PCDH15

Protein identityUniProt · HPA

UniProt accession

Q96QU1

Gene

PCDH15

Ensembl

ENSG00000150275

Chromosome

10

Canonical length

1955 aa

Protein class

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

Subcellular location

Nucleoplasm,Golgi apparatus,Vesicles,Plasma membrane,Focal adhesion sites

Secretome location

Intracellular and membrane

OverviewNCBI Gene

This gene is a member of the cadherin superfamily. Family members encode integral membrane proteins that mediate calcium-dependent cell-cell adhesion. It plays an essential role in maintenance of normal retinal and cochlear function. Mutations in this gene result in hearing loss and Usher Syndrome Type IF (USH1F). Extensive alternative splicing resulting in multiple isoforms has been observed in the mouse ortholog. Similar alternatively spliced transcripts are inferred to occur in human, and additional variants are likely to occur. [provided by RefSeq, Dec 2008]

Canonical amino-acid sequenceUniProt

1955 residues, UniProt reviewed canonical sequence.

>Q96QU1|PCDH15
     1  MFRQFYLWTC LASGIILGSL FEICLGQYDD DCKLARGGPP ATIVAIDEES RNGTILVDNM
    61  LIKGTAGGPD PTIELSLKDN VDYWVLMDPV KQMLFLNSTG RVLDRDPPMN IHSIVVQVQC
   121  INKKVGTIIY HEVRIVVRDR NDNSPTFKHE SYYATVNELT PVGTTIFTGF SGDNGATDID
   181  DGPNGQIEYV IQYNPDDPTS NDTFEIPLML TGNIVLRKRL NYEDKTRYFV IIQANDRAQN
   241  LNERRTTTTT LTVDVLDGDD LGPMFLPCVL VPNTRDCRPL TYQAAIPELR TPEELNPIIV
   301  TPPIQAIDQD RNIQPPSDRP GILYSILVGT PEDYPRFFHM HPRTAELSLL EPVNRDFHQK
   361  FDLVIKAEQD NGHPLPAFAG LHIEILDENN QSPYFTMPSY QGYILESAPV GATISDSLNL
   421  TSPLRIVALD KDIEDTKDPE LHLFLNDYTS VFTVTQTGIT RYLTLLQPVD REEQQTYTFS
   481  ITAFDGVQES EPVIVNIQVM DANDNTPTFP EISYDVYVYT DMRPGDSVIQ LTAVDADEGS
   541  NGEITYEILV GAQGDFIINK TTGLITIAPG VEMIVGRTYA LTVQAADNAP PAERRNSICT
   601  VYIEVLPPNN QSPPRFPQLM YSLEISEAMR VGAVLLNLQA TDREGDSITY AIENGDPQRV
   661  FNLSETTGIL TLGKALDRES TDRYILIITA SDGRPDGTST ATVNIVVTDV NDNAPVFDPY
   721  LPRNLSVVEE EANAFVGQVK ATDPDAGING QVHYSLGNFN NLFRITSNGS IYTAVKLNRE
   781  VRDYYELVVV ATDGAVHPRH STLTLAIKVL DIDDNSPVFT NSTYTVLVEE NLPAGTTILQ
   841  IEAKDVDLGA NVSYRIRSPE VKHFFALHPF TGELSLLRSL DYEAFPDQEA SITFLVEAFD
   901  IYGTMPPGIA TVTVIVKDMN DYPPVFSKRI YKGMVAPDAV KGTPITTVYA EDADPPGLPA
   961  SRVRYRVDDV QFPYPASIFE VEEDSGRVIT RVNLNEEPTT IFKLVVVAFD DGEPVMSSSA
  1021  TVKILVLHPG EIPRFTQEEY RPPPVSELAT KGTMVGVISA AAINQSIVYS IVSGNEEDTF
  1081  GINNITGVIY VNGPLDYETR TSYVLRVQAD SLEVVLANLR VPSKSNTAKV YIEIQDENNH
  1141  PPVFQKKFYI GGVSEDARMF TSVLRVKATD KDTGNYSVMA YRLIIPPIKE GKEGFVVETY
  1201  TGLIKTAMLF HNMRRSYFKF QVIATDDYGK GLSGKADVLV SVVNQLDMQV IVSNVPPTLV
  1261  EKKIEDLTEI LDRYVQEQIP GAKVVVESIG ARRHGDAFSL EDYTKCDLTV YAIDPQTNRA
  1321  IDRNELFKFL DGKLLDINKD FQPYYGEGGR ILEIRTPEAV TSIKKRGESL GYTEGALLAL
  1381  AFIIILCCIP AILVVLVSYR QFKVRQAECT KTARIQAALP AAKPAVPAPA PVAAPPPPPP
  1441  PPPGAHLYEE LGDSSILFLL YHFQQSRGNN SVSEDRKHQQ VVMPFSSNTI EAHKSAHVDG
  1501  SLKSNKLKSA RKFTFLSDED DLSAHNPLYK ENISQVSTNS DISQRTDFVD PFSPKIQAKS
  1561  KSLRGPREKI QRLWSQSVSL PRRLMRKVPN RPEIIDLQQW QGTRQKAENE NTGICTNKRG
  1621  SSNPLLTTEE ANLTEKEEIR QGETLMIEGT EQLKSLSSDS SFCFPRPHFS FSTLPTVSRT
  1681  VELKSEPNVI SSPAECSLEL SPSRPCVLHS SLSRRETPIC MLPIETERNI FENFAHPPNI
  1741  SPSACPLPPP PPISPPSPPP APAPLAPPPD ISPFSLFCPP PSPPSIPLPL PPPTFFPLSV
  1801  STSGPPTPPL LPPFPTPLPP PPPSIPCPPP PSASFLSTEC VCITGVKCTT NLMPAEKIKS
  1861  SMTQLSTTTV CKTDPQREPK GILRHVKNLA ELEKSVANMY SQIEKNYLRT NVSELQTMCP
  1921  SEVTNMEITS EQNKGSLNNI VEGTEKQSHS QSTSL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PCDH15 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)

