ABCMdb

ABCC7 p.Gln1412*

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Publications

PMID: 10419506 [PubMed] Haardt M et al: "C-terminal truncations destabilize the cystic fibrosis transmembrane conductance regulator without impairing its biogenesis. A novel class of mutation."

No. Sentence Comment

19 Premature stop codons were as follows: Q1412X (A. Wallace and M. Tassabehji; ⌬70); S1455X and L1399X (⌬26 and ⌬82, respectively). Login to comment
86 RESULTS AND DISCUSSION Analysis of mutations found in the Cystic Fibrosis Genetic Consortium Database revealed that the shortest truncation, which manifests in CF with pancreatic insufficiency and recurrent pulmonary infection, is Q1412X (the genotype and clinical symptoms of the patient were kindly provided by C. J. Taylor, University of Sheffield, UK). Login to comment

PMID: 10773783 [PubMed] Zielenski J et al: "Genotype and phenotype in cystic fibrosis."

No. Sentence Comment

99 These are usually nonsense or frameshift mutations (Q1412X, 4326delTC, 4279insA) causing a 70to 100-bp truncation of the C-terminus of the CFTR [28] and associated with severe CF presentation. Login to comment

PMID: 11966405 [PubMed] Sangiuolo F et al: "Towards the pharmacogenomics of cystic fibrosis."

No. Sentence Comment

116 Q1412X, 4326delTC, 4279insA Severe Functional but unstable CFTR at the apical membrane See text Modified from [56,102]. Login to comment

PMID: 12414835 [PubMed] Reboul MP et al: "Splice mutation 1811+1.6kbA>G causes severe cystic fibrosis with pancreatic insufficiency: report of 11 compound heterozygous and two homozygous patients."

No. Sentence Comment

157 This is the case for nonsense and frameshift mutations always associated with severe CF with PI: they come into class I (for instance, G542X) when they lead to an absence of functional CFTR and into the "new" class V (for instance, Q1412X) when they cause the presence of a functional but unstable CFTR at the apical membrane. Login to comment

PMID: 12578973 [PubMed] Ostedgaard LS et al: "Effects of C-terminal deletions on cystic fibrosis transmembrane conductance regulator function in cystic fibrosis airway epithelia."

No. Sentence Comment

7 Deletion of 26 C-terminal residues by the S1455X mutation was associated with elevated sweat Cl- concentrations, but not other manifestations of CF (4), whereas deletion of the last 70 residues by the Q1412X mutation caused CF (C. J. Taylor, personal communication). Login to comment
117 In addition, whole-cell patch-clamp studies of BHK-21 and IB3-1 cells reported that the S1455X mutation had no effect on current, but the Q1412X mutation reduced current by 90% (4, 19). Login to comment
249 In contrast, the much longer Q1412X deletion appeared to cause CF. Login to comment

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

No. Sentence Comment

85 The shortest truncation reported that caused CF with pancreatic insufficiency and recurrent pulmonary infection is Q1412X, that lacks 70 amino acids (CF Genetic Analysis Consortium). Login to comment

PMID: 16088579 [PubMed] Gallati S et al: "Genetics of cystic fibrosis."

No. Sentence Comment

60 ClassVI: Decreased Stability Nonsense and frameshift mutations (e.g., Q1412X, 4326delTC, 4279insA) causing a 70to 100-bp truncation of the C-terminus of the CFTR lead to a marked instability of an otherwise fully processed and functional variant,24 and as a consequence to a severe CF presentation. Login to comment

PMID: 16648884 [PubMed] Mishra A et al: "The relevance of sweat testing for the diagnosis of cystic fibrosis in the genomic era."

No. Sentence Comment

121 Predicted mutations in the CFTR promoter can have similar effects by reducing the level of transcription.2,67 Class VI: Reduced Protein Stability Mutations in this novel class include protein stability mutants which cause lability of the CFTR protein, such as mutations resulting in absence of the 70-98 residues of the CFTR C-terminus.70,79 Although the C-terminus is not required for the biogenesis and chloride channel function of CFTR, it is indispensable for maintaining the stability of complex-glycosylated CFTR.2 The shortest truncation reported that causedCFwithpancreaticinsufficiencyandrecurrentpulmonary infection is Q1412X which lacks 70 amino acids. Login to comment

PMID: 18506640 [PubMed] Voter KZ et al: "Diagnosis of cystic fibrosis."

No. Sentence Comment

114 Figure reproduced from Ref. [6], with permission Table 7 Classes of CFTR gene mutations associated with CF disease Mutation class Mechanism of action Examples I Absence of protein synthesis because of a stop codon in the gene G542X II Improper folding and processing ΔF508 III Reduced response to regulatory molecules G551D IV Reduce ion conductance R117H V Decreased protein production due to splice defects or promoter mutations 3,849+10 kb C→T VI Decreased protein stability Q1412X 104 measurement of transepithelial ion flow in the nasal mucosa [28-30]. Login to comment

PMID: 19903491 [PubMed] Kreindler JL et al: "Cystic fibrosis: exploiting its genetic basis in the hunt for new therapies."

No. Sentence Comment

405 Table 1 Classification of CFTR mutations. Class Mutation example Cellular/molecular phenotype I W1282X Absent CFTR production due to nonsense mutations, frameshift mutations, or abnormal mRNA splicing II ΔF508 Improper intracellular processing of CFTR with less than normal amounts of CFTR protein at the apical plasma membrane III G551D Defective regulation of CFTR channels at the apical plasma membrane IV R117H Defective permeation of anions through CFTR channels at the apical plasma membrane V 3849+10KbCNT Reduced synthesis of normal CFTR VI Q1412X Altered apical membrane residence time of CFTR channels with truncated c-termini 4. Login to comment

PMID: 23069118 [PubMed] Thursfield RM et al: "Cystic Fibrosis: therapies targeting specific gene defects."

No. Sentence Comment

42 Arg117His previously termed R117H] V Splicing defect: leads to decreased amount of CFTR protein at the cell surface [eg 3849+10 kb C>T] VI Functional but unstable with decreased half life at the cell surface [eg Gln1412X previously termed Q1412X] R.M. Thursfield, J.C. Davies / Paediatric Respiratory Reviews (2012) 215-219216 difference (nPD) measurement. Login to comment

PMID: 23045527 [PubMed] Duan Y et al: "Keratin K18 increases CFTR surface expression by binding to its C-terminal hydrophobic patch."

No. Sentence Comment

23 Interestingly, clinical studies suggest that the deletion of CFTR`s C-terminal 26 residues by the S1455X mutation elevates the chloride concentration in sweat without producing any other CF symptoms, while the deletion of the C-terminal 69 residues by Q1412X mutation results in severe CF (8-10). Login to comment
238 It is possible that mutation Q1412X in CFTR, but not mutation S1455X, disrupts the K18 binding site and thus leads to the loss of plasmalemmal CFTR in epithelia and causes severe CF in patients. Login to comment
17 Interestingly, clinical studies suggest that the deletion of the CFTR C-terminal 26 residues by the S1455X mutation elevates the chloride concentration in sweat without producing any other CF symptoms, whereas the deletion of the C-terminal 69 residues by the Q1412X mutation results in severe CF (8-10). Login to comment
291 It is possible that mutation Q1412X in CFTR, but not mutation S1455X, disrupts the K18-binding site and thus leads to the loss of plasmalemmal CFTR in epithelia and causes severe CF in patients. Login to comment

PMID: 16436643 [PubMed] Elahi E et al: "A haplotype framework for cystic fibrosis mutations in Iran."

No. Sentence Comment

111 of Patients Total alleles* Associated haplotype Global distributionHom Het Exon 1 c.134TϾC M1T 1 1 Rare Exon 3 c.386GϾA G85E 1 1 Global Exon 4 c.460GϾC D110H 1 1 H2 Europe Exon 7 c.1132CϾT R334W 1 1 H2 Global Exon 7 c.1145CϾT T338I 1 1 Europe Intron 9 c.1525-1GϾA Mis-splicing 1 1 H8 Pakistan Exon 10 c.1529CϾG S466X 1 2 H4 Germany Exon 10 c.1531CϾT L467F 1 1 Rare Exon 10 c.1649TϾC I506T 1 2 H8 Lebanon Exon 10 c.1652del3† ⌬F508 6 7 19 H5 Global Exon 10 c.1677delTA 515fs 4 1 9 H1 Europe Exon 11 c.1756GϾT G542X 1 1 H5 Global Exon 12 c.1821CϾA Y563X 2 2 Europe Exon 13 c.2183AAϾG 684fs 3 6 H3 Europe Exon 17a c.3170CϾT P1013L 1 1 Turkey Exon 19 c.3616CϾT R1162X 2 2 H2 Germany Exon 19 c.3661AϾT K1177X 1 1 3 H2 Bahrain Intron 20 c.4005ϩ1GϾA Mis-splicing 1 2 H2 Europe Exon 21 c.4041CϾG N1303K 3 1 7 H5 Global Exon 23 c.4363CϾT Q1412X 1 1 Rare *A total of 64 (53%) of the 120 expected alleles were observed. Login to comment

PMID: 12013742 [PubMed] Wallace AJ et al: "SSCP/heteroduplex analysis."

No. Sentence Comment

204 Also note how Q1412X gives rise only to a SSCP shift. Login to comment

PMID: 8956039 [PubMed] Hughes DJ et al: "Mutation characterization of CFTR gene in 206 Northern Irish CF families: thirty mutations, including two novel, account for approximately 94% of CF chromosomes."

No. Sentence Comment

84 4048insCC, Q1313X E1371X Q1412X 4279insA 4521 G or A (p) S1196X, S1235R 10-60 20-80 20-80 0-50 20-70 20-70 20-70 20-70 20-70 10-60 20-70 20-70 0-50 20-80 20-80 20-80 20-80 20-70 20-70 20-80 20-80 20-70 20-70 20-70 20-70 20-70 20-70 20-80 20-70 20-70 40-80 75 75 150 75 150 150 150 75 150 150 150 75 150 75 75 75 150 150 150 95 150 150 150 150 150 150 150 150 150 150 150 9 9 4.5 6.5 4 4 4.5 7.5 4 5 4 7.5 4 7 7 7 4 4 4 6.5 4 4 3.5 4 4 5 4 6.5 4.5 4 4 ^Allmutationshave been reported to the CysticFibrosis Genetic AnalysisConsortium.The five polymorphisms are marked with a p in parenthesis. Login to comment

PMID: 24586523 [PubMed] Zietkiewicz E et al: "CFTR mutations spectrum and the efficiency of molecular diagnostics in Polish cystic fibrosis patients."

No. Sentence Comment

60 The c.1116+2T.A (no chloride data available) was in trans with Q1412X; for the c.2817_2820delTACTC (PS; normal chloride values: 33 and 52 mmol/L), no second mutation was identified. Login to comment
71 Exon / intron (legacy) Exon / intron (Ensembl) Protein change SVM value cDNA (HGVS nomenclature) gDNA (cDNA +132 bp) Number of PL CF chromosomes Reference a Mutations in trans Pathogenic mutations 1 1 L15Ffs10X c.43delC 175delC 1 CFMDB 1717-1G.A 2 2 G27V 21.92 c.80G.T 212G.T 1 Novel F508del 2 2 S18RfsX16 c.54-5940_273 +10250del21kb exon2,3del21kb 66 IL19 various CF mutations i2 i2 IVS2_Donor c.164+1G.A 296+1G.A 3 CFMDB various CF mutations 3 3 G85E 22.61 c.254G.A 386G.A 1 IL17 unknown 3 3 E60X c.178G.T 310G.T 0 IL17 x 3 3 L88IfsX22 c.262_263delTT 394delTT 0 IL17 x 4 4 E92K 21.92 c.274G.A 406G.A 2 CFMDB c.164+1G.A; c.2051- 2AA.G 4 4 L101X c.302T.G 434T.G 1 CFMDB c.3717+12191C.T 4 4 K114IfsX5 c.341_353del13bp 473del13bp 1 Novel F508del 4 4 R117H 20.35 c.350G.A 482G.A 5 IL17 F508del; 2x unknown 4 4 R117C 22.07 c.349C.T 481C.T 2 CFMDB S1206X;1x unknown 4 4 L137_L138insT c.412_413insACT L138ins 1 CFMDB F508del 4 4 R153I 22.61 c.458G.T 590G.T 2 Novel F508del; c.3527delC i4 i4 IVS4_Donor c.489+1G.T 621+1G.T 5 IL17 F508del; c.489+1G.T 5 5 L165X c.494T.A 626T.A 1 Novel F508del i5 i5 IVS5_Donor c.579+1G.T 711+1G.T 0 IL19 x i5 i5 IVS5_Donor c.579+3A.G 711+3A.G 2 CFMDB 2,3del21kb; c.2052-3insA i5 i5 IVS5_Donor c.579+5G.A 711+5G.A 0 IL17 x 7 8 F311L 20.90 c.933C.G 965C.G 2 CFMDB 2x F508 7 8 G314R 20.58 c.940G.A 1072G.A 4 CFMDB various CF mutations 7 8 F316LfsX12 c.948delT 1078delT 1 IL17 unkown 7 8 R334W 22.41 c.1000C.T 1132C.T 6 IL17 various CF mutations 7 8 I336K 22.07 c.1007T.A 1139T.A 2 CFMDB 2,3de21kb; F508del 7 8 R347P 22.27 c.1040G.C 1172G.C 11 IL17 various CF mutations i7 i8 IVS8_Donor c.1116+2T.A 1248+2T.A 1 Novel Q1412X 9 10 A455E 22.61 c.1364C.A 1496C.A 0 IL17 x i9 i10 IVS10_Donor c.1392+1G.A 1524+1G.A 1 CFMDB c.3816-7delGT 10 11 S466X c.1397C.G 1529C.G 1 CFMDB G542X 10 11 I507del c.1519_1521delATC 1651delATC 2 IL19 F508del 10 11 F508del c.1521_1523delCTT 1654delCTT 805 IL19 various CF mutations i10 i11 IVS11_Acceptor c.1585-1G.A 1717-1G.A 27 IL19 various CF mutations 11 12 G542X c.1624G.T 1756G.T 25 IL19 various CF mutations 11 12 G551D 21.24 c.1624G.T 1756G.T 5 IL19 various CF mutations 11 12 Q552X c.1654C.T 1786C.T 0 IL19 x 11 12 R553X c.1657C.T 1789C.T 14 IL19 various CF mutations 11 12 R560T 21.92 c.1679G.C 1811G.C 0 IL19 x i12 i13 IVS13_Donor c.1766+1G.A 1898+1G.A 6 IL19 various CF mutations i12 i13 IVS13_Donor c.1766+1G.C 1898+1G.C 1 CFMDB F508del 13 14 H620P 21.73 c.1859A.C 1991A.C 1 CFMDB F508del 13 14 R668C//G576A 21.61//1.73 c.2002C.T//c.1727G.C 2134C.T// 1859G.C 5 b CFMDB// rs1800098 c.1585-1G.A; 4 unknown 13 14 L671X c.2012delT 2143delT 27 IL17 various CF mutations 13 14 K684SfsX38 c.2051_2052delAAinsG 2183AA.G 10 IL17 various CF mutations 13 14 K684NfsX38 c.2052delA 2184delA 0 IL17 x 13 14 Q685TfsX4 c.2052_2053insA 2184insA 15 CFMDB various CF mutationsc , 1 unknown Table 2. Cont. Exon / intron (legacy) Exon / intron (Ensembl) Protein change SVM value cDNA (HGVS nomenclature) gDNA (cDNA +132 bp) Number of PL CF chromosomes Reference a Mutations in trans 13 14 L732X c.2195T.G 2327T.G 1 CFMDB F508del 14A 15 R851X c.2551C.T 2683C.T 3 CFMDB various CF mutations 14A 15 I864SfsX28 c.2589_2599del11bp 2721del11bp 2 CFMDB F508del; 2,3del21kb i14B i16 IVS16_Donor c.2657+2_2657+3insA 2789+2insA 1 CFMDB F508del i14B i16 IVS16_Donor c.2657+5G.A 2789+5G.A 0 IL17 unkown 15 17 Y919C 21.02 c.2756A.G 2888A.G 1 CFMDB unknown 15 17 H939HfsX27 c.2817_2820delTACTC 2949delTACTC 1 Novel unkown i15 i17 IVS17_Donor c.2908+3A.C 3040+3A.C 1 Novel F508del i16 i18 IVS18_Donor c.2988+1G.A 3120+1G.A 0 IL19 x 17A 19 I1023_V1024del c.3067_3072delATAGTG 3199del6 0 IL19 x i17A i19 IVS19 c.3140-26A.G 3272-26A.G 9 IL19 various CF mutations 17B 20 L1065R 21.90 c.3194T.G 3326T.G 1 CFMDB F508del 17B 20 Y1092X c.3276C.A 3408C.A 1 CFMDB R334W i18 i21 IVS21_Donor c.3468+2_3468+3insT 3600+2insT 11 CFMDB various CF mutationsd , 1 unknown 18 21 E1126EfsX7 c.3376_3379delGAAG 3508delGAAG 1 Novel F508del 19 22 R1158X c.3472C.T 3604C.T 2 CFMDB F508del; R553X 19 22 R1162X c.3484C.T 3616C.T 1 IL17 F508del 19 22 L1177SfsX15 c.3528delC 3659delC 4 IL17 various CF mutations 19 22 S1206X c.3617C.A 3749C.A 1 CFMDB R117C i19 i22 IVS22 c.3717+12191C.T 3849+10kbC.T 58 IL17 various CF mutations 20 23 G1244R 22.62 c.3730G.C 3862G.C 1 CFMDB F508del 20 23 S1251N 22.28 c.3752G.A 3884G.A 0 IL19 x 20 23 L1258FfsX7 c.3773_3774insT 3905insT 0 IL19 x 20 23 V1272VfsX28 c.3816_3817delGT 3944delGT 1 CFMDB c.1392+1G.A 20 23 W1282X c.3846G.A 3978G.A 9 IL19 various CF mutations 21 24 N1303K 22.62 c.3909C.G 4041C.G 18 IL19 various CF mutations 22 25 V1327X c.3979delG 4111delG 1 Novel F508del 22 25 S1347PfsX13 c.4035_4038dupCCTA c.4167dupCCTA 1 CFMDB 2,3del21kb 23 26 Q1382X c.4144C.T 4276C.T 1 CFMDB F508del 23 26 Q1412X c.4234C.T 4366C.T 2 CFMDB F508del; c.1116+2T.A i23 i26 IVS26_Donor c.4242+1G.T 4374+1G.T 1 CFMDB F508del Sequence changes of uncertain pathogenic effect, tentatively counted as mutations 6A 6 E217G 0.30 c.650A.G 782A.G 1 CFMDB; rs1219109046 unknown 7 8 R352Q 20.01 c.1055G.A 1187G.A 1 CFMDB; rs121908753 F508del 7 8 Q359R 0.33 c.1076A.G 1208A.G 1 CFMDB F508del i8 i9 IVS9 c.1210-12T5_1210- 34_35 (TG)12 1332-12Tn_- 34TGm 6 CFMDB F508del; 3x unknown i8 i9 IVS9 c.1210-12T5_1210- 34_35 (TG)13 1332-12Tn_- 34TGm 2 CFMDB 2143delT; 1x unknown i8 i9 IVS9 c.1210-12T8 1332-12Tn 1 Novel unknown 10 11 I506V 20.21 c.1516A.G 1648A.G 1 CFMDB; rs1800091 unknown 12 13 V562L 0.79 c.1684G.C 1816G.C 1 CFMDB; rs1800097 unknown 13 14 G723V 0.44 c.2168G.T 2300G.T 1 CFMDB; rs200531709 unknown 15 17 D924N 0.03 c.2770G.A 2902G.A 1 CFMDB; rs201759207 unknown patient with F508del on another allele) was not supported by the SVM value (+0.35); the patient was PS and had ambiguous chloride values (45, 64 and 83 mmol/L). 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154 Table 4. Cont. Mutations a Poland Czechs Slovakia c Germany Lithuania W. Ukraine E. Hungary Romania c Bulgaria Serbia Greece Number of chromosomes 1476 1200 856 700 98 264 80 256 208 352 874 F311L 0.14 0 NA 0 0 0 0 NA 0 0 0 Q1412X 0.14 0 NA 0 0 0 0 NA 0 0 0 Other reported 1.52 8.51 NA 7.10 2.0 1.14 7.50 3.8 12,03 4.28 17.83 Not detected 17.5 0.50 13.89 4.57 35.8 16.29 6.25 27.7 8.17 17.43 9.15 Estimated efficiency of INNOLiPA tests 75.5 89.9 84.0 88.7 61.2 74.6 87.5 69.1 80.3 78.7 73.3 Legend: Data are given in %. Login to comment

PMID: 24727426 [PubMed] Wang Y et al: "Understanding how cystic fibrosis mutations disrupt CFTR function: from single molecules to animal models."

No. Sentence Comment

2033 For example, the CF-PI mutation Q1412X, which truncates the last 70 amino acids of CFTR, generated macroscopic cAMP-stimulated Cl-currents with similar biophysical properties, but reduced magnitude compared to wild-type CFTR (Haardt et al., 1999). Login to comment
2034 Biochemical studies demonstrated that Q1412X was without effect on CFTR processing and intracellular transport, but greatly reduced the stability of mature CFTR protein (half-life in COS cells: wild-type CFTR, 14 h; Q1412X, 3.5 h). Login to comment

PMID: 26021452 [PubMed] Corvol H et al: "[Challenges of personalized medicine for cystic fibrosis]."

No. Sentence Comment

56 Ce sont principalement des mutations ge &#b4;ne &#b4;rant des prote &#b4;ines tronque &#b4;es dans leur partie C-terminale comme Q1412X et 4326delTC. Login to comment