CAMK2N2

Chr 3

calcium/calmodulin dependent protein kinase II inhibitor 2

Also known as: CAM-KIIN, CAMKIIN

NCBI Gene: 94032 ENSG00000163888 UniProt: Q96S95 OMIM: 608721

This gene encodes a protein that is highly similar to the rat CaM-KII inhibitory protein, an inhibitor of calcium/calmodulin-dependent protein kinase II (CAMKII). CAMKII regulates numerous physiological functions, including neuronal synaptic plasticity through the phosphorylation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate (AMPA) receptors. Studies of the similar protein in rat suggest that this protein may function as a negative regulator of CaM-KII and may act to inhibit the phosphorylation of AMPA receptors. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.45

Clinical Summary— CAMK2N2

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.

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ClinVar Variants

5 VUS of 5 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.45LOEUF

pLI 0.220

Z-score 1.08

OE 0.33 (0.12–1.45)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.57Z-score

OE missense 0.76 (0.58–1.01)

34 obs / 44.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.33 (0.12–1.45)

0≤0.351.4

Missense OE?0.76 (0.58–1.01)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 1 / 3.0Missense obs/exp: 34 / 44.7Syn Z: 0.59

This gene — mechanism propensity

0.6743th %ile

GOF

0.75top 25%

LOF

0.3647th %ile

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

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

5 submitted variants in ClinVar

ClinVar

Classification Summary

VUS5

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	5	5
Likely Benign	0	0
Benign	0	0
Total	5	5

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

View in ClinVar →

41 pathogenic / likely-pathogenic (of 48) ClinVar copy-number / structural variants overlap CAMK2N2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →