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    PKHD1 polycystic kidney and hepatic disease 1 (autosomal recessive) [ Homo sapiens (human) ]

    Gene ID: 5314, updated on 22-May-2013
    Official Symbol
    PKHD1provided by HGNC
    Official Full Name
    polycystic kidney and hepatic disease 1 (autosomal recessive)provided by HGNC
    Primary source
    HGNC:9016
    See related
    Ensembl:ENSG00000170927; HPRD:05987; MIM:606702; Vega:OTTHUMG00000014841
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    FCYT; ARPKD; TIGM1
    Summary
    The protein encoded by this gene is predicted to have a single transmembrane (TM)-spanning domain and multiple copies of an immunoglobulin-like plexin-transcription-factor domain. Alternative splicing results in two transcript variants encoding different isoforms. Other alternatively spliced transcripts have been described, but the full length sequences have not been determined. Several of these transcripts are predicted to encode truncated products which lack the TM and may be secreted. Mutations in this gene cause autosomal recessive polycystic kidney disease, also known as polycystic kidney and hepatic disease-1. [provided by RefSeq, Jul 2008]
    Location :
    6p12.2
    Sequence :
    Chromosome: 6; NC_000006.11 (51480145..51952423, complement)
    See PKHD1 in Epigenomics, MapViewer

    Chromosome 6 - NC_000006.11Genomic Context describing neighboring genes Neighboring gene Wilms tumor 1 associated protein pseudogene Neighboring gene ribosomal protein S15a pseudogene 20 Neighboring gene microRNA 133b Neighboring gene microRNA 206

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details

    Related articles in PubMed

    1. Exome sequencing identifies compound heterozygous PKHD1 mutations as a cause of autosomal recessive polycystic kidney disease. Zhang D, et al. Chin Med J (Engl), 2012 Jul. PMID 22882926.
    2. Hepatorenal findings in obligate heterozygotes for autosomal recessive polycystic kidney disease. Gunay-Aygun M, et al. Mol Genet Metab, 2011 Dec. PMID 21945273.
    3. Down-regulation of PKHD1 induces cell apoptosis through PI3K and NF-κB pathways. Sun L, et al. Exp Cell Res, 2011 Apr 15. PMID 21300060.
    4. Germline PKHD1 mutations are protective against colorectal cancer. Ward CJ, et al. Hum Genet, 2011 Mar. PMID 21274727.
    5. Identification of PKHD1 multiexon deletions using multiplex ligation-dependent probe amplification and quantitative polymerase chain reaction. Zvereff V, et al. Genet Test Mol Biomarkers, 2010 Aug. PMID 20575693.

    See all (44) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. Data identified that the compound heterozygous PKHD1 gene mutations are the molecular basis of the patient with ARPKD.
      Title: Exome sequencing identifies compound heterozygous PKHD1 mutations as a cause of autosomal recessive polycystic kidney disease.
    2. Our data suggest that carrier status for PKHD1 mutations in autosomal recessive polycystic kidney disease is a predisposition to polycystic liver disease and renal involvement
      Title: Hepatorenal findings in obligate heterozygotes for autosomal recessive polycystic kidney disease.
    3. Data suggest that the PI3K/Akt pathway is involved in apoptotic function in PKHD1-silenced cells, and PI3K/Akt inhibition correlates with upregulation of NF-kappaB activity.
      Title: Down-regulation of PKHD1 induces cell apoptosis through PI3K and NF-κB pathways.
    4. Screening for the most common PKHD1 mutation (T36M) in a European cohort indicated that heterozygous PKHD1 mutations are not a risk factor but rather are protective for colorectal cancer.
      Title: Germline PKHD1 mutations are protective against colorectal cancer.
    5. Multiplex ligation-dependent probe amplification is a sensitive and rapid method to identify PKHD1 deletions.
      Title: Identification of PKHD1 multiexon deletions using multiplex ligation-dependent probe amplification and quantitative polymerase chain reaction.
    6. PKHD1 localizes to the mitotic spindle in patients with autosomal recessive polycystic kidney disease.
      Title: Polycystic kidney disease protein fibrocystin localizes to the mitotic spindle and regulates spindle bipolarity.
    7. There is wide variability in severity of renal disease among patients carrying the same PKHD1 mutations, even within the same family.
      Title: Correlation of kidney function, volume and imaging findings, and PKHD1 mutations in 73 patients with autosomal recessive polycystic kidney disease.
    8. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    9. the presence of two truncating mutations of the PKHD1 gene is associated with the most severe renal forms of prenatally detected autosomal recessive polycystic kidney disease
      Title: Genotype-phenotype correlations in fetuses and neonates with autosomal recessive polycystic kidney disease.
    10. Data suggest that fibrocystin-1 is a component of the normal focal adhesion complex and that actin and fibrocystin-1 are lost from autosomal recessive polycystic kidney disease complexes.
      Title: Abnormalities in focal adhesion complex formation, regulation, and function in human autosomal recessive polycystic kidney disease epithelial cells.
    Submit: New GeneRIF Correction See all (32)

