DGKE

Chr 17AR

diacylglycerol kinase epsilon

Also known as: AHUS7, DAGK5, DAGK6, DGK, NPHS7

NCBI Gene: 8526ENSG00000153933UniProt: P52429

Diacylglycerol kinases are thought to be involved mainly in the regeneration of phosphatidylinositol (PI) from diacylglycerol in the PI-cycle during cell signal transduction. When expressed in mammalian cells, DGK-epsilon shows specificity for arachidonyl-containing diacylglycerol. DGK-epsilon is expressed predominantly in testis. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

{Hemolytic uremic syndrome, atypical, susceptibility to, 7}MIM #615008
AR
Nephrotic syndrome, type 7MIM #615008
AR
1
Active trials
48
Pathogenic / LP
331
ClinVar variants
6
Pubs (1 yr)
0.6
Missense Z
0.71
LOEUF
Clinical Summary— DGKE
🧬
Gene-Disease Validity (ClinGen)
atypical hemolytic-uremic syndrome with DGKE deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
48 Pathogenic / Likely Pathogenic· 141 VUS of 331 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
📖
GeneReview available — DGKE
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.71LOEUF
pLI 0.000
Z-score 2.82
OE 0.45 (0.30–0.71)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.59Z-score
OE missense 0.90 (0.82–1.00)
276 obs / 305.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.45 (0.30–0.71)
0≤0.351.4
Missense OE0.90 (0.82–1.00)
0≤0.61.4
Synonymous OE1.16
0≤1.21.6
LoF obs/exp: 14 / 30.9Missense obs/exp: 276 / 305.0Syn Z: -1.33
GOFDN
DN
0.6453th %ile
GOF
0.7029th %ile
LOF
0.2776th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

331 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic11
VUS141
Likely Benign105
Benign31
Conflicting6
37
Pathogenic
11
Likely Pathogenic
141
VUS
105
Likely Benign
31
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
1
20
0
37
Likely Pathogenic
5
5
1
0
11
VUS
1
132
5
3
141
Likely Benign
0
3
44
58
105
Benign
0
0
27
4
31
Conflicting
—6
Total221419765331

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

View in ClinVar →

DGKE · protein map & ClinVar variants

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

Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Novel Heterozygous Missense Variants in Diacylglycerol Kinase Epsilon and Complement Factor I: Potential Pathogenic Association With Atypical Hemolytic Uremic Syndrome
Abughanimeh OK et al.·Cureus
2024
Diacylglycerol kinase epsilon protects against renal ischemia/reperfusion injury in mice through Kruppel-like factor 15/klotho pathway
Wang Z et al.·Ren Fail
2022
Atypical hemolytic uremic syndrome due to DGKE mutation and response to eculizumab: lessons for the clinical nephrologist.
Husain D et al.·J Nephrol
2021
Lipid metabolism patterns and relevant clinical and molecular features of coronary artery disease patients: an integrated bioinformatic analysis
Liao Y et al.·Lipids Health Dis
2022Cohort
MicroRNA, mRNA, and Proteomics Biomarkers and Therapeutic Targets for Improving Lung Cancer Treatment Outcomes
Ye Q et al.·Cancers (Basel)
2023
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Management of pediatric hemolytic uremic syndrome.
Gülhan B et al.·Turk J Pediatr
2024Review
Thrombotic microangiopathy in children.
Palma LMP et al.·Pediatr Nephrol
2022Review
Pediatric Atypical Hemolytic Uremic Syndrome Advances.
Raina R et al.·Cells
2021Review
Defining the genetics of thrombotic microangiopathies.
Vieira-Martins P et al.·Transfus Apher Sci
2016Review
Pregnancy-related Thrombotic Microangiopathy has a spectrum of underlying causes.
Livson S et al.·Pregnancy Hypertens
2025
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Interaction of ROMK2 channel with lipid kinases DGKE and AGK: Potential channel activation by localized anionic lipid synthesis.
Krajewska M et al.·Biochim Biophys Acta Mol Cell Biol Lipids
2024
Clinical features and management of atypical hemolytic uremic syndrome patient with DGKE gene variants: a case report.
Dai X et al.·Front Pediatr
2023Open AccessCase report
A patient with a homozygous diacylglycerol kinase epsilon (DGKE) gene mutation with atypical haemolytic uraemic syndrome and low C3 responded well to eculizumab: a case report.
Alabdulqader M et al.·BMC Nephrol
2021Open AccessCase report
Cyclosporine A relieved proteinuria and hypoproteinemia in DGKE nephropathy.
Fu W et al.·Clin Chim Acta
2021
Novel Mutations in the DGKE Gene in Two Indian Patients with Early-onset Atypical Haemolytic Uraemic Syndrome.
Sharma J et al.·Indian J Nephrol
2021Open AccessCohort
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