PKHD1
Polycystic Kidney and Hepatic Disease 1 (Autosomal Recessive)
Gene Information Card
| Symbol | PKHD1 |
|---|---|
| Full Name | PKHD1 ciliary IPT domain containing fibrocystin/polyductin |
| Gene Type | protein-coding |
| Chromosomal Location | 6p12.3-p12.2 |
| NCBI Gene ID | 5313 ncbi.nlm.nih.gov/gene/5313 |
| Ensembl ID | ENSG00000170927 |
| UniProt ID | P08F94 |
| OMIM ID | 606702 |
| HGNC ID | 9016 |
| Aliases | ARPKD, FCYT, TIG3, polyductin, fibrocystin |
Description
PKHD1 (polycystic kidney and hepatic disease 1) encodes fibrocystin/polyductin, a large receptor-like protein localized to primary cilia, basal bodies, and the plasma membrane. It is essential for normal ciliary function and tubular morphogenesis in the kidney and bile ducts. Mutations in PKHD1 cause autosomal recessive polycystic kidney disease (ARPKD), characterized by enlarged echogenic kidneys and congenital hepatic fibrosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal Recessive Polycystic Kidney Disease (ARPKD) | Loss-of-function mutations in PKHD1 disrupt fibrocystin function in renal and biliary cilia, leading to ductal plate malformation and cyst formation. | ClinVar, OMIM |
| Congenital Hepatic Fibrosis | Defective fibrocystin in bile duct cilia causes abnormal biliary development and progressive fibrosis. | OMIM, NCBI |
| Caroli Disease | Biallelic PKHD1 mutations can present with Caroli syndrome (dilated intrahepatic bile ducts) as part of the ARPKD spectrum. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Liver | 8.3 | Medium |
| Pancreas | 6.1 | Low |
| Testis | 4.2 | Low |
| Lung | 2.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.0 | Embryonic kidney cell line |
| HepG2 | 10.5 | Hepatocellular carcinoma cell line |
| ARPE-19 | 7.2 | Retinal pigment epithelium |
| MCF7 | 1.5 | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.107C>T (p.Thr36Met) | Missense | Common in ARPKD | Reduced protein stability |
| c.1486C>T (p.Arg496*) | Nonsense | 1-5% | Premature truncation, loss of function |
| c.5895dupA (p.Glu1966Argfs*12) | Frameshift | Rare | Null allele |
| c.274C>T (p.Arg92Trp) | Missense | Found in compound heterozygotes | Impaired ciliary localization |
Mutation functional classification
Loss of Function (LOF)
Most PKHD1 mutations are loss-of-function (nonsense, frameshift, splice-site) leading to truncated or absent fibrocystin, causing ARPKD.
Gain of Function (GOF)
No gain-of-function mutations reported for PKHD1.
Dominant Negative (DN)
No dominant-negative mutations reported; ARPKD is strictly autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ciliopathy pathway (KEGG: hsa05200)
• Hedgehog signaling (involved in ciliary function)
• Planar cell polarity pathway
Protein Summary
Fibrocystin/polyductin is a large (4074 amino acids) type I transmembrane protein with multiple IPT (immunoglobulin-like plexin transcription factor) domains and a single transmembrane domain. It localizes to primary cilia and is thought to function as a receptor mediating cell-cell or cell-matrix interactions. The protein undergoes proteolytic cleavage and is involved in ciliary signaling, tubular morphogenesis, and maintenance of ductal structures in kidney and liver.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PKHD1 Knockout HEK293 Cell Line | EDJ-KQ2009 | Human | 5314 | Details Get a Quote |
| PKHD1L1 Knockout HEK293 Cell Line | EDJ-KQ11150 | Human | 93035 | Details Get a Quote |
| PKHD1 Knockout HeLa Cell Line | EDJ-KQ54148 | Human | 5314 | Details Get a Quote |
| PKHD1L1 Knockout HeLa Cell Line | EDJ-KQ57853 | Human | 93035 | Details Get a Quote |
| PKHD1 Knockout A-549 Cell Line | EDJ-KQ62640 | Human | 5314 | Details Get a Quote |
| PKHD1L1 Knockout A-549 Cell Line | EDJ-KQ66350 | Human | 93035 | Details Get a Quote |
| PKHD1 Knockout HCT 116 Cell Line | EDJ-KQ71108 | Human | 5314 | Details Get a Quote |
| PKHD1L1 Knockout HCT 116 Cell Line | EDJ-KQ74773 | Human | 93035 | Details Get a Quote |
