PICK1
protein-codingprotein interacting with PRKCA 1, the group of PDZ domain containing|AH domain containing
Gene summary
The protein encoded by this gene contains a PDZ domain, through which it interacts with protein kinase C, alpha (PRKCA). This protein may function as an adaptor that binds to and organizes the subcellular localization of a variety of membrane proteins. It has been shown to interact with multiple glutamate receptor subtypes, monoamine plasma membrane transporters, as well as non-voltage gated sodium channels, and may target PRKCA to these membrane proteins and thus regulate their distribution and function. This protein has also been found to act as an anchoring protein that specifically targets PRKCA to mitochondria in a ligand-specific manner. Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]
- PRKCABP
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~19.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0015746
Submitter: Orphanet
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PICK1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012407.4. 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 | 1 | 1 | 2 | |||
| missense | 33 | 33 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 38 | 1 | 1 | 40 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036539.1 | 12 | MANE Select | |
| Ensembl | ENSP00000349465.3 | 12 | MANE Select | |
| RefSeq | NP_001034672.1 | 12 | Standard | |
| RefSeq | NP_001034673.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neuronal System
- Cell surface interactions at the vascular wall
- Hemostasis
- Trafficking of GluR2-containing AMPA receptors
- Trafficking of AMPA receptors
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
Molecular Function
- G protein-coupled receptor binding
- protein kinase C binding
- signaling receptor binding
- protein binding
- phospholipid binding
Cellular Component
- cytoplasm
- mitochondrion
- Golgi apparatus
- cytosol
- cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000404072
- Coding exons
- 12
- Length
- 19391
- Individuals with no LoFs
- 125451
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 295
- Defined
- 125746
- p
- 0.00117
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.01 | 172 | 264 | 0.651 | 0.0000186 | 2703 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00033 | 0.00031 | rare |
| Latino/Admixed American | 0.0040 | 0.0034 | notable |
| Ashkenazi Jewish | 0.0046 | 0.0039 | notable |
| East Asian | 0.00023 | 0.00022 | rare |
| Finnish | 0.0028 | 0.0026 | notable |
| European (Non-Finnish) | 0.00058 | 0.00055 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.0014 | 0.0013 | notable |
dbNSFP Gene Annotations
Source:
- 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}.;
Recessive Scores
- pRec
- 0.270
Intolerance Scores
- LoFtool
- 0.397
- RVIS EVS
- -0.8
- RVIS percentile EVS
- 12.24
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.945
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |