PICK1

Chr 22

protein interacting with PRKCA 1

Also known as: PICK, PRKCABP

NCBI Gene: 9463ENSG00000100151UniProt: Q9NRD5OMIM: 605926

The PICK1 protein functions as an adapter that organizes subcellular localization of membrane proteins and regulates synaptic plasticity by controlling AMPA receptor trafficking and internalization. Mutations in PICK1 cause neurodevelopmental disorders with intellectual disability and seizures. The gene shows autosomal recessive inheritance and is not highly constrained to loss-of-function variants.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.67
Clinical Summary— PICK1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
26 unique Pathogenic / Likely Pathogenic· 34 VUS of 79 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.67LOEUF
pLI 0.008
Z-score 2.64
OE 0.36 (0.20–0.67)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
2.01Z-score
OE missense 0.65 (0.57–0.74)
172 obs / 264.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.36 (0.20–0.67)
0≤0.351.4
Missense OE0.65 (0.57–0.74)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 7 / 19.6Missense obs/exp: 172 / 264.0Syn Z: -0.06
DN
0.6646th %ile
GOF
0.74top 25%
LOF
0.3648th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

79 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic3
VUS34
Likely Benign1
Benign3
Conflicting1
23
Pathogenic
3
Likely Pathogenic
34
VUS
1
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
23
0
23
Likely Pathogenic
0
0
3
0
3
VUS
0
33
1
0
34
Likely Benign
0
0
0
1
1
Benign
0
0
2
1
3
Conflicting
—1
Total03329265

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PICK1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients