Isolation of a Candidate Gene for Menkes Disease and Evidence That It Encodes a Copper-Transporting ATPase

Nat Genet. 1993 Jan;3(1):7-13. doi: 10.1038/ng0193-7.

Abstract

Menkes disease is an X-linked disorder of copper transport characterized by progressive neurological degeneration and death in early childhood. We have isolated a candidate gene (Mc1) for Menkes disease and find qualitative or quantitative abnormalities in the mRNA in sixteen of twenty-one Menkes patients. Four patients lacking Mc1RNA showed rearrangements of the Menkes gene. The gene codes for a 1,500 amino acid protein, predicted to be a P-type cation-transporting ATPase. The gene product is most similar to a bacterial copper-transporting ATPase and additionally contains six putative metal-binding motifs at the N-terminus. The gene is transcribed in all cell types tested except liver, consistent with the expression of the Menkes defect.

MeSH terms

  • Adenosine Triphosphatases / genetics*
  • Adenosine Triphosphatases / metabolism
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Biological Transport, Active
  • Blotting, Southern
  • Carrier Proteins / genetics*
  • Cation Transport Proteins*
  • Cells, Cultured
  • Chromosome Mapping
  • Cloning, Molecular
  • Copper / metabolism*
  • Copper-Transporting ATPases
  • DNA / isolation & purification
  • Gene Expression
  • Gene Rearrangement
  • Humans
  • Menkes Kinky Hair Syndrome / enzymology
  • Menkes Kinky Hair Syndrome / genetics*
  • Molecular Sequence Data
  • Organ Specificity / genetics
  • Recombinant Fusion Proteins*
  • Translocation, Genetic
  • X Chromosome

Substances

  • Carrier Proteins
  • Cation Transport Proteins
  • Recombinant Fusion Proteins
  • Copper
  • DNA
  • Adenosine Triphosphatases
  • ATP7A protein, human
  • Copper-Transporting ATPases

Associated data

  • GENBANK/A24414
  • GENBANK/A25823
  • GENBANK/A25939
  • GENBANK/A30802
  • GENBANK/A31671
  • GENBANK/A32561
  • GENBANK/A36558
  • GENBANK/A36691
  • GENBANK/B28065
  • GENBANK/B39083
  • GENBANK/J02729
  • GENBANK/J04004
  • GENBANK/L06133
  • GENBANK/M24144
  • GENBANK/M90750
  • GENBANK/P20649
  • GENBANK/S00503
  • GENBANK/S03632