Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease

Nat Genet. 1999 Mar;21(3):271-7. doi: 10.1038/6784.


Darier disease (DD) is an autosomal-dominant skin disorder characterized by loss of adhesion between epidermal cells (acantholysis) and abnormal keratinization. Recently we constructed a 2.4-Mb, P1-derived artificial chromosome contig spanning the DD candidate region on chromosome 12q23-24.1. After screening several genes that mapped to this region, we identified mutations in the ATP2A2 gene, which encodes the sarco/endoplasmic reticulum Ca2(+)-ATPase type 2 isoform (SERCA2) and is highly expressed in keratinocytes. Thirteen mutations were identified, including frameshift deletions, in-frame deletions or insertions, splice-site mutations and non-conservative missense mutations in functional domains. Our results demonstrate that mutations in ATP2A2 cause DD and disclose a role for this pump in a Ca(2+)-signalling pathway regulating cell-to-cell adhesion and differentiation of the epidermis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Calcium-Transporting ATPases / genetics*
  • Calcium-Transporting ATPases / metabolism
  • Darier Disease / genetics*
  • Female
  • Gene Expression Regulation
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Keratinocytes / physiology
  • Male
  • Molecular Sequence Data
  • Mutation*


  • Isoenzymes
  • Calcium-Transporting ATPases

Associated data

  • GENBANK/AC006088
  • GENBANK/AF006086
  • GENBANK/H73417
  • GENBANK/M21812
  • GENBANK/M23114
  • GENBANK/M23115
  • GENBANK/M25488
  • GENBANK/P11508
  • GENBANK/P11606
  • GENBANK/P11719
  • GENBANK/P12947
  • GENBANK/P16614
  • GENBANK/P16615
  • GENBANK/P17403
  • GENBANK/P36873
  • GENBANK/P38759
  • GENBANK/P43490
  • GENBANK/P47914
  • GENBANK/Q00779
  • GENBANK/Q93084
  • GENBANK/U49083
  • GENBANK/U80218
  • GENBANK/U96781
  • GENBANK/X15940
  • GENBANK/X74008