PLCB1

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

Basic information

Region (hg38): 20:8077250-8968360

Links

ENSG00000182621 ∙ NCBI:23236 ∙ OMIM:607120 ∙ HGNC:15917 ∙ Uniprot:Q9NQ66 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 12 (Strong), mode of inheritance: AR
• developmental and epileptic encephalopathy, 12 (Strong), mode of inheritance: AR
• developmental and epileptic encephalopathy, 12 (Moderate), mode of inheritance: AR
• West syndrome (Supportive), mode of inheritance: AD
• malignant migrating partial seizures of infancy (Supportive), mode of inheritance: AD
• developmental and epileptic encephalopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 12	AR	Neurologic	Individuals may manifest with seizures, and specific knowledge of the underlying cause can help direct selection of optimal therapies for management based on the genetic etiology	Neurologic	20833646; 22690784; 28331464
As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLCB1 gene.

• Developmental and epileptic encephalopathy, 12 (815 variants)
• not provided (250 variants)
• Inborn genetic diseases (123 variants)
• Early Infantile Epileptic Encephalopathy, Autosomal Recessive (34 variants)
• not specified (30 variants)
• Abnormal brain morphology (1 variants)
• Seizure (1 variants)
• Developmental and epileptic encephalopathy, 1 (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLCB1 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			8	195	2	205
missense		1	338	2	1	342
nonsense	2	1				3
start loss						0
frameshift	4	1	2			7
inframe indel			3			3
splice donor/acceptor (+/-2bp)	1	7	1			9
splice region			28	40	2	70
non coding			54	182	106	342
Total	7	10	406	379	109

Variants in PLCB1

This is a list of pathogenic ClinVar variants found in the PLCB1 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-8132322-C-T		Developmental and epileptic encephalopathy, 12	Conflicting classifications of pathogenicity (Jul 01, 2023)
20-8132341-T-G		Developmental and epileptic encephalopathy, 12	Uncertain significance (Jan 13, 2018)
20-8132356-A-G		Developmental and epileptic encephalopathy, 12	Uncertain significance (Jan 13, 2018)
20-8132430-C-G		Developmental and epileptic encephalopathy, 12	Uncertain significance (Jan 13, 2018)
20-8132482-C-A		Developmental and epileptic encephalopathy, 12	Benign/Likely benign (Dec 01, 2020)
20-8132484-G-A		Developmental and epileptic encephalopathy, 12	Uncertain significance (Jan 12, 2018)
20-8132651-G-C		Developmental and epileptic encephalopathy, 12	Uncertain significance (Jan 13, 2018)
20-8132657-C-G		Developmental and epileptic encephalopathy, 12	Likely benign (Dec 18, 2021)
20-8132657-C-T		Developmental and epileptic encephalopathy, 12	Likely benign (Jun 04, 2023)
20-8132663-T-C		Developmental and epileptic encephalopathy, 12	Likely benign (Dec 10, 2020)
20-8132664-C-G		Inborn genetic diseases	Uncertain significance (Aug 13, 2021)
20-8132666-A-T			Uncertain significance (Mar 30, 2017)
20-8132669-C-T		Developmental and epileptic encephalopathy, 12	Likely benign (Feb 01, 2024)
20-8132671-G-T		Inborn genetic diseases	Uncertain significance (Jun 23, 2023)
20-8132672-A-C			Uncertain significance (Oct 24, 2013)
20-8132673-G-T			Uncertain significance (Jun 28, 2018)
20-8132679-G-T		Developmental and epileptic encephalopathy, 12 • Inborn genetic diseases • PLCB1-related disorder	Conflicting classifications of pathogenicity (Jan 22, 2024)
20-8132680-C-G		Developmental and epileptic encephalopathy, 12	Uncertain significance (Jul 12, 2022)
20-8132680-C-T		Developmental and epileptic encephalopathy, 12	Uncertain significance (Jul 31, 2021)
20-8132682-T-G		Developmental and epileptic encephalopathy, 12 • Inborn genetic diseases	Uncertain significance (Aug 31, 2021)
20-8132693-G-A		Developmental and epileptic encephalopathy, 12 • Inborn genetic diseases • PLCB1-related disorder	Likely benign (Oct 22, 2023)
20-8132696-C-A		Developmental and epileptic encephalopathy, 12	Likely benign (Apr 22, 2023)
20-8132696-C-G		Developmental and epileptic encephalopathy, 12	Likely benign (Jun 24, 2018)
20-8132705-G-A		Developmental and epileptic encephalopathy, 12 • PLCB1-related disorder	Likely benign (Jun 16, 2023)
20-8132713-G-A		Developmental and epileptic encephalopathy, 12	Uncertain significance (Aug 22, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLCB1	protein_coding	protein_coding	ENST00000338037	32	836180

