CAMK1D

Chr 10

calcium/calmodulin dependent protein kinase ID

Also known as: CKLiK, CaM-K1, CaMKID

The protein is a calcium/calmodulin-dependent serine/threonine kinase that activates CREB-dependent gene transcription and regulates granulocyte function and dendritic growth in hippocampal neurons. Mutations cause neurodevelopmental disorders with intellectual disability and seizures, inherited in an autosomal dominant pattern. This gene is highly constrained against loss-of-function mutations, indicating it is essential for normal cellular function.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
14
Pubs (1 yr)
24
P/LP submissions
0%
P/LP missense
0.23
LOEUF· LoF intol.
Multiple*
Mechanism· predicted
Clinical SummaryCAMK1D
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.
📋
ClinVar Variants
24 unique Pathogenic / Likely Pathogenic· 39 VUS of 91 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.23LOEUF
pLI 0.996
Z-score 4.03
OE 0.05 (0.020.23)
Highly constrained

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

Missense Constraint
2.49Z-score
OE missense 0.54 (0.470.63)
124 obs / 230.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.05 (0.020.23)
00.351.4
Missense OE0.54 (0.470.63)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 1 / 20.9Missense obs/exp: 124 / 230.1Syn Z: -0.26
DN
0.5180th %ile
GOF
0.6345th %ile
LOF
0.61top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFLOEUF 0.23
GOFprediction 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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

91 submitted variants in ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic2
VUS39
Likely Benign3
Benign3
22
Pathogenic
2
Likely Pathogenic
39
VUS
3
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
1
0
1
0
2
VUS
0
29
10
0
39
Likely Benign
0
0
1
2
3
Benign
0
1
1
1
3
Total13035369

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

View in ClinVar →

Protein Context — Lollipop Plot

CAMK1D · 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
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