PICK1

Chr 22

protein interacting with PRKCA 1

Also known as: PICK, PRKCABP

NCBI Gene: 9463ENSG00000100151UniProt: Q9NRD5

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]

78
ClinVar variants
26
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— PICK1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 33 VUS of 78 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.67LOEUF
pLI 0.008
Z-score 2.64
OE 0.36 (0.20–0.67)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.36 (0.20–0.67)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.65 (0.57–0.74)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 7 / 19.6Missense obs/exp: 172 / 264.0Syn Z: -0.06

ClinVar Variant Classifications

78 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic3
VUS33
Likely Benign1
Benign3
Conflicting1
23
Pathogenic
3
Likely Pathogenic
33
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
32
1
0
33
Likely Benign
0
0
0
1
1
Benign
0
0
2
1
3
Conflicting
—1
Total03229264

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The schizophrenic faces of PICK1.
Dev KK et al.·Trends Pharmacol Sci
2006Review
Multi-omics study identifies that PICK1 deficiency causes male infertility by inhibiting vesicle trafficking in Sertoli cells.
Jin J et al.·Reprod Biol Endocrinol
2023
Truncating PICK1 Variant Identified in Azoospermia Affected Mitochondrial Dysfunction in Knockout Mice.
Du YQ et al.·Curr Med Sci
2023
Rescuing infertility of Pick1 knockout mice by generating testis-specific transgenic mice via testicular infection.
Li X et al.·Sci Rep
2013
The TGF-β signalling negative regulator PICK1 represses prostate cancer metastasis to bone.
Dai Y et al.·Br J Cancer
2017
PICK1 modulates the proliferation and migration of gastric cancer cells by regulating TLR4.
Li K et al.·J Zhejiang Univ Sci B
2025
PICK1 Genetic Variation and Cognitive Function in Patients with Schizophrenia.
Chen YT et al.·Sci Rep
2017Cohort
PICK1 deficiency causes male infertility in mice by disrupting acrosome formation.
Xiao N et al.·J Clin Invest
2009
Identification and treatment of men with phospholipase Cζ-defective spermatozoa.
Cheung S et al.·Fertil Steril
2020
Single-center thorough evaluation and targeted treatment of globozoospermic men.
Cheung S et al.·J Assist Reprod Genet
2021Clinical trial
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Discovery of novel pyrrolidine-2,5-dione scaffold PICK1 PDZ inhibitors as anti-ischemic stroke agents.
Jiang Y et al.·Eur J Med Chem
2026
PICK1 overexpression ameliorates endotoxin-induced acute lung injury by regulating mitochondrial quality control via maintaining Nrf-2 stabilization through activating the PI3K/Akt/GSK-3β pathway and disrupting the E3 ubiquitin ligase adapter β-TrCP.
Qian M et al.·Int Immunopharmacol
2025
Exploration of the multiomics-based mechanisms of Gancao Nourishing-Yin decoction in regulating mitochondrial metabolic genes CYB5R3 and PICK1 to influence glioma progression.
Chen Y et al.·Discov Oncol
2025🔓 Open AccessFunctional
PICK1 links KIBRA and AMPA receptor subunit GluA2 in coiled-coil-driven supramolecular complexes.
Shao X et al.·J Biol Chem
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools