PLCB3
protein-codingphospholipase C beta 3, the group of C2 domain containing phospholipases|Phospholipases
Gene summary
This gene encodes a member of the phosphoinositide phospholipase C beta enzyme family that catalyze the production of the secondary messengers diacylglycerol and inositol 1,4,5-triphosphate from phosphatidylinositol in G-protein-linked receptor-mediated signal transduction. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~17.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0030074
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0016763
Submitter: Franklin by Genoox
Two affected cusins from a consanguineous family with a new autosomal recessive (AR) SMD associated with intellectual disability and corneal dystrophy (SMDCD) were found to carry a homozygous variant in PLCB3 gene.
Inheritance Pattern: Unknown
Disease ID:MONDO:0030074
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic
Intervention: Cardiovascular
Rationale: The condition can involve congenital cardiac anomalies, and awareness may allow early management
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PLCB3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000932.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 9 | 2 | 12 | ||
| missense | 1 | 133 | 8 | 3 | 145 | |
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 1 | 139 | 17 | 5 | 162 |
Highest pathogenic variant AF is 0.000017458213
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000923.1 | 31 | MANE Select | |
| Ensembl | ENSP00000279230.6 | 31 | MANE Select | |
| RefSeq | NP_001171812.1 | 29 | Standard | |
| RefSeq | NP_001303243.1 | 31 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| plcb3 | Danio rerio | Structure: osteoblast Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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)
Biological Process
- regulation of systemic arterial blood pressure
- G protein-coupled receptor signaling pathway
- Wnt signaling pathway, calcium modulating pathway
- lipid catabolic process
- inositol trisphosphate biosynthetic process
Molecular Function
- phosphatidylinositol phospholipase C activity
- phospholipase C activity
- calcium ion binding
- protein binding
- calmodulin binding
Cellular Component
- nucleoplasm
- cytosol
- membrane
- protein-containing complex
- postsynaptic cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000540288
- Coding exons
- 31
- Length
- 17628
- Individuals with no LoFs
- 125723
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 24
- Defined
- 125747
- p
- 0.0000954
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.27 | 512 | 766 | 0.668 | 0.0000533 | 7922 |
| Missense (PolyPhen) | 150 | 313.86 | 0.47791 | 3377 | ||
| Synonymous | -0.285 | 330 | 323 | 1.02 | 0.0000224 | 2468 |
| Loss of Function | 6.06 | 13 | 66.2 | 0.196 | 0.00000356 | 734 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00026 | 0.00025 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00011 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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.;
Recessive Scores
- pRec
- 0.173
Intolerance Scores
- LoFtool
- 0.488
- RVIS EVS
- -0.64
- RVIS percentile EVS
- 16.74
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.818
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |