PCDH15 explained

Protocadherin-15 is a protein that in humans is encoded by the PCDH15 gene.^{[1] [2]}

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. It is thought to interact with CDH23 to form tip-link filaments.^[3]

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.^[4] Variation within it has also been found to be associated with normal differences in human facial appearance.^[5]

Further reading

• Alagramam KN, Murcia CL, Kwon HY, Pawlowski KS, Wright CG, Woychik RP . 32444699 . The mouse Ames waltzer hearing-loss mutant is caused by mutation of Pcdh15, a novel protocadherin gene . Nature Genetics . 27 . 1 . 99–102 . January 2001 . 11138007 . 10.1038/83837 .
• Alagramam KN, Yuan H, Kuehn MH, Murcia CL, Wayne S, Srisailpathy CR, Lowry RB, Knaus R, Van Laer L, Bernier FP, Schwartz S, Lee C, Morton CC, Mullins RF, Ramesh A, Van Camp G, Hageman GS, Woychik RP, Smith RJ, Hagemen GS . 6 . Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F . Human Molecular Genetics . 10 . 16 . 1709–18 . August 2001 . 11487575 . 10.1093/hmg/10.16.1709 . free .
• Ben-Yosef T, Ness SL, Madeo AC, Bar-Lev A, Wolfman JH, Ahmed ZM, Desnick RJ, Willner JP, Avraham KB, Ostrer H, Oddoux C, Griffith AJ, Friedman TB . 6 . A mutation of PCDH15 among Ashkenazi Jews with the type 1 Usher syndrome . The New England Journal of Medicine . 348 . 17 . 1664–70 . April 2003 . 12711741 . 10.1056/NEJMoa021502 . free .
• Zheng QY, Yan D, Ouyang XM, Du LL, Yu H, Chang B, Johnson KR, Liu XZ . 6 . 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 . January 2005 . 15537665 . 2858222 . 10.1093/hmg/ddi010 .
• Ouyang XM, Yan D, Du LL, Hejtmancik JF, Jacobson SG, Nance WE, Li AR, Angeli S, Kaiser M, Newton V, Brown SD, Balkany T, Liu XZ . 22812718 . 6 . Characterization of Usher syndrome type I gene mutations in an Usher syndrome patient population . Human Genetics . 116 . 4 . 292–9 . March 2005 . 15660226 . 10.1007/s00439-004-1227-2 .
• Roux AF, Faugère V, Le Guédard S, Pallares-Ruiz N, Vielle A, Chambert S, Marlin S, Hamel C, Gilbert B, Malcolm S, Claustres M . 6 . 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 . September 2006 . 16679490 . 2564578 . 10.1136/jmg.2006.041954 .
• Zheng QY, Yu H, Washington JL, Kisley LB, Kikkawa YS, Pawlowski KS, Wright CG, Alagramam KN . 6 . A new spontaneous mutation in the mouse protocadherin 15 gene . Hearing Research . 219 . 1–2 . 110–20 . September 2006 . 16887306 . 2855306 . 10.1016/j.heares.2006.06.010 .
• Le Guédard S, Faugère V, Malcolm S, Claustres M, Roux AF . Large genomic rearrangements within the PCDH15 gene are a significant cause of USH1F syndrome . Molecular Vision . 13 . 102–7 . January 2007 . 17277737 . 2533038 .

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)

Notes and References

1. Ahmed ZM, Riazuddin S, Bernstein SL, Ahmed Z, Khan S, Griffith AJ, Morell RJ, Friedman TB, Riazuddin S, Wilcox ER . 6 . Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F . American Journal of Human Genetics . 69 . 1 . 25–34 . July 2001 . 11398101 . 1226045 . 10.1086/321277 .
2. Ahmed ZM, Riazuddin S, Ahmad J, Bernstein SL, Guo Y, Sabar MF, Sieving P, Riazuddin S, Griffith AJ, Friedman TB, Belyantseva IA, Wilcox ER . 14028314 . 6 . 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 . December 2003 . 14570705 . 10.1093/hmg/ddg358 . free .
3. Kazmierczak P, Sakaguchi H, Tokita J, Wilson-Kubalek EM, Milligan RA, Müller U, Kachar B . 4414814 . Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells . Nature . 449 . 7158 . 87–91 . September 2007 . 17805295 . 10.1038/nature06091 . 2007Natur.449...87K .
4. Web site: Entrez Gene: PCDH15 protocadherin 15.
5. Crouch DJ, Winney B, Koppen WP, Christmas WJ, Hutnik K, Day T, Meena D, Boumertit A, Hysi P, Nessa A, Spector TD, Kittler J, Bodmer WF . 6 . 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 . January 2018 . 29301965 . 10.1073/pnas.1708207114 . 5789906 . free . 2018PNAS..115E.676C .