PCLO

piccolo presynaptic cytomatrix protein, the group of Zinc fingers PCLO-type|PDZ domain containing|C2 domain containing

Basic information

Region (hg38): 7:82754012-83162930

Links

ENSG00000186472 ∙ NCBI:27445 ∙ OMIM:604918 ∙ HGNC:13406 ∙ Uniprot:Q9Y6V0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pontocerebellar hypoplasia type 3 (Moderate), mode of inheritance: AR
• pontocerebellar hypoplasia type 3 (Supportive), mode of inheritance: AR
• pontocerebellar hypoplasia type 3 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pontocerebellar hypoplasia, type 3	AR	General	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	Craniofacial; Musculoskeletal; Neurologic	25832664

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PCLO gene.

• not provided (49 variants)
• Pontocerebellar hypoplasia type 3 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PCLO gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			11	774	33	818
missense		1	1515	40	32	1588
nonsense	31	1	1			33
start loss						0
frameshift	19	1				20
inframe indel			43	2	4	49
splice donor/acceptor (+/-2bp)		2				2
splice region			15	76	6	97
non coding			4	102	12	118
Total	50	5	1574	918	81

Highest pathogenic variant AF is 0.00000657

Variants in PCLO

This is a list of pathogenic ClinVar variants found in the PCLO region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-82758578-A-G			Likely benign (Aug 09, 2022)
7-82758579-T-C			Likely benign (Jan 22, 2024)
7-82758581-C-A			Likely benign (Nov 17, 2021)
7-82758581-C-T			Likely benign (Sep 05, 2023)
7-82758582-G-A			Uncertain significance (Jan 18, 2021)
7-82758589-T-C			Uncertain significance (Aug 16, 2022)
7-82758591-G-A			Uncertain significance (May 03, 2022)
7-82758604-G-C			Uncertain significance (Oct 28, 2021)
7-82758625-T-G			Likely benign (Nov 28, 2022)
7-82758639-A-T			Uncertain significance (Jun 14, 2022)
7-82758643-T-G			Uncertain significance (Jul 14, 2022)
7-82758644-G-A			Benign (Feb 01, 2024)
7-82758648-A-G			Uncertain significance (Dec 11, 2023)
7-82758659-G-A			Likely benign (Dec 02, 2022)
7-82758665-A-G			Likely benign (Nov 01, 2022)
7-82758671-C-T			Likely benign (Dec 02, 2023)
7-82758698-A-G			Likely benign (Nov 18, 2023)
7-82758699-T-C		Inborn genetic diseases	Uncertain significance (Dec 20, 2022)
7-82758705-A-G			Uncertain significance (Sep 18, 2021)
7-82758711-A-G		Inborn genetic diseases	Uncertain significance (Apr 06, 2023)
7-82758715-T-C			Uncertain significance (Aug 22, 2021)
7-82758719-G-T			Likely benign (Aug 13, 2022)
7-82758719-G-GA		PCLO-related disorder	Benign (Jan 24, 2023)
7-82758730-CA-C			Benign (May 16, 2022)
7-82758735-A-G			Likely benign (Nov 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PCLO	protein_coding	protein_coding	ENST00000333891	25	408918

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	7.27e-20	124611	0	40	124651	0.000160

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.46	2752	2.54e+3	1.08	0.000131	33180
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00140	0.000821
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000558	0.0000556
Finnish	0.000140	0.000139
European (Non-Finnish)	0.000162	0.000150
Middle Eastern	0.0000558	0.0000556
South Asian	0.000207	0.000163
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• 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.
• Pathway: Insulin secretion - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.0851

Intolerance Scores

• rvis_EVS: -0.18
• rvis_percentile_EVS: 40.57

Haploinsufficiency Scores

• pHI: 0.207
• hipred: Y
• hipred_score: 0.514
• ghis: 0.551

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.687

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Pclo
• Phenotype: normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); growth/size/body region phenotype

Gene ontology

• Biological process: cytoskeleton organization;synapse assembly;synaptic vesicle exocytosis;regulation of exocytosis;cAMP-mediated signaling;insulin secretion;protein localization to synapse;maintenance of presynaptic active zone structure;synaptic vesicle clustering;presynapse to nucleus signaling pathway
• Cellular component: cytoskeleton;postsynaptic density;cell junction;synapse;cytoskeleton of presynaptic active zone;extracellular exosome
• Molecular function: calcium ion binding;profilin binding;calcium-dependent phospholipid binding;structural constituent of presynaptic active zone