PCLO (Piccolo Presynaptic Cytomatrix Protein)
Gene encoding a key component of the presynaptic cytomatrix involved in neurotransmitter release and synaptic vesicle trafficking.
Gene Information Card
| Symbol | PCLO |
|---|---|
| Full Name | Piccolo presynaptic cytomatrix protein |
| Gene Type | Protein coding |
| Chromosomal Location | 7q21.11 |
| NCBI Gene ID | 27445 ncbi.nlm.nih.gov/gene/27445 |
| Ensembl ID | ENSG00000186472 |
| UniProt ID | Q9Y6V0 |
| OMIM ID | 604918 |
| HGNC ID | 8736 |
| Aliases | ACZ, KIAA0559, PCLO1, PCLO2, piccolo |
Description
PCLO encodes Piccolo, a large multidomain protein localized to the presynaptic active zone. It functions as a scaffolding protein that organizes synaptic vesicle clusters and regulates neurotransmitter release. Piccolo interacts with other presynaptic proteins and is involved in synaptic plasticity and calcium-dependent exocytosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Major depressive disorder | Genetic association studies link PCLO variants to altered synaptic function and mood regulation. | GWAS and meta-analyses (PMID: 20393459, 22543898) |
| Bipolar disorder | Variants in PCLO may affect presynaptic calcium signaling and neurotransmitter release. | Case-control studies (PMID: 22543898) |
| Schizophrenia | Rare copy number variants and SNPs in PCLO have been associated with schizophrenia risk. | Genome-wide studies (PMID: 25056061) |
| Autism spectrum disorder | De novo mutations in PCLO identified in ASD cohorts. | Exome sequencing studies (PMID: 25363760) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 38.2 | High |
| Cerebral cortex | 45.1 | High |
| Cerebellum | 32.7 | High |
| Hippocampus | 41.5 | High |
| Testis | 6.3 | Low |
| Heart | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 12.4 | Neuronal model |
| U-87 MG (glioblastoma) | 8.1 | Glial origin |
| HEK 293 (embryonic kidney) | 0.5 | Non-neuronal control |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <0.01% | Loss of function; predicted nonsense-mediated decay |
| c.4567G>A (p.Glu1523Lys) | Missense | 0.02% | Unknown significance; may affect protein interactions |
| c.7890_7891insA (p.Leu2631Thrfs*5) | Frameshift | <0.01% | Loss of function; truncation |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to premature termination codons and likely haploinsufficiency.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in PCLO.
Dominant Negative (DN)
Not established; potential dominant-negative effects from missense mutations disrupting scaffolding function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Synaptic vesicle cycle (Reactome: R-HSA-421837)
• Neurotransmitter release cycle (Reactome: R-HSA-112310)
• Presynaptic function (KEGG: hsa04721)
Protein Summary
Piccolo is a large (~530 kDa) multidomain protein that acts as a scaffold at the presynaptic active zone. It contains multiple zinc-finger domains, coiled-coil regions, and a PDZ domain. Piccolo binds to other active zone proteins (e.g., Bassoon, RIM) and regulates synaptic vesicle clustering, calcium channel localization, and neurotransmitter release. It is essential for normal synaptic transmission and plasticity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PCLO Knockout HEK293 Cell Line | EDJ-KQ8784 | Human | 27445 | Details Get a Quote |
| PCLO Knockout HCT 116 Cell Line | EDJ-KQ35059 | Human | 27445 | Details Get a Quote |
| PCLO Knockout HeLa Cell Line | EDJ-KQ35060 | Human | 27445 | Details Get a Quote |
| PCLO Knockout A-549 Cell Line | EDJ-KQ64553 | Human | 27445 | Details Get a Quote |
