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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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DGKA
diacylglycerol kinase alpha
Chromosome 12 · 12q13.2
NCBI Gene: 1606Ensembl: ENSG00000065357.21HGNC: HGNC:2849UniProt: P23743
70PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Kinase
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
ATP-dependent diacylglycerol kinase activitydiacylglycerol metabolic processcytosollipid bindingautoimmune diseaseazoospermiacanceracute myeloid leukemia
✦AI Summary

DGKA (diacylglycerol kinase alpha) is a metabolic enzyme that converts diacylglycerol (DAG) into phosphatidic acid (PA), thereby regulating the balance between these two critical lipid second messengers 1. This enzymatic activity positions DGKA as a central switch in cellular signaling pathways with diverse biological effects 1. In cancer contexts, DGKA exhibits dual roles in promoting tumor progression and therapeutic resistance. The enzyme enhances metastasis in non-small cell lung cancer through direct interactions with SRC and FAK proteins, phosphorylating SRC at Tyr416 and FAK at Tyr397 to activate downstream WNT/β-catenin and VEGF signaling pathways that promote epithelial-mesenchymal transition and angiogenesis 2. DGKA also drives platinum resistance in ovarian cancer by activating c-JUN-WEE1 signaling, where its product PA facilitates c-JUN nuclear localization and activation 1. Additionally, DGKA mediates resistance to PD-1 immunotherapy by exacerbating T-cell exhaustion 3. In lung cancer, DGKA promotes tumorigenesis through regulation of cyclin D3 expression 4. These findings establish DGKA as a promising therapeutic target across multiple cancer types, with its inhibition showing potential to overcome various resistance mechanisms and enhance treatment efficacy.

Sources cited
1
DGKA converts DAG to PA and acts as central switch in signaling pathways; drives platinum resistance via c-JUN-WEE1 signaling
PMID: 32341033
2
DGKA interacts with SRC/FAK proteins and promotes NSCLC metastasis through phosphorylation and downstream signaling
PMID: 35131384
3
DGKA mediates resistance to PD-1 blockade by exacerbating T-cell exhaustion
PMID: 33608256
4
DGKA promotes lung tumorigenesis by regulating cyclin D3 expression
PMID: 36965165
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
autoimmune diseaseOpen Targets
0.10Suggestive
azoospermiaOpen Targets
0.09Suggestive
cancerOpen Targets
0.09Suggestive
acute myeloid leukemiaOpen Targets
0.09Suggestive
glioblastoma multiformeOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.08Suggestive
Pallister-Hall syndromeOpen Targets
0.07Suggestive
Male infertility with spermatogenesis disorder due to single gene mutationOpen Targets
0.07Suggestive
nasopharyngeal carcinomaOpen Targets
0.07Suggestive
esophageal squamous cell carcinomaOpen Targets
0.07Suggestive
Female infertility due to fertilization defectOpen Targets
0.07Suggestive
liver dysplastic noduleOpen Targets
0.07Suggestive
non-small cell lung carcinomaOpen Targets
0.07Suggestive
Rare genetic female infertilityOpen Targets
0.07Suggestive
partial chromosome Y deletionOpen Targets
0.07Suggestive
lung cancerOpen Targets
0.07Suggestive
spermatogenic failure 3Open Targets
0.06Suggestive
spermatogenic failure 55Open Targets
0.06Suggestive
spermatogenic failure 53Open Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
DGKBShared pathway100%PLCG2Protein interaction96%RASGRP1Protein interaction96%PLD2Protein interaction94%PLD1Protein interaction94%MBOAT2Protein interaction94%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
47%
Ovary
34%
Heart
11%
Brain
11%
Liver
10%
Gene Interaction Network
Click a node to explore
DGKADGKBPLCG2RASGRP1PLD2PLD1MBOAT2
PROTEIN STRUCTURE
Preparing viewer…
PDB6IIE · 2.14 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.42Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.32 [0.24–0.42]
RankingsWhere DGKA stands among ~20K protein-coding genes
  • #6,707of 20,598
    Most Researched70
  • #2,206of 17,882
    Most Constrained (LOEUF)0.42 · top quartile
Genes detectedDGKA
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Multiomics analysis reveals metabolic subtypes and identifies diacylglycerol kinase α (DGKA) as a potential therapeutic target for intrahepatic cholangiocarcinoma.
PMID: 38143235
Cancer Commun (Lond) · 2024
1.00
2
DGKA interacts with SRC/FAK to promote the metastasis of non-small cell lung cancer.
PMID: 35131384
Cancer Lett · 2022
0.90
3
PLA2G4A and ACHE modulate lipid profiles via glycerophospholipid metabolism in platinum-resistant gastric cancer.
PMID: 38454407
J Transl Med · 2024
0.80
4
DGKA Provides Platinum Resistance in Ovarian Cancer Through Activation of c-JUN-WEE1 Signaling.
PMID: 32341033
Clin Cancer Res · 2020
0.70
5
DGKA Mediates Resistance to PD-1 Blockade.
PMID: 33608256
Cancer Immunol Res · 2021
0.60