PLCB4: Phospholipase C Beta 4
A key enzyme in phosphoinositide signaling, associated with uveal melanoma and developmental disorders.
Gene Information Card
| Symbol | PLCB4 |
|---|---|
| Full Name | Phospholipase C Beta 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 20p12.3-p12.2 |
| NCBI Gene ID | 5332 ncbi.nlm.nih.gov/gene/5332 |
| Ensembl ID | ENSG00000101333 |
| UniProt ID | Q15147 |
| OMIM ID | 600810 |
| HGNC ID | 9059 |
| Aliases | PLC-beta-4, PI-PLC, PLCB4A, PLCB4B |
Description
PLCB4 encodes phospholipase C beta 4, an enzyme that hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to generate second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). It is activated by G-protein alpha subunits (Gq/11) and plays a critical role in intracellular calcium signaling and cell proliferation. Mutations in PLCB4 are recurrent in uveal melanoma and cause auriculocondylar syndrome.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Uveal melanoma | Activating mutations (e.g., D630Y) in the catalytic domain lead to constitutive activation of the PLC pathway, promoting tumorigenesis via MAPK and YAP signaling. | PMID: 23583978, COSMIC |
| Auriculocondylar syndrome (ARCND) | Loss-of-function or dominant-negative mutations disrupt G-protein signaling during craniofacial development, resulting in mandibular hypoplasia and ear malformations. | PMID: 22581970, OMIM #614669 |
| Isolated microtia | Heterozygous missense variants in PLCB4 are associated with isolated ear malformations. | PMID: 28492532 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Retina | 8.2 | Medium |
| Heart | 4.1 | Low |
| Liver | 1.3 | Not detected |
| Kidney | 3.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 6.8 | Moderate expression |
| SK-MEL-28 (melanoma) | 9.5 | High expression |
| MCF7 | 2.1 | Low expression |
| HepG2 | 1.5 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| D630Y | Missense | Recurrent in uveal melanoma (5-10%) | Gain-of-function; constitutive activation |
| E574K | Missense | Rare in uveal melanoma | Gain-of-function |
| R621H | Missense | Germline in ARCND | Loss-of-function/dominant-negative |
| S493L | Missense | Germline in ARCND | Loss-of-function |
Mutation functional classification
Loss of Function (LOF)
Germline missense variants (e.g., R621H, S493L) reduce catalytic activity or disrupt G-protein coupling, leading to auriculocondylar syndrome.
Gain of Function (GOF)
Somatic missense mutations (e.g., D630Y, E574K) in the catalytic domain increase PIP2 hydrolysis, driving uveal melanoma.
Dominant Negative (DN)
Some ARCND mutations (e.g., R621H) may interfere with wild-type PLCB4 dimerization or signaling.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004435 - phosphatidylinositol phospholipase C activity | • GO:0004871 - signal transducer activity |
| • GO:0005509 - calcium ion binding | • GO:0006629 - lipid metabolic process |
| • GO:0007165 - signal transduction | • GO:0016020 - membrane |
Pathways
• Phospholipase C beta signaling (Reactome: R-HSA-112043)
• G alpha (q) signaling events (Reactome: R-HSA-416476)
• GPCR downstream signaling (KEGG: hsa04020)
Protein Summary
PLCB4 is a 1,176-amino-acid protein containing a pleckstrin homology (PH) domain, four EF-hand motifs, a catalytic TIM barrel domain, and a C-terminal C2 domain. It is membrane-associated and activated by Gq/11 subunits. The protein is highly expressed in the brain and retina. Structural mutations in the catalytic domain are oncogenic in uveal melanoma, while loss-of-function variants cause craniofacial developmental defects.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PLCB4 Knockout HEK293 Cell Line | EDJ-KQ322 | Human | 5332 | Details Get a Quote |
| PLCB4 Knockout A-549 Cell Line | EDJ-KQ18472 | Human | 5332 | Details Get a Quote |
| PLCB4 Knockout HCT 116 Cell Line | EDJ-KQ18473 | Human | 5332 | Details Get a Quote |
| PLCB4 Knockout HeLa Cell Line | EDJ-KQ18474 | Human | 5332 | Details Get a Quote |
| PLCB4 Knockout HAP1 Cell Line | EDC08134 | Human | 5332 | Details Get a Quote |
Displaying Records 1 To 5 Of 5 Records
