PICK1

protein interacting with PRKCA 1, the group of PDZ domain containing|AH domain containing

Basic information

Region (hg38): 22:38056310-38075701

Previous symbols: [ "PRKCABP" ]

Links

ENSG00000100151 ∙ NCBI:9463 ∙ OMIM:605926 ∙ HGNC:9394 ∙ Uniprot:Q9NRD5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• male infertility due to globozoospermia (Supportive), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PICK1 gene.

• Inborn genetic diseases (9 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PICK1 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					1	1
missense			9			9
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	9	0	1

Variants in PICK1

This is a list of pathogenic ClinVar variants found in the PICK1 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-38057829-A-G		not specified	Uncertain significance (Jun 29, 2022)
22-38065062-G-C		not specified	Uncertain significance (Oct 29, 2021)
22-38069027-G-A		PICK1-related disorder	Benign/Likely benign (Aug 14, 2019)
22-38069083-G-A		not specified	Uncertain significance (Apr 26, 2023)
22-38071738-C-G		not specified	Uncertain significance (Jan 08, 2024)
22-38071742-G-A		not specified	Uncertain significance (Apr 07, 2022)
22-38072497-G-A		not specified	Uncertain significance (Jul 25, 2023)
22-38072522-C-G		not specified	Uncertain significance (Oct 03, 2023)
22-38073028-A-G		not specified	Uncertain significance (Mar 01, 2023)
22-38073806-G-A		not specified	Uncertain significance (Aug 17, 2022)
22-38074340-G-A		not specified	Uncertain significance (Dec 19, 2023)
22-38074449-A-G		not specified	Uncertain significance (Oct 17, 2023)
22-38074931-C-T			Benign (Mar 30, 2018)
22-38074932-G-A		not specified	Uncertain significance (Aug 28, 2023)
22-38075025-G-A		not specified	Uncertain significance (Aug 17, 2022)
22-38075035-A-G		not specified	Uncertain significance (Jan 04, 2022)
22-38075083-G-A		not specified	Uncertain significance (Oct 20, 2023)
22-38075140-G-A		PICK1-related disorder	Benign (Jun 10, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PICK1	protein_coding	protein_coding	ENST00000404072	12	19391

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00818	0.989	125451	0	295	125746	0.00117

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.01	172	264	0.651	0.0000186	2703
Missense in Polyphen		53	97.808	0.54188		962
Synonymous	-0.0573	110	109	1.01	0.00000802	789
Loss of Function	2.64	7	19.6	0.357	8.55e-7	252

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00434	0.00432
Ashkenazi Jewish	0.00463	0.00388
East Asian	0.000228	0.000217
Finnish	0.00276	0.00264
European (Non-Finnish)	0.000583	0.000554
Middle Eastern	0.000228	0.000217
South Asian	0.0000334	0.0000327
Other	0.00143	0.00130

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable adapter protein that bind to and organize the subcellular localization of a variety of membrane proteins containing some PDZ recognition sequence. Involved in the clustering of various receptors, possibly by acting at the receptor internalization level. Plays a role in synaptic plasticity by regulating the trafficking and internalization of AMPA receptors. May be regulated upon PRKCA activation. May regulate ASIC1/ASIC3 channel. Regulates actin polymerization by inhibiting the actin-nucleating activity of the Arp2/3 complex; the function is competetive with nucleation promoting factors and is linked to neuronal morphology regulation and AMPA receptor (AMPAR) endocytosis. Via interaction with the Arp2/3 complex involved in regulation of synaptic plasicity of excitatory synapses and required for spine shrinkage during long-term depression (LTD). Involved in regulation of astrocyte morphology, antagonistic to Arp2/3 complex activator WASL/N-WASP function. {ECO:0000269|PubMed:20403402}.
• Pathway: Neuronal System;Cell surface interactions at the vascular wall;Hemostasis;Trafficking of GluR2-containing AMPA receptors;Trafficking of AMPA receptors;Glutamate binding, activation of AMPA receptors and synaptic plasticity;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses (Consensus)

Recessive Scores

• pRec: 0.270

Intolerance Scores

• loftool: 0.397
• rvis_EVS: -0.8
• rvis_percentile_EVS: 12.24

Haploinsufficiency Scores

• pHI: 0.238
• hipred: Y
• hipred_score: 0.785
• ghis: 0.680

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.945

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pick1
• Phenotype: endocrine/exocrine gland phenotype; cellular phenotype; 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); reproductive system phenotype

Gene ontology

• Biological process: positive regulation of receptor internalization;protein phosphorylation;intracellular protein transport;retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum;protein kinase C-activating G protein-coupled receptor signaling pathway;monoamine transport;glial cell development;negative regulation of Arp2/3 complex-mediated actin nucleation;cellular response to decreased oxygen levels;cellular response to glucose starvation;DNA methylation involved in embryo development;DNA methylation involved in gamete generation;receptor clustering;neuronal ion channel clustering;long-term synaptic depression;dendritic spine organization;dendritic spine maintenance
• Cellular component: cytoplasm;mitochondrion;Golgi apparatus;cytosol;cytoskeleton;plasma membrane;synaptic vesicle;postsynaptic density;aggresome;cell junction;endocytic vesicle membrane;trans-Golgi network membrane;presynaptic membrane;neuron projection;synapse;postsynaptic membrane;perinuclear region of cytoplasm;postsynaptic early endosome
• Molecular function: G protein-coupled receptor binding;protein kinase C binding;signaling receptor binding;protein binding;phospholipid binding;protein C-terminus binding;enzyme binding;protein domain specific binding;identical protein binding;metal ion binding;actin filament binding;Arp2/3 complex binding