ABCMdb

ABCC7 p.Glu826Lys

None has been submitted yet.

Publications

PMID: 16442101 [PubMed] Frelet A et al: "Insight in eukaryotic ABC transporter function by mutation analysis."

No. Sentence Comment

345 E822K and E826K reduced channel conductance and opening [160,165]. Login to comment

PMID: 10792060 [PubMed] Ostedgaard LS et al: "A functional R domain from cystic fibrosis transmembrane conductance regulator is predominantly unstructured in solution."

No. Sentence Comment

198 From this region, the mutations R792G, A800G, E822K, and E826K increase or decrease current, but have not been reported to alter channel properties (38, 39). Login to comment

PMID: 11950844 [PubMed] Xie J et al: "A short segment of the R domain of cystic fibrosis transmembrane conductance regulator contains channel stimulatory and inhibitory activities that are separable by sequence modification."

No. Sentence Comment

232 Three mutations are reported in the NEG2 region (E822K, E826K, and D836Y), two of which were obtained from patients with cystic fibrosis (E822K and D836Y). Login to comment
233 Single channel studies of E822K and E826K indicate that both mutations result in reduced Po compared with wt-CFTR (34). Login to comment

PMID: 12940920 [PubMed] Rowntree RK et al: "The phenotypic consequences of CFTR mutations."

No. Sentence Comment

79 Furthermore, mutants T665S and E826K showed no difference from the wild-type channel conductance. Login to comment

PMID: 16126774 [PubMed] Morea A et al: "Gender-sensitive association of CFTR gene mutations and 5T allele emerging from a large survey on infertility."

No. Sentence Comment

76 This test involved nine subjects from the infertile group, revealing the occurrence of the following rare mutations: E217G, T1054A, W356X, D443Y and 3667insTC in males and L997F and R297Q in females and 29 subjects from the control, in which we found: A1009T, D110Y, E826K, G1069R, G1130A, G194V, I556V, L320F, M348K, M82V, P1290T, R117C, R352W, R74W, S42F, S660T, S911R, S912L, T1086A, T582S, V920L and Y89C. Login to comment
144 *Genotypes include subjects (whose number is indicated within parentheses) that carry the following CFTR mutations 2789+5G/A, E826K, ∆F508, D443Y, 3849+10Kb C/T 1717-8G/A and 3667insTCAA. Login to comment

PMID: 17489851 [PubMed] Tzetis M et al: "Contribution of the CFTR gene, the pancreatic secretory trypsin inhibitor gene (SPINK1) and the cationic trypsinogen gene (PRSS1) to the etiology of recurrent pancreatitis."

No. Sentence Comment

93 a Additional mutations found in the controls: p.R1162L (1.66%), p.D565G (0.47%), p.A120T (0.47%) and 0.24% each for p.R297Q, p.L997F, p.E826K, p.I807M, p.S495Y and p.C491S. Login to comment

PMID: 9736778 [PubMed] Vankeerberghen A et al: "Characterization of 19 disease-associated missense mutations in the regulatory domain of the cystic fibrosis transmembrane conductance regulator."

No. Sentence Comment

9 Finally, T665S and E826K CFTR had single channel properties not significantly different from wild-type CFTR. Login to comment
68 Primers used for mutagenesis Primer Sequence I601F (a1933t) 5'-CTA ACA AAA CTA GGT TTT TGG TCA CTT C-3' L610S (t1961c) 5'-CTA AAA TGG AAC ATT CAA AGA AAG CTG-3' A613T (g1969a) 5'-CAT TTA AAG AAA ACT GAC AAA ATA TTA-3' D614G (a1973g) 5'-CAT TTA AAG AAA GCT GGC AAA ATA TTA A-3' I618T (t1985c) 5'-GAC AAA ATA TTA ACT TTG CAT GAA GG-3' L619S (t1988c) 5'-GAC AAA ATA TTA ATT TCG CAT GAA GGT-3' H620P (a1991c) 5'-CAA AAT ATT AAT TTT GCC TGA AGG TAG C-3' H620Q (t1992g) 5'-AAT ATT AAT TTT GCA GGA AGG TAG CAG-3' G622D (g1997a) 5'-TTG CAT GAA GAT AGC AGC TAT TTT TAT G-3' G628R (g2014c) 5'-GCA GCT ATT TTT ATC GGA CAT TTT C-3' L633P (t2030c) 5'-CAT TTT CAG AAC CCC AAA ATC TAC AGC-3' D648V (a2075t) 5'-CTC ATG GGA TGT GTT TCT TTC GAC C-3' T665S (a2125t) 5'-CAA TCC TAA CTG AGT CCT TAC ACC G-3' F693L (t2209c) 5'-CAG ACT GGA GAG CTT GGG GAA AAA AG-3' R766M (g2429t) 5'-GCA CGA AGG ATG CAG TCT GTC CTG-3' R792G (c2506g) 5'-CAG CAT CCA CAG GAA AAG TGT CAC TG-3' A800G (c2531g) 5'-CTG GCC CCT CAG GGA AAC TTG ACT G-3' I807M (a2553g) 5'-CTG AAC TGG ATA TGT ATT CAA GAA GG-3' E822K (g2596a) 5'-GGC TTG GAA ATA AGT AAA GAA ATT AAC G-3' E826K (g2608a) 5'-GAA GAA ATT AAC AAA GAA GAC TTA AAG-3' Selection primer BstBI 5'-CTC TGG GGT CCG GAA TGA CCG AC-3' Two primers were used for each mutagenesis reaction. Login to comment
77 Mutations detected in patients (I601F, L610S, A613T, D614G, I618T, L619S, H620P, H620Q, D622G, G628R, L633P, T665S, F693L, K698R, V754M, R766M, R792G, A800G, I807M, E822K and E826K) are indicated in bold and underlined, the PKA phosphorylation sites by an arrow and the two acidic domains are boxed. Login to comment
83 Four mutations (T665S, R792G, E822K and E826K) caused a significant reduction in the cAMP-induced chloride current. Login to comment
87 Maturation pattern of RD mutations and their associated phenotype found in patients with the indicated genotype (when the mutation is associated with CF, only the pancreas status is given) Mutation A-form B-form C-form Clinical data Genotype Phenotype Reference I601F + + - I601F/G542X PS M. Schwarz, personal communication L610S + + - Unknown Unknown A613T + + - Unknown Unknown D614G + + - D614G/unknown PI 14 I618T + + - I618T/dF508 PS G.R. Cutting, personal communication L619S + + - L619S/unknown PI B. Tümmler, personal communication H620P + + - H620P/R1158X PS M. Schwarz, personal communication H620Q + + + H620Q/dF508 PI T. Dörk, personal communication G622D + + + G622D/unknown Oligospermia J. Zielenski, personal communication G628R + + - Unknown Unknown L633P + + - L633P/3659delC M. Schwarz, personal communication D648V + + + D648V/3849+10kb C/T PI C. Ferec, personal communication T665S + + + Unknown Unknown F693L + + + F693L/W1282X Healthy C. Ferec; CF Genetic Analysis Consortium R766M + + + R766M/R792G CBAVD D. Glavac, personal communication R792G + + + R766M/R792G CBAVD D. Glavac, personal communication A800G + + + A800G/unknown CBAVD 34 I807M + + + I807M/unknown CBAVD Our observation E822K + + + E822K/unknown PI 35 E826K + + + E826K/unknown Thoracic sarcoidosis C. Bombieri, personal communication +, the protein matures up to that form; -, the protein does not reach the respective maturation step. Login to comment
123 Mutations that did not affect maturation (H620Q, G622D, D648V, T665S, F693L, R766M, R792G, A800G, I807M, E822K and E826K) were subsequently analysedat theelectrophysiologi- cal level. Login to comment
131 The remaining mutations (D648V, T665S, F693L, R766M, I807M and E826K) caused no significant alterations in intrinsic chloride channel activity. Login to comment

PMID: 9921909 [PubMed] Bombieri C et al: "Complete mutational screening of the CFTR gene in 120 patients with pulmonary disease."

No. Sentence Comment

4 Four new mutations were identified: D651N, 2377C/T, E826K, and P1072L. Login to comment
63 Three novel mutations were first identified in this study: D651N, E826K, and P1072L. Login to comment
77 E826K, a G to A substitution, was found at nucleotide 2608 in exon 13. Login to comment
88 of cases CFTR gene PolyTb status tested mutationa DBE 23 1 G576A-R668C/L997F 7/9 1 ∆F508/L997F 9/9 1 ∆F508/- 7/9 1 R1066C/- 5/7 1 3667ins4/- 5/7 1 R75Q/- 7/7 1 M1137V/- 7/7 1 -/- 5/5 3 -/- 5/7 10 -/- 7/7 2 -/- 7/9 CB 27 1 P111L/- 7/7 1 R117H/- 7/7 1 E585X/- 7/7 1 P1072L/- 7/7 1 -/- 5/7 15 -/- 7/7 6 -/- 7/9 1 -/- 9/9 E 25 1 R668C/- 7/7 6 -/- 5/7 16 -/- 7/7 6 -/- 7/9 S 8 1 E826K/- 7/7 1 ∆F508/- 7/9 1 4382delA/- 7/7 1 L997F/- 7/9 1 V754M/- 7/9 3 -/- 7/7 LC 26 1 I148T/- 5/7 1 D1270N-R74W 5/7 1 D651N/- 7/7 1 Y301C/- 7/7 1 -/- 5/7 16 -/- 7/7 5 -/- 7/9 TB 4 1 -/- 5/7 1 -/- 7/7 2 -/- 7/9 Pneumonia 5 4 -/- 7/7 1 -/- 5/7 Pnx 2 2 -/- 7/7 Controls 68 1 L997F/- 7/9 1 R31C/- 7/7 1 I506V/- 5/7 1 -/- 5/7 1 -/- 5/9 23 -/- 7/7 4 -/- 7/9 1 -/- 9/9 2 ? Login to comment
105 Two deletions (∆F508 and 4382delA, a frameshift deletion generating a stop codon 15 amino acids downstream) and three missense mutations (V754M, E826K, L997F) were detected. Login to comment

PMID: 9849891 [PubMed] Wei L et al: "Phosphorylation site independent single R-domain mutations affect CFTR channel activity."

No. Sentence Comment

1 All mutations were found in cystic fibrosis (CF) patients (H620Q, E822K and E826K). Login to comment
2 The macroscopic CFTR chloride conductance induced by phosphorylation was significantly enhanced in Xenopus oocytes injected with mRNA of H620Q but reduced in the E822K and E826K mutants compared to wild type CFTR. Login to comment
4 Cell attached single channel studies in COS cells revealed that both open channel probability and/or the number of functional channels were either higher (H620Q) or lower (E822K and E826K) than in wild type CFTR. Login to comment
25 Three di¡erent mutations, t1992g (= H620Q), g2596a (= E822K) and g2608a (= E826K), were introduced using the Transformer Site-Directed Mutagenesis kit (Clontech). Login to comment
76 COS cells were transfected with wt CFTR, E822K CFTR (top), H620Q CFTR (bottom) and E826K CFTR (bottom) and selected for 2 weeks with G418. Login to comment
88 In this study, the maturation pattern of three mutant R-domain proteins (H620Q-CFTR, E822K-CFTR and E826K-CFTR) has been characterized. Login to comment
92 Whole cells currents of mutants in Xenopus oocytes Whole cell membrane currents were recorded from Xenopus oocytes injected with RNA transcribed from either wild type or mutant (H620Q, E822K, E826K) constructs. Login to comment
100 The two R-domain proteins E822K and E826K, in which a negatively charged glutamic acid was exchanged for a positively charged lysine, showed a signi'cantly smaller phos-cock activated conductance. Login to comment
101 Oocytes expressing the mutant R-domain protein (H620Q), in which a predominantly positively charged histidine was substituted by a less charged glutamine (at pH 7.2), showed a much larger conductance activated by application of phos-cock. Login to comment
103 The conductance for E822K and E826K was 3.55 þ 0.44 WS (n = 6) and 4.24 þ 0.37 WS (n = 6), as compared to 7.57 þ 0.65 WS (n = 14) in the wild type. Login to comment
134 We found that the open probability of the E822K and E826K mutants was signi'cantly lower than that of wild type CFTR, whereas that of the H620Q mutant was strongly enhanced compared to wild type (not shown). Login to comment
136 The average number of activated channels is 2.6 þ 0.306 (n = 10) for wild-type CFTR, 3.51 þ 0.428 (n = 6) for H620Q, 1.0 þ 0.000 (n = 4) for E822K and 1.66 þ 0.211 (n = 6) for E826K. Login to comment
137 The di¡erences between wild type CFTR and E822K and E826K are signi'- cant (P 6 0.05). Login to comment
141 All the mutations studied here are located outside the phosphorylation sites, which may suggest that other regions in the R-domain, especially the highly conserved regions where E822K and E826K were l,ocated are important for the regulation of the CFTR Cl3 channel. Login to comment
145 A comparison of the three R-domain mutants leads to a remarkable conclusion: both mutations, E822K and E826K, in which negatively charged glutamic acids were replaced by positively charged lysine had a signi'cantly reduced CFTR channel activity, whereas the H620Q mutation, in which positively charged histidine was replaced by the more neutral amino acid glutamine, had a much higher channel activity. Login to comment
74 COS cells were transfected with wt CFTR, E822K CFTR (top), H620Q CFTR (bottom) and E826K CFTR (bottom) and selected for 2 weeks with G418. Login to comment
86 In this study, the maturation pattern of three mutant R-domain proteins (H620Q-CFTR, E822K-CFTR and E826K-CFTR) has been characterized. Login to comment
90 Whole cells currents of mutants in Xenopus oocytes Whole cell membrane currents were recorded from Xenopus oocytes injected with RNA transcribed from either wild type or mutant (H620Q, E822K, E826K) constructs. Login to comment
98 The two R-domain proteins E822K and E826K, in which a negatively charged glutamic acid was exchanged for a positively charged lysine, showed a signi'cantly smaller phos-cock activated conductance. Login to comment
132 We found that the open probability of the E822K and E826K mutants was signi'cantly lower than that of wild type CFTR, whereas that of the H620Q mutant was strongly enhanced compared to wild type (not shown). Login to comment
135 The di&#a1;erences between wild type CFTR and E822K and E826K are signi'- cant (P 6 0.05). Login to comment
139 All the mutations studied here are located outside the phosphorylation sites, which may suggest that other regions in the R-domain, especially the highly conserved regions where E822K and E826K were l,ocated are important for the regulation of the CFTR Cl3 channel. Login to comment
143 A comparison of the three R-domain mutants leads to a remarkable conclusion: both mutations, E822K and E826K, in which negatively charged glutamic acids were replaced by positively charged lysine had a signi'cantly reduced CFTR channel activity, whereas the H620Q mutation, in which positively charged histidine was replaced by the more neutral amino acid glutamine, had a much higher channel activity. Login to comment

