DAPK1

Chr 9

death associated protein kinase 1

Also known as: DAPK, ROCO3

NCBI Gene: 1612ENSG00000196730UniProt: P53355

DAPK1 encodes a calcium/calmodulin-dependent serine/threonine kinase that regulates apoptosis, autophagy, and cell survival pathways, and phosphorylates multiple targets including NMDA receptor subunits to mediate neuronal death during cerebral ischemia. The gene is highly intolerant to loss-of-function variants (pLI 0.998, LOEUF 0.275), but specific Mendelian disorders caused by DAPK1 mutations have not been established in the provided data. The inheritance pattern and clinical phenotypes associated with pathogenic variants remain to be defined.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
55
Pubs (1 yr)
0
P/LP submissions
—
P/LP missense
0.28
LOEUF· LoF intol.
—
Mechanism
Clinical Summary— DAPK1
⚡
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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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.28LOEUF
pLI 0.998
Z-score 6.29
OE 0.17 (0.10–0.28)
Highly constrained

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

Missense Constraint
2.57Z-score
OE missense 0.76 (0.71–0.81)
664 obs / 878.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.17 (0.10–0.28)
0≤0.351.4
Missense OE0.76 (0.71–0.81)
0≤0.61.4
Synonymous OE1.04
0≤1.21.6
LoF obs/exp: 11 / 66.3Missense obs/exp: 664 / 878.1Syn Z: -0.60

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

DAPK1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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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 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
H3K27ac-Activated lncRNA-DAPK1-IT1 Aggravated Oxidative Stress Damage Induced by Focal Cerebral Ischemia/Reperfusion via the miR-25-3p/HMGB1 Molecular Axis.
Zhang H et al.·Mol Neurobiol
2026
DAPK1 orchestrates cell division and junction to control corneal epithelial development.
Yang M et al.·Eur J Cell Biol
2026
KLHL20 alleviates high glucose-induced mitochondrial apoptosis in renal tubular cells by targeting DAPK1 for ubiquitination and degradation.
Lei Y et al.·Biochem Biophys Res Commun
2026
Selective degradation of DAPK1 via a novel hydrophobic tagging attenuates tau pathology in Alzheimer's disease.
Li R et al.·J Adv Res
2025
The LRRK2 P1446L mutation triggers dopaminergic neurodegeneration via DAPK1-mediated microglial neuroinflammation and neuronal apoptosis.
Ding L et al.·NPJ Parkinsons Dis
2025Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients