Pkhd1 polycystic kidney and hepatic disease 1 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Pkhd1provided by MGI
Official Full Name: polycystic kidney and hepatic disease 1provided by MGI
Primary source: MGI:MGI:2155808
See related: Ensembl:ENSMUSG00000043760 AllianceGenome:MGI:2155808
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: FPC; Tigm1
Summary: Involved in several processes, including establishment of mitotic spindle orientation; negative regulation of epithelial cell apoptotic process; and regulation of establishment of planar polarity. Acts upstream of with a positive effect on branching morphogenesis of an epithelial tube and cell-cell junction organization. Acts upstream of or within cilium assembly and kidney development. Located in several cellular components, including 9+0 non-motile cilium; apical plasma membrane; and extracellular exosome. Is expressed in several structures, including adrenal cortex; gut; mesonephric tubule; metanephros; and ureteric bud. Used to study Caroli syndrome; autosomal recessive polycystic kidney disease; and polycystic kidney disease 4. Human ortholog(s) of this gene implicated in autosomal recessive polycystic kidney disease and polycystic kidney disease 4. Orthologous to human PKHD1 (PKHD1 ciliary IPT domain containing fibrocystin/polyductin). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Biased expression in kidney adult (RPKM 6.2), genital fat pad adult (RPKM 1.3) and 3 other tissues See more
Orthologs: human all
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Genomic context

Location:: 1 A4; 1 6.27 cM

Exon count:: 70

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	1	NC_000067.7 (20128003..20688306, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	1	NC_000067.6 (20057779..20618082, complement)

Chromosome 1 - NC_000067.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A novel ARPKD mouse model with near-complete deletion of the Polycystic Kidney and Hepatic Disease 1 (Pkhd1) genomic locus presents with multiple phenotypes but not renal cysts.
Title: A novel ARPKD mouse model with near-complete deletion of the Polycystic Kidney and Hepatic Disease 1 (Pkhd1) genomic locus presents with multiple phenotypes but not renal cysts.
Mutated Pkhd1 alone is sufficient to cause autoimmune biliary disease on the nonobese diabetic (NOD) genetic background.
Title: Mutated Pkhd1 alone is sufficient to cause autoimmune biliary disease on the nonobese diabetic (NOD) genetic background.
Therapeutic Potential for CFTR Correctors in Autosomal Recessive Polycystic Kidney Disease.
Title: Therapeutic Potential for CFTR Correctors in Autosomal Recessive Polycystic Kidney Disease.
when aged to ~1.5 yr, the Pkhd1(C642*) heterozygotes developed prominent cystic liver changes; tissue analyses revealed biliary cysts and increased number of bile ducts without signs of congenital hepatic fibrosis-like portal field inflammation and fibrosis that was seen in Pkhd1(C642*) homozygotes.
Title: Heterozygous Pkhd1(C642*) mice develop cystic liver disease and proximal tubule ectasia that mimics radiographic signs of medullary sponge kidney.
This work indicates a novel role for non-canonical Wnt/planar cell polarity signalling in Autosomal Recessive Polycystic Kidney Disease and suggests ATMIN as a modulator of PKHD1.
Title: Atmin modulates Pkhd1 expression and may mediate Autosomal Recessive Polycystic Kidney Disease (ARPKD) through altered non-canonical Wnt/Planar Cell Polarity (PCP) signalling.
Pkhd1(Flox67HA) is a valid mouse model of autosomal recessive polycystic kidney disease to track Pkhd1-derived products containing the C-terminus. Significantly, exon 67 containing the nuclear localization signal and the polycystin-2 binding domain is not essential for Fibrocystin function in this model.
Title: A novel model of autosomal recessive polycystic kidney questions the role of the fibrocystin C-terminus in disease mechanism.
this study shows that loss of functional Pkhd1 on the NOD background produces early bile duct abnormalities, initiating a break in tolerance that leads to autoimmune cholangitis in NOD.Abd3 congenic mice
Title: A Novel Pkhd1 Mutation Interacts with the Nonobese Diabetic Genetic Background To Cause Autoimmune Cholangitis.
fibrocystin-defective cholangiocytes are characterized by a beta-catenin-dependent secretion of a range of chemokines which stimulate bone marrow-derived macrophage recruitment
Title: Macrophage recruitment by fibrocystin-defective biliary epithelial cells promotes portal fibrosis in congenital hepatic fibrosis.
Intragenic motifs regulate the transcriptional complexity of Pkhd1/PKHD1
Title: Intragenic motifs regulate the transcriptional complexity of Pkhd1/PKHD1.
Mutations in the Pkhd1 gene result in autosomal recessive polycystic kidney disease (ARPKD) in humans.
Title: Cystogenesis in ARPKD results from increased apoptosis in collecting duct epithelial cells of Pkhd1 mutant kidneys.

Submit: New GeneRIF Correction See all GeneRIFs (24)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Chemically induced (ENU) (2) 1 citation
Endonuclease-mediated (4)
Spontaneous (1) 1 citation
Targeted (11) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AI182499 (e-PCR)
- UniSTS:158777

D1Mit276 (e-PCR), detects polymorphism
- UniSTS:128626

D1Mit52 (e-PCR), detects polymorphism
- UniSTS:128887

D1Mit52.2 (e-PCR), detects polymorphism
- UniSTS:128888

15.MMHAP97FRE9.seq (e-PCR)
- UniSTS:123282

AI118496 (e-PCR)
- UniSTS:178361

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_positive_effect branching morphogenesis of an epithelial tube	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_positive_effect cell-cell junction organization	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cilium assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in epithelial cell morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in establishment of centrosome localization	ISS Inferred from Sequence or Structural Similarity more info
involved_in establishment of mitotic spindle orientation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular calcium ion homeostasis	IEA Inferred from Electronic Annotation more info
involved_in intracellular calcium ion homeostasis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within kidney development	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of NF-kappaB transcription factor activity	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of NF-kappaB transcription factor activity	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of epithelial cell apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cell population proliferation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of epithelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of ERK1 and ERK2 cascade	IEA Inferred from Electronic Annotation more info
involved_in regulation of ERK1 and ERK2 cascade	ISO Inferred from Sequence Orthology more info
involved_in regulation of TOR signaling	IEA Inferred from Electronic Annotation more info
involved_in regulation of TOR signaling	ISO Inferred from Sequence Orthology more info
involved_in regulation of cell adhesion	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of cell-cell adhesion	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of cell-matrix adhesion	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of centrosome duplication	IEA Inferred from Electronic Annotation more info
involved_in regulation of centrosome duplication	ISO Inferred from Sequence Orthology more info
involved_in regulation of cholangiocyte proliferation	ISO Inferred from Sequence Orthology more info
involved_in regulation of cholangiocyte proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of establishment of planar polarity	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in 9+0 non-motile cilium	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in apical plasma membrane	ISO Inferred from Sequence Orthology more info
located_in centrosome	IEA Inferred from Electronic Annotation more info
located_in centrosome	ISO Inferred from Sequence Orthology more info
located_in chromosome, centromeric region	IEA Inferred from Electronic Annotation more info
located_in ciliary basal body	IEA Inferred from Electronic Annotation more info
located_in ciliary basal body	ISO Inferred from Sequence Orthology more info
located_in cilium	IDA Inferred from Direct Assay more info	PubMed
located_in cilium	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular exosome	IDA Inferred from Direct Assay more info	PubMed
located_in mitotic spindle	IEA Inferred from Electronic Annotation more info
located_in mitotic spindle	ISO Inferred from Sequence Orthology more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
located_in perinuclear region of cytoplasm	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: fibrocystin

Names: TIG multiple domains 1; polycystic kidney and hepatic disease 1 protein; polyductin; tigmin

NCBI Reference Sequences (RefSeq)

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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.

mRNA and Protein(s)

NM_153179.3 → NP_694819.2 fibrocystin precursor

Status: VALIDATED

Source sequence(s)

AC161178, AC166488, AC166770, AY130764, AY438374, BB661186

Consensus CDS

CCDS14841.1

UniProtKB/Swiss-Prot

E9PZ36

UniProtKB/TrEMBL

Q8CIS7

Related

ENSMUSP00000085794.6, ENSMUST00000088448.12

Conserved Domains (4) summary

cd00603
Location:257 → 339

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 ...

pfam01833
Location:1106 → 1188

TIG; IPT/TIG domain

pfam10162
Location:1929 → 2047

G8; G8 domain

pfam13229
Location:2996 → 3169

Beta_helix; Right handed beta helix region

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000067.7 Reference GRCm39 C57BL/6J

Range

20128003..20688306 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011238384.3 → XP_011236686.1 fibrocystin isoform X1

UniProtKB/TrEMBL

Q8CIS7

Conserved Domains (4) summary

cd00603
Location:257 → 339

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 ...

pfam01833
Location:1106 → 1188

TIG; IPT/TIG domain

pfam10162
Location:1929 → 2047

G8; G8 domain

pfam13229
Location:2996 → 3169

Beta_helix; Right handed beta helix region
XM_006495521.2 → XP_006495584.1 fibrocystin isoform X2

Conserved Domains (3) summary

cd00603
Location:257 → 339

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 ...

pfam01833
Location:1106 → 1188

TIG; IPT/TIG domain

pfam10162
Location:1929 → 2047

G8; G8 domain
XM_011238385.1 → XP_011236687.1 fibrocystin isoform X3

Conserved Domains (3) summary

cd00603
Location:257 → 339

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 ...

pfam01833
Location:1106 → 1188

TIG; IPT/TIG domain

pfam10162
Location:1929 → 2047

G8; G8 domain