PDZK1: PDZ Domain Containing 1
A scaffold protein regulating cholesterol metabolism, bile acid transport, and renal phosphate homeostasis.
Gene Information Card
| Symbol | PDZK1 |
|---|---|
| Full Name | PDZ domain containing 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q21.1 |
| NCBI Gene ID | 5174 ncbi.nlm.nih.gov/gene/5174 |
| Ensembl ID | ENSG00000143149 |
| UniProt ID | Q5T2W1 |
| OMIM ID | 603831 |
| HGNC ID | 8821 |
| Aliases | NHERF3, PDZD1, CLAMP, CAP70, NaPi-Cap1 |
Description
PDZK1 encodes a scaffold protein containing four PDZ domains. It is involved in the regulation of cholesterol and bile acid metabolism by interacting with the scavenger receptor class B type I (SR-BI) and the apical sodium-dependent bile acid transporter (ASBT). PDZK1 also plays a role in renal phosphate reabsorption by binding to the sodium-phosphate cotransporter NaPi-IIa. The protein is widely expressed in liver, kidney, small intestine, and other tissues.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypercholesterolemia | PDZK1 deficiency impairs SR-BI-mediated hepatic uptake of HDL cholesterol, leading to elevated plasma cholesterol levels. | Mouse models (PMID: 12671074); human association studies (PMID: 17951249) |
| Nephrolithiasis (kidney stones) | Altered PDZK1 expression may affect renal phosphate handling and calcium-phosphate precipitation. | GWAS (PMID: 21743469) |
| Cholestasis | PDZK1 modulates ASBT activity; dysregulation can impair bile acid reabsorption. | Functional studies in cell lines (PMID: 15247290) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 68.5 | High |
| Kidney | 55.2 | High |
| Small Intestine | 42.1 | High |
| Adrenal Gland | 12.3 | Medium |
| Lung | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 45.2 | Hepatocellular carcinoma cell line |
| HK-2 | 38.7 | Proximal tubule epithelial cell line |
| Caco-2 | 29.5 | Colorectal adenocarcinoma cell line |
| HEK293 | 5.1 | Embryonic kidney cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.112C>T (p.Arg38Cys) | Missense | <0.01% | Reduced binding to SR-BI; associated with altered HDL metabolism |
| c.454G>A (p.Glu152Lys) | Missense | <0.01% | Impaired interaction with NaPi-IIa; potential role in phosphate wasting |
| c.789_790del (p.Glu264fs) | Frameshift | <0.01% | Loss of function; predicted nonsense-mediated decay |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense variants (e.g., p.Glu264fs) lead to truncated protein lacking C-terminal PDZ domains, disrupting scaffold function.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in PDZK1.
Dominant Negative (DN)
Missense variants (e.g., p.Arg38Cys) may act dominant-negative by competing with wild-type PDZK1 for binding partners.
View complete mutation data：
Gene Ontology (GO)
Pathways
• HDL-mediated lipid transport (Reactome: R-HSA-8963896)
• Bile acid and bile salt metabolism (Reactome: R-HSA-194068)
• Transport of inorganic cations/anions (Reactome: R-HSA-425393)
Protein Summary
PDZK1 is a 519-amino-acid scaffold protein with four PDZ domains. It localizes to the apical and basolateral membranes of polarized epithelial cells. Through its PDZ domains, PDZK1 binds to the C-terminal PDZ-binding motifs of membrane transporters and receptors, including SR-BI, ASBT, and NaPi-IIa. This interaction is essential for proper trafficking, membrane retention, and function of these proteins. PDZK1 is a key regulator of cholesterol uptake, bile acid homeostasis, and renal phosphate reabsorption.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PDZK1 Knockout HEK293 Cell Line | EDJ-KQ1078 | Human | 5174 | Details Get a Quote |
| PDZK1IP1 Knockout HEK293 Cell Line | EDJ-KQ6928 | Human | 10158 | Details Get a Quote |
| PDZK1 Knockout A-549 Cell Line | EDJ-KQ18873 | Human | 5174 | Details Get a Quote |
| PDZK1 Knockout HeLa Cell Line | EDJ-KQ20218 | Human | 5174 | Details Get a Quote |
| PDZK1IP1 Knockout A-549 Cell Line | EDJ-KQ31574 | Human | 10158 | Details Get a Quote |
| PDZK1IP1 Knockout HeLa Cell Line | EDJ-KQ55330 | Human | 10158 | Details Get a Quote |
| PDZK1 Knockout HCT 116 Cell Line | EDJ-KQ71076 | Human | 5174 | Details Get a Quote |
| PDZK1IP1 Knockout HCT 116 Cell Line | EDJ-KQ72273 | Human | 10158 | Details Get a Quote |
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