PCDH15

Protein-coding gene in the species Homo sapiens
PCDH15
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

4APX, 4AQ8, 4AQA, 4AQE, 4AXW

Identifiers
AliasesPCDH15, CDHR15, DFNB23, USH1F, protocadherin-related 15, protocadherin related 15
External IDsOMIM: 605514; MGI: 1891428; HomoloGene: 23401; GeneCards: PCDH15; OMA:PCDH15 - orthologs
Gene location (Human)
Chromosome 10 (human)
Chr.Chromosome 10 (human)[1]
Chromosome 10 (human)
Genomic location for PCDH15
Genomic location for PCDH15
Band10q21.1Start53,802,771 bp[1]
End55,627,942 bp[1]
Gene location (Mouse)
Chromosome 10 (mouse)
Chr.Chromosome 10 (mouse)[2]
Chromosome 10 (mouse)
Genomic location for PCDH15
Genomic location for PCDH15
Band10 B5.3|10 37.43 cMStart73,099,342 bp[2]
End74,649,737 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • left adrenal cortex

  • testicle

  • right adrenal cortex

  • amygdala

  • hypothalamus

  • anterior cingulate cortex

  • right frontal lobe

  • nucleus accumbens

  • C1 segment

  • anterior pituitary
Top expressed in
  • neural layer of retina

  • zygote

  • substantia nigra

  • lumbar subsegment of spinal cord

  • secondary oocyte

  • Rostral migratory stream

  • epithelium of lens

  • Bowman's capsule

  • mammillary body

  • primary visual cortex
More reference expression data
BioGPS
n/a
Gene ontology
Molecular function
  • calcium ion binding
Cellular component
  • integral component of membrane
  • extracellular region
  • plasma membrane
  • photoreceptor outer segment
  • synapse
  • membrane
  • stereocilium
  • extracellular space
  • integral component of plasma membrane
Biological process
  • inner ear development
  • photoreceptor cell maintenance
  • sensory perception of light stimulus
  • hearing
  • equilibrioception
  • homophilic cell adhesion via plasma membrane adhesion molecules
  • cell adhesion
  • cell-cell signaling
  • nervous system development
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

65217

11994

Ensembl

ENSG00000150275

ENSMUSG00000052613

UniProt

Q96QU1

Q99PJ1

RefSeq (mRNA)
NM_033056
NM_001142763
NM_001142764
NM_001142765
NM_001142766

NM_001142767
NM_001142768
NM_001142769
NM_001142770
NM_001142771
NM_001142772
NM_001142773
NM_001354404
NM_001354411
NM_001354420
NM_001354429
NM_001354430
NM_001384140

NM_001142735
NM_001142736
NM_001142737
NM_001142738
NM_001142739

NM_001142740
NM_001142741
NM_001142742
NM_001142743
NM_001142746
NM_001142747
NM_001142748
NM_001142760
NM_023115

RefSeq (protein)
NP_001136235
NP_001136236
NP_001136237
NP_001136238
NP_001136239

NP_001136240
NP_001136241
NP_001136242
NP_001136243
NP_001136244
NP_001136245
NP_149045
NP_001341333
NP_001341340
NP_001341349
NP_001341358
NP_001341359
NP_001371069

NP_001136207
NP_001136208
NP_001136209
NP_001136210
NP_001136211

NP_001136212
NP_001136213
NP_001136214
NP_001136215
NP_001136218
NP_001136219
NP_001136220
NP_001136232
NP_075604

Location (UCSC)Chr 10: 53.8 – 55.63 MbChr 10: 73.1 – 74.65 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Protocadherin-15 is a protein that in humans is encoded by the PCDH15 gene.[5][6][7]

Function

This gene is a member of the cadherin superfamily. Family members encode integral membrane proteins that mediate calcium-dependent cell-cell adhesion. The protein product of this gene consists of a signal peptide, 11 extracellular calcium-binding domains, a transmembrane domain and a unique cytoplasmic domain. It plays an essential role in maintenance of normal retinal and cochlear function.[7] It is thought to interact with CDH23 to form tip-link filaments.[8]

