PLCE1 (phospholipase C epsilon 1)

Gene

• Entrez ID: 51196
• Gene name: Phospholipase C epsilon 1
• Gene symbol: PLCE1
• Synonyms: NPHS3, PLCE, PPLC
• Chromosome: 10
• Chromosome location: 10q23.33
• Summary: This gene encodes a phospholipase enzyme that catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate to generate two second messengers: inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG). These second messengers subsequently regulate various processes affecting cell growth, differentiation, and gene expression. This enzyme is regulated by small monomeric GTPases of the Ras and Rho families and by heterotrimeric G proteins. In addition to its phospholipase C catalytic activity, this enzyme has an N-terminal domain with guanine nucleotide exchange (GEF) activity. Mutations in this gene cause early-onset nephrotic syndrome; characterized by proteinuria, edema, and diffuse mesangial sclerosis or focal and segmental glomerulosclerosis. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Sep 2009]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121912601	C>T	Pathogenic	Stop gained, coding sequence variant
rs121912602	C>G,T	Pathogenic	Stop gained, missense variant, coding sequence variant
rs121912604	C>T	Pathogenic	Genic downstream transcript variant, stop gained, coding sequence variant
rs121912605	C>T	Pathogenic	Missense variant, coding sequence variant
rs267606954	C>T	Pathogenic	Coding sequence variant, genic upstream transcript variant, stop gained
rs267606955	C>A,G,T	Pathogenic	Coding sequence variant, stop gained, synonymous variant, missense variant
rs752029771	G>T	Likely-pathogenic	Coding sequence variant, missense variant
rs762245091	A>G	Likely-pathogenic	Coding sequence variant, missense variant
rs775052849	C>A,T	Pathogenic	Coding sequence variant, synonymous variant, stop gained, genic downstream transcript variant
rs876657369	G>-	Pathogenic	Coding sequence variant, frameshift variant, genic upstream transcript variant
rs876657370	G>-	Pathogenic	Coding sequence variant, frameshift variant
rs895782232	C>T	Pathogenic	Coding sequence variant, stop gained
rs1589413498	G>A	Pathogenic	Coding sequence variant, stop gained
rs1589433172	T>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1589509476	T>G	Likely-pathogenic	Genic downstream transcript variant, coding sequence variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017291	hsa-miR-335-5p	Microarray	18185580
MIRT024850	hsa-miR-215-5p	Microarray	19074876
MIRT026288	hsa-miR-192-5p	Microarray	19074876
MIRT607398	hsa-miR-6715b-5p	HITS-CLIP	24906430
MIRT607398	hsa-miR-6715b-5p	HITS-CLIP	23824327
MIRT607398	hsa-miR-6715b-5p	HITS-CLIP	23313552
MIRT607398	hsa-miR-6715b-5p	HITS-CLIP	27418678
MIRT607399	hsa-miR-4269	HITS-CLIP	24906430
MIRT607399	hsa-miR-4269	HITS-CLIP	23824327
MIRT607399	hsa-miR-4269	HITS-CLIP	23313552
MIRT607399	hsa-miR-4269	HITS-CLIP	27418678
MIRT607400	hsa-miR-5582-5p	HITS-CLIP	24906430
MIRT607400	hsa-miR-5582-5p	HITS-CLIP	23824327
MIRT607400	hsa-miR-5582-5p	HITS-CLIP	23313552
MIRT607400	hsa-miR-5582-5p	HITS-CLIP	27418678
MIRT607401	hsa-miR-6768-5p	HITS-CLIP	24906430
MIRT607401	hsa-miR-6768-5p	HITS-CLIP	23824327
MIRT607401	hsa-miR-6768-5p	HITS-CLIP	23313552
MIRT607401	hsa-miR-6768-5p	HITS-CLIP	27418678
MIRT607402	hsa-miR-8485	HITS-CLIP	24906430
MIRT607402	hsa-miR-8485	HITS-CLIP	23824327
MIRT607402	hsa-miR-8485	HITS-CLIP	23313552
MIRT607402	hsa-miR-8485	HITS-CLIP	27418678
MIRT614860	hsa-miR-1200	HITS-CLIP	23824327
MIRT614861	hsa-miR-3188	HITS-CLIP	23824327
MIRT614862	hsa-miR-6884-5p	HITS-CLIP	23824327
