ABCMdb

ABCA4 p.Leu1971Arg

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Publications

PMID: 9781034 [PubMed] Rozet JM et al: "Spectrum of ABCR gene mutations in autosomal recessive macular dystrophies."

No. Sentence Comment

45 Furthermore, all ABCR missense mutations Table 1 Mutations in the ABCR gene in STGD and FFM families Conserved aa in: Nucleotide change Amino acid change Domain ABCs RmP Phenotype Families Comment (571-2)A®G splicing mutation STGD 1 HAD1 (1938-2)A®G splicing mutation STGD 1 (4668+2)T®C splicing mutation STGD 1 (4735+2)T®A splicing mutation STGD 1 del(5196+1-5196+6 splicing mutation STGD 1 LOZ2 2570 delT frameshift mutation STGD 1 3209insGT frameshift mutation STGD 2 CHE2 G3754T E1252X STGD 1 C3994T Q1332X STGD 1 C6337G I2113X STGD 1 JEG2 C52T R18W IC - + STGD 1 C634T R212C EC - + STGD 5 GEN2, JEG2 G1908T Q636H IC - + STGD 1 LOZ2 C3056T T1019M IC - + STGD 1 C3322T R1107C IC - + STGD 1 JUL2 C4916T R1640W IC + + STGD 2 MAR1 G5929A G1977S ATP2 + + STGD 1 GEN2 G6320A R2107H IC + + STGD 1 JUL2 C3114T A1038V IC - + STGD 2 CHE2 +FFM +1 VII2 T1622C L541P EC - + FFM 1 VII2 T31C L11P IC + + FFM 1 G3272A G1090E IC + + FFM 1 G4522T G1508C IC + + FFM 1 C5908T L1970F IC + + FFM 1 GON2 T5912G L1971R IC + + FFM 1 GON2 Mutations refer to the standard nomenclature. Login to comment

PMID: 19230850 [PubMed] Molday RS et al: "The role of the photoreceptor ABC transporter ABCA4 in lipid transport and Stargardt macular degeneration."

No. Sentence Comment

134 Disease mutations, which are substituted in Stargardt disease, are shown in red italics - NBD1 (N965S, T971N, A1038V, S1071V, E1087K, R1108C); NBD2 (G1961E, L1971R, G1977S, L2027F, R2038W, R2077W, R2106C, R2107H). Login to comment
225 A subset of missense mutations reside in NBD1 (N965S, T971N, A1038V, S1071V, E1087K, R1108C, R1129L) and NBD2 (G1961E, L1971R, G1977S, L2027F, R2038W, R2077W, R2106C, R2107H). Login to comment
226 Several of these, including N965S, T971N, E1087K, L1971R, G1977S, reside inside or close to the Walker A and B motifs [29,90,92,95,97,100,102]. Login to comment

PMID: 12962493 [PubMed] Biswas-Fiss EE et al: "Functional analysis of genetic mutations in nucleotide binding domain 2 of the human retina specific ABC transporter."

No. Sentence Comment

73 The NBD2 expression vector pET29aNBD2 was used as template, 12 cycles of PCR, and each cycle was 30 s at 95 °C, 30 s at 50 °C, and 15 min at 68°C using complimentary oligonucleotides to produce the mutations L1971R, R2038W, G2146D, K2175A, and D2177N. Login to comment
74 The primers used for mutagenesis were as follows: L1971R, CGC CCT GGA GAG TGC TTT GGC CTC CGG GGA GTG AAT GGT GCC GGC AAA AC; R2038W, CTT TAC CTT TAT GCC AGG CTT CGA GGT GTA CCA GC, G2146D, CTG GCC ATC ATG GTA AAG GAC GCC TTT CGA TGT AT; D2177N, ATC AAA TCC CCG AAG GAC AAC CTG CTT CCT GAC CTG AAC; K2175A, CA ATG AAG ATC AAA TCC CCG GCG GAC GAC CTG CTT CCT GA. All of the mutations were disease-associated with the exception of K2175A. Login to comment
103 The locations of the disease associated mutations investigated in this study; L1971R, R2038W, G2146D, L2027F, and D2177N are indicated. Login to comment
144 Here, we have used site-specific mutagenesis to create disease-related genetic mutations: L1971R, D2177N, L2027F, R2038W, and G2146D as well as a synthetic mutation, K2175A. Login to comment
153 Lane 1: protein molecular weight standards; lane 2, wild-type NBD2; lane 3, L2027F mutant; lane 4, L1971R mutant; lane 5, D2177N; lane 6, G2146D; lane 7, R2038W mutant; lane 8, K2175A. Login to comment
168 The amino acid change, L1971R, is associated with mild to moderate forms of macular degeneration (Fundus flavimaculatus) (24). Login to comment
169 Analysis of NBD2 polypeptides harboring this mutation demonstrated that its effect on ATP hydrolysis was significant (i.e., a 57% decrease in specific activity with respect to the wild type control), and the observed rates of hydrolysis for L1971R (72 nmol/min/mg) were attenuated in comparison to the wild-type NBD2 (Figure 5, Table 1). Login to comment
225 The binding affinity of mutant L1971R decreased approximately 4-fold from that of the wild type and Kd was determined to be 2.1 × 10-6 M (Figure 6A). Login to comment
253 The curves represent a least squares nonlinear regression curve fit of the data representing the (A) L1971R mutant, (B) D2177N mutant, (C) G2146D mutant, (D) R2038W mutant, and (E) K2175A mutant. Login to comment
259 We observed only slight differences in the quenching profile of the L1971R mutant, both in the presence and in the absence of nucleotide binding (Figure 7B, Table 1). Login to comment
260 The L1971R mutation is associated with a "milder form" of macular degeneration, Fundus Flavimaculatus. Login to comment
261 The L1971R mutant was observed to have a reduced rate of ATP hydrolysis, 62% that of the wild type. Login to comment
267 Stern Volmer plots of the (A) wild-type NBD2, (B) L1971R mutant, (C) L2027F mutant, (D) D2177N mutant, (E) R2038W mutant, (F) G2146D mutant, and (F) K2175A mutant. Login to comment
303 The mutation L1971R has been identified with individuals suffering from the milder form of macular degeneration, Fundus Flavimaculatus, while G2146D and R2038W are associated with STGD1 and CRD, both of which are more severe forms of degeneration. Login to comment
305 In this study, the mutations R2038W, L1971R and G2146D led to comparable (~50%) decreases in ATP hydrolysis relative to the wild-type control. Login to comment
347 In the case of L1971R, dramatic changes in the quenching profiles between the wild type and mutant protein were not observed. Login to comment
348 The rate of ATP hydrolysis for L1971R was 62% of that observed for NBD2 wild type. Login to comment
352 Although L1971R was associated with a 62% decrease in ATP hydrolysis as compared to the wild type control, it was not significantly affected in terms of its structural response to nucleotide binding. Login to comment

PMID: 11804194 [PubMed] Sun H et al: "Mechanistic studies of ABCR, the ABC transporter in photoreceptor outer segments responsible for autosomal recessive Stargardt disease."

No. Sentence Comment

109 Among the variants tested in NBD-2, L1971R eliminates both basal and retinal-stimulated ATP hydrolysis, whereas G1977S and E2096K resemble G1961E in showing inhibition rather than stimulation of ATPase by retinal. Login to comment
110 The complete or nearly complete elimination of all ATPase activity produced by single NBD mutations-T971N, A1038V, or L1971R-implies that the two NBDs are allosterically coupled. Login to comment