs/exp: 166 / 393.1Syn Z: 0.22

ClinVar Variant Classifications

588 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3
Likely Pathogenic3
VUS258
Likely Benign297
Benign10
Conflicting17
3
Pathogenic
3
Likely Pathogenic
258
VUS
297
Likely Benign
10
Benign
17
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
2
0
3
Likely Pathogenic
0
2
1
0
3
VUS
44
169
37
8
258
Likely Benign
1
38
146
112
297
Benign
0
6
3
1
10
Conflicting
—17
Total45216189121588

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

View in ClinVar →

Protein Context — Lollipop Plot

CAMK2B · protein map & ClinVar variants

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

Gene2Phenotype Curations

CAMK2B-related intellectual disability

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder, autosomal dominant 54

MIM #617799

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Role of CAMK2D in neurodevelopment and associated conditions.
Rigter PMF et al.·Am J Hum Genet
2024
FAM134B oligomerization drives endoplasmic reticulum membrane scission for ER-phagy.
Jiang X et al.·EMBO J
2020
Qi-Po-Sheng-Mai granule ameliorates Ach-CaCl(2) -induced atrial fibrillation by regulating calcium homeostasis in cardiomyocytes.
Shi S et al.·Phytomedicine
2023
Understanding the pathogenetic mechanisms underlying altered neuronal function associated with CAMK2B mutations.
Borghi R et al.·Neurosci Biobehav Rev
2023Review
Identification of new targets for glioblastoma therapy based on a DNA expression microarray.
Larriba E et al.·Comput Biol Med
2024
Downregulation of ARFGEF1 and CAMK2B by promoter hypermethylation in breast cancer cells.
Kim JH et al.·BMB Rep
2011
Severe intellectual disability, absence of language, epilepsy, microcephaly and progressive cerebellar atrophy related to the recurrent de novo variant p.(P139L) of the CAMK2B gene: A case report and brief review.
Rizzi S et al.·Am J Med Genet A
2020Case report
Insights Into the Antigenic Repertoire of Unclassified Synaptic Antibodies.
Gilligan M et al.·Ann Clin Transl Neurol
2026
Targeted ablation of p38α MAPK suppresses denervation-induced muscle atrophy.
Yuasa K et al.·Sci Rep
2018
Balanced chromosomal rearrangements implicate YIPF5 and SPATC1L in non-obstructive oligoasthenozoospermia and oligozoospermia and of a derivative chromosome 22 in recurrent miscarriage.
David D et al.·Gene
2023
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
CAMK2Calcium/Calmodulin-dependent Protein Kinase 2

CAMK2-related Synapthopathies Natural History Study

RECRUITING
NCT07372833Erasmus Medical CenterStarted 2021-02-09
No intervention

External Resources

Links to major genomics databases and tools