MIRT614863	hsa-miR-485-5p	HITS-CLIP	23824327
MIRT614864	hsa-miR-2467-5p	HITS-CLIP	23824327
MIRT614865	hsa-miR-3975	HITS-CLIP	23824327
MIRT614866	hsa-miR-4649-3p	HITS-CLIP	23824327
MIRT614867	hsa-miR-544b	HITS-CLIP	23824327
MIRT614868	hsa-miR-4324	HITS-CLIP	23824327
MIRT614869	hsa-miR-4789-3p	HITS-CLIP	23824327
MIRT614869	hsa-miR-4789-3p	HITS-CLIP	23313552
MIRT645790	hsa-miR-6807-5p	HITS-CLIP	23824327
MIRT645791	hsa-miR-4653-3p	HITS-CLIP	23824327
MIRT645792	hsa-miR-18a-3p	HITS-CLIP	23824327
MIRT645793	hsa-miR-324-3p	HITS-CLIP	23824327
MIRT645794	hsa-miR-1913	HITS-CLIP	23824327
MIRT645795	hsa-miR-4438	HITS-CLIP	23824327
MIRT674658	hsa-miR-665	HITS-CLIP	23824327
MIRT674659	hsa-miR-6779-5p	HITS-CLIP	23824327
MIRT674660	hsa-miR-6780a-5p	HITS-CLIP	23824327
MIRT674661	hsa-miR-3689c	HITS-CLIP	23824327
MIRT674662	hsa-miR-3689b-3p	HITS-CLIP	23824327
MIRT674663	hsa-miR-3689a-3p	HITS-CLIP	23824327
MIRT674664	hsa-miR-30b-3p	HITS-CLIP	23824327
MIRT674665	hsa-miR-1273h-5p	HITS-CLIP	23824327
MIRT674666	hsa-miR-7847-3p	HITS-CLIP	23824327
MIRT674666	hsa-miR-7847-3p	PAR-CLIP	27292025
MIRT674667	hsa-miR-6880-5p	HITS-CLIP	23824327
MIRT674667	hsa-miR-6880-5p	PAR-CLIP	27292025
MIRT674668	hsa-miR-6799-5p	HITS-CLIP	23824327
MIRT674669	hsa-miR-6883-5p	HITS-CLIP	23824327
MIRT674670	hsa-miR-6785-5p	HITS-CLIP	23824327
MIRT674671	hsa-miR-4728-5p	HITS-CLIP	23824327
MIRT674672	hsa-miR-149-3p	HITS-CLIP	23824327
MIRT674673	hsa-miR-7106-5p	HITS-CLIP	23824327
MIRT674674	hsa-miR-6851-5p	HITS-CLIP	23824327
MIRT674674	hsa-miR-6851-5p	PAR-CLIP	27292025
MIRT674675	hsa-miR-3689d	HITS-CLIP	23824327
MIRT674675	hsa-miR-3689d	PAR-CLIP	27292025
MIRT674676	hsa-miR-7160-5p	HITS-CLIP	23824327
MIRT674677	hsa-miR-4722-5p	HITS-CLIP	23824327
MIRT674677	hsa-miR-4722-5p	PAR-CLIP	27292025
MIRT674678	hsa-miR-6086	HITS-CLIP	23824327
MIRT674679	hsa-miR-377-5p	HITS-CLIP	23824327
MIRT674680	hsa-miR-6134	HITS-CLIP	23824327
MIRT674680	hsa-miR-6134	PAR-CLIP	27292025
MIRT674681	hsa-miR-1827	HITS-CLIP	23824327
MIRT674681	hsa-miR-1827	PAR-CLIP	27292025
MIRT674682	hsa-miR-3192-5p	HITS-CLIP	23824327
MIRT674682	hsa-miR-3192-5p	PAR-CLIP	27292025
MIRT674683	hsa-miR-4768-3p	HITS-CLIP	23824327
MIRT674684	hsa-miR-6500-3p	HITS-CLIP	23824327
MIRT674684	hsa-miR-6500-3p	PAR-CLIP	27292025
MIRT674685	hsa-miR-3614-5p	HITS-CLIP	23824327
MIRT674685	hsa-miR-3614-5p	PAR-CLIP	27292025
MIRT674686	hsa-miR-4478	HITS-CLIP	23824327
MIRT674687	hsa-miR-4419b	HITS-CLIP	23824327
MIRT674688	hsa-miR-3929	HITS-CLIP	23824327
MIRT674689	hsa-miR-940	HITS-CLIP	23824327
MIRT674689	hsa-miR-940	PAR-CLIP	27292025
MIRT674690	hsa-miR-6893-5p	HITS-CLIP	23824327
MIRT674690	hsa-miR-6893-5p	PAR-CLIP	27292025
MIRT674691	hsa-miR-6808-5p	HITS-CLIP	23824327
MIRT674691	hsa-miR-6808-5p	PAR-CLIP	27292025
MIRT674692	hsa-miR-7851-3p	HITS-CLIP	23824327
MIRT674692	hsa-miR-7851-3p	PAR-CLIP	27292025
MIRT674693	hsa-miR-34b-3p	HITS-CLIP	23824327
MIRT674693	hsa-miR-34b-3p	PAR-CLIP	27292025
MIRT674694	hsa-miR-490-3p	HITS-CLIP	23824327
MIRT674694	hsa-miR-490-3p	PAR-CLIP	27292025
MIRT713654	hsa-miR-3611	HITS-CLIP	19536157
MIRT713655	hsa-miR-6126	HITS-CLIP	19536157
MIRT713656	hsa-miR-4493	HITS-CLIP	19536157
MIRT713657	hsa-miR-605-3p	HITS-CLIP	19536157
MIRT713658	hsa-miR-4277	HITS-CLIP	19536157
MIRT713659	hsa-miR-584-3p	HITS-CLIP	19536157
MIRT713660	hsa-miR-5000-5p	HITS-CLIP	19536157
MIRT735519	hsa-miR-328-3p	, Luciferase reporter assay, qRT-PCR, Western blot	26773497
MIRT735542	hsa-miR-145-3p	Luciferase reporter assay, qRT-PCR, Western blot, Immunofluorescence	26657507
MIRT785674	hsa-miR-4307	HITS-CLIP	27418678

