PubMed:1303173 JSONTXT

{"project":"DisGeNET5_variant_disease","denotations":[{"id":"1303173-5#117#129#geners1050828","span":{"begin":694,"end":706},"obj":"geners1050828"},{"id":"1303173-5#26#38#geners1050828","span":{"begin":603,"end":615},"obj":"geners1050828"},{"id":"1303173-5#172#187#diseaseC2939465","span":{"begin":749,"end":764},"obj":"diseaseC2939465"}],"relations":[{"id":"117#129#geners1050828172#187#diseaseC2939465","pred":"associated_with","subj":"1303173-5#117#129#geners1050828","obj":"1303173-5#172#187#diseaseC2939465"},{"id":"26#38#geners1050828172#187#diseaseC2939465","pred":"associated_with","subj":"1303173-5#26#38#geners1050828","obj":"1303173-5#172#187#diseaseC2939465"}],"text":"Both mutations in G6PD A- are necessary to produce the G6PD deficient phenotype.\nThe high prevalence of glucose 6-phosphate dehydrogenase (G6PD) deficiency in African populations is due almost entirely to the enzyme variant A-, which differs from the wild-type G6PD B by two amino acid replacements, 68 Val--\u003eMet and 126 Asn--\u003eAsp. The non-deficient polymorphic variant G6PD A contains only the mutation 126 Asn--\u003eAsp. The frequencies of the G6PD A and of the G6PD A- genes in parts of Africa are both about 0.2. The 68 Val--\u003eMet mutation has not been found in a B background. This could be because the 68 Val--\u003eMet mutation happened to arise in an A gene in the first instance, or because the 68 Val--\u003eMet mutation alone is not sufficient to cause G6PD deficiency. We have approached this question by producing G6PD B, A, A-, and G6PD 68 Val--\u003eMet in a bacterial expression system and analysing their biochemical properties. With each single mutation we found a slight decrease in both the specific activity and the yield of enzyme when compared to G6PD B. When both mutations were introduced together, there was a roughly additive effect on specific activity, but a much more drastic effect on enzyme yield (4% of normal). This synergistic effect was also demonstrated on thermal stability, especially at low NADP concentrations. Comparable results were produced when the replacement 119 Gln--\u003eGlu was studied instead of 126 Asn--\u003eAsp. We infer that the coexistence of the two mutations is responsible for enzyme deficiency in G6PD A- because they act synergistically in causing instability of the enzyme."}

{"project":"NCBIDiseaseCorpus","denotations":[{"id":"T1","span":{"begin":55,"end":69},"obj":"Modifier:D005955"},{"id":"T2","span":{"begin":104,"end":155},"obj":"SpecificDisease:D005955"},{"id":"T3","span":{"begin":749,"end":764},"obj":"SpecificDisease:D005955"},{"id":"T4","span":{"begin":1508,"end":1533},"obj":"SpecificDisease:D005955"}],"text":"Both mutations in G6PD A- are necessary to produce the G6PD deficient phenotype.\nThe high prevalence of glucose 6-phosphate dehydrogenase (G6PD) deficiency in African populations is due almost entirely to the enzyme variant A-, which differs from the wild-type G6PD B by two amino acid replacements, 68 Val--\u003eMet and 126 Asn--\u003eAsp. The non-deficient polymorphic variant G6PD A contains only the mutation 126 Asn--\u003eAsp. The frequencies of the G6PD A and of the G6PD A- genes in parts of Africa are both about 0.2. The 68 Val--\u003eMet mutation has not been found in a B background. This could be because the 68 Val--\u003eMet mutation happened to arise in an A gene in the first instance, or because the 68 Val--\u003eMet mutation alone is not sufficient to cause G6PD deficiency. We have approached this question by producing G6PD B, A, A-, and G6PD 68 Val--\u003eMet in a bacterial expression system and analysing their biochemical properties. With each single mutation we found a slight decrease in both the specific activity and the yield of enzyme when compared to G6PD B. When both mutations were introduced together, there was a roughly additive effect on specific activity, but a much more drastic effect on enzyme yield (4% of normal). This synergistic effect was also demonstrated on thermal stability, especially at low NADP concentrations. Comparable results were produced when the replacement 119 Gln--\u003eGlu was studied instead of 126 Asn--\u003eAsp. We infer that the coexistence of the two mutations is responsible for enzyme deficiency in G6PD A- because they act synergistically in causing instability of the enzyme."}

{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":1529,"end":1533},"obj":"gene:2539"},{"id":"T1","span":{"begin":1508,"end":1525},"obj":"disease:C0149676"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"Both mutations in G6PD A- are necessary to produce the G6PD deficient phenotype.\nThe high prevalence of glucose 6-phosphate dehydrogenase (G6PD) deficiency in African populations is due almost entirely to the enzyme variant A-, which differs from the wild-type G6PD B by two amino acid replacements, 68 Val--\u003eMet and 126 Asn--\u003eAsp. The non-deficient polymorphic variant G6PD A contains only the mutation 126 Asn--\u003eAsp. The frequencies of the G6PD A and of the G6PD A- genes in parts of Africa are both about 0.2. The 68 Val--\u003eMet mutation has not been found in a B background. This could be because the 68 Val--\u003eMet mutation happened to arise in an A gene in the first instance, or because the 68 Val--\u003eMet mutation alone is not sufficient to cause G6PD deficiency. We have approached this question by producing G6PD B, A, A-, and G6PD 68 Val--\u003eMet in a bacterial expression system and analysing their biochemical properties. With each single mutation we found a slight decrease in both the specific activity and the yield of enzyme when compared to G6PD B. When both mutations were introduced together, there was a roughly additive effect on specific activity, but a much more drastic effect on enzyme yield (4% of normal). This synergistic effect was also demonstrated on thermal stability, especially at low NADP concentrations. Comparable results were produced when the replacement 119 Gln--\u003eGlu was studied instead of 126 Asn--\u003eAsp. We infer that the coexistence of the two mutations is responsible for enzyme deficiency in G6PD A- because they act synergistically in causing instability of the enzyme."}

{"project":"NCBI-Disease-Train","denotations":[{"id":"T4902","span":{"begin":55,"end":69},"obj":"Modifier"},{"id":"T4903","span":{"begin":104,"end":155},"obj":"SpecificDisease"},{"id":"T4904","span":{"begin":749,"end":764},"obj":"SpecificDisease"},{"id":"T4905","span":{"begin":1508,"end":1533},"obj":"SpecificDisease"}],"attributes":[{"id":"A4902","pred":"database_id","subj":"T4902","obj":"D005955"},{"id":"A4903","pred":"database_id","subj":"T4903","obj":"D005955"},{"id":"A4904","pred":"database_id","subj":"T4904","obj":"D005955"},{"id":"A4905","pred":"database_id","subj":"T4905","obj":"D005955"}],"text":"Both mutations in G6PD A- are necessary to produce the G6PD deficient phenotype.\nThe high prevalence of glucose 6-phosphate dehydrogenase (G6PD) deficiency in African populations is due almost entirely to the enzyme variant A-, which differs from the wild-type G6PD B by two amino acid replacements, 68 Val--\u003eMet and 126 Asn--\u003eAsp. The non-deficient polymorphic variant G6PD A contains only the mutation 126 Asn--\u003eAsp. The frequencies of the G6PD A and of the G6PD A- genes in parts of Africa are both about 0.2. The 68 Val--\u003eMet mutation has not been found in a B background. This could be because the 68 Val--\u003eMet mutation happened to arise in an A gene in the first instance, or because the 68 Val--\u003eMet mutation alone is not sufficient to cause G6PD deficiency. We have approached this question by producing G6PD B, A, A-, and G6PD 68 Val--\u003eMet in a bacterial expression system and analysing their biochemical properties. With each single mutation we found a slight decrease in both the specific activity and the yield of enzyme when compared to G6PD B. When both mutations were introduced together, there was a roughly additive effect on specific activity, but a much more drastic effect on enzyme yield (4% of normal). This synergistic effect was also demonstrated on thermal stability, especially at low NADP concentrations. Comparable results were produced when the replacement 119 Gln--\u003eGlu was studied instead of 126 Asn--\u003eAsp. We infer that the coexistence of the two mutations is responsible for enzyme deficiency in G6PD A- because they act synergistically in causing instability of the enzyme."}

{"project":"NCBI-Disease-Corpus-All","denotations":[{"id":"T4902","span":{"begin":55,"end":69},"obj":"Modifier"},{"id":"T4903","span":{"begin":104,"end":155},"obj":"SpecificDisease"},{"id":"T4904","span":{"begin":749,"end":764},"obj":"SpecificDisease"},{"id":"T4905","span":{"begin":1508,"end":1533},"obj":"SpecificDisease"}],"attributes":[{"id":"A4902","pred":"database_id","subj":"T4902","obj":"D005955"},{"id":"A4903","pred":"database_id","subj":"T4903","obj":"D005955"},{"id":"A4904","pred":"database_id","subj":"T4904","obj":"D005955"},{"id":"A4905","pred":"database_id","subj":"T4905","obj":"D005955"}],"text":"Both mutations in G6PD A- are necessary to produce the G6PD deficient phenotype.\nThe high prevalence of glucose 6-phosphate dehydrogenase (G6PD) deficiency in African populations is due almost entirely to the enzyme variant A-, which differs from the wild-type G6PD B by two amino acid replacements, 68 Val--\u003eMet and 126 Asn--\u003eAsp. The non-deficient polymorphic variant G6PD A contains only the mutation 126 Asn--\u003eAsp. The frequencies of the G6PD A and of the G6PD A- genes in parts of Africa are both about 0.2. The 68 Val--\u003eMet mutation has not been found in a B background. This could be because the 68 Val--\u003eMet mutation happened to arise in an A gene in the first instance, or because the 68 Val--\u003eMet mutation alone is not sufficient to cause G6PD deficiency. We have approached this question by producing G6PD B, A, A-, and G6PD 68 Val--\u003eMet in a bacterial expression system and analysing their biochemical properties. With each single mutation we found a slight decrease in both the specific activity and the yield of enzyme when compared to G6PD B. When both mutations were introduced together, there was a roughly additive effect on specific activity, but a much more drastic effect on enzyme yield (4% of normal). This synergistic effect was also demonstrated on thermal stability, especially at low NADP concentrations. Comparable results were produced when the replacement 119 Gln--\u003eGlu was studied instead of 126 Asn--\u003eAsp. We infer that the coexistence of the two mutations is responsible for enzyme deficiency in G6PD A- because they act synergistically in causing instability of the enzyme."}

{"project":"NCBI-Disease-Corpus-2stage-All","denotations":[{"id":"T1","span":{"begin":55,"end":69},"obj":"DiseaseClass"},{"id":"T2","span":{"begin":104,"end":155},"obj":"SpecificDisease"},{"id":"T3","span":{"begin":749,"end":764},"obj":"SpecificDisease"}],"text":"Both mutations in G6PD A- are necessary to produce the G6PD deficient phenotype.\nThe high prevalence of glucose 6-phosphate dehydrogenase (G6PD) deficiency in African populations is due almost entirely to the enzyme variant A-, which differs from the wild-type G6PD B by two amino acid replacements, 68 Val--\u003eMet and 126 Asn--\u003eAsp. The non-deficient polymorphic variant G6PD A contains only the mutation 126 Asn--\u003eAsp. The frequencies of the G6PD A and of the G6PD A- genes in parts of Africa are both about 0.2. The 68 Val--\u003eMet mutation has not been found in a B background. This could be because the 68 Val--\u003eMet mutation happened to arise in an A gene in the first instance, or because the 68 Val--\u003eMet mutation alone is not sufficient to cause G6PD deficiency. We have approached this question by producing G6PD B, A, A-, and G6PD 68 Val--\u003eMet in a bacterial expression system and analysing their biochemical properties. With each single mutation we found a slight decrease in both the specific activity and the yield of enzyme when compared to G6PD B. When both mutations were introduced together, there was a roughly additive effect on specific activity, but a much more drastic effect on enzyme yield (4% of normal). This synergistic effect was also demonstrated on thermal stability, especially at low NADP concentrations. Comparable results were produced when the replacement 119 Gln--\u003eGlu was studied instead of 126 Asn--\u003eAsp. We infer that the coexistence of the two mutations is responsible for enzyme deficiency in G6PD A- because they act synergistically in causing instability of the enzyme."}

{"project":"NCBI-Disease-Corpus-rezarta-All","denotations":[{"id":"T1","span":{"begin":55,"end":69},"obj":"Modifier"},{"id":"T2","span":{"begin":104,"end":155},"obj":"SpecificDisease"},{"id":"T3","span":{"begin":749,"end":764},"obj":"SpecificDisease"},{"id":"T4","span":{"begin":1508,"end":1525},"obj":"Modifier"}],"text":"Both mutations in G6PD A- are necessary to produce the G6PD deficient phenotype.\nThe high prevalence of glucose 6-phosphate dehydrogenase (G6PD) deficiency in African populations is due almost entirely to the enzyme variant A-, which differs from the wild-type G6PD B by two amino acid replacements, 68 Val--\u003eMet and 126 Asn--\u003eAsp. The non-deficient polymorphic variant G6PD A contains only the mutation 126 Asn--\u003eAsp. The frequencies of the G6PD A and of the G6PD A- genes in parts of Africa are both about 0.2. The 68 Val--\u003eMet mutation has not been found in a B background. This could be because the 68 Val--\u003eMet mutation happened to arise in an A gene in the first instance, or because the 68 Val--\u003eMet mutation alone is not sufficient to cause G6PD deficiency. We have approached this question by producing G6PD B, A, A-, and G6PD 68 Val--\u003eMet in a bacterial expression system and analysing their biochemical properties. With each single mutation we found a slight decrease in both the specific activity and the yield of enzyme when compared to G6PD B. When both mutations were introduced together, there was a roughly additive effect on specific activity, but a much more drastic effect on enzyme yield (4% of normal). This synergistic effect was also demonstrated on thermal stability, especially at low NADP concentrations. Comparable results were produced when the replacement 119 Gln--\u003eGlu was studied instead of 126 Asn--\u003eAsp. We infer that the coexistence of the two mutations is responsible for enzyme deficiency in G6PD A- because they act synergistically in causing instability of the enzyme."}

{"project":"NCBI-Disease-Corpus-4oGuideline-All","denotations":[{"id":"T1","span":{"begin":55,"end":79},"obj":"SpecificDisease"},{"id":"T2","span":{"begin":104,"end":155},"obj":"SpecificDisease"},{"id":"T3","span":{"begin":749,"end":764},"obj":"SpecificDisease"}],"text":"Both mutations in G6PD A- are necessary to produce the G6PD deficient phenotype.\nThe high prevalence of glucose 6-phosphate dehydrogenase (G6PD) deficiency in African populations is due almost entirely to the enzyme variant A-, which differs from the wild-type G6PD B by two amino acid replacements, 68 Val--\u003eMet and 126 Asn--\u003eAsp. The non-deficient polymorphic variant G6PD A contains only the mutation 126 Asn--\u003eAsp. The frequencies of the G6PD A and of the G6PD A- genes in parts of Africa are both about 0.2. The 68 Val--\u003eMet mutation has not been found in a B background. This could be because the 68 Val--\u003eMet mutation happened to arise in an A gene in the first instance, or because the 68 Val--\u003eMet mutation alone is not sufficient to cause G6PD deficiency. We have approached this question by producing G6PD B, A, A-, and G6PD 68 Val--\u003eMet in a bacterial expression system and analysing their biochemical properties. With each single mutation we found a slight decrease in both the specific activity and the yield of enzyme when compared to G6PD B. When both mutations were introduced together, there was a roughly additive effect on specific activity, but a much more drastic effect on enzyme yield (4% of normal). This synergistic effect was also demonstrated on thermal stability, especially at low NADP concentrations. Comparable results were produced when the replacement 119 Gln--\u003eGlu was studied instead of 126 Asn--\u003eAsp. We infer that the coexistence of the two mutations is responsible for enzyme deficiency in G6PD A- because they act synergistically in causing instability of the enzyme."}

{"project":"NCBI-Disease-Corpus-Simple-All","denotations":[{"id":"T1","span":{"begin":55,"end":79},"obj":"SpecificDisease"},{"id":"T2","span":{"begin":104,"end":155},"obj":"SpecificDisease"},{"id":"T3","span":{"begin":749,"end":764},"obj":"SpecificDisease"},{"id":"T4","span":{"begin":1508,"end":1514},"obj":"Modifier"},{"id":"T5","span":{"begin":1600,"end":1606},"obj":"Modifier"}],"text":"Both mutations in G6PD A- are necessary to produce the G6PD deficient phenotype.\nThe high prevalence of glucose 6-phosphate dehydrogenase (G6PD) deficiency in African populations is due almost entirely to the enzyme variant A-, which differs from the wild-type G6PD B by two amino acid replacements, 68 Val--\u003eMet and 126 Asn--\u003eAsp. The non-deficient polymorphic variant G6PD A contains only the mutation 126 Asn--\u003eAsp. The frequencies of the G6PD A and of the G6PD A- genes in parts of Africa are both about 0.2. The 68 Val--\u003eMet mutation has not been found in a B background. This could be because the 68 Val--\u003eMet mutation happened to arise in an A gene in the first instance, or because the 68 Val--\u003eMet mutation alone is not sufficient to cause G6PD deficiency. We have approached this question by producing G6PD B, A, A-, and G6PD 68 Val--\u003eMet in a bacterial expression system and analysing their biochemical properties. With each single mutation we found a slight decrease in both the specific activity and the yield of enzyme when compared to G6PD B. When both mutations were introduced together, there was a roughly additive effect on specific activity, but a much more drastic effect on enzyme yield (4% of normal). This synergistic effect was also demonstrated on thermal stability, especially at low NADP concentrations. Comparable results were produced when the replacement 119 Gln--\u003eGlu was studied instead of 126 Asn--\u003eAsp. We infer that the coexistence of the two mutations is responsible for enzyme deficiency in G6PD A- because they act synergistically in causing instability of the enzyme."}