NPM1 is a protein-coding gene that encodes the nucleophosmin 1(NPM1)protein.The NPM1 protein exhibits dynamic shuttling between the nucleus and cytoplasm and is involved in various cellular processes,such as centrosom...NPM1 is a protein-coding gene that encodes the nucleophosmin 1(NPM1)protein.The NPM1 protein exhibits dynamic shuttling between the nucleus and cytoplasm and is involved in various cellular processes,such as centrosome duplication,protein chaperoning,and DNA repair.Mutations of the NPM1 gene are associated with human acute myeloid leukemia(AML).AML is a complex hematopoietic cell disorder characterized by excessive proliferation of hematopoietic cells of the myeloid lineage in the bone marrow.This study aimed to predict highly damaging missense single-nucleotide polymorphism(SNPs)in the human NPM1 gene that may be associated with AML.In this investigation,we employed a range of in silico tools to analyze the functional and structural consequences of missense SNPs in the human NPM1 gene.The missense SNPs of the NPM1 gene were retrieved from the Ensembl database.We evaluated the functional and structural impacts of missense SNPs using bioinformatics tools,specifically SIFT,PROVEAN,PolyPhen-2,I-Mutant 3.0,MUpro,and MutPred2.The secondary structure was predicted with PSIPRED.The 3-dimensional structure of the NPM1 protein was obtained from AlphaFold,visualization along with mutant models was generated using PyMOL,and all information about physiological properties was taken from the HOPE project.The protein–protein interactions of the NPM1 protein were investigated using STRING.In silico analysis revealed 8 missense mutations(K54N,I59T,L79S,P152A,K193R,K193N,A283G,and I284F)in the human NPM1 gene.These mutations lead to structural alterations in the protein,which disrupt its normal function and may contribute to the development of AML in humans.展开更多
1 Introduction Dissecting the dynamics of cell statesiscrucial for understanding various biological processes,such as tissue development and tumor drug responses.Recent advancements in single-cell lineage tracing(scLT...1 Introduction Dissecting the dynamics of cell statesiscrucial for understanding various biological processes,such as tissue development and tumor drug responses.Recent advancements in single-cell lineage tracing(scLT)technologies provide effective ways to track single-cell lineages through heritable cellular barcodes,while simultaneously detecting the molecular states of cells by sequencing[1].展开更多
文摘NPM1 is a protein-coding gene that encodes the nucleophosmin 1(NPM1)protein.The NPM1 protein exhibits dynamic shuttling between the nucleus and cytoplasm and is involved in various cellular processes,such as centrosome duplication,protein chaperoning,and DNA repair.Mutations of the NPM1 gene are associated with human acute myeloid leukemia(AML).AML is a complex hematopoietic cell disorder characterized by excessive proliferation of hematopoietic cells of the myeloid lineage in the bone marrow.This study aimed to predict highly damaging missense single-nucleotide polymorphism(SNPs)in the human NPM1 gene that may be associated with AML.In this investigation,we employed a range of in silico tools to analyze the functional and structural consequences of missense SNPs in the human NPM1 gene.The missense SNPs of the NPM1 gene were retrieved from the Ensembl database.We evaluated the functional and structural impacts of missense SNPs using bioinformatics tools,specifically SIFT,PROVEAN,PolyPhen-2,I-Mutant 3.0,MUpro,and MutPred2.The secondary structure was predicted with PSIPRED.The 3-dimensional structure of the NPM1 protein was obtained from AlphaFold,visualization along with mutant models was generated using PyMOL,and all information about physiological properties was taken from the HOPE project.The protein–protein interactions of the NPM1 protein were investigated using STRING.In silico analysis revealed 8 missense mutations(K54N,I59T,L79S,P152A,K193R,K193N,A283G,and I284F)in the human NPM1 gene.These mutations lead to structural alterations in the protein,which disrupt its normal function and may contribute to the development of AML in humans.
基金supported by the National Key Research and Development Program of China(Nos.2020YFA0712403 and 2021YFF1200901)the National Natural Science Foundation of China(NSFC)(Grant Nos.62133006 and 92268104)+1 种基金the Tsinghua University Initiative Scientific Research Program(No.20221080076)the China Postdoctoral Science Foundation(No.2022M721839).
文摘1 Introduction Dissecting the dynamics of cell statesiscrucial for understanding various biological processes,such as tissue development and tumor drug responses.Recent advancements in single-cell lineage tracing(scLT)technologies provide effective ways to track single-cell lineages through heritable cellular barcodes,while simultaneously detecting the molecular states of cells by sequencing[1].
