PDZK1

Chr 1

PDZ domain containing 1

Also known as: CAP70, CLAMP, NHERF-3, NHERF3, PDZD1

NCBI Gene: 5174ENSG00000174827UniProt: Q5T2W1

This gene encodes a PDZ domain-containing scaffolding protein. PDZ domain-containing molecules bind to and mediate the subcellular localization of target proteins. The encoded protein mediates the localization of cell surface proteins and plays a critical role in cholesterol metabolism by regulating the HDL receptor, scavenger receptor class B type 1. Single nucleotide polymorphisms in this gene may be associated with metabolic syndrome, and overexpression of this gene may play a role in drug resistance of multiple myeloma. Pseudogenes of this gene are located on the long arm of chromosome 1. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

275
ClinVar variants
132
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PDZK1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
132 Pathogenic / Likely Pathogenic· 119 VUS of 275 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.
1.71LOEUF
pLI 0.000
Z-score -0.34
OE 1.11 (0.72–1.71)
Tolerant

Highly tolerant — LoF variants common in population

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.
-0.05Z-score
OE missense 1.01 (0.89–1.15)
173 obs / 171.2 exp
Tolerant

Tolerant to missense variation

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.1.11 (0.72–1.71)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.89–1.15)
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.0.88
0≤1.21.6
LoF obs/exp: 13 / 11.7Missense obs/exp: 173 / 171.2Syn Z: 0.76

ClinVar Variant Classifications

275 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic113
Likely Pathogenic19
VUS119
Likely Benign6
Benign8
Conflicting2
113
Pathogenic
19
Likely Pathogenic
119
VUS
6
Likely Benign
8
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
113
0
113
Likely Pathogenic
0
0
19
0
19
VUS
0
42
77
0
119
Likely Benign
0
3
2
1
6
Benign
0
1
7
0
8
Conflicting
—2
Total0462181267

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

View in ClinVar →

Protein Context — Lollipop Plot

PDZK1 · 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
PDZK1 suppresses TNBC development and sensitizes TNBC cells to erlotinib via the EGFR pathway.
Ma Y et al.·Cell Death Dis
2024
Common variant of PDZ domain containing 1 (PDZK1) gene is associated with gout susceptibility: A replication study and meta-analysis in Japanese population.
Higashino T et al.·Drug Metab Pharmacokinet
2016Meta-analysis
PDZK1 inhibits MRP2-mediated oxaliplatin chemosensitivity in hepatocellular carcinoma.
Duan Z et al.·Sci Rep
2025
Roles of circ_0000135/miR-140-3p/PDZK1 network in cervical cancer.
Wang N et al.·Clin Transl Oncol
2022
PDZK1 induces resistance to apoptosis in esophageal adenocarcinoma cells.
Handa O et al.·Esophagus
2021
Loss of PDZK1 expression activates PI3K/AKT signaling via PTEN phosphorylation in gastric cancer.
Zhao C et al.·Cancer Lett
2019
PDZK1 Interacting Protein 1 Promotes the Progression of Papillary Thyroid Cancer.
Wang K et al.·J Clin Endocrinol Metab
2022
PDZK1 confers sensitivity to sunitinib in clear cell renal cell carcinoma by suppressing the PDGFR-β pathway.
Wang H et al.·Br J Cancer
2024
A non-coding genetic variant maximally associated with serum urate levels is functionally linked to HNF4A-dependent PDZK1 expression.
Ketharnathan S et al.·Hum Mol Genet
2018Functional
PDZK1 inhibits the development and progression of renal cell carcinoma by suppression of SHP-1 phosphorylation.
Tao T et al.·Oncogene
2017
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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