SIFT: predicting amino acid changes that affect protein function
Pauline C. Ng,Steven Henikoff +1 more
TLDR
SIFT is a program that predicts whether an amino acid substitution affects protein function so that users can prioritize substitutions for further study and can distinguish between functionally neutral and deleterious amino acid changes in mutagenesis studies and on human polymorphisms.Abstract:
Single nucleotide polymorphism (SNP) studies and random mutagenesis projects identify amino acid substitutions in protein-coding regions. Each substitution has the potential to affect protein function. SIFT (Sorting Intolerant From Tolerant) is a program that predicts whether an amino acid substitution affects protein function so that users can prioritize substitutions for further study. We have shown that SIFT can distinguish between functionally neutral and deleterious amino acid changes in mutagenesis studies and on human polymorphisms. SIFT is available at http://blocks.fhcrc.org/sift/SIFT.html.read more
Citations
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Temporal order of RNase IIIb and loss-of-function mutations during development determines phenotype in pleuropulmonary blastoma / DICER1 syndrome: a unique variant of the two-hit tumor suppression model.
Mark Brenneman,Amanda Field,Jiandong Yang,Gretchen M. Williams,Leslie Doros,Christopher T. Rossi,Kris Ann P. Schultz,Avi Z. Rosenberg,Jennifer Ivanovich,Joyce Turner,Heather Gordish-Dressman,Douglas R. Stewart,Weiying Yu,Anne K. Harris,Peter Schoettler,Paul J. Goodfellow,Louis P. Dehner,Louis P. Dehner,Yoav H. Messinger,D. Ashley Hill +19 more
TL;DR: It is proposed that acquisition of a neomorphic RNase IIIb domain mutation is the rate limiting event in DICER1-associated tumorigenesis, and that distinct clinical phenotypes associated with mutational categories reflect the temporal order in which LOF and RNaseIIIb domain mutations are acquired during development.
Journal ArticleDOI
A rare lysosomal enzyme gene SMPD1 variant (p.R591C) associates with Parkinson's disease
Jia Nee Foo,Herty Liany,Jin Xin Bei,Xue Qing Yu,Jianjun Liu,Wing Lok Au,Kumar M. Prakash,Kumar M. Prakash,Louis C.S. Tan,Eng-King Tan +9 more
TL;DR: To investigate the role of mutations in the sphingomyelin phosphodiesterase (SMPD1) gene in Parkinson's disease (PD), all the exons of this gene were sequenced and a novel, rare SMPD1 variant was identified which increased the risk of PD.
Journal ArticleDOI
Functional characterization of non-synonymous single nucleotide polymorphisms in the gene encoding human multidrug resistance protein 1 (MRP1/ABCC1).
TL;DR: The data suggest that none of the MRP1/ABCC1 variants studied are likely by themselves to have major deleterious effects in healthy individuals, and the SIFT and PolyPhen algorithms appear to be poor predictors of the phenotypic consequences of these MRp1 mutations at least in vitro.
Journal ArticleDOI
De novo assembly of a haplotype-resolved human genome
Hongzhi Cao,Honglong Wu,Ruibang Luo,Shujia Huang,Yuhui Sun,Xin Tong,Yinlong Xie,Binghang Liu,Hailong Yang,Hancheng Zheng,Jian Li,Bo Li,Yu Wang,Fang Yang,Peng Sun,Siyang Liu,Peng Gao,Haodong Huang,Sun Jing,Dan Chen,Guangzhu He,Weihua Huang,Zheng Huang,Li Yue,Laurent C. A. M. Tellier,Xiao Liu,Qiang Feng,Xun Xu,Xiuqing Zhang,Lars Bolund,Anders Krogh,Karsten Kristiansen,Radoje Drmanac,Snezana Drmanac,Rasmus Nielsen,Songgang Li,Jian Wang,Huanming Yang,Yingrui Li,Gane Ka-Shu Wong,Jun Wang +40 more
TL;DR: This haplotype-resolved diploid genome represents the most complete de novo human genome assembly to date and should aid in translating genotypes to phenotypes for the development of personalized medicine.
Journal ArticleDOI
Identification and in silico analysis of functional SNPs of the BRCA1 gene.
TL;DR: It is proposed that an nsSNP (rs1800751) could be an important candidate for the breast cancer caused by the BRCA1 gene from a comparison of the stabilizing residues of the native and mutant proteins.
References
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Journal ArticleDOI
Database resources of the National Center for Biotechnology Information
David L. Wheeler,Deanna M. Church,Ron Edgar,Scott Federhen,Wolfgang Helmberg,Thomas L. Madden,Joan Pontius,Gregory D. Schuler,Lynn M. Schriml,Edwin Sequeira,Tugba O. Suzek,Tatiana Tatusova,Lukas Wagner +12 more
TL;DR: In addition to maintaining the GenBank(R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides data analysis and retrieval resources for the data in GenBank and other biological data made available through NCBI’s website.
Journal ArticleDOI
dbSNP: the NCBI database of genetic variation
Stephen T. Sherry,Minghong Ward,Michael Kholodov,Jonathan Baker,Lon Phan,Elizabeth M. Smigielski,Karl Sirotkin +6 more
TL;DR: The dbSNP database is a general catalog of genome variation to address the large-scale sampling designs required by association studies, gene mapping and evolutionary biology, and is integrated with other sources of information at NCBI such as GenBank, PubMed, LocusLink and the Human Genome Project data.
Journal ArticleDOI
The SWISS-PROT protein sequence data bank and its supplement TrEMBL in 1999.
Amos Marc Bairoch,Rolf Apweiler +1 more
TL;DR: The Human Proteomics Initiative (HPI), a major project to annotate all known human sequences according to the quality standards of SWISS-PROT, is described.
Journal ArticleDOI
Predicting Deleterious Amino Acid Substitutions
Pauline C. Ng,Steven Henikoff +1 more
TL;DR: A tool that uses sequence homology to predict whether a substitution affects protein function is constructed, which may be used to identify plausible disease candidates among the SNPs that cause missense substitutions.
Journal ArticleDOI
Human non‐synonymous SNPs: server and survey
TL;DR: A World Wide Web server is presented to predict the effect of an nsSNP on protein structure and function and the dependence of selective pressure on the structural and functional properties of proteins is studied.