PMID: 11001817 [PubMed] Chen JM et al: "Definition of a "functional R domain" of the cystic fibrosis transmembrane conductance regulator."

No. Sentence Comment

47 Conversely, E822K and E826K both change a stringently or well-conserved, negatively charged residue to a positively charged one and therefore would be speculated to produce some functional consequences. Login to comment

PMID: 26493493 [PubMed] Destouni A et al: "Single-cell high resolution melting analysis: A novel, generic, pre-implantation genetic diagnosis (PGD) method applied to cystic fibrosis (HRMA CF-PGD)."

No. Sentence Comment

101 PGD case no. Genotype combination (HGVS CFTR reference sequences NM000492.3 and NG016465.1) LSC exons (legacy nomenclature) (Montgomery et al., 2007) No. of blastomeres received for diagnosis No. of blastomeres amplified No. of blastomeres genotyped No. of unaffected blastomeres Pregnancy Confirmation of PGD result by PNDa 1 p.Arg334Gln and c.489+3ANG 7.2 and 4.2 5 4 4 2 No N/A 2 p.Phe508del and p.Phe508del 10 11 10 10 6 Yes Yes 3 p.Phe508del and c.489+1GNT 10 and 4.2 8 7 7 4 Yes Yes 4 p.Phe508del and p.Leu732X 10 and 13.3 10 8 8 5 Yes Yes 5 p.Phe508del and p.Asp1152His 10 and 18 4 3 3 3 Yes Yes 6 p.Phe508del and c.2051_2052delAAinsG 10 and 13.2 5 4 4 3 Yes Yes 7 p.Phe508del and p.Gly1069Arg 10 and 17bA1 9 9 9 4 Yes No (BP) 8 p.Phe508del and p.Gly542X 10 and 11 3 3 3 2 Yes Yes 9 p.Phe508del and c.3140-26ANG 10 and 17bA1 8 8 7 3 No N/A 10 p.Gly542X and p.Gly542X 11 2 2 2 1 No transfer 11 p.Glu826Lys and p.Phe508del 13.4 and 10 6 6 4 3 Yes Miscarried 12 p.D1312G and c.489+1GNT 21 and 4.2 11 9 9 8 Yes Miscarried 13 p.Glu279Asp and p.Phe508del 6b and 10 7 7 5 3 No N/A 14 p.Phe508del and p.Gly1069Arg 10 and 17bA1 9 8 8 5 Yes No (BP) 15 p.Glu822X and p.Gly1069Arg 13.4 and 17bA1 5 5 5 5 Yesb Miscarried Total 103 93 88 57 N/A: non-applicable, BP: biochemical pregnancy. Login to comment