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.983	0.0166	125727	0	21	125748	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.83	381	658	0.579	0.0000350	8034
Missense in Polyphen		50	165.45	0.30221		2020
Synonymous	-1.21	259	235	1.10	0.0000132	2185
Loss of Function	6.30	13	69.8	0.186	0.00000356	895

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000121	0.000121
Ashkenazi Jewish	0.000100	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000926	0.0000924
European (Non-Finnish)	0.0000883	0.0000879
Middle Eastern	0.0000544	0.0000544
South Asian	0.000131	0.000131
Other	0.00	0.00

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.
• Disease: DISEASE: Epileptic encephalopathy, early infantile, 12 (EIEE12) [MIM:613722]: A form of epilepsy characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high- voltage bursts alternating with almost flat suppression phases. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG. {ECO:0000269|PubMed:20833646}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Platelet activation - Homo sapiens (human);Cortisol synthesis and secretion - Homo sapiens (human);Relaxin signaling pathway - Homo sapiens (human);Aldosterone synthesis and secretion - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);Inositol phosphate metabolism - Homo sapiens (human);Long-term potentiation - Homo sapiens (human);Retrograde endocannabinoid signaling - Homo sapiens (human);Serotonergic synapse - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Glutamatergic synapse - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Thyroid hormone synthesis - Homo sapiens (human);Long-term depression - Homo sapiens (human);GnRH signaling pathway - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);Gap junction - Homo sapiens (human);African trypanosomiasis - Homo sapiens (human);Gastric acid secretion - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);Endocrine and other factor-regulated calcium reabsorption - Homo sapiens (human);Renin secretion - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Salivary secretion - Homo sapiens (human);Pancreatic secretion - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Insulin secretion - Homo sapiens (human);Melanogenesis - Homo sapiens (human);Proton Pump Inhibitor Pathway, Pharmacodynamics;Platelet Aggregation Inhibitor Pathway, Pharmacodynamics;Selective Serotonin Reuptake Inhibitor Pathway, Pharmacodynamics;Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;Disopyramide Action Pathway;Procainamide (Antiarrhythmic) Action Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Fosphenytoin (Antiarrhythmic) Action Pathway;Bopindolol Action Pathway;Timolol Action Pathway;Carteolol Action Pathway;Bevantolol Action Pathway;Practolol Action Pathway;Phosphatidylinositol Phosphate Metabolism;Dobutamine Action Pathway;Isoprenaline Action Pathway;Arbutamine Action Pathway;Amiodarone Action Pathway;Levobunolol Action Pathway;Metipranolol Action Pathway;Mexiletine Action Pathway;Lidocaine (Antiarrhythmic) Action Pathway;Quinidine Action Pathway;Sotalol Action Pathway;Epinephrine Action Pathway;Betaxolol Action Pathway;Atenolol Action Pathway;Alprenolol Action Pathway;Acebutolol Action Pathway;Muscle/Heart Contraction;Joubert syndrome;Diltiazem Action Pathway;Propranolol Action Pathway;Pindolol Action Pathway;Penbutolol Action Pathway;Oxprenolol Action Pathway;Metoprolol Action Pathway;Esmolol Action Pathway;Bisoprolol Action Pathway;Bupranolol Action Pathway;Nebivolol Action Pathway;Amlodipine Action Pathway;Verapamil Action Pathway;Nitrendipine Action Pathway;Nisoldipine Action Pathway;Nimodipine Action Pathway;Ibutilide Action Pathway;Tocainide Action Pathway;Flecainide Action Pathway;Isradipine Action Pathway;Nifedipine Action Pathway;Felodipine Action Pathway;Nadolol Action Pathway;Carvedilol Action Pathway;Labetalol Action Pathway;AMP-activated Protein Kinase (AMPK) Signaling;Human Thyroid Stimulating Hormone (TSH) signaling pathway;Alzheimers Disease;Endothelin Pathways;Signal Transduction of S1P Receptor;Cell-type Dependent Selectivity of CCK2R Signaling;GPR40 Pathway;Chemokine signaling pathway;Wnt Signaling Pathway;Signaling by GPCR;D-<i>myo</i>-inositol (1,4,5)-trisphosphate biosynthesis;Signaling by WNT;Signal Transduction;aspirin blocks signaling pathway involved in platelet activation;regulation of ck1/cdk5 by type 1 glutamate receptors;phospholipase c signaling pathway;cadmium induces dna synthesis and proliferation in macrophages;ccr3 signaling in eosinophils;pkc-catalyzed phosphorylation of inhibitory phosphoprotein of myosin phosphatase;eicosanoid metabolism;thrombin signaling and protease-activated receptors;GPCR GroupI metabotropic glutamate receptor;GPCR signaling-G alpha q;Inositol phosphate metabolism;Metabolism;phospholipases;Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion;D-<i>myo</i>-inositol-5-phosphate metabolism;superpathway of inositol phosphate compounds;Presynaptic function of Kainate receptors;Activation of kainate receptors upon glutamate binding;Acetylcholine regulates insulin secretion;Free fatty acids regulate insulin secretion;Regulation of insulin secretion;Neuronal System;activation of pkc through g-protein coupled receptors;Phosphatidylinositol phosphate metabolism;Synthesis of IP3 and IP4 in the cytosol;Ca2+ pathway;Beta-catenin independent WNT signaling;CXCR4-mediated signaling events;fmlp induced chemokine gene expression in hmc-1 cells;Inositol phosphate metabolism;IL2;PLC beta mediated events;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;G-protein mediated events;Opioid Signalling;G alpha (i) signalling events;G beta:gamma signalling through PLC beta;Integration of energy metabolism;G alpha (q) signalling events;G-protein beta:gamma signalling;GPCR downstream signalling;PAR1-mediated thrombin signaling events;IL8- and CXCR1-mediated signaling events;Plasma membrane estrogen receptor signaling;Nongenotropic Androgen signaling;Endothelins;IL8- and CXCR2-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.190