Clinical significance

Mutations in this gene have been associated with hearing loss, which is consistent with its location at the Usher syndrome type 1F (USH1F) critical region on chromosome 10.[7] Variation within it has also been found to be associated with normal differences in human facial appearance.[9]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000150275 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000052613 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Ahmed ZM, Riazuddin S, Bernstein SL, Ahmed Z, Khan S, Griffith AJ, et al. (July 2001). "Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F". American Journal of Human Genetics. 69 (1): 25–34. doi:10.1086/321277. PMC 1226045. PMID 11398101.
  6. ^ Ahmed ZM, Riazuddin S, Ahmad J, Bernstein SL, Guo Y, Sabar MF, et al. (December 2003). "PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant alleles are responsible for both USH1F and DFNB23". Human Molecular Genetics. 12 (24): 3215–23. doi:10.1093/hmg/ddg358. PMID 14570705. S2CID 14028314.
  7. ^ a b c "Entrez Gene: PCDH15 protocadherin 15".
  8. ^ Kazmierczak P, Sakaguchi H, Tokita J, Wilson-Kubalek EM, Milligan RA, Müller U, Kachar B (September 2007). "Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells". Nature. 449 (7158): 87–91. Bibcode:2007Natur.449...87K. doi:10.1038/nature06091. PMID 17805295. S2CID 4414814.
  9. ^ Crouch DJ, Winney B, Koppen WP, Christmas WJ, Hutnik K, Day T, et al. (January 2018). "Genetics of the human face: Identification of large-effect single gene variants". Proceedings of the National Academy of Sciences of the United States of America. 115 (4): E676–E685. Bibcode:2018PNAS..115E.676C. doi:10.1073/pnas.1708207114. PMC 5789906. PMID 29301965.

Further reading

  • Alagramam KN, Murcia CL, Kwon HY, Pawlowski KS, Wright CG, Woychik RP (January 2001). "The mouse Ames waltzer hearing-loss mutant is caused by mutation of Pcdh15, a novel protocadherin gene". Nature Genetics. 27 (1): 99–102. doi:10.1038/83837. PMID 11138007. S2CID 32444699.
  • Alagramam KN, Yuan H, Kuehn MH, Murcia CL, Wayne S, Srisailpathy CR, et al. (August 2001). "Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F". Human Molecular Genetics. 10 (16): 1709–18. doi:10.1093/hmg/10.16.1709. PMID 11487575.
  • Ben-Yosef T, Ness SL, Madeo AC, Bar-Lev A, Wolfman JH, Ahmed ZM, et al. (April 2003). "A mutation of PCDH15 among Ashkenazi Jews with the type 1 Usher syndrome". The New England Journal of Medicine. 348 (17): 1664–70. doi:10.1056/NEJMoa021502. PMID 12711741.
  • Zheng QY, Yan D, Ouyang XM, Du LL, Yu H, Chang B, et al. (January 2005). "Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans". Human Molecular Genetics. 14 (1): 103–11. doi:10.1093/hmg/ddi010. PMC 2858222. PMID 15537665.
  • Ouyang XM, Yan D, Du LL, Hejtmancik JF, Jacobson SG, Nance WE, et al. (March 2005). "Characterization of Usher syndrome type I gene mutations in an Usher syndrome patient population". Human Genetics. 116 (4): 292–9. doi:10.1007/s00439-004-1227-2. PMID 15660226. S2CID 22812718.
  • Roux AF, Faugère V, Le Guédard S, Pallares-Ruiz N, Vielle A, Chambert S, et al. (September 2006). "Survey of the frequency of USH1 gene mutations in a cohort of Usher patients shows the importance of cadherin 23 and protocadherin 15 genes and establishes a detection rate of above 90%". Journal of Medical Genetics. 43 (9): 763–8. doi:10.1136/jmg.2006.041954. PMC 2564578. PMID 16679490.
  • Zheng QY, Yu H, Washington JL, Kisley LB, Kikkawa YS, Pawlowski KS, et al. (September 2006). "A new spontaneous mutation in the mouse protocadherin 15 gene". Hearing Research. 219 (1–2): 110–20. doi:10.1016/j.heares.2006.06.010. PMC 2855306. PMID 16887306.
  • Le Guédard S, Faugère V, Malcolm S, Claustres M, Roux AF (January 2007). "Large genomic rearrangements within the PCDH15 gene are a significant cause of USH1F syndrome". Molecular Vision. 13: 102–7. PMC 2533038. PMID 17277737.

External links

  • GeneReviews/NCBI/NIH/UW entry on Usher Syndrome Type I
  • PDBe-KB provides an overview of all the structure information available in the PDB for Human Protocadherin-15 (PCDH15)
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