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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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DGKI
diacylglycerol kinase iota
Chromosome 7 · 7q33
NCBI Gene: 9162Ensembl: ENSG00000157680.17HGNC: HGNC:2855UniProt: E7EWQ4
22PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Kinase
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
ATP-dependent diacylglycerol kinase activityprotein bindingsynapselipid phosphorylationAbnormality of the skeletal systemschizophreniaobesityAbnormal erythrocyte morphology
✦AI Summary

DGKI (diacylglycerol kinase iota) is a lipid kinase that converts diacylglycerol (DAG) into phosphatidic acid (PA), functioning as a molecular switch between two signaling pathways with opposing effects 12. The enzyme acts as a regulator of multiple biological processes, including potential roles in presynaptic signaling and neurotransmitter release during glutamate receptor-dependent long-term depression. DGKI negatively regulates Rap1 signaling by controlling DAG-mediated activation of RASGRP3. Clinically, DGKI has emerged as relevant to multiple diseases. Genetic variants show positive selection in polycystic ovary syndrome (PCOS) populations, suggesting evolutionary advantage despite the disorder's reproductive burden 3. In glioblastoma, DGKI methylation status serves as a biomarker for treatment response; selective DGKI demethylation enhances temozolomide sensitivity 4. DGKI is associated with obesity risk in genome-wide association studies 5 and specific learning disorders including dyslexia 67. In thyroid carcinoma, higher DGKI expression correlates with improved survival outcomes 8. Additionally, DGKI inhibition reduces airway smooth muscle cell proliferation relevant to asthma pathology 9, and blocking DGK enzymes enhances tumor-infiltrating lymphocyte function in cancer immunotherapy 10.

Sources cited
1
DGKI converts DAG into PA and regulates these two bioactive lipids
PMID: 23949095
2
DGKI enzyme function in DAG-PA conversion without preference for specific acyl chain composition
PMID: 9830018
3
DGKI variants show positive selection in PCOS populations
PMID: 37982420
4
DGKI methylation status serves as biomarker in glioblastoma; selective DGKI demethylation enhances temozolomide sensitivity
PMID: 40886022
5
DGKI identified as prioritized gene in BMI/obesity-associated loci
PMID: 38754426
6
DGKI variants associated with dyslexia in Finnish and German populations
PMID: 21203819
7
DGKI genetic variants detected in specific learning disorder families
PMID: 37629793
8
Higher DGKI expression in thyroid carcinoma associated with better survival outcomes
PMID: 36059514
9
DGKI inhibition reduces airway smooth muscle cell proliferation relevant to asthma
PMID: 36233170
10
DGK inhibition enhances tumor-infiltrating lymphocyte function in cancer immunotherapy
PMID: 41459935
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.41Moderate
schizophreniaOpen Targets
0.36Weak
obesityOpen Targets
0.35Weak
Abnormal erythrocyte morphologyOpen Targets
0.33Weak
neurodegenerative diseaseOpen Targets
0.32Weak
smoking initiationOpen Targets
0.30Weak
liver diseaseOpen Targets
0.30Weak
migraine disorderOpen Targets
0.30Weak
cardiomyopathyOpen Targets
0.27Weak
brain aneurysmOpen Targets
0.26Weak
alcoholic liver diseaseOpen Targets
0.25Weak
ovarian dysfunctionOpen Targets
0.25Weak
alcohol drinkingOpen Targets
0.23Weak
osteoarthritis, hipOpen Targets
0.22Weak
osteoarthritis, kneeOpen Targets
0.22Weak
risk-taking behaviourOpen Targets
0.22Weak
Abnormality of the gastrointestinal tractOpen Targets
0.21Weak
obsessive-compulsive disorderOpen Targets
0.21Weak
autism spectrum disorderOpen Targets
0.20Weak
insomniaOpen Targets
0.19Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MBOAT2Protein interaction94%CEPT1Protein interaction93%DGAT2Protein interaction91%MOGAT1Protein interaction91%PLD1Protein interaction91%RASGRP3Protein interaction90%
Tissue Expression6 tissues
Brain
100%
Heart
25%
Bone Marrow
1%
Ovary
1%
Lung
1%
Liver
1%
Gene Interaction Network
Click a node to explore
DGKIMBOAT2CEPT1DGAT2MOGAT1PLD1RASGRP3
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt O75912
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.43Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.32 [0.25–0.43]
RankingsWhere DGKI stands among ~20K protein-coding genes
  • #13,645of 20,598
    Most Researched22
  • #2,299of 17,882
    Most Constrained (LOEUF)0.43 · top quartile
Genes detectedDGKI
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Evidence of positive selection of genetic variants associated with PCOS.
PMID: 37982420
Hum Reprod · 2023
1.00
2
Selective disruption of DNMT1/ELK1 interactions induces DGKI re-expression and promotes temozolomide sensitivity of MGMT
PMID: 40886022
Clin Epigenetics · 2025
0.90
3
An integrative framework to prioritize genes in more than 500 loci associated with body mass index.
PMID: 38754426
Am J Hum Genet · 2024
0.80
4
Specific Learning Disorders: Variation Analysis of 15 Candidate Genes in 9 Multiplex Families.
PMID: 37629793
Medicina (Kaunas) · 2023
0.70
5
Key molecules associated with thyroid carcinoma prognosis: A study based on transcriptome sequencing and GEO datasets.
PMID: 36059514
Front Immunol · 2022
0.60