Human Gene PKHD1 (uc003pah.1) Description and Page Index
  Description: Homo sapiens polycystic kidney and hepatic disease 1 (autosomal recessive) (PKHD1), transcript variant 1, mRNA.
RefSeq Summary (NM_138694): 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].
Transcript (Including UTRs)
   Position: hg19 chr6:51,480,145-51,952,423 Size: 472,279 Total Exon Count: 67 Strand: -
Coding Region
   Position: hg19 chr6:51,483,879-51,949,731 Size: 465,853 Coding Exon Count: 66 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsOther NamesGeneReviewsModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr6:51,480,145-51,952,423)mRNA (may differ from genome)Protein (4074 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedStanford SOURCETreefamUniProtKB

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Fibrocystin; AltName: Full=Polycystic kidney and hepatic disease 1 protein; AltName: Full=Polyductin; AltName: Full=Tigmin; Flags: Precursor;
FUNCTION: May be required for correct bipolar cell division through the regulation of centrosome duplication and mitotic spindle assembly. May be a receptor protein that acts in collecting-duct and biliary differentiation.
SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein (Probable). Cytoplasm, cytoskeleton, cilium basal body. Cell projection, cilium. Cytoplasm, cytoskeleton, spindle. Cytoplasm, cytoskeleton, centrosome.
TISSUE SPECIFICITY: Predominantly expressed in fetal and adult kidney. In the kidney, it is found in the cortical and medullary collecting ducts. Also present in the adult pancreas, but at much lower levels. Detectable in fetal and adult liver. Rather indistinct signal in fetal brain.
DISEASE: Defects in PKHD1 are the cause of polycystic kidney disease autosomal recessive (ARPKD) [MIM:263200]. ARPKD is a severe form of polycystic kidney disease affecting the kidneys and the hepatic biliary tract. The clinical spectrum is widely variable, with most cases presenting during infancy. The fetal phenotypic features classically include enlarged and echogenic kidneys, as well as oligohydramnios secondary to a poor urine output. Up to 50% of the affected neonates die shortly after birth, as a result of severe pulmonary hypoplasia and secondary respiratory insufficiency. In the subset that survives the perinatal period, morbidity and mortality are mainly related to severe systemic hypertension, renal insufficiency, and portal hypertension due to portal-tract fibrosis.
SIMILARITY: Contains 2 G8 domains.
SIMILARITY: Contains 12 IPT/TIG domains.
SIMILARITY: Contains 9 PbH1 repeats.
WEB RESOURCE: Name=Mutation Database Autosomal Recessive Polycystic Kidney Disease (ARPKD/PKHD1); URL="";
WEB RESOURCE: Name=GeneReviews; URL="";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): PKHD1
CDC HuGE Published Literature: PKHD1
Positive Disease Associations: Amyotrophic Lateral Sclerosis , Cholesterol, LDL , Electrocardiography , Lipids , prostate cancer , Prostatic Neoplasms , Triglycerides , waist circumference
Related Studies:
  1. Amyotrophic Lateral Sclerosis
    Jennifer C Schymick et al. Lancet neurology 2007, Genome-wide genotyping in amyotrophic lateral sclerosis and neurologically normal controls: first stage analysis and public release of data., Lancet neurology. [PubMed 17362836]
    We generated publicly available genotype data for sporadic ALS patients and controls. No single locus was definitively associated with increased risk of developing disease, although potentially associated candidate SNPs were identified.
  2. Cholesterol, LDL
    , , . [PubMed 0]
  3. Cholesterol, LDL
    , , . [PubMed 0]
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: PKHD1
Diseases sorted by gene-association score: polycystic kidney disease 4, with or without hepatic disease* (1707), cystic kidney disease* (432), caroli disease, isolated* (350), oligohydramnios (43), caroli disease (34), polycystic kidney disease (33), kidney disease (30), congenital hepatic fibrosis (29), autosomal dominant polycystic kidney disease (18), renal-hepatic-pancreatic dysplasia (9), polycystic liver disease (9), portal hypertension (6), polycystic liver disease 1 (5), polycystic kidney disease 2 (5), nephronophthisis (2), autosomal genetic disease (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 6.79 RPKM in Kidney - Cortex
Total median expression: 12.62 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -73.19276-0.265 Picture PostScript Text
3' UTR -1022.053734-0.274 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR019316 - G8_domain
IPR013783 - Ig-like_fold
IPR014756 - Ig_E-set
IPR002909 - IPT_TIG_rcpt
IPR006626 - PbH1
IPR012334 - Pectin_lyas_fold
IPR011050 - Pectin_lyase_fold/virulence

Pfam Domains:
PF01833 - IPT/TIG domain
PF10162 - G8 domain
PF13229 - Right handed beta helix region

SCOP Domains:
81296 - E set domains
51126 - Pectin lyase-like
56988 - Anthrax protective antigen

ModBase Predicted Comparative 3D Structure on P08F94
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0038023 signaling receptor activity

Biological Process:
GO:0001822 kidney development
GO:0006874 cellular calcium ion homeostasis
GO:0007165 signal transduction
GO:0008284 positive regulation of cell proliferation
GO:0010824 regulation of centrosome duplication
GO:0032006 regulation of TOR signaling
GO:0032088 negative regulation of NF-kappaB transcription factor activity
GO:0042592 homeostatic process
GO:0043066 negative regulation of apoptotic process
GO:0051271 negative regulation of cellular component movement
GO:0051898 negative regulation of protein kinase B signaling
GO:0060271 cilium assembly
GO:0070372 regulation of ERK1 and ERK2 cascade
GO:0098609 cell-cell adhesion

