ABCC7 p.Glu116Asp
| ClinVar: |
c.346G>A
,
p.Glu116Lys
?
, not provided
c.346G>C , p.Glu116Gln ? , not provided |
| CF databases: |
c.346G>A
,
p.Glu116Lys
(CFTR1)
D
, A missense mutation in exon 4 of the CFTR gene was detected by DGGE and identified by direct sequencing. The nucleotide position 478 is chnaged from G to A, leading to a subsitution of glutamic acid for lysine at position 116. This mutation abolishes a MnI restriction site. The mutation on the other chromosome is the deletion of [delta]F508
c.346G>C , p.Glu116Gln (CFTR1) ? , This mutation was detected in a thirty year old male with UAVD by multiplex heteroduplex analysis on the MDE gel matrix and direct sequencing. The patient was also heterozygous for the [delta]F508 mutation. Clinical Data: UAVD, borderline sweat test, chronic sinusitis |
| Predicted by SNAP2: | A: N (72%), C: D (59%), D: N (87%), F: D (71%), G: N (61%), H: D (63%), I: N (61%), K: N (61%), L: N (57%), M: D (63%), N: N (78%), P: N (57%), Q: N (82%), R: N (57%), S: N (78%), T: N (78%), V: N (66%), W: D (75%), Y: D (66%), |
| Predicted by PROVEAN: | A: N, C: D, D: N, F: D, G: N, H: N, I: N, K: N, L: D, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: N, Y: D, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[hide] Three charged amino acids in extracellular loop 1 ... J Gen Physiol. 2014 Aug;144(2):159-79. doi: 10.1085/jgp.201311122. Epub 2014 Jul 14. Cui G, Rahman KS, Infield DT, Kuang C, Prince CZ, McCarty NA
Three charged amino acids in extracellular loop 1 are involved in maintaining the outer pore architecture of CFTR.
J Gen Physiol. 2014 Aug;144(2):159-79. doi: 10.1085/jgp.201311122. Epub 2014 Jul 14., [PMID:25024266]
Abstract [show]
The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) bears six extracellular loops (ECL1-6); ECL1 is the site of several mutations associated with CF. Mutation R117H has been reported to reduce current amplitude, whereas D110H, E116K, and R117C/L/P may impair channel stability. We hypothesized that these amino acids might not be directly involved in ion conduction and permeation but may contribute to stabilizing the outer vestibule architecture in CFTR. We used cRNA injected oocytes combined with electrophysiological techniques to test this hypothesis. Mutants bearing cysteine at these sites were not functionally modified by extracellular MTS reagents and were blocked by GlyH-101 similarly to WT-CFTR. These results suggest that these three residues do not contribute directly to permeation in CFTR. In contrast, mutants D110R-, E116R-, and R117A-CFTR exhibited instability of the open state and significantly shortened burst duration compared with WT-CFTR and failed to be locked into the open state by AMP-PNP (adenosine 5'-(beta,gamma-imido) triphosphate); charge-retaining mutants showed mainly the full open state with comparably longer open burst duration. These interactions suggest that these ECL1 residues might be involved in maintaining the outer pore architecture of CFTR. A CFTR homology model suggested that E116 interacts with R104 in both the closed and open states, D110 interacts with K892 in the fully closed state, and R117 interacts with E1126 in the open state. These interactions were confirmed experimentally. The results suggest that D110, E116, and R117 may contribute to stabilizing the architecture of the outer pore of CFTR by interactions with other charged residues.
Comments [show]
None has been submitted yet.
No. Sentence Comment
182 We generated D110E-, E116D-, and R117K-CFTR and observed their single-channel behavior with the inside-out patch technique in symmetrical 150 mM Cl&#e032; solution at VM = &#e032;100 mV.
X
ABCC7 p.Glu116Asp 25024266:182:21
status: NEW185 Similar results were observed when the burst durations of E116D-CFTR and E116R-CFTR were compared (P < 0.001; Fig. 7, B and E).
X
ABCC7 p.Glu116Asp 25024266:185:58
status: NEW218 D110, E116, and R117 do not interact with each other locally Because charge-retaining ECL1 amino acid mutations D110E, E116D, and R117K partially rescued a steady Figure 6.ߓ Some ECL1 mutants exhibit altered rectification.
X
ABCC7 p.Glu116Asp 25024266:218:119
status: NEW246 (A-C) Representative single-channel currents of D110R- and D110E- (A), E116R- and E116D- (B), and R117A- and R117K-CFTR (C) recorded under the same conditions as Fig. 2 A.
X
ABCC7 p.Glu116Asp 25024266:246:82
status: NEW248 (D) Mean single-channel amplitude of WT-, D110R-, D110E-, E116R-, E116D-, R117A-, and R117K-CFTR.
X
ABCC7 p.Glu116Asp 25024266:248:66
status: NEW250 (E) Mean burst duration of WT-, D110R-, D110E-, E116R-, E116D-, R117A-, and R117K-CFTR.
X
ABCC7 p.Glu116Asp 25024266:250:56
status: NEW251 #, P < 0.001 indicates differences between D110R- and D110E-CFTR or E116R- and E116D-CFTR; *, P < 0.05 indicates differences between R117A- and R117K-CFTR.
X
ABCC7 p.Glu116Asp 25024266:251:79
status: NEW423 As shown here, mean burst durations of charge-retaining mutants D110E-, E116D-, and R117K-CFTR are significantly longer than their related charge-reversing or charge-destroying mutants D110R-, E116R-, and R117A-CFTR but distinctly shorter than that of WT-CFTR (Fig. 7).
X
ABCC7 p.Glu116Asp 25024266:423:72
status: NEW