ArticleNucleic acids research2011
Predicting the functional impact of protein mutations: application to cancer genomics.
Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,229 papers, 4 of them syntheses that pooled it.
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Who cites it
1,229 citing papers in PubMed, 4 syntheses or guidelines pooled it, 2,107 citations in OpenAlex.
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- Comprehensive Molecular Analysis in NRG Oncology/RTOG 9813: A Phase 3 Study of Radiation and Temozolomide Versus Radiation and BCNU/CCNU in Anaplastic Astrocytoma.International journal of radiation oncology, biology, physics · 2025Trial
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- Report of two patients with variants in FOXL2 and KASH5 and review of gestational trophoblastic neoplasia after recurrent moles.Journal of assisted reproduction and genetics · 2026Article
- Multi-omics analysis of HLTF context-dependent regulation across TCGA cohorts revealed its potential as new biomarker in tumour.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- Novel Compound Heterozygous Variants inJournal of clinical medicine · 2026Article
- Defining the molecular tolerance-to-damage landscape of SMARCA4 helicase genetic alterations.bioRxiv : the preprint server for biology · 2026Article
- Protocol for identifying genetic modifiers of phenotypes in individuals with disease-associated variants.STAR protocