DAPK1

Chr 9

death associated protein kinase 1

Also known as: DAPK, ROCO3

NCBI Gene: 1612ENSG00000196730UniProt: P53355OMIM: 600831

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.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.28
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.
📋
ClinVar Variants
27 unique Pathogenic / Likely Pathogenic· 101 VUS of 202 total submissions
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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

202 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic4
VUS101
Likely Benign14
Benign16
23
Pathogenic
4
Likely Pathogenic
101
VUS
14
Likely Benign
16
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
23
0
23
Likely Pathogenic
0
0
4
0
4
VUS
0
96
5
0
101
Likely Benign
0
6
1
7
14
Benign
0
1
8
7
16
Total01034114158

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

View in 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
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
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