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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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DIPK2A
divergent protein kinase domain 2A
Chromosome 3 · 3q24
NCBI Gene: 205428Ensembl: ENSG00000181744.9HGNC: HGNC:28490UniProt: B3KTD4
40PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
negative regulation of smooth muscle cell apoptotic processregulation of phosphatidylinositol 3-kinase/protein kinase B signal transductioncardiac muscle cell proliferationpositive regulation of protein kinase C activitymathematical abilityrisk-taking behaviourhypertensionsmoking initiation
✦AI Summary

DIPK2A (divergent protein kinase domain 2A) is a Golgi and late endosome/lysosome-localized kinase that regulates multiple cellular processes critical for cardiac and neurological function. Mechanistically, DIPK2A promotes autophagosome-lysosome fusion by binding to VAMP7B, thereby inhibiting its competition with functional VAMP7A for STX17 interaction and enhancing autophagic degradation of mitochondrial proteins 1. As a secreted paracrine factor (also termed HASF), DIPK2A stimulates cardiomyocyte proliferation through the PI3K-AKT-CDK7 signaling cascade 2. Additionally, DIPK2A modulates heparan sulfate proteoglycan (HSPG) homeostasis through Golgi trafficking; deletion of DIPK2A impairs α-synuclein fibril uptake by preventing cell surface binding, suggesting a role in neurodegeneration-related pathways 3. DIPK2A has been associated with multiple disease states: de novo mutations in DIPK2A occur more frequently than expected in non-syndromic cleft lip/palate 4, and genetic variants are linked to periodontal disease 5. The protein belongs to the FAM69/calcium-regulated kinase family implicated in neurological disorders 6, with involvement in PCOS pathophysiology through ceRNA networks 7.

Sources cited
1
DIPK2A binds VAMP7B and promotes autophagosome-lysosome fusion by enhancing STX17-VAMP7A interaction
PMID: 31251111
2
C3orf58/HASF (DIPK2A) is a paracrine protein stimulating cardiomyocyte proliferation via PI3K-AKT-CDK7 pathway
PMID: 23784961
3
DIPK2A deletion impairs α-synuclein fibril uptake by affecting heparan sulfate homeostasis and Golgi trafficking
PMID: 41053297
4
DIPK2A carries more de novo mutations than expected in non-syndromic cleft lip/palate cases
PMID: 35701113
5
DIPK2A variants are associated with periodontal disease in GWAS analysis
PMID: 41006734
6
DIPK2A (C3ORF58) is a calcium-regulated kinase family member linked to neurological disorders
PMID: 23840464
7
DIPK2A is involved in lncRNA-miRNA-mRNA ceRNA networks in PCOS pathophysiology
PMID: 36374793
Disease Associationsⓘ20
mathematical abilityOpen Targets
0.42Moderate
risk-taking behaviourOpen Targets
0.40Moderate
hypertensionOpen Targets
0.35Weak
smoking initiationOpen Targets
0.30Weak
JaundiceOpen Targets
0.26Weak
Abnormality of the skeletal systemOpen Targets
0.25Weak
pyogenic granulomaOpen Targets
0.19Weak
ovarian dysfunctionOpen Targets
0.13Weak
gastric ulcerOpen Targets
0.13Weak
PhlebitisOpen Targets
0.13Weak
ThrombophlebitisOpen Targets
0.13Weak
essential hypertensionOpen Targets
0.12Weak
breast benign neoplasmOpen Targets
0.12Weak
pathological myopiaOpen Targets
0.12Weak
DNA methylationOpen Targets
0.08Suggestive
chondrocalcinosisOpen Targets
0.05Suggestive
scleritisOpen Targets
0.04Suggestive
ovarian neoplasmOpen Targets
0.03Suggestive
bladder neck obstructionOpen Targets
0.02Suggestive
malunion fractureOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PCDH10Protein interaction84%SLC9A6Protein interaction82%NPAS4Protein interaction82%PCDH18Protein interaction76%ARCN1Protein interaction76%COPAProtein interaction76%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
31%
Brain
26%
Liver
24%
Heart
21%
Lung
15%
Gene Interaction Network
Click a node to explore
DIPK2APCDH10SLC9A6NPAS4PCDH18ARCN1COPA
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8NDZ4
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.00LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.72 [0.52–1.00]
RankingsWhere DIPK2A stands among ~20K protein-coding genes
  • #10,157of 20,598
    Most Researched40
  • #9,733of 17,882
    Most Constrained (LOEUF)1.00
Genes detectedDIPK2A
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Novel regulators of heparan sulfate proteoglycans modulate cellular uptake of α-synuclein fibrils.
PMID: 41053297
Commun Biol · 2025
1.00
2
DIPK2A promotes STX17- and VAMP7-mediated autophagosome-lysosome fusion by binding to VAMP7B.
PMID: 31251111
Autophagy · 2020
0.90
3
Tempol modulates lncRNA-miRNA-mRNA ceRNA networks in ovaries of DHEA induced PCOS rats.
PMID: 36374793
J Steroid Biochem Mol Biol · 2023
0.80
4
Genetic susceptibility to oral and atherosclerotic cardiovascular diseases based on dental and heart SCORE studies.
PMID: 41006734
Sci Rep · 2025
0.70
5
[Exploring the association between
PMID: 35701113
Beijing Da Xue Xue Bao Yi Xue Ban · 2022
0.60