    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Polycystic kidney disease, infantile type

    Summary from GeneReviews: Polycystic Kidney Disease, Autosomal Recessive Go to GeneReviews

    Disease Characteristics
    The majority of individuals with autosomal recessive polycystic kidney disease (ARPKD) present in the neonatal period with enlarged echogenic kidneys. At initial presentation, approximately 45% of infants have liver abnormalities, including hepatomegaly, dilated intrahepatic (and occasionally extrahepatic) biliary ducts, and mildly increased echogenicity. Pulmonary hypoplasia resulting from oligohydramnios occurs in a number of affected infants. Approximately 30% of affected infants die in the neonatal period or within the first year of life primarily of respiratory insufficiency or superimposed pulmonary infections. More than 50% of affected children progress to end-stage renal disease (ESRD), usually in the first decade of life. With neonatal respiratory support and renal replacement therapies, the ten-year survival of those who live beyond the first year of life has improved to 82%. Fifteen-year survival is estimated to be 67%-79%, and may be improving. A minority present in older childhood or young adulthood with hepatosplenomegaly and evidence of portal hypertension.
    Diagnosis Testing
    The diagnosis of ARPKD is based on clinical findings in the proband and the absence of renal cysts in the proband's parents. Molecular genetic testing of PKHD1, the only gene known to be associated with ARPKD, is clinically available.
    Genetic Counseling
    ARPKD is inherited in an autosomal recessive manner. Each sib of a proband has a 25% chance of inheriting both disease-causing alleles and being affected, a 50% chance of inheriting a disease-causing allele and being a carrier, and a 25% chance of inheriting neither disease-causing allele and not being a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if both disease-causing alleles have been identified in the family or if linkage studies are informative. No systematic data are available on the sensitivity and specificity of prenatal ultrasound examination in establishing the diagnosis of ARPKD in pregnancies at 25% risk.
    References
    Products Interactant Other Gene Complex Source Pubs Description
    Q8TCZ9 P49069 CAMLG    HPRD  PubMed  

    Markers

    Genotypes

    Homology

    Clone Names

    • FLJ46150, DKFZp686C01112

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    receptor activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    cell-cell adhesion ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    cilium assembly ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    homeostatic process NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    kidney development ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    negative regulation of cellular component movement ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    regulation of centrosome duplication IMP
    Inferred from Mutant Phenotype
    more info
    		  
    Component Evidence Code Pubs
    anchored to external side of plasma membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 
    apical plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    centrosome IDA
    Inferred from Direct Assay
    more info
    		  
    cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    integral to membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    microtubule basal body IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    mitotic spindle IDA
    Inferred from Direct Assay
    more info
    		  
    primary cilium IDA
    Inferred from Direct Assay
    more info
    		  
    Preferred Names
    fibrocystin
    Names
    fibrocystin
    tigmin
    polyductin
    TIG multiple domains 1
    polycystic kidney and hepatic disease 1 protein

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_008753.1 RefSeqGene

      Range
      5001..477279
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_138694.3 → NP_619639.3  fibrocystin isoform 1 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform of this protein.
      Source sequence(s)
      AY074797
      Consensus CDS
      CCDS4935.1
      UniProtKB/Swiss-Prot
      P08F94
      Related
      ENSP00000360158, OTTHUMP00000016598, ENST00000371117, OTTHUMT00000040893
      Conserved Domains (5) summary
      cd00603
      Location:260 – 315
      Blast Score: 142
      IPT_PCSR; IPT domain of Plexins and Cell Surface Receptors (PCSR) and related proteins . This subgroup contains IPT domains of plexins, receptors, like the plasminogen-related growth factor receptors, the hepatocyte growth factor-scatter factors, and the ...
      pfam10162
      Location:1932 – 2053
      Blast Score: 378
      G8; G8 domain
      pfam01833
      Location:1486 – 1569
      Blast Score: 119
      TIG; IPT/TIG domain
      pfam13229
      Location:3002 – 3177
      Blast Score: 124
      Beta_helix; Right handed beta helix region
      cl15674
      Location:1197 – 1294
      Blast Score: 89
      IPT; Immunoglobulin-like fold, Plexins, Transcription factors (IPT). IPTs are also known as Transcription factor ImmunoGlobin (TIG) domains. They are present in intracellular transcription factors, cell surface receptors (such as plexins and scatter factor ...

