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Table 1 Effect of mutations in Cx26 (GJB2) on the functional state of HCs and GJCs evaluated in a heterologous expression system, the domain that is affected and its phenotype

From: Connexinopathies: a structural and functional glimpse

Domain Mutation GJCs Function HCs Function Deafness Phenotype
NT M1V, T8M, G12V [13], [123], [132]–[136] (−) n.d. NS, Profound, Moderate
G11E [130], [136], [137] n.d. (+) S, Profound. KID
G12R(+*), N14K [13], [123], [136], [138] (−) (+) S, Mild, Severe. KID/EKV
N14D [139] n.d. (−) NS, Moderate
N14Y(+*) [13], [39], [136] (−) (+) S, Profound. KID
S17F(+*) [13], [40], [123], [136] (−) (−) S, SNHL. KID
TM1 V27I [140] Normal Normal NS, HL and Normal
I33T [141] (−) n.d. NS, Severe to Profound
M34T [36], [115], [142]–[146] (−) (−) NS, Mild to Moderate; S, Profound. PPK
V37I, A40G [113], [143], [147]–[149] (−) (−) NS, Mild-Moderate, Severe
A40V [124], [136], [150], [151] Normal (+) S, Profound. KID
ECL1 DelE42, D66H [152]–[159] (−) n.d. S, Profound, Moderate to Profound. PPK
W44C, W44S, D46E, T55N [142], [143], [152], [153], [159]–[163] (−) n.d. NS, Severe to Profound, HL, Moderate, Severe
G45E [124], [130], [150], [164]–[166] Normal (+) S, Profound. KID
E47K [164], [167] (−) (−) NS, Severe to Profound
D50A [168], [169] n.d. (+) S, Profound. KID
D50N [123], [137], [151], [170]–[172] (−) (+) S, Profound. KID
G59V [144], [173] n.d. (−) NS, Profound
R75Q, R75W [37], [134], [136], [141], [152]–[154], [174] (−) (−) S, Severe to Profound. PPK
TM2 W77R, F83L, L90V, V95M [37], [135], [142], [143], [147], [173], [175], [176] (−) n.d. NS, Moderate to Profound, Moderate, Profound
I82M [144], [177] n.d. (−) NS, Profound
V84L [51], [147], [148], [178], [179] Normal/No IP3 transfer n.d NS. Profound
T86R, A88S, L90P [132], [143], [144], [147], [160], [180] (−) (−) NS, Profound, Moderate to Profound, Mild to Moderate
A88V [136], [168], [181] n.d. (+) S, Severe to Profound. KID
ICL E114G, R127H [115], [140], [144], [173], [178], [182], [183] (−) (−) NS, Severe to Profound, Profound
DelE120 [141], [143], [147] (−) n.d. NS, Severe to Profound
TM3 R143Q, R153I [133], [152], [153], [183], [184] (−) n.d. NS, Profound
R143W [133], [144], [178], [185], [186] (−) (−) NS, Profound
ECL2 F161S, P173R, D179N, R165W, W172R, R184P, R184Q [132], [141], [143], [147], [152], [153], [187]–[190] (−) n.d. NS, HL, Severe to Profound, Profound
M163L [191] n.d (+) NS, Moderate to Profound
S183F [136], [192] (−) n.d. S, High Frequency HL. PPK
TM4 M195T, A197S,206S, L214P [133], [135], [190], [193], [194] (−) n.d. NS, HL, Moderate, Profound
C202F [153], [193], [195] n.d. (−) NS, Mild to Moderate
I203T, L205V [179], [193], [196] (−) (−) NS, HL, Profound
  1. NS Non-syndromic, S Syndromic, KID Keratitis-Ichthyosis-Deafness, EKV Erythrokeratodermia variabilis, PPK Palmoplantar Keratoderma-deafness, HL Hearing loss. (+*) = Generate gain of HC function when they are coexpressed with wild type Cx26 or Cx43 [13]
  2. (−) = Loss of function. (+) = Gain of function. n.d. = not determined