PKD1: Polycystin-1, Key Regulator in Autosomal Dominant Polycystic Kidney Disease
Comprehensive genomic and proteomic overview of PKD1, its role in renal cystogenesis, and clinical significance.
Gene Information Card
| Symbol | PKD1 |
|---|---|
| Full Name | polycystin 1, transient receptor potential channel interacting |
| Gene Type | protein-coding |
| Chromosomal Location | 16p13.3 |
| NCBI Gene ID | 5310 ncbi.nlm.nih.gov/gene/5310 |
| Ensembl ID | ENSG00000008710 |
| UniProt ID | P98161 |
| OMIM ID | 601313 |
| HGNC ID | 9008 |
| Aliases | PBP, PKD1_HUMAN, TRPP1, PC1 |
Description
PKD1 encodes polycystin-1, a large transmembrane protein involved in cell-cell/matrix interactions, mechanosensation, and calcium signaling. It forms a complex with polycystin-2 (PKD2) to regulate tubular morphogenesis and renal epithelial homeostasis. Loss-of-function mutations in PKD1 are the primary cause of autosomal dominant polycystic kidney disease (ADPKD), accounting for ~85% of cases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal dominant polycystic kidney disease (ADPKD) | Loss-of-function mutations in PKD1 disrupt polycystin-1/polycystin-2 complex, impairing calcium signaling and leading to uncontrolled cyst growth in renal tubules. | ClinVar, OMIM |
| Polycystic liver disease | PKD1 mutations can also cause hepatic cystogenesis due to defective polycystin-1 function in biliary epithelium. | OMIM, PubMed |
| Intracranial aneurysm | ADPKD patients with PKD1 mutations have increased risk of intracranial aneurysms, possibly due to altered vascular smooth muscle cell mechanotransduction. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Liver | 8.3 | Low |
| Pancreas | 6.1 | Low |
| Brain | 4.7 | Low |
| Heart | 3.9 | Low |
| Lung | 2.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression in embryonic kidney cell line |
| HepG2 | 9.8 | Moderate expression in liver carcinoma cells |
| A549 | 4.1 | Low expression in lung carcinoma cells |
| MCF7 | 2.3 | Low expression in breast cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.12664C>T (p.Arg4222*) | Nonsense | ~2% of ADPKD cases | Premature stop, loss of polycystin-1 function |
| c.5014_5015delAG (p.Arg1672Glyfs*12) | Frameshift | ~1.5% of ADPKD cases | Frameshift leading to truncated protein |
| c.10990C>T (p.Arg3664Cys) | Missense | ~0.8% of ADPKD cases | Altered protein folding and reduced function |
| c.12445-1G>A | Splice site | ~1% of ADPKD cases | Exon skipping, loss of functional protein |
Mutation functional classification
Loss of Function (LOF)
Majority of PKD1 mutations are loss-of-function (nonsense, frameshift, splice site, large deletions), leading to haploinsufficiency or complete loss of polycystin-1, which disrupts the polycystin complex and causes cyst formation.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported for PKD1 in ADPKD or cancer.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg3664Cys) may exert dominant-negative effects by interfering with polycystin-1/polycystin-2 complex assembly, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Calcium signaling pathway (KEGG: hsa04020)
• Polycystin-1/Polycystin-2 complex signaling
• Mechanotransduction and ciliary signaling
• Wnt signaling (modulation by polycystin-1)
Protein Summary
Polycystin-1 (PC1) is a 4302-amino acid transmembrane protein with a large extracellular N-terminal region containing multiple domains (e.g., PKD repeats, LDL-A, C-type lectin) involved in cell adhesion and ligand binding. The intracellular C-terminal tail contains a G-protein-binding domain and a coiled-coil region that interacts with polycystin-2. PC1 functions as a mechanosensor in primary cilia, regulating calcium influx and downstream signaling pathways essential for renal tubular maintenance. Mutations in PKD1 lead to defective ciliary signaling and cystogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PKD1L2 Knockout HEK293 Cell Line | EDJ-KQ7456 | Human | 114780 | Details Get a Quote |
| PKD1L1 Knockout HEK293 Cell Line | EDJ-KQ12114 | Human | 168507 | Details Get a Quote |
| PKD1L3 Knockout HEK293 Cell Line | EDJ-KQ12136 | Human | 342372 | Details Get a Quote |
| PKD1 Knockout HEK293 Cell Line | EDJ-KQ14777 | Human | 5310 | Details Get a Quote |
| PKD1 Knockout HeLa Cell Line | EDJ-KQ43925 | Human | 5310 | Details Get a Quote |
| PKD1L2 Knockout A-549 Cell Line | EDJ-KQ32669 | Human | 114780 | Details Get a Quote |
| PKD1L2 Knockout HCT 116 Cell Line | EDJ-KQ32670 | Human | 114780 | Details Get a Quote |
| PKD1L2 Knockout HeLa Cell Line | EDJ-KQ32671 | Human | 114780 | Details Get a Quote |
| PKD1 Knockout A-549 Cell Line | EDJ-KQ45174 | Human | 5310 | Details Get a Quote |
| PKD1 Knockout HCT 116 Cell Line | EDJ-KQ45175 | Human | 5310 | Details Get a Quote |
| PKD1 Knockout H1 Cell Line | EDJ-KZ401 | Human | 5310 | Details Get a Quote |
| PKD1L1 Knockout HeLa Cell Line | EDJ-KQ58916 | Human | 168507 | Details Get a Quote |
| PKD1L3 Knockout HeLa Cell Line | EDJ-KQ59725 | Human | 342372 | Details Get a Quote |
| PKD1L1 Knockout A-549 Cell Line | EDJ-KQ67404 | Human | 168507 | Details Get a Quote |
| PKD1L3 Knockout A-549 Cell Line | EDJ-KQ68197 | Human | 342372 | Details Get a Quote |
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