Table 2: Phenotype of CCC mutations.

CCCLocationMutationSpeciesNeurological effectRef.

KCC1UbiquitousKnockoutMouseNone seen[92]
KCC2BrainKCC2a and KCC2b knockoutMouseDeath at birth [93]
BrainKCC2b knockoutMouseSeizures, low weight, early mortality [94]
BrainHypomorphMouseIncreased seizure susceptibility and anxiety [95]
BrainHeterozygoteMouseHyperexcitability [96]
KCC3UbiquitousKCC3a-c knockoutHuman, mousePeripheral neuropathy; seizures have been reported [97100]
KCC4Kidney, heart, lungs, liverKnockoutMouseDeafness[101]
NKCC1UbiquitousNKCC1a knockoutMouseDeafness, circling behavior [102]
UbiquitousNKCC1a and NKCC1b knockoutMouseDeafness, circling behavior, growth retardation, defective spermatogenesis, increased threshold to thermal stimulation [103, 104]
NKCC2KidneyKnockoutHumanBartter’s syndrome[105]