PCLO
protein-codingpiccolo presynaptic cytomatrix protein, the group of Zinc fingers PCLO-type|PDZ domain containing|C2 domain containing
Gene summary
The protein encoded by this gene is part of the presynaptic cytoskeletal matrix, which is involved in establishing active synaptic zones and in synaptic vesicle trafficking. Variations in this gene have been associated with bipolar disorder and major depressive disorder. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~408.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0011948
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0011948
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0011948
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0011948
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Musculoskeletal; Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PCLO variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_033026.6. 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 | 10 | 981 | 17 | 1008 | ||
| missense | 1831 | 104 | 22 | 1957 | ||
| nonsense | 37 | 3 | 7 | 47 | ||
| start loss | 0 | |||||
| frameshift | 29 | 5 | 13 | 47 | ||
| splice donor/acceptor (+/-2bp) | 4 | 3 | 7 | |||
| Total | 66 | 12 | 1864 | 1085 | 39 | 3066 |
Highest pathogenic variant AF is 0.0000065731524
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_149015.2 | 25 | MANE Select | |
| Ensembl | ENSP00000334319.8 | 25 | MANE Select | |
| RefSeq | NP_055325.2 | 20 | Standard | |
| Ensembl | ENSP00000404191.2 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Insulin secretion - Homo sapiens (human)
Biological Process
- cytoskeleton organization
- synapse assembly
- synaptic vesicle exocytosis
- regulation of exocytosis
- cAMP-mediated signaling
Molecular Function
- calcium ion binding
- profilin binding
- calcium-dependent phospholipid binding
- structural constituent of presynaptic active zone
Cellular Component
- cytoskeleton
- postsynaptic density
- cell junction
- synapse
- cytoskeleton of presynaptic active zone
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000333891
- Coding exons
- 25
- Length
- 408918
- Individuals with no LoFs
- 124611
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 40
- Defined
- 124651
- p
- 0.000160
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.46 | 2752 | 2.54e+3 | 1.08 | 0.000131 | 33180 |
| Missense (PolyPhen) | 6 | 9.1628 | 0.65482 | 105 | ||
| Synonymous | -3.93 | 1084 | 932 | 1.16 | 0.0000483 | 10421 |
| Loss of Function | 11.6 | 15 | 186 | 0.0809 | 0.0000105 | 2428 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0012 | 0.00065 | notable |
| Latino/Admixed American | 0.00017 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00016 | 0.00015 | rare |
| South Asian | 0.00021 | 0.00016 | rare |
| Other | 0.00017 | 0.00017 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May act as a scaffolding protein involved in the organization of synaptic active zones and in synaptic vesicle trafficking. {ECO:0000250|UniProtKB:Q9QYX7}.;
- Disease
- DISEASE: Pontocerebellar hypoplasia 3 (PCH3) [MIM:608027]: A form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum. Brain MRI shows an abnormally small cerebellum and brainstem, decreased cerebral white matter, and a thin corpus callosum. PCH3 features include seizures, short stature, optic atrophy, progressive microcephaly, severe developmental delay. {ECO:0000269|PubMed:25832664}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.0851
Intolerance Scores
- RVIS EVS
- -0.18
- RVIS percentile EVS
- 40.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.687
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |