PLCE1

phospholipase C epsilon 1, the group of C2 domain containing phospholipases|Phospholipases

Basic information

Region (hg38): 10:93993931-94332823

Links

ENSG00000138193 ∙ NCBI:51196 ∙ OMIM:608414 ∙ HGNC:17175 ∙ Uniprot:Q9P212 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• nephrotic syndrome, type 3 (Definitive), mode of inheritance: AR
• nephrotic syndrome, type 3 (Strong), mode of inheritance: AR
• nephrotic syndrome, type 3 (Strong), mode of inheritance: AR
• familial idiopathic steroid-resistant nephrotic syndrome (Supportive), mode of inheritance: AD
• nephrotic syndrome, type 3 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nephrotic syndrome, type 3	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Renal	17086182; 18065803; 20591883; 21415313; 23349334; 23595123
Most described individuals have had steroid-resistant disease

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLCE1 gene.

• Nephrotic_syndrome,_type_3 (427 variants)
• not_provided (327 variants)
• Inborn_genetic_diseases (245 variants)
• PLCE1-related_disorder (54 variants)
• not_specified (18 variants)
• Kidney_disorder (15 variants)
• Nephrotic_syndrome (12 variants)
• Focal_segmental_glomerulosclerosis (9 variants)
• Polycystic_kidney_disease (2 variants)
• Proteinuria (2 variants)
• Glomerulonephritis (1 variants)
• Finnish_congenital_nephrotic_syndrome (1 variants)
• Microscopic_hematuria (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLCE1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016341.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			29	102	3	134
missense	1	4	477	48	3	533
nonsense	19	6				25
start loss						0
frameshift	15	14	2			31
splice donor/acceptor (+/-2bp)	1	5				6
Total	36	29	508	150	6

Highest pathogenic variant AF is 0.0000588742

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLCE1	protein_coding	protein_coding	ENST00000371380	31	338835

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.68e-11	1.00	124708	0	107	124815	0.000429

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.38	1061	1.20e+3	0.888	0.0000663	15223
Missense in Polyphen		349	481.35	0.72504		6118
Synonymous	0.613	443	460	0.964	0.0000279	4348
Loss of Function	6.30	39	110	0.353	0.00000684	1310

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00101	0.00101
Ashkenazi Jewish	0.000497	0.000497
East Asian	0.000334	0.000334
Finnish	0.0000928	0.0000928
European (Non-Finnish)	0.000354	0.000344
Middle Eastern	0.000334	0.000334
South Asian	0.00108	0.000752
Other	0.000331	0.000330

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. PLCE1 is a bifunctional enzyme which also regulates small GTPases of the Ras superfamily through its Ras guanine- exchange factor (RasGEF) activity. As an effector of heterotrimeric and small G-protein, it may play a role in cell survival, cell growth, actin organization and T-cell activation. {ECO:0000269|PubMed:11022047, ECO:0000269|PubMed:11395506, ECO:0000269|PubMed:11715024, ECO:0000269|PubMed:11877431, ECO:0000269|PubMed:12721365, ECO:0000269|PubMed:16537651, ECO:0000269|PubMed:17086182}.
• Disease: DISEASE: Nephrotic syndrome 3 (NPHS3) [MIM:610725]: A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure. Most patients with NPHS3 show diffuse mesangial sclerosis on renal biopsy, which is a pathologic entity characterized by mesangial matrix expansion with no mesangial hypercellularity, hypertrophy of the podocytes, vacuolized podocytes, thickened basement membranes, and diminished patency of the capillary lumen. {ECO:0000269|PubMed:17086182}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Inositol phosphate metabolism - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Proton Pump Inhibitor Pathway, Pharmacodynamics;Primary Focal Segmental Glomerulosclerosis FSGS;GPR40 Pathway;Ras Signaling;EGF-EGFR Signaling Pathway;Regulation of Ras family activation;D-<i>myo</i>-inositol (1,4,5)-trisphosphate biosynthesis;phospholipase c-epsilon pathway;Inositol phosphate metabolism;Metabolism;phospholipases;D-<i>myo</i>-inositol-5-phosphate metabolism;superpathway of inositol phosphate compounds;Phosphatidylinositol phosphate metabolism;EGFR1;Synthesis of IP3 and IP4 in the cytosol;Inositol phosphate metabolism (Consensus)

Recessive Scores

• pRec: 0.116

Intolerance Scores

• loftool: 0.802
• rvis_EVS: 0.36
• rvis_percentile_EVS: 74.59

Haploinsufficiency Scores

• pHI: 0.0818
• hipred: Y
• hipred_score: 0.698
• ghis: 0.470

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.398

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Plce1
• Phenotype: homeostasis/metabolism phenotype; muscle phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); neoplasm

Zebrafish Information Network

• Gene name: plce1
• Affected structure: pronephric glomerular basement membrane
• Phenotype tag: abnormal
• Phenotype quality: disorganized

Gene ontology

• Biological process: activation of MAPK activity;regulation of cell growth;diacylglycerol biosynthetic process;regulation of smooth muscle contraction;cytoskeleton organization;epidermal growth factor receptor signaling pathway;phospholipase C-activating G protein-coupled receptor signaling pathway;positive regulation of cytosolic calcium ion concentration;Ras protein signal transduction;heart development;regulation of G protein-coupled receptor signaling pathway;cell population proliferation;lipid catabolic process;calcium-mediated signaling;glomerulus development;inositol trisphosphate biosynthetic process;inositol phosphate metabolic process;regulation of protein kinase activity;regulation of Ras protein signal transduction;phosphatidylinositol-mediated signaling;inositol phosphate-mediated signaling;release of sequestered calcium ion into cytosol
• Cellular component: Golgi membrane;cytosol;plasma membrane
• Molecular function: phosphatidylinositol phospholipase C activity;phospholipase C activity;guanyl-nucleotide exchange factor activity;protein binding;Ras GTPase binding;enzyme binding;metal ion binding