PubMed:26197705 JSONTXT

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    sonoma2

    {"project":"sonoma2","denotations":[{"id":"T0","span":{"begin":64,"end":87},"obj":"GENE"},{"id":"T1","span":{"begin":128,"end":151},"obj":"GENE"},{"id":"T2","span":{"begin":153,"end":157},"obj":"GENE"},{"id":"T3","span":{"begin":253,"end":270},"obj":"DISEASE"},{"id":"T4","span":{"begin":305,"end":341},"obj":"GENE"},{"id":"T5","span":{"begin":343,"end":347},"obj":"GENE"},{"id":"T6","span":{"begin":357,"end":369},"obj":"MPA"},{"id":"T7","span":{"begin":383,"end":398},"obj":"MPA"},{"id":"T8","span":{"begin":492,"end":522},"obj":"DISEASE"},{"id":"T9","span":{"begin":524,"end":528},"obj":"GENE"},{"id":"T10","span":{"begin":528,"end":532},"obj":"GENE"},{"id":"T11","span":{"begin":539,"end":549},"obj":"REG"},{"id":"T12","span":{"begin":602,"end":611},"obj":"VAR"},{"id":"T13","span":{"begin":621,"end":629},"obj":"VAR"},{"id":"T14","span":{"begin":636,"end":645},"obj":"VAR"},{"id":"T15","span":{"begin":727,"end":736},"obj":"VAR"},{"id":"T16","span":{"begin":737,"end":741},"obj":"GENE"},{"id":"T17","span":{"begin":741,"end":745},"obj":"GENE"},{"id":"T18","span":{"begin":749,"end":751},"obj":"NEGREG"},{"id":"T19","span":{"begin":752,"end":777},"obj":"MPA"},{"id":"T20","span":{"begin":785,"end":789},"obj":"MPA"},{"id":"T21","span":{"begin":793,"end":805},"obj":"MPA"},{"id":"T22","span":{"begin":830,"end":837},"obj":"INTERACTION"},{"id":"T23","span":{"begin":851,"end":860},"obj":"MPA"},{"id":"T24","span":{"begin":880,"end":891},"obj":"VAR"},{"id":"T25","span":{"begin":1001,"end":1011},"obj":"MPA"},{"id":"T26","span":{"begin":1066,"end":1073},"obj":"NEGREG"},{"id":"T27","span":{"begin":1090,"end":1100},"obj":"MPA"},{"id":"T28","span":{"begin":1106,"end":1115},"obj":"VAR"},{"id":"T29","span":{"begin":1120,"end":1122},"obj":"VAR"},{"id":"T30","span":{"begin":1144,"end":1151},"obj":"VAR"},{"id":"T31","span":{"begin":1164,"end":1180},"obj":"NEGREG"},{"id":"T32","span":{"begin":1182,"end":1185},"obj":"NEGREG"},{"id":"T33","span":{"begin":1203,"end":1212},"obj":"VAR"},{"id":"T34","span":{"begin":1233,"end":1236},"obj":"NEGREG"}],"relations":[{"id":"R0","pred":"ThemeOf","subj":"T9","obj":"T12"},{"id":"R1","pred":"ThemeOf","subj":"T9","obj":"T13"},{"id":"R2","pred":"ThemeOf","subj":"T9","obj":"T14"},{"id":"R3","pred":"CauseOf","subj":"T12","obj":"T11"},{"id":"R4","pred":"ThemeOf","subj":"T13","obj":"T12"},{"id":"R5","pred":"CauseOf","subj":"T13","obj":"T11"},{"id":"R6","pred":"CauseOf","subj":"T14","obj":"T11"},{"id":"R7","pred":"CauseOf","subj":"T15","obj":"T18"},{"id":"R8","pred":"ThemeOf","subj":"T16","obj":"T15"},{"id":"R9","pred":"ThemeOf","subj":"T19","obj":"T18"},{"id":"R10","pred":"ThemeOf","subj":"T20","obj":"T18"},{"id":"R11","pred":"ThemeOf","subj":"T20","obj":"T19"},{"id":"R12","pred":"ThemeOf","subj":"T21","obj":"T18"},{"id":"R13","pred":"ThemeOf","subj":"T21","obj":"T19"},{"id":"R14","pred":"ThemeOf","subj":"T27","obj":"T26"},{"id":"R15","pred":"CauseOf","subj":"T28","obj":"T26"},{"id":"R16","pred":"CauseOf","subj":"T29","obj":"T26"},{"id":"R17","pred":"CauseOf","subj":"T30","obj":"T31"},{"id":"R18","pred":"CauseOf","subj":"T30","obj":"T32"},{"id":"R19","pred":"CauseOf","subj":"T33","obj":"T31"},{"id":"R20","pred":"CauseOf","subj":"T33","obj":"T32"},{"id":"R21","pred":"CauseOf","subj":"T33","obj":"T34"}],"text":"Identification and functional characterization of natural human melanocortin 1 receptor mutant alleles in Pakistani population.\nMelanocortin 1 receptor (MC1R), a Gs protein-coupled receptor of the melanocyte's plasma membrane, is a major determinant of skin pigmentation and phototype. Upon activation by α-melanocyte stimulating hormone, MC1R triggers the cAMP cascade to stimulate eumelanogenesis. We used whole-exome sequencing to identify causative alleles in Pakistani families with skin and hair hypopigmentation. Six MC1R mutations segregated with the phenotype in seven families, including a p.Val174del in-frame deletion and a p.Tyr298* nonsense mutation, that were analyzed for function in heterologous HEK293 cells. p.Tyr298* MC1R showed no agonist-induced signaling to the cAMP or ERK pathways, nor detectable agonist binding. Conversely, signaling was comparable for p.Val174del and wild-type in HEK cells overexpressing the proteins, but binding analysis suggested impaired cell surface expression. Flow cytometry and confocal imaging studies revealed reduced plasma membrane expression of p.Val174del and p.Tyr298*. Therefore, p.Tyr298* was a total loss-of-function (LOF) allele, while p.Val174del displayed a partial LOF attribute."}

    kaiyin_test

    {"project":"kaiyin_test","denotations":[{"id":"T2","span":{"begin":727,"end":736},"obj":"Var"},{"id":"T3","span":{"begin":737,"end":741},"obj":"Gene"},{"id":"T4","span":{"begin":749,"end":751},"obj":"NegReg"},{"id":"T5","span":{"begin":752,"end":777},"obj":"MPA"},{"id":"T6","span":{"begin":785,"end":789},"obj":"Pathway"},{"id":"T7","span":{"begin":793,"end":805},"obj":"Pathway"},{"id":"T8","span":{"begin":807,"end":810},"obj":"NegReg"},{"id":"T9","span":{"begin":822,"end":837},"obj":"Interaction"},{"id":"T10","span":{"begin":880,"end":891},"obj":"Var"},{"id":"T11","span":{"begin":979,"end":987},"obj":"NegReg"},{"id":"T12","span":{"begin":988,"end":1011},"obj":"MPA"},{"id":"T13","span":{"begin":1066,"end":1073},"obj":"NegReg"},{"id":"T14","span":{"begin":1074,"end":1100},"obj":"MPA"},{"id":"T15","span":{"begin":1104,"end":1115},"obj":"Var"},{"id":"T16","span":{"begin":1120,"end":1129},"obj":"Var"},{"id":"T17","span":{"begin":1142,"end":1151},"obj":"Var"},{"id":"T18","span":{"begin":1164,"end":1180},"obj":"NegReg"},{"id":"T19","span":{"begin":1201,"end":1212},"obj":"Var"},{"id":"T20","span":{"begin":1225,"end":1236},"obj":"NegReg"}],"relations":[{"id":"R1","pred":"ThemeOf","subj":"T3","obj":"T2"},{"id":"R10","pred":"ThemeOf","subj":"T14","obj":"T13"},{"id":"R11","pred":"CauseOf","subj":"T15","obj":"T13"},{"id":"R12","pred":"CauseOf","subj":"T16","obj":"T13"},{"id":"R13","pred":"CauseOf","subj":"T17","obj":"T18"},{"id":"R14","pred":"CauseOf","subj":"T19","obj":"T20"},{"id":"R2","pred":"CauseOf","subj":"T2","obj":"T4"},{"id":"R3","pred":"CauseOf","subj":"T2","obj":"T8"},{"id":"R4","pred":"ThemeOf","subj":"T9","obj":"T8"},{"id":"R5","pred":"ThemeOf","subj":"T4","obj":"T5"},{"id":"R6","pred":"ThemeOf","subj":"T6","obj":"T5"},{"id":"R7","pred":"ThemeOf","subj":"T7","obj":"T5"},{"id":"R8","pred":"CauseOf","subj":"T10","obj":"T11"},{"id":"R9","pred":"ThemeOf","subj":"T12","obj":"T11"}],"text":"Identification and functional characterization of natural human melanocortin 1 receptor mutant alleles in Pakistani population.\nMelanocortin 1 receptor (MC1R), a Gs protein-coupled receptor of the melanocyte's plasma membrane, is a major determinant of skin pigmentation and phototype. Upon activation by α-melanocyte stimulating hormone, MC1R triggers the cAMP cascade to stimulate eumelanogenesis. We used whole-exome sequencing to identify causative alleles in Pakistani families with skin and hair hypopigmentation. Six MC1R mutations segregated with the phenotype in seven families, including a p.Val174del in-frame deletion and a p.Tyr298* nonsense mutation, that were analyzed for function in heterologous HEK293 cells. p.Tyr298* MC1R showed no agonist-induced signaling to the cAMP or ERK pathways, nor detectable agonist binding. Conversely, signaling was comparable for p.Val174del and wild-type in HEK cells overexpressing the proteins, but binding analysis suggested impaired cell surface expression. Flow cytometry and confocal imaging studies revealed reduced plasma membrane expression of p.Val174del and p.Tyr298*. Therefore, p.Tyr298* was a total loss-of-function (LOF) allele, while p.Val174del displayed a partial LOF attribute."}