Cellular Component:
GO:0000775 chromosome, centromeric region
GO:0005694 chromosome
GO:0005737 cytoplasm
GO:0005813 centrosome
GO:0005819 spindle
GO:0005856 cytoskeleton
GO:0005886 plasma membrane
GO:0005929 cilium
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0016324 apical plasma membrane
GO:0031362 anchored component of external side of plasma membrane
GO:0036064 ciliary basal body
GO:0042995 cell projection
GO:0048471 perinuclear region of cytoplasm
GO:0070062 extracellular exosome
GO:0072686 mitotic spindle

-  Descriptions from all associated GenBank mRNAs
  AY074797 - Homo sapiens polycystic kidney and hepatic disease 1 (PKHD1) mRNA, complete cds.
BX647896 - Homo sapiens mRNA; cDNA DKFZp686C01112 (from clone DKFZp686C01112).
AK091971 - Homo sapiens cDNA FLJ34652 fis, clone KIDNE2018254.
AX747285 - Sequence 810 from Patent EP1308459.
AF480064 - Homo sapiens polycystic kidney and hepatic disease 1 (PKHD1) mRNA, complete cds.
AK128031 - Homo sapiens cDNA FLJ46150 fis, clone TESTI4000703.
AY092083 - Homo sapiens TIG multiple domains-1 (TIGM1) mRNA, complete cds.
BX538137 - Homo sapiens mRNA; cDNA DKFZp686H16117 (from clone DKFZp686H16117).
JD240698 - Sequence 221722 from Patent EP1572962.
JD353928 - Sequence 334952 from Patent EP1572962.
JD134525 - Sequence 115549 from Patent EP1572962.
JD304631 - Sequence 285655 from Patent EP1572962.
JD393962 - Sequence 374986 from Patent EP1572962.
JD233561 - Sequence 214585 from Patent EP1572962.
JD172184 - Sequence 153208 from Patent EP1572962.
JD163014 - Sequence 144038 from Patent EP1572962.
JD509079 - Sequence 490103 from Patent EP1572962.
JD392530 - Sequence 373554 from Patent EP1572962.
JD392237 - Sequence 373261 from Patent EP1572962.
JD086459 - Sequence 67483 from Patent EP1572962.
JD260923 - Sequence 241947 from Patent EP1572962.
JD551981 - Sequence 533005 from Patent EP1572962.
JD146716 - Sequence 127740 from Patent EP1572962.
JD563925 - Sequence 544949 from Patent EP1572962.
JD155650 - Sequence 136674 from Patent EP1572962.
JD516078 - Sequence 497102 from Patent EP1572962.
JD521710 - Sequence 502734 from Patent EP1572962.
JD528479 - Sequence 509503 from Patent EP1572962.
JD068892 - Sequence 49916 from Patent EP1572962.
JD518373 - Sequence 499397 from Patent EP1572962.
JD232646 - Sequence 213670 from Patent EP1572962.
JD428015 - Sequence 409039 from Patent EP1572962.
JD235125 - Sequence 216149 from Patent EP1572962.
JD327418 - Sequence 308442 from Patent EP1572962.
JD410718 - Sequence 391742 from Patent EP1572962.
JD267167 - Sequence 248191 from Patent EP1572962.
JD346982 - Sequence 328006 from Patent EP1572962.
JD305925 - Sequence 286949 from Patent EP1572962.
JD350683 - Sequence 331707 from Patent EP1572962.
JD444034 - Sequence 425058 from Patent EP1572962.
JD094987 - Sequence 76011 from Patent EP1572962.
JD514364 - Sequence 495388 from Patent EP1572962.
JD552726 - Sequence 533750 from Patent EP1572962.
JD439009 - Sequence 420033 from Patent EP1572962.
JD152597 - Sequence 133621 from Patent EP1572962.
JD109881 - Sequence 90905 from Patent EP1572962.
JD375115 - Sequence 356139 from Patent EP1572962.
JD547474 - Sequence 528498 from Patent EP1572962.
JD200640 - Sequence 181664 from Patent EP1572962.
JD091591 - Sequence 72615 from Patent EP1572962.
JD100707 - Sequence 81731 from Patent EP1572962.
JD369265 - Sequence 350289 from Patent EP1572962.
JD543716 - Sequence 524740 from Patent EP1572962.
JD479663 - Sequence 460687 from Patent EP1572962.
JD538478 - Sequence 519502 from Patent EP1572962.

-  Other Names for This Gene
  Alternate Gene Symbols: FCYT, NM_138694, NP_619639, P08F94, PKHD1_HUMAN, Q5VUA2, Q5VUA3, Q5VWV1, Q86Z26, Q8TCZ9, TIGM1
UCSC ID: uc003pah.1
RefSeq Accession: NM_138694
Protein: P08F94 (aka PKHD1_HUMAN or PKHD_HUMAN)
CCDS: CCDS4935.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene PKHD1:
hepatic-fibrosis (Congenital Hepatic Fibrosis Overview)
pkd-ar (Polycystic Kidney Disease, Autosomal Recessive)

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_138694.3
exon count: 67CDS single in 3' UTR: no RNA size: 16235
ORF size: 12225CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 23759.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.