CAMK2G

Chr 10AD

calcium/calmodulin dependent protein kinase II gamma

Also known as: CAMK, CAMK-II, CAMKG, MRD59

NCBI Gene: 818 ENSG00000148660 UniProt: Q13555 OMIM: 602123

CAMK2G encodes the gamma subunit of calcium/calmodulin-dependent protein kinase II, which regulates calcium signaling, synaptic plasticity, and neurite formation in the central nervous system. Mutations cause autosomal dominant intellectual developmental disorder. This gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.24), indicating that even heterozygous disruption can cause disease.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

MultiplemechanismADLOEUF 0.241 OMIM phenotype

Clinical Summary— CAMK2G

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Gene-Disease Validity (ClinGen)

intellectual developmental disorder 59 · ADLimited

Limited evidence — not for standalone diagnostic reporting

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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.

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Clinical Trials

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

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint

0.24LOEUF

pLI 0.999

Z-score 5.11

OE 0.11 (0.05–0.24)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint

3.80Z-score

OE missense 0.42 (0.37–0.48)

145 obs / 343.3 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios

LoF OE0.11 (0.05–0.24)

0≤0.351.4

Missense OE0.42 (0.37–0.48)

0≤0.61.4

Synonymous OE0.90

0≤1.21.6

LoF obs/exp: 4 / 37.9Missense obs/exp: 145 / 343.3Syn Z: 0.92

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongCAMK2G-related intellectual developmental disorderOTHERAD

0.5279th %ile

GOF

0.6247th %ile

LOF

0.64top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · LOEUF 0.24

GOF1 literature citation

Literature Evidence

GOFThe intellectual disability-associated CAMK2G p.Arg292Pro mutation acts as a pathogenic gain-of-function.PMID:30184290

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