CAMK1

Chr 3

calcium/calmodulin dependent protein kinase I

Also known as: CAMKI

Calcium/calmodulin-dependent protein kinase I phosphorylates multiple substrates to regulate neuronal differentiation, neurite outgrowth, synaptic formation, and long-term potentiation in response to calcium influx. This gene is extremely intolerant to loss-of-function variants (pLI near 1.0), suggesting that mutations would likely cause severe developmental disorders, though specific associated diseases have not yet been established. Given the critical role in early neuronal development and synaptic function, pathogenic variants would be expected to follow an autosomal dominant inheritance pattern.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.82
Clinical SummaryCAMK1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.82LOEUF
pLI 0.000
Z-score 2.21
OE 0.49 (0.310.82)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.52Z-score
OE missense 0.90 (0.801.01)
201 obs / 223.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.49 (0.310.82)
00.351.4
Missense OE0.90 (0.801.01)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 11 / 22.3Missense obs/exp: 201 / 223.0Syn Z: -0.08
DN
0.77top 25%
GOF
0.80top 10%
LOF
0.2484th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CAMK1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