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    GENE:

    PKHD1 (PKHD1 Ciliary IPT Domain Containing Fibrocystin/Polyductin)

    i
    Other names: PKHD1, PKHD1 Ciliary IPT Domain Containing Fibrocystin/Polyductin, FCYT, Fibrocystin, Polyductin, Tigmin, ARPKD, TIGM1, FPC, Polycystic Kidney And Hepatic Disease 1 (Autosomal Recessive), Polycystic Kidney And Hepatic Disease 1 Protein, Fibrocystin/Polyductin Complex, PKHD1, Fibrocystin/Polyductin, TIG Multiple Domains 1, PKD4
    Associations

    News

    Trials
    2d
    Disruption of the human cystin-1 myristoyl-electrostatic switch causes polycystic kidney disease that phenocopies autosomal recessive polycystic kidney disease. (PubMed, Kidney Int)
    Cystin-1 intracellular trafficking and function are regulated by a myristoyl-electrostatic switch mechanism. Cystic kidneys in three individuals with homozygous CYS1 pathogenic variants provide further support that cystin-1 deficiency causes polycystic kidney disease that phenocopies ARPKD.
    Journal
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    PKHD1 (PKHD1 Ciliary IPT Domain Containing Fibrocystin/Polyductin) • PPM1A (Protein Phosphatase Mg2+/Mn2+ Dependent 1A)
    11ms
    Heart dysfunction in a rat model with autosomal recessive polycystic kidney disease. (PubMed, J Physiol)
    Heart dysfunctions are associated with a dysregulation of cardiokine signalling such as Irisin, in PCK rats. Irisin could be a new marker of diastolic function in ARPKD and chronic kidney disease patients.
    Preclinical • Journal
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    GDF15 (Growth differentiation factor 15) • FGF23 (Fibroblast Growth Factor 23) • PKHD1 (PKHD1 Ciliary IPT Domain Containing Fibrocystin/Polyductin) • ST2 (Suppression Of Tumorigenicity)
    11ms
    Co-Occurrence of Neurofibromatosis Type 1 and Polycystic Liver Disease: A Case of Hypertension with PKHD1 Variant. (PubMed, Am J Case Rep)
    CONCLUSIONS Our case highlights the diagnostic challenges of atypical phenotypes among individuals with NF1, which can depend on the background of other genes. With increasing affordability of WES, its utility in uncovering the possibility of being affected by 2 inherited genetic conditions should be considered when findings are incompatible with the primary disease.
    Journal
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    NF1 (Neurofibromin 1) • PKHD1 (PKHD1 Ciliary IPT Domain Containing Fibrocystin/Polyductin)
    1year
    An extracellular vesicle based hypothesis for the genesis of the polycystic kidney diseases. (PubMed, Extracell Vesicle)
    The PKD-ELV is also critical in the transfer of mRNA and miRNAs between cells and as a vector for extracellular proteinases and hyaluronidases involved in tissue remodeling. A PKD-ELV centric view of polycystic disease (EV theory) can explain the requirement for primary cilium function in ADPKD (where the primary cilium is the PKD-ELV receptor), the observation of defective mitochondria in the disease, the abnormalities detected in the extracellular matrix (ECM) as well as the resistance to carcinoma noted in ADPKD patients and individuals carrying PKHD1 mutations, see graphical abstract.
    Journal
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    PKD1 (Polycystin 1) • PKHD1 (PKHD1 Ciliary IPT Domain Containing Fibrocystin/Polyductin) • PRKD1 (Protein Kinase D1)
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    CD33 positive
    1year
    AIRE mutation in an elderly Caroli's patient with cholangitis and sepsis: a case report. (PubMed, J Med Case Rep)
    This finding suggests that AIRE mutations may be associated with Caroli's disease, with a risk of death and difficulty in curing.
    Journal
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    PKHD1 (PKHD1 Ciliary IPT Domain Containing Fibrocystin/Polyductin)
    over1year
    The PKHD1 gene inhibits tumor proliferation and invasion in intrahepatic cholangiocarcinoma by activating the Notch pathway. (PubMed, Int J Med Sci)
    Moreover, tumor proliferation, migration, and invasion were promoted in loss-of-function experiments in vitro and in vivo, which was partially reversed by DAPT. PKHD1 inhibits the proliferation, migration, and invasion of ICC, and the Notch pathway may be the downstream mechanism of the negative regulatory effect of PKHD1 during the progression of ICC.
    Journal
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    NOTCH1 (Notch 1) • PKHD1 (PKHD1 Ciliary IPT Domain Containing Fibrocystin/Polyductin)
    over1year
