DGKE
Chr 17ARdiacylglycerol kinase epsilon
Also known as: AHUS7, DAGK5, DAGK6, DGK, NPHS7
The DGKE protein is a membrane-bound diacylglycerol kinase that converts diacylglycerol into phosphatidic acid, regulating the balance of these bioactive lipids in cellular signaling pathways and complex lipid biosynthesis. Mutations cause autosomal recessive atypical hemolytic uremic syndrome and nephrotic syndrome, primarily affecting kidney function. The gene shows low constraint against loss-of-function variants (pLI near 0), consistent with its recessive inheritance pattern.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
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.
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
341 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 23 | 1 | 13 | 0 | 37 |
Likely Pathogenic | 6 | 5 | 0 | 0 | 11 |
VUS | 1 | 136 | 3 | 3 | 143 |
Likely Benign | 0 | 3 | 44 | 58 | 105 |
Benign | 0 | 0 | 27 | 4 | 31 |
Conflicting | — | 6 | |||
| Total | 30 | 145 | 87 | 65 | 333 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
DGKE · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools