PKHD1

Protein identityUniProt · HPA

UniProt accession

P08F94

Gene

PKHD1

Ensembl

ENSG00000170927

Chromosome

6

Canonical length

4074 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Primary cilium,Basal body,Cytosol

Secretome location

Intracellular and membrane

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

4074 residues, UniProt reviewed canonical sequence.

>P08F94|PKHD1
     1  MTAWLISLMS IEVLLLAVRH LSLHIEPEEG SLAGGTWITV IFDGLELGVL YPNNGSQLEI
    61  HLVNVNMVVP ALRSVPCDVF PVFLDLPVVT CRTRSVLSEA HEGLYFLEAY FGGQLVSSPN
   121  PGPRDSCTFK FSKAQTPIVH QVYPPSGVPG KLIHVYGWII TGRLETFDFD AEYIDSPVIL
   181  EAQGDKWVTP CSLINRQMGS CYPIQEDHGL GTLQCHVEGD YIGSQNVSFS VFNKGKSMVH
   241  KKAWLISAKQ DLFLYQTHSE ILSVFPETGS LGGRTNITIT GDFFDNSAQV TIAGIPCDIR
   301  HVSPRKIECT TRAPGKDVRL TTPQPGNRGL LFEVGDAVEG LELTEATPGY RWQIVPNASS
   361  PFGFWSQEGQ PFRARLSGFF VAPETNNYTF WIQADSQASL HFSWSEEPRT KVKVASISVG
   421  TADWFDSWEQ NRDEGTWQQK TPKLELLGGA MYYLEAEHHG IAPSRGMRIG VQIHNTWLNP
   481  DVVTTYLREK HQIRVRAQRL PEVQVLNVSG RGNFFLTWDN VSSQPIPANA TAHLIQTTIE
   541  ELLAVKCKLE PLWSNILLRL GFERGPEVSN SDGDLTSGTE PFCGRFSLRQ PRHLVLTPPA
   601  AQKGYRLDQY THLCLAYKGH MNKILKMIVS FTIGFQNMVK NTTCDWSLTR TSPESWQFDC
   661  TDLWETCVRC FGDLQPPPAN SPVLVHQINL LPLAQETGLF YVDEIIIADT NVTVSQADSG
   721  TARPGGNLVE SVSVVGSPPV YSVTSWLAGC GTELPLITAR SVPTEGTEEG SGLVLVTTQR
   781  RQRTSPPLGG HFRIQLPNTV ISDVPVQISA HHLHQLLQNN ADDFTSRYLN ASDFTVKEDL
   841  YTCYEHVWTL SWSTQIGDLP NFIRVSDENL TGVNPAAATR VVYDGGVFLG PIFGDMLATA
   901  NQHTQVVVRV NDVPAHCPGS CSFQYLQGST PCVHSVWYSI DGDINLMIYI TGTGFSGDSQ
   961  FLQVTVNKTS CKVIFSNQTN VVCQTDLLPV GMHRILMLVR PSGLAISATG EDLFLNVKPR
  1021  LDMVEPSRAA DIGGLWATIR GSSLEGVSLI LFGSYSCAIN VATSNSSRIQ CKVPPRGKDG
  1081  RIVNVTVIRG DYSAVLPRAF TYVSSLNPVI VTLSRNISNI AGGETLVIGV ARLMNYTDLD
  1141  VEVHVQDALA PVHTQSAWGL EVALPPLPAG LHRISVSING VSIHSQGVDL HIQYLTEVFS
  1201  IEPCCGSLLG GTILSISGIG FSRDPALVWV LVGNRSCDIV NLTEASIWCE TLPAPQIPDA
  1261  GAPTVPAAVE VWAGNRFFAR GPSPSLVGKG FTFMYEAAAT PVVTAMQGEI TNSSLSLHVG
  1321  GSNLSNSVIL LGNLNCDVET QSFQGNVSLS GCSIPLHSLE AGIYPLQVRQ KQMGFANMSV
  1381  VLQQFAVMPR IMAIFPSQGS ACGGTILTVR GLLLNSRRRS VRVDLSGPFT CVILSLGDHT
  1441  ILCQVSLEGD PLPGASFSLN VTVLVNGLTS ECQGNCTLFI REEASPVMDA LSTNTSGSLT
  1501  TVLIRGQRLA TTADEPMVFV DDQLPCNVTF FNASHVVCQT RDLAPGPHYL SVFYTRNGYA
  1561  CSGNVSRHFY IMPQVFHYFP KNFSLHGGSL LTIEGTGLRG QNTTSVYIDQ QTCLTVNIGA
  1621  ELIRCIVPTG NGSVALEIEV DGLWYHIGVI GYNKAFTPEL ISISQSDDIL TFAVAQISGA
  1681  ANIDIFIGMS PCVGVSGNHT VLQCVVPSLP AGEYHVRGYD CIRGWASSAL VFTSRVIITA
  1741  VTENFGCLGG RLVHVFGAGF SPGNVSAAVC GAPCRVLANA TVSAFSCLVL PLDVSLAFLC
  1801  GLKREEDSCE AARHTYVQCD LTVAMATEQL LESWPYLYIC EESSQCLFVP DHWAESMFPS
  1861  FSGLFISPKL ERDEVLIYNS SCNITMETEA EMECETPNQP ITVKITEIRK RWGQNTQGNF
  1921  SLQFCRRWSR THSWFPERLP QDGDNVTVEN GQLLLLDTNT SILNLLHIKG GKLIFMAPGP
  1981  IELRAHAILV SDGGELRIGS EDKPFQGRAQ ITLYGSSYST PFFPYGVKFL AVRNGTLSLH
  2041  GSLPEVIVTC LRATAHALDT VLALEDAVDW NPGDEVVIIS GTGVKGAKPM EEIVTVETVQ
  2101  DTDLYLKSPL RYSHNFTENW VAGEHHILKA TVALLSRSIT IQGNLTNERE KLLVSCQEAN
  2161  APEGNLQHCL YSMSEKMLGS RDMGARVIVQ SFPEEPSQVQ LKGVQFQVLG QAFHKHLSSL
  2221  TLVGAMRESF IQGCTVRNSF SRGLSMCGTL GLKVDSNVFY NILGHALLVG TCTEMRYISW
  2281  EAIHGRKDDW SGHGNIIRNN VIIQVSGAEG LSNPEMLTPS GIYICSPTNV IEGNRVCGAG
  2341  YGYFFHLMTN QTSQAPLLSF TQNIAHSCTR YGLFVYPKFQ PPWDNVTGTT LFQSFTVWES
  2401  AGGAQIFRSS NLRLKNFKVY SCRDFGIDVL ESDANTSVTD SLLLGHFAHK GSLCMSSGIK
  2461  TPKRWELMVS NTTFVNFDLI NCVAIRTCSD CSQGQGGFTV KTSQLKFTNS SNLVAFPFPH
  2521  AAILEDLDGS LSGKNRSHIL ASMETLSASC LVNSSFGRVV HGSACGGGVL FHRMSIGLAN
  2581  TPEVSYDLTM TDSRNKTTTV NYVRDTLSNP RGWMALLLDQ ETYSLQSENL WINRSLQYSA
  2641  TFDNFAPGNY LLLVHTDLPP YPDILLRCGS RVGLSFPFLP SPGQNQGCDW FFNSQLRQLT
  2701  YLVSGEGQVQ VILRVKEGMP PTISASTSAP ESALKWSLPE TWQGVEEGWG GYNNTIPGPG
  2761  DDVLILPNRT VLVDTDLPFF KGLYVMGTLD FPVDRSNVLS VACMVIAGGE LKVGTLENPL
  2821  EKEQKLLILL RASEGVFCDR MNGIHIDPGT IGVYGKVHLY SAYPKNSWTH LGADIASGNE
  2881  RIIVEDAVDW RPHDKIVLSS SSYEPHEAEV LTVKEVKGHH VRIYERLKHR HIGSVHVTED
  2941  GRHIRLAAEV GLLTRNIQIQ PDVSCRGRLF VGSFRKSSRE EFSGVLQLLN VEIQNFGSPL
  3001  YSSVEFSNVS AGSWIISSTL HQSCGGGIHA AASHGVLLND NIVFGTAGHG IDLEGQAYTV
  3061  TNNLVVLMTQ PAWSTIWVAG IKVNQVKDIN LHGNVVAGSE RLGFHIRGHK CSSCELLWSD
  3121  NVAHSSLHGL HLYKESGLDN CTRISGFLAF KNFDYGAMLH VENSVEIENI TLVDNTIGLL
  3181  AVVYVFSAPQ NSVKKVQIVL RNSVIVATSS SFDCIQDKVK PHSANLTSTD RAPSNPRGGR
  3241  IGILWPVFTS EPNQWPQEPW HKVRNDHSIS GIMKLQDVTF SSFVKSCYSD DLDVCILPNA
  3301  ENSGIMHPIT AERTRMLKIK DKNKFYFPSL QPRKDLGKVV CPELDCASPR KYLFKDLDGR
  3361  ALGLPPPVSV FPKTEAEWTA SFFNAGTFRE EQKCTYQFLM QGFICKQTDQ VVLILDSADA
  3421  IWAIQKLYPV VSVTSGFVDV FSSVNANIPC STSGSVSTFY SILPIRQITK VCFMDQTPQV
  3481  LRFFLLGNKS TSKLLLAVFY HELQSPHVFL GESFIPPTLV QSASLLLNES IGANYFNIMD
  3541  NLLYVVLQGE EPIEIRSGVS IHLALTVMVS VLEKGWEIVI LERLTNFLQI GQNQIRFIHE
  3601  MPGHEETLKA IADSRAKRKR NCPTVTCTSH YRRVGQRRPL MMEMNSHRAS PPMTVETISK
  3661  VIVIEIGDSP TVRSTGMISS LSSNKLQNLA HRVITAQQTG VLENVLNMTI GALLVTQSKG
  3721  VIGYGNTSSF KTGNLIYIRP YALSILVQPS DGEVGNELPV QPQLVFLDEQ NRRVESLGPP
  3781  SEPWTISASL EGASDSVLKG CTQAETQDGY VSFYNLAVLI SGSNWHFIFT VTSPPGVNFT
  3841  ARSKPFAVLP VTRKEKSTII LAASLSSVAS WLALSCLVCC WLKRSKSRKT KPEEIPESQT
  3901  NNQNIHIHIS SKRRESQGPK KEDTVVGEDM RMKVMLGKVN QCPHQLMNGV SRRKVSRHIV
  3961  REEEAAVPAP GTTGITSHGH ICAPGAPAQQ VYLQETGNWK EGQEQLLRYQ LAGQNQLLLL
  4021  CPDFRQERQQ LPGQSRLSKQ SGSLGLSQEK KASCGATEAF CLHSVHPETI QEQL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PKHD1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0

Highest tissue expression

13 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PKHD1.

Disease | AllUniProt

Conditions PKHD1 is implicated in, by any mechanism.

• Polycystic kidney disease 4, with or without polycystic liver disease (PKD4) MIM:263200

Disease | GeneticClinVar

1,568 pathogenic / likely-pathogenic of 6,859 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autosomal recessive polycystic kidney disease
• Polycystic kidney disease 4
• PKHD1-related disorder
• Autosomal dominant polycystic liver disease
• Polycystic kidney disease

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.68

gnomAD pLI

0

gnomAD missense Z

-0.98

DepMap mean gene effect

-0.13

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• branching morphogenesis of an epithelial tube
• cell-cell adhesion
• cell-cell junction organization
• cilium assembly
• epithelial cell morphogenesis
• establishment of centrosome localization
• establishment of mitotic spindle orientation
• homeostatic process
• intracellular calcium ion homeostasis
• kidney development
• negative regulation of apoptotic process
• negative regulation of epithelial cell apoptotic process
• negative regulation of NF-kappaB transcription factor activity
• negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• positive regulation of cell population proliferation
• positive regulation of epithelial cell proliferation
• regulation of cell adhesion
• regulation of cell-cell adhesion
• regulation of cell-matrix adhesion
• regulation of centrosome duplication
• regulation of ERK1 and ERK2 cascade
• regulation of establishment of planar polarity
• regulation of TOR signaling
• regulation of cholangiocyte proliferation

Molecular functions

• signaling receptor activity

Cellular components

• 9+0 non-motile cilium
• apical plasma membrane
• centrosome
• chromosome, centromeric region
• ciliary basal body
• cilium
• cytoplasm
• cytosol
• endoplasmic reticulum
• external side of plasma membrane
• extracellular exosome
• Golgi apparatus
• mitotic spindle
• nucleus
• perinuclear region of cytoplasm

Protein domainsUniProt · Pfam · InterPro

• IPT domain
• Parallel beta-helix repeat
• Pectin lyase fold/virulence factor
• Pectin lyase fold
• Immunoglobulin-like fold
• Immunoglobulin E-set
• G8 domain
• PA14/GLEYA domain
• Right handed beta helix domain
• Fibrocystin
• CEMIP, beta-helix domain
• IPT/TIG domain
• G8 domain
• Right handed beta helix region
• CEMIP beta-helix

KeywordsUniProt

• Cell membrane
• Cell projection
• Centromere
• Chromosome
• Ciliopathy
• Cilium
• Cytoplasm
• Cytoskeleton
• Endoplasmic reticulum
• Glycoprotein
• Golgi apparatus
• Membrane
• Nucleus
• Receptor
• Repeat
• Secreted
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of PKHD1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CAMLG
• PKD2