    Von-Meyenburg Complex: A Case of Elevated Gamma-GT. (PubMed, Cureus)
    However, their imaging characteristics can mimic malignancy, and they possess a rare potential for progression to hepatocellular carcinoma. Familial clusters suggest a potential genetic basis, with the polycystic kidney and hepatic disease 1 (PKHD1) gene most commonly associated.
    Journal
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    PKHD1 (PKHD1 Ciliary IPT Domain Containing Fibrocystin/Polyductin)
    over1year
    Refining the genetic diagnostic puzzle: A case report on a Chinese ARPKD patient with a reciprocal balanced translocation and c.2507 T > C (p.V836A) in PKHD1. (PubMed, Nephrology (Carlton))
    We identified an infrequent variant combination, c.2507T>C (p.V836A) in PKHD1 and an RBT with broken PKHD1, which extends the genetic spectrum of ARPKD, and provide a basis for further genetic counselling to the family.
    Journal
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    PKHD1 (PKHD1 Ciliary IPT Domain Containing Fibrocystin/Polyductin)
    over1year
    Cholangiocyte ciliary defects induce sustained epidermal growth factor receptor signaling. (PubMed, Hepatology)
    This study's findings shed light on ciliary function and robust EGFR signaling with slower receptor turnover. We could use therapies that restore the function of primary cilia to treat EGFR-driven diseases in PLD and CCA.
    Journal
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    EGFR (Epidermal growth factor receptor) • PKHD1 (PKHD1 Ciliary IPT Domain Containing Fibrocystin/Polyductin)
    over1year
    High-Grade Appendiceal Mucinous Neoplasm Mimicking Appendiceal Tubulovillous Adenoma: A Case Report and Literature Review. (PubMed, Int J Surg Pathol)
    Molecular testing showed 1 KRAS mutation, 2 PIK3CA mutations, and 1 BRCA2, EP300, TGFBR2, CHD4, CREBBP, FANCC, PKHD1 mutation each in the tumor. The patient was followed up for 1 year with no evidence of disease.
    Review • Journal • BRCA Biomarker
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    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA2 (Breast cancer 2, early onset) • CREBBP (CREB binding protein) • EP300 (E1A binding protein p300) • TGFBR2 (Transforming Growth Factor Beta Receptor 2) • CHD4 (Chromodomain Helicase DNA Binding Protein 4) • FANCC (FA Complementation Group C) • PKHD1 (PKHD1 Ciliary IPT Domain Containing Fibrocystin/Polyductin)
    over1year
    Genomic Alterations Correlated to Trastuzumab Resistance and Clinical Outcomes in HER2+/HR- Breast Cancers of Patients Living in Northwestern China. (PubMed, J Cancer)
    Ultimately, we identified a unique cancer-related gene mutation profile and a subset of genes associated with primary resistance to trastuzumab and RFS in patients with HER2+/HR- breast cancer in Northwest China. These findings could lay the groundwork for future studies aimed at elucidating the mechanisms of resistance to trastuzumab and improving HER2-targeted treatment strategies.
    Clinical data • Journal • BRCA Biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • TOP2A (DNA topoisomerase 2-alpha) • FGFR4 (Fibroblast growth factor receptor 4) • CDK12 (Cyclin dependent kinase 12) • FAT1 (FAT atypical cadherin 1) • FANCA (FA Complementation Group A) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • STAG2 (Stromal Antigen 2) • EPAS1 (Endothelial PAS domain protein 1) • KMT2B (Lysine Methyltransferase 2B) • PKHD1 (PKHD1 Ciliary IPT Domain Containing Fibrocystin/Polyductin)
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    Herceptin (trastuzumab)
    over1year
    Molecular Profiling and the Interaction of Somatic Mutations with Transcriptomic Profiles in Non-Melanoma Skin Cancer (NMSC) in a Population Exposed to Arsenic. (PubMed, Cells)
    We also demonstrate that the presence of non-synonymous SMs in the top mutated genes (like PTCH1, NOTCH1, SYNE1, PKHD1 in BCC and TP53 in SCC) significantly affects the magnitude of differential expressions of major genes and gene pathways (basal cell carcinoma pathways, NOTCH signaling, IL-17 signaling, p53 signaling, Wnt signaling pathway). These findings may help select groups of patients for targeted therapy, like hedgehog signaling inhibitors, IL17 inhibitors, etc., in the future.
    Journal
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    NOTCH1 (Notch 1) • PTCH1 (Patched 1) • IL17A (Interleukin 17A) • SYNE1 (Spectrin Repeat Containing Nuclear Envelope Protein 1) • PKHD1 (PKHD1 Ciliary IPT Domain Containing Fibrocystin/Polyductin)