KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness

Cell. 1999 Feb 5;96(3):437-46. doi: 10.1016/s0092-8674(00)80556-5.


Potassium channels regulate electrical signaling and the ionic composition of biological fluids. Mutations in the three known genes of the KCNQ branch of the K+ channel gene family underlie inherited cardiac arrhythmias (in some cases associated with deafness) and neonatal epilepsy. We have now cloned KCNQ4, a novel member of this branch. It maps to the DFNA2 locus for a form of nonsyndromic dominant deafness. In the cochlea, it is expressed in sensory outer hair cells. A mutation in this gene in a DFNA2 pedigree changes a residue in the KCNQ4 pore region. It abolishes the potassium currents of wild-type KCNQ4 on which it exerts a strong dominant-negative effect. Whereas mutations in KCNQ1 cause deafness by affecting endolymph secretion, the mechanism leading to KCNQ4-related hearing loss is intrinsic to outer hair cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chromosome Mapping
  • Cloning, Molecular
  • DNA, Complementary / isolation & purification
  • Ear, Inner / metabolism
  • Female
  • Gene Expression Regulation
  • Genes, Dominant*
  • Hair Cells, Auditory, Outer / metabolism*
  • Hearing Loss, Sensorineural / genetics*
  • Hearing Loss, Sensorineural / metabolism
  • Humans
  • KCNQ Potassium Channels
  • Mice
  • Molecular Sequence Data
  • Mutation*
  • Oocytes
  • Pedigree
  • Potassium Channels / biosynthesis*
  • Potassium Channels / genetics*
  • Potassium Channels / physiology
  • Potassium Channels, Voltage-Gated*
  • Xenopus laevis


  • DNA, Complementary
  • KCNQ Potassium Channels
  • KCNQ4 protein, human
  • Kcnq4 protein, mouse
  • Potassium Channels
  • Potassium Channels, Voltage-Gated

Associated data

  • GENBANK/AF105202
  • GENBANK/AF105203
  • GENBANK/AF105204
  • GENBANK/AF105205
  • GENBANK/AF105206
  • GENBANK/AF105207
  • GENBANK/AF105208
  • GENBANK/AF105209
  • GENBANK/AF105210
  • GENBANK/AF105211
  • GENBANK/AF105212
  • GENBANK/AF105213
  • GENBANK/AF105214
  • GENBANK/AF105215
  • GENBANK/AF105216