0.4

Highest tissue expression

57 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PCDH15.

Disease | AllUniProt

Conditions PCDH15 is implicated in, by any mechanism.

• Usher syndrome 1F (USH1F) MIM:602083
• Usher syndrome 1D/F (USH1DF) MIM:601067
• Deafness, autosomal recessive, 23 (DFNB23) MIM:609533

Disease | GeneticClinVar

529 pathogenic / likely-pathogenic of 3,828 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autosomal recessive nonsyndromic hearing loss 23
• Usher syndrome type 1F
• Usher syndrome type 1D
• Rare genetic deafness
• Usher syndrome

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)

0.79

gnomAD pLI

0

gnomAD missense Z

-1.68

DepMap mean gene effect

0.05

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell adhesion
• equilibrioception
• homophilic cell adhesion via plasma membrane adhesion molecules
• inner ear development
• photoreceptor cell maintenance
• sensory perception of light stimulus
• sensory perception of sound

Molecular functions

• calcium ion binding
• cell adhesion molecule binding

Cellular components

• extracellular region
• extracellular space
• photoreceptor outer segment
• plasma membrane
• stereocilium
• synapse

Protein domainsUniProt · Pfam · InterPro

• Cadherin-like
• Cadherin-like superfamily
• Cadherin conserved site
• Cadherin domain-containing protein
• Cadherin domain
• Extracellular cadherin domain superfamily
• Extracellular cadherin domain
• Protocadherin-15 domain
• Extracellular Cadherin domain
• PCDH15-like domain

KeywordsUniProt

• Calcium
• Cell adhesion
• Cell membrane
• Deafness
• Disulfide bond
• Glycoprotein
• Hearing
• Membrane
• Non-syndromic deafness
• Repeat
• Retinitis pigmentosa
• Secreted
• Signal
• Transmembrane
• Transmembrane helix
• Usher syndrome

InteractionsUniProt · HPA

Protein binding partners of PCDH15 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MYO7A
• TOMT
• USH1G
• PIEZO1