    2. NM_170724.2 → NP_733842.2  fibrocystin isoform 2 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks several exons and includes an alternate exon in the 3' coding region and UTR, compared to variant 1. Isoform 2 is shorter and has a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AL157774, AY074797
      Consensus CDS
      CCDS4936.1
      UniProtKB/Swiss-Prot
      P08F94
      Related
      ENSP00000341097, OTTHUMP00000016599, ENST00000340994, OTTHUMT00000040894
      Conserved Domains (5) summary
      cd00603
      Location:260 – 315
      Blast Score: 142
      IPT_PCSR; IPT domain of Plexins and Cell Surface Receptors (PCSR) and related proteins . This subgroup contains IPT domains of plexins, receptors, like the plasminogen-related growth factor receptors, the hepatocyte growth factor-scatter factors, and the ...
      pfam10162
      Location:1932 – 2053
      Blast Score: 378
      G8; G8 domain
      pfam01833
      Location:1486 – 1569
      Blast Score: 118
      TIG; IPT/TIG domain
      pfam13229
      Location:3002 – 3177
      Blast Score: 122
      Beta_helix; Right handed beta helix region
      cl15674
      Location:1197 – 1294
      Blast Score: 89
      IPT; Immunoglobulin-like fold, Plexins, Transcription factors (IPT). IPTs are also known as Transcription factor ImmunoGlobin (TIG) domains. They are present in intracellular transcription factors, cell surface receptors (such as plexins and scatter factor ...

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p10 Primary Assembly

    Genomic

    1. NC_000006.11 Reference GRCh37.p10 Primary Assembly

      Range
      51480145..51952423, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000138.1 Alternate HuRef

      Range
      51314936..51783413, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.0

    Genomic

    1. NC_018917.1 Alternate CHM1_1.0

      Range
      51393704..51865022, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    genomic ABBA01050561.1 (67402..71120) None
    genomic ABBA01050562.1 None
    genomic ABBA01050563.1 None
    genomic ABBA01050564.1 None
    genomic ABBA01050565.1 None
    genomic ABBA01050566.1 None
    genomic ABBA01050567.1 None
    genomic ABBA01050568.1 None
    genomic ABBA01050569.1 None
    genomic ABBA01050570.1 None
    genomic AL121946.20 (101..138961) None
    genomic AL157774.14 (101..154055) None
    genomic AL355997.10 (26358..94924) None
    genomic AL391221.15 (2001..22758) None
    genomic AL590391.9 (2001..92138) None
    genomic AMYH01016346.1 (271752..530474) None
    genomic AMYH01016347.1 None
    genomic AMYH01016348.1 None
    genomic AMYH01016349.1 None
    genomic AY129465.1 AAM93492.1
    genomic CH471081.1 EAX04359.1
      EAX04360.1
    mRNA AF480064.1 AAM44232.1
    mRNA AK091971.1 BAC03782.1
    mRNA AK128031.1 None
    mRNA AY074797.1 AAL74290.1
    mRNA AY092083.1 AAM18186.1
    mRNA BX538137.1 None
    mRNA BX647896.1 None
    Protein Accession Links
    GenPept Link UniProtKB Link
    P08F94.1 GenPept UniProtKB/Swiss-Prot:P08F94

    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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      Supplemental Content

      Table of contents

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        Related medical variations
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        Conserved Domain Database Links between Entrez Gene and Conserved Domain Database (CDD) are calculated from the domains annotated by the CDD group on Reference Sequence proteins.
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        Links between Gene and PubMed are the result of the following: 1. Manual curation within NCBI. Part of the process of generating a REVIEWED RefSeq is an analysis of the current literature. Papers that are seminal in defining the gene, its sequence, and its function are added to the record at that time. Alert users point out gaps or errors in papers associated with a Gene record. These messages are reviewed and implemented as required. 2. Integration of information from other public databases. Gene integrates gene-citation from resources external to NCBI such as model organism-specific databases, Gene Ontology (GO), groups curating interactions, and sequence databases. The assumption in using these source is that they report citations specific to a gene in a known species. Gene does not process citations from OMIM automatically, because many of citations in OMIM refer to studies of genes in species other than human.
      • PubMed (GeneRIF)
        GeneRIF -- Gene Reference Into Function Staff of the Index Section in the National Library of Medicine review the current literature. When they find articles focused on the structure and function of a gene, they write a brief summary of the impact of the paper and make the connection between the citation (PubMed) and Gene. An interface exists for interested users to submit such data as well. http://www.ncbi.nlm.nih.gov/projects/GeneRIF/GeneRIFhelp.html
      • PubMed (OMIM)
        Links are provided when Gene has a link to a record in OMIM, and OMIM explicitly cites these publications in PubMed.
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        Citations in PubMed identified from shared sequence and PMC links.
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        Link to Protein RefSeqs
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        Link to related taxonomy entry
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        Related UniSTS records

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