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000139	Component	Golgi membrane	IEA
GO:0000187	Process	Activation of MAPK activity	IDA	11022047
GO:0001558	Process	Regulation of cell growth	TAS	11022047
GO:0004435	Function	Phosphatidylinositol phospholipase C activity	IBA	21873635
GO:0004435	Function	Phosphatidylinositol phospholipase C activity	IDA	11022047, 11022048
GO:0004629	Function	Phospholipase C activity	IDA	11022047
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	TAS	11022047
GO:0005515	Function	Protein binding	IPI	11022048, 29058690
GO:0005829	Component	Cytosol	IDA	11022048
GO:0005886	Component	Plasma membrane	IDA	11022048
GO:0005886	Component	Plasma membrane	TAS
GO:0006651	Process	Diacylglycerol biosynthetic process	IMP	29058690
GO:0006651	Process	Diacylglycerol biosynthetic process	TAS	11022047
GO:0006940	Process	Regulation of smooth muscle contraction	TAS	11022047
GO:0007010	Process	Cytoskeleton organization	NAS	11022047
GO:0007173	Process	Epidermal growth factor receptor signaling pathway	IMP	29058690
GO:0007173	Process	Epidermal growth factor receptor signaling pathway	NAS	11022048
GO:0007200	Process	Phospholipase C-activating G protein-coupled receptor signaling pathway	IDA	11022047, 11022048
GO:0007204	Process	Positive regulation of cytosolic calcium ion concentration	TAS	11022047
GO:0007265	Process	Ras protein signal transduction	IDA	11022048
GO:0007507	Process	Heart development	TAS	11022047
GO:0008277	Process	Regulation of G protein-coupled receptor signaling pathway	IDA	11022047
GO:0010592	Process	Positive regulation of lamellipodium assembly	IMP	29058690
GO:0016042	Process	Lipid catabolic process	IEA
GO:0019722	Process	Calcium-mediated signaling	NAS	11022048
GO:0019722	Process	Calcium-mediated signaling	TAS	11022047
GO:0019899	Function	Enzyme binding	IPI	11022048
GO:0030027	Component	Lamellipodium	IDA	29058690
GO:0031267	Function	Small GTPase binding	IDA	11022048
GO:0032835	Process	Glomerulus development	IMP	17086182
GO:0043647	Process	Inositol phosphate metabolic process	TAS
GO:0045859	Process	Regulation of protein kinase activity	IDA	11022047
GO:0046578	Process	Regulation of Ras protein signal transduction	IDA	11022047
GO:0046872	Function	Metal ion binding	IEA
GO:0048015	Process	Phosphatidylinositol-mediated signaling	IBA	21873635
GO:0048016	Process	Inositol phosphate-mediated signaling	TAS	11022047

