PCLO piccolo presynaptic cytomatrix protein [Homo sapiens (human)] - Gene

Summary

Official Symbol: PCLOprovided by HGNC
Official Full Name: piccolo presynaptic cytomatrix proteinprovided by HGNC
Primary source: HGNC:HGNC:13406
See related: Ensembl:ENSG00000186472 MIM:604918; AllianceGenome:HGNC:13406
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ACZ; PCH3
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]
Expression: Biased expression in brain (RPKM 4.9), adrenal (RPKM 1.4) and 9 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 7q21.11

Exon count:: 26

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	7	NC_000007.14 (82754012..83162884, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	7	NC_060931.1 (84005231..84414103, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	7	NC_000007.13 (82383328..82792200, complement)

Chromosome 7 - NC_000007.14 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

No symphony without bassoon and piccolo: changes in synaptic active zone proteins in Huntington's disease.
Title: No symphony without bassoon and piccolo: changes in synaptic active zone proteins in Huntington's disease.
In an analysis comparing 1,942 cases with lifetime diagnosis of MDD and 4,565 controls, PCLO showed a genome-wide significant association with major depressive disorder at SNP (rs2715157, p = 2.91 x 10-8) and gene-based (p = 1.48 x 10-7) level.
Title: Genome-Wide Significance for PCLO as a Gene for Major Depressive Disorder.
The results showed that Piccolo, a protein that is essential in the maintenance of active zone structure, constitutes a potential serological correlate of recovery from GBS.
Title: Quantitative proteomics reveals Piccolo as a candidate serological correlate of recovery from Guillain-Barré syndrome.
we report an additional patient with the 7q21.11 deletion syndrome and provide evidence that haploinsufficiency for a single gene may not be the disease mechanism. In vitro studies of the interaction between PCLO and CACNA2D1 will be required to examine the hypothesis that combined haploinsufficiency for these two synaptic proteins results in neuronal dysfunction
Title: A 7q21.11 microdeletion presenting with apparent intellectual disability without epilepsy.
Piccolo contributes to tumor aggressiveness in esophageal squamous cell carcinoma, likely by stabilizing EGFR and promoting EGFR-dependent signaling.
Title: Piccolo mediates EGFR signaling and acts as a prognostic biomarker in esophageal squamous cell carcinoma.
Results provide some support for the involvement of BICC1 and PCLO in late-life depressive disorders and preliminary evidence that these genetic variants may also influence brain structural volumes
Title: GWAS-identified risk variants for major depressive disorder: Preliminary support for an association with late-life depressive symptoms and brain structural alterations.
Study created and characterized a knock-in mouse model carrying the PCLO Ser to Ala missense variant rs2522833, which has shown suggestive association with major depressive disorder in human population studies
Title: Functional characterization of the PCLO p.Ser4814Ala variant associated with major depressive disorder reveals cellular but not behavioral differences.
PCLO intron rs13438494 is associated with drug abuse and contributes to the pathogenesis of psychiatric disorders via modulation of neurotransmitter turnover.
Title: The Piccolo Intronic Single Nucleotide Polymorphism rs13438494 Regulates Dopamine and Serotonin Uptake and Shows Associations with Dependence-Like Behavior in Genomic Association Study.
PCLO risk allele carrying remitted depressed patients did not show more negatively biased memory than non-risk allele carriers, not even patients with stressful childhood events.
Title: No evidence for the association between a polymorphism in the PCLO depression candidate gene with memory bias in remitted depressed patients and healthy individuals.
The subsequent validation study on 68 LCBs identified recurrent mutations in TERT promoter, chromatin regulators (BAP1, PBRM1 and ARID2), a synapse organization gene (PCLO), IDH genes and KRAS.
Title: Whole-genome mutational landscape of liver cancers displaying biliary phenotype reveals hepatitis impact and molecular diversity.

Submit: New GeneRIF Correction See all GeneRIFs (30)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Pontocerebellar hypoplasia type 3 MedGen: C1842687 OMIM: 608027 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome-wide association analysis of gender differences in major depressive disorder in the Netherlands NESDA and NTR population-based samples. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Nef	nef	Genome-wide shRNA screening identifies PCLO, which is required for HIV-1 Nef-induced downregulation of CD4 in HeLa CD4+ cells	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:1317140 (e-PCR)
- UniSTS:55043

RH12234 (e-PCR)
- UniSTS:62986

PCLO (e-PCR)
- UniSTS:503576

GDB:1317692 (e-PCR)
- UniSTS:80155

SHGC-79596 (e-PCR)
- UniSTS:103711

RH123768 (e-PCR)
- UniSTS:137792

WI-22119 (e-PCR)
- UniSTS:48706

GDB:1317962 (e-PCR)
- UniSTS:56647

GDB:1318334 (e-PCR)
- UniSTS:10070

D7S2095E (e-PCR)
- UniSTS:24408

D7S2121E (e-PCR)
- UniSTS:24163

SHGC-56116 (e-PCR)
- UniSTS:24164

SHGC-56120 (e-PCR)
- UniSTS:34164

D7S758 (e-PCR)
- UniSTS:48508

D7S2364 (e-PCR)
- UniSTS:44674

SHGC-31231 (e-PCR)
- UniSTS:49830

D7S1450 (e-PCR)
- UniSTS:60360

GDB:1318573 (e-PCR)
- UniSTS:82904

D7S2350 (e-PCR)
- UniSTS:38621

SHGC-144472 (e-PCR)
- UniSTS:172259

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calcium ion binding	ISS Inferred from Sequence or Structural Similarity more info
enables calcium-dependent phospholipid binding	ISS Inferred from Sequence or Structural Similarity more info
enables profilin binding	ISS Inferred from Sequence or Structural Similarity more info
enables structural constituent of presynaptic active zone	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in cytoskeleton organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in insulin secretion	IEA Inferred from Electronic Annotation more info
involved_in maintenance of presynaptic active zone structure	IEA Inferred from Electronic Annotation more info
involved_in presynaptic actin cytoskeleton organization	IEA Inferred from Electronic Annotation more info
involved_in presynaptic active zone assembly	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein localization to synapse	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of exocytosis	IEA Inferred from Electronic Annotation more info
involved_in synaptic vesicle clustering	IEA Inferred from Electronic Annotation more info
involved_in synaptic vesicle exocytosis	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
is_active_in GABA-ergic synapse	IBA Inferred from Biological aspect of Ancestor more info
is_active_in axon	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoskeleton	NAS Non-traceable Author Statement more info	PubMed
is_active_in cytoskeleton of presynaptic active zone	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoskeleton of presynaptic active zone	TAS Traceable Author Statement more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
is_active_in glutamatergic synapse	IBA Inferred from Biological aspect of Ancestor more info
located_in postsynaptic density	IEA Inferred from Electronic Annotation more info
located_in synapse	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: protein piccolo

Names: aczonin

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_047145.1 RefSeqGene

Range

4998..413870

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_014510.3 → NP_055325.2 protein piccolo isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks several 3' terminal exons and differs at the 3' end compared to variant 1. The resulting isoform (2) has a shorter and distinct C-terminus compared to isoform 1.

Source sequence(s)

AB011131, AC004082, AC004886, AC004903, AC093461, BG913494, DN990884

Consensus CDS

CCDS47631.1

UniProtKB/Swiss-Prot

Q9Y6V0

Related

ENSP00000388393.2, ENST00000423517.6

Conserved Domains (6) summary

PHA03160
Location:446 → 560

PHA03160; hypothetical protein; Provisional

cd04031
Location:4694 → 4826

C2A_RIM1alpha; C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins

cd00992
Location:4496 → 4587

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd15774
Location:587 → 648

FYVE1_PCLO; FYVE-related domain 1 found in protein piccolo

pfam05715
Location:1057 → 1115

zf-piccolo; Piccolo Zn-finger

pfam06346
Location:386 → 531

Drf_FH1; Formin Homology Region 1
NM_033026.6 → NP_149015.2 protein piccolo isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC004006, AC004082, AC004886, AC004903, AC080093, AC093461

Consensus CDS

CCDS47630.1

UniProtKB/Swiss-Prot

A4D1A7, A6NNX9, O43373, O60305, Q08E72, Q9BVC8, Q9UIV2, Q9Y6U9, Q9Y6V0

Related

ENSP00000334319.8, ENST00000333891.14

Conserved Domains (10) summary

cd04031
Location:4694 → 4826

C2A_RIM1alpha; C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins

cd00992
Location:4496 → 4587

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd15774
Location:587 → 648

FYVE1_PCLO; FYVE-related domain 1 found in protein piccolo

pfam05715
Location:1057 → 1115

zf-piccolo; Piccolo Zn-finger

cl14603
Location:5005 → 5134

C2; C2 domain

cl25580
Location:947 → 1027

OxoGdeHyase_C; 2-oxoglutarate dehydrogenase C-terminal

cl26386
Location:32 → 411

DNA_pol3_gamma3; DNA polymerase III subunits gamma and tau domain III

cl26464
Location:308 → 905

Atrophin-1; Atrophin-1 family

cl26511
Location:1157 → 1700

Neuromodulin_N; Gap junction protein N-terminal region

cl28087
Location:3460 → 3965

FtsK; DNA segregation ATPase FtsK/SpoIIIE and related proteins [Cell cycle control, cell division, chromosome partitioning]