DGKE

diacylglycerol kinase epsilon, the group of Diacylglycerol kinases

Basic information

Region (hg38): 17:56834106-56869567

Links

ENSG00000153933 ∙ NCBI:8526 ∙ OMIM:601440 ∙ HGNC:2852 ∙ Uniprot:P52429 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunoglobulin-mediated membranoproliferative glomerulonephritis (Moderate), mode of inheritance: AR
• atypical hemolytic-uremic syndrome with DGKE deficiency (Supportive), mode of inheritance: AR
• immunoglobulin-mediated membranoproliferative glomerulonephritis (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nephrotic syndrome, type 7	AR	Renal	In Hemolytic-uremic syndrome, some individuals have been described as responding to medical treatment (eg, immunosuppression, ACE inhibitors), and the choice of specific treatment modalitie, as well as decision to perform renal transplant, may be dictated by genetic diagnosis; Certain agents/precipitating factors should be avoided (eg, certain medications)	Renal	23274426; 23542698
Immunosuppressive therapy, as well as medical management (eg, with ACE inhibitors) have been described as beneficial in some individuals, but it is not clear that early (genetic) diagnosis would be beneficial; Renal transplant has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DGKE gene.

• not provided (123 variants)
• Immunoglobulin-mediated membranoproliferative glomerulonephritis (28 variants)
• Inborn genetic diseases (20 variants)
• not specified (8 variants)
• Atypical hemolytic-uremic syndrome (5 variants)
• Kidney disorder (4 variants)
• DGKE-related condition (2 variants)
• Hemolytic uremic syndrome, atypical, susceptibility to, 1 (2 variants)
• Hemolytic uremic syndrome, atypical, susceptibility to, 7 (1 variants)
• Nephrotic syndrome (1 variants)
• Hemolytic uremic syndrome with DGKE deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DGKE gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	22	5	28
missense		2	54	1		57
nonsense	4					4
start loss						0
frameshift	6	4				10
inframe indel			1			1
splice donor/acceptor (+/-2bp)	2					2
splice region			2	4	1	7
non coding				19	25	44
Total	12	6	56	42	30

Highest pathogenic variant AF is 0.000151

Variants in DGKE

This is a list of pathogenic ClinVar variants found in the DGKE region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-56834477-G-T			Benign (Dec 25, 2019)
17-56834568-G-A			Benign (Nov 11, 2018)
17-56834790-G-A		DGKE-related disorder	Likely benign (Dec 19, 2022)
17-56834796-A-T		Atypical hemolytic-uremic syndrome	Likely pathogenic (Apr 24, 2017)
17-56834815-C-T			Uncertain significance (Feb 01, 2022)
17-56834816-G-A			Likely benign (Jun 24, 2022)
17-56834816-G-C			Likely benign (Jan 25, 2023)
17-56834827-C-A		Hemolytic uremic syndrome, atypical, susceptibility to, 7 • Atypical hemolytic-uremic syndrome	Likely pathogenic; risk factor (May 01, 2013)
17-56834830-C-T		not specified • Kidney disorder • DGKE-related disorder	Conflicting classifications of pathogenicity (Jan 15, 2024)
17-56834836-A-G		not specified	Uncertain significance (Dec 22, 2023)
17-56834837-G-A			Likely benign (Jul 19, 2022)
17-56834842-TG-CT			Uncertain significance (May 05, 2023)
17-56834854-G-A		Kidney disorder	Benign/Likely benign (Jan 29, 2024)
17-56834856-C-CACCT		Immunoglobulin-mediated membranoproliferative glomerulonephritis	Pathogenic (Jun 30, 2021)
17-56834859-C-T			Likely benign (Apr 01, 2022)
17-56834878-G-A			Uncertain significance (May 22, 2022)
17-56834881-C-G			Uncertain significance (Aug 24, 2022)
17-56834892-C-T			Uncertain significance (Jul 23, 2022)
17-56834893-C-G			Uncertain significance (May 12, 2022)
17-56834912-G-C		not specified	Uncertain significance (Oct 20, 2023)
17-56834922-C-T		Immunoglobulin-mediated membranoproliferative glomerulonephritis	Pathogenic (Feb 01, 2013)
17-56834924-G-A		Immunoglobulin-mediated membranoproliferative glomerulonephritis	Benign/Likely benign (Jan 22, 2024)
17-56834925-C-A			Likely benign (Feb 20, 2023)
17-56834936-G-A			Likely benign (May 31, 2022)
17-56834950-G-A			Uncertain significance (Jul 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DGKE	protein_coding	protein_coding	ENST00000284061	11	34577

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000549	0.999	125688	0	60	125748	0.000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.590	276	305	0.905	0.0000149	3701
Missense in Polyphen		123	138.45	0.88842		1696
Synonymous	-1.33	135	117	1.16	0.00000605	1061
Loss of Function	2.82	14	30.9	0.453	0.00000168	345

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000428	0.000424
Ashkenazi Jewish	0.00	0.00
East Asian	0.000279	0.000272
Finnish	0.0000952	0.0000924
European (Non-Finnish)	0.000308	0.000308
Middle Eastern	0.000279	0.000272
South Asian	0.000264	0.000261
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Highly selective for arachidonate-containing species of diacylglycerol (DAG). May terminate signals transmitted through arachidonoyl-DAG or may contribute to the synthesis of phospholipids with defined fatty acid composition.
• Disease: DISEASE: Hemolytic uremic syndrome atypical 7 (AHUS7) [MIM:615008]: An atypical form of hemolytic uremic syndrome characterized by acute onset in the first year of life of microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. After the acute episode, most patients develop chronic renal insufficiency. Unlike other genetic forms of aHUS, AHUS7 is not related to abnormal activation of the complement system. {ECO:0000269|PubMed:23542698}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Glycerolipid metabolism - Homo sapiens (human);Glycerophospholipid metabolism - Homo sapiens (human);Choline metabolism in cancer - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Signaling by GPCR;Signal Transduction;Effects of PIP2 hydrolysis;Platelet activation, signaling and aggregation;Glycerophospholipid metabolism;Hemostasis;G alpha (q) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.230

Intolerance Scores

• loftool: 0.435
• rvis_EVS: -0.38
• rvis_percentile_EVS: 28.01

Haploinsufficiency Scores

• pHI: 0.176
• hipred: Y
• hipred_score: 0.554
• ghis: 0.570

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.969

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Dgke
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: protein kinase C-activating G protein-coupled receptor signaling pathway;phospholipid biosynthetic process;platelet activation;intracellular signal transduction;diacylglycerol metabolic process;glycerolipid metabolic process;lipid phosphorylation;modulation of chemical synaptic transmission
• Cellular component: nucleus;cytoplasm;cytosol;plasma membrane;membrane;integral component of membrane;glutamatergic synapse
• Molecular function: NAD+ kinase activity;diacylglycerol kinase activity;ATP binding;kinase activity;metal ion binding