Other IDs

• MIM: 608414
• HGNC: 17175
• e!Ensembl: ENSG00000138193

Protein

• UniProt ID: Q9P212
• Protein name: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 (EC 3.1.4.11) (Pancreas-enriched phospholipase C) (Phosphoinositide phospholipase C-epsilon-1) (Phospholipase C-epsilon-1) (PLC-epsilon-1)
• Protein 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. In podocytes, is involved in the regulation of lamellipodia formation. Acts downtream of AVIL to allow ARP2/3 complex assembly (PubMed:29058690).
• PDB: 2BYE, 2BYF, 2C5L
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00617	RasGEF	534 → 762	RasGEF domain	Family
  PF09279	EF-hand_like	1323 → 1381	Phosphoinositide-specific phospholipase C, efhand-like	Domain
  PF00388	PI-PLC-X	1394 → 1541	Phosphatidylinositol-specific phospholipase C, X domain	Family
  PF00387	PI-PLC-Y	1740 → 1844	Phosphatidylinositol-specific phospholipase C, Y domain	Family
  PF00168	C2	1870 → 1971	C2 domain	Domain
  PF00788	RA	2135 → 2238	Ras association (RalGDS/AF-6) domain	Domain

• Sequence:

  MTSEEMTASVLIPVTQRKVVSAQSAADESSEKVSDINISKAHTVRRSGETSHTISQLNKL
  KEEPSGSNLPKILSIAREKIVSDENSNEKCWEKIMPDSAKNLNINCNNILRNHQHGLPQR
  QFYEMYNSVAEEDLCLETGIPSPLERKVFPGIQLELDRPSMGISPLGNQSVIIETGRAHP
  DSRRAVFHFHYEVDRRMSDTFCTLSENLILDDCGNCVPLPGGEEKQKKNYVAYTCKLMEL
  AKNCDNKNEQLQCDHCDTLNDKYFCFEGSCEKVDMVYSGDSFCRKDFTDSQAAKTFLSHF
  EDFPDNCDDVEEDAFKSKKERSTLLVRRFCKNDREVKKSVYTGTRAIVRTLPSGHIGLTA
  WSYIDQKRNGPLLPCGRVMEPPSTVEIRQDGSQRLSEAQWYPIYNAVRREETENTVGSLL
  HFLTKLPASETAHGRISVGPCLKQCVRDTVCEYRATLQRTSISQYITGSLLEATTSLGAR
  SGLLSTFGGSTGRMMLKERQPGPSVANSNALPSSSAGISKELIDLQPLIQFPEEVASILM
  EQEQTIYRRVLPVDYLCFLTRDLGTPECQSSLPCLKASISASILTTQNGEHNALEDLVMR
  FNEVSSWVTWLILTAGSMEEKREVFSYLVHVAKCCWNMGNYNAVMEFLAGLRSRKVLKMW
  QFMDQSDIETMRSLKDAMAQHESSCEYRKVVTRALHIPGCKVVPFCGVFLKELCEVLDGA
  SGLMKLCPRYNSQEETLEFVADYSGQDNFLQRVGQNGLKNSEKESTVNSIFQVIRSCNRS
  LETDEEDSPSEGNSSRKSSLKDKSRWQFIIGDLLDSDNDIFEQSKEYDSHGSEDSQKAFD
  HGTELIPWYVLSIQADVHQFLLQGATVIHYDQDTHLSARCFLQLQPDNSTLTWVKPTTAS
  PASSKAKLGVLNNTAEPGKFPLLGNAGLSSLTEGVLDLFAVKAVYMGHPGIDIHTVCVQN
  KLGSMFLSETGVTLLYGLQTTDNRLLHFVAPKHTAKMLFSGLLELTRAVRKMRKFPDQRQ
  QWLRKQYVSLYQEDGRYEGPTLAHAVELFGGRRWSARNPSPGTSAKNAEKPNMQRNNTLG
  ISTTKKKKKILMRGESGEVTDDEMATRKAKMHKECRSRSGSDPQDINEQEESEVNAIANP
  PNPLPSRRAHSLTTAGSPNLAAGTSSPIRPVSSPVLSSSNKSPSSAWSSSSWHGRIKGGM
  KGFQSFMVSDSNMSFVEFVELFKSFSVRSRKDLKDLFDVYAVPCNRSGSESAPLYTNLTI
  DENTSDLQPDLDLLTRNVSDLGLFIKSKQQLSDNQRQISDAIAAASIVTNGTGIESTSLG
  IFGVGILQLNDFLVNCQGEHCTYDEILSIIQKFEPSISMCHQGLMSFEGFARFLMDKENF
  ASKNDESQENIKELQLPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDC
  WDGDDGMPIIYHGHTLTTKIPFKEVVEAIDRSAFINSDLPIIISIENHCSLPQQRKMAEI
  FKTVFGEKLVTKFLFETDFSDDPMLPSPDQLRKKVLLKNKKLKAHQTPVDILKQKAHQLA
  SMQVQAYNGGNANPRPANNEEEEDEEDEYDYDYESLSDDNILEDRPENKSCNDKLQFEYN
  EEIPKRIKKADNSACNKGKVYDMELGEEFYLDQNKKESRQIAPELSDLVIYCQAVKFPGL
  STLNASGSSRGKERKSRKSIFGNNPGRMSPGETASFNKTSGKSSCEGIRQTWEESSSPLN
  PTTSLSAIIRTPKCYHISSLNENAAKRLCRRYSQKLTQHTACQLLRTYPAATRIDSSNPN
  PLMFWLHGIQLVALNYQTDDLPLHLNAAMFEANGGCGYVLKPPVLWDKNCPMYQKFSPLE
  RDLDSMDPAVYSLTIVSGQNVCPSNSMGSPCIEVDVLGMPLDSCHFRTKPIHRNTLNPMW
  NEQFLFHVHFEDLVFLRFAVVENNSSAVTAQRIIPLKALKRGYRHLQLRNLHNEVLEISS
  LFINSRRMEENSSGNTMSASSMFNTEERKCLQTHRVTVHGVPGPEPFTVFTINGGTKAKQ
  LLQQILTNEQDIKPVTTDYFLMEEKYFISKEKNECRKQPFQRAIGPEEEIMQILSSWFPE
  EGYMGRIVLKTQQENLEEKNIVQDDKEVILSSEEESFFVQVHDVSPEQPRTVIKAPRVST
  AQDVIQQTLCKAKYSYSILSNPNPSDYVLLEEVVKDTTNKKTTTPKSSQRVLLDQECVFQ
  AQSKWKGAGKFILKLKEQVQASREDKKKGISFASELKKLTKSTKQPRGLTSPSQLLTSES
  IQTKEEKPVGGLSSSDTMDYRQ

• Sequence length: 2302