    name_no

    {"project":"name_no","denotations":[{"id":"T2","span":{"begin":727,"end":736},"obj":"Var"},{"id":"T3","span":{"begin":737,"end":741},"obj":"Gene"},{"id":"T4","span":{"begin":749,"end":751},"obj":"NegReg"},{"id":"T5","span":{"begin":752,"end":777},"obj":"MPA"},{"id":"T6","span":{"begin":785,"end":789},"obj":"Pathway"},{"id":"T7","span":{"begin":793,"end":805},"obj":"Pathway"},{"id":"T8","span":{"begin":807,"end":810},"obj":"NegReg"},{"id":"T9","span":{"begin":822,"end":837},"obj":"Interaction"},{"id":"T10","span":{"begin":880,"end":891},"obj":"Var"},{"id":"T11","span":{"begin":979,"end":987},"obj":"NegReg"},{"id":"T12","span":{"begin":988,"end":1011},"obj":"MPA"},{"id":"T13","span":{"begin":1066,"end":1073},"obj":"NegReg"},{"id":"T14","span":{"begin":1074,"end":1100},"obj":"MPA"},{"id":"T15","span":{"begin":1104,"end":1115},"obj":"Var"},{"id":"T16","span":{"begin":1120,"end":1129},"obj":"Var"},{"id":"T17","span":{"begin":1142,"end":1151},"obj":"Var"},{"id":"T18","span":{"begin":1164,"end":1180},"obj":"NegReg"},{"id":"T19","span":{"begin":1201,"end":1212},"obj":"Var"},{"id":"T20","span":{"begin":1225,"end":1236},"obj":"NegReg"}],"relations":[{"id":"R1","pred":"ThemeOf","subj":"T3","obj":"T2"},{"id":"R10","pred":"ThemeOf","subj":"T14","obj":"T13"},{"id":"R11","pred":"CauseOf","subj":"T15","obj":"T13"},{"id":"R12","pred":"CauseOf","subj":"T16","obj":"T13"},{"id":"R13","pred":"CauseOf","subj":"T17","obj":"T18"},{"id":"R14","pred":"CauseOf","subj":"T19","obj":"T20"},{"id":"R2","pred":"CauseOf","subj":"T2","obj":"T4"},{"id":"R3","pred":"CauseOf","subj":"T2","obj":"T8"},{"id":"R4","pred":"ThemeOf","subj":"T9","obj":"T8"},{"id":"R5","pred":"ThemeOf","subj":"T4","obj":"T5"},{"id":"R6","pred":"ThemeOf","subj":"T6","obj":"T5"},{"id":"R7","pred":"ThemeOf","subj":"T7","obj":"T5"},{"id":"R8","pred":"CauseOf","subj":"T10","obj":"T11"},{"id":"R9","pred":"ThemeOf","subj":"T12","obj":"T11"}],"text":"Identification and functional characterization of natural human melanocortin 1 receptor mutant alleles in Pakistani population.\nMelanocortin 1 receptor (MC1R), a Gs protein-coupled receptor of the melanocyte's plasma membrane, is a major determinant of skin pigmentation and phototype. Upon activation by α-melanocyte stimulating hormone, MC1R triggers the cAMP cascade to stimulate eumelanogenesis. We used whole-exome sequencing to identify causative alleles in Pakistani families with skin and hair hypopigmentation. Six MC1R mutations segregated with the phenotype in seven families, including a p.Val174del in-frame deletion and a p.Tyr298* nonsense mutation, that were analyzed for function in heterologous HEK293 cells. p.Tyr298* MC1R showed no agonist-induced signaling to the cAMP or ERK pathways, nor detectable agonist binding. Conversely, signaling was comparable for p.Val174del and wild-type in HEK cells overexpressing the proteins, but binding analysis suggested impaired cell surface expression. Flow cytometry and confocal imaging studies revealed reduced plasma membrane expression of p.Val174del and p.Tyr298*. Therefore, p.Tyr298* was a total loss-of-function (LOF) allele, while p.Val174del displayed a partial LOF attribute."}