Intolerance Scores

• loftool: 0.581
• rvis_EVS: -0.84
• rvis_percentile_EVS: 11.48

Haploinsufficiency Scores

• pHI: 0.465
• hipred: Y
• hipred_score: 0.652
• ghis: 0.549

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.804

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Plcb1
• Phenotype: craniofacial phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system 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); renal/urinary system phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;signal transduction;G protein-coupled receptor signaling pathway;G protein-coupled acetylcholine receptor signaling pathway;glutamate receptor signaling pathway;Wnt signaling pathway, calcium modulating pathway;memory;regulation of G protein-coupled receptor signaling pathway;lipid catabolic process;cerebral cortex development;positive regulation of interleukin-12 production;inositol trisphosphate biosynthetic process;intracellular signal transduction;interleukin-12-mediated signaling pathway;interleukin-15-mediated signaling pathway;positive regulation of embryonic development;positive regulation of GTPase activity;inositol phosphate metabolic process;fat cell differentiation;positive regulation of myoblast differentiation;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of JNK cascade;phosphatidylinositol metabolic process;insulin-like growth factor receptor signaling pathway;phosphatidylinositol-mediated signaling;positive regulation of developmental growth;release of sequestered calcium ion into cytosol;activation of meiosis involved in egg activation;interleukin-1-mediated signaling pathway;regulation of fertilization;postsynaptic modulation of chemical synaptic transmission;regulation of retrograde trans-synaptic signaling by endocanabinoid;positive regulation of G1/S transition of mitotic cell cycle;positive regulation of acrosome reaction;negative regulation of monocyte extravasation;positive regulation of CD24 biosynthetic process
• Cellular component: nuclear chromatin;nucleus;cytoplasm;cytosol;nuclear speck;nuclear membrane;myelin sheath;extracellular exosome;postsynapse;glutamatergic synapse;GABA-ergic synapse
• Molecular function: phosphatidylinositol phospholipase C activity;phospholipase C activity;GTPase activator activity;calcium ion binding;protein binding;calmodulin binding;lamin binding;phosphatidylinositol-4,5-bisphosphate binding;enzyme binding;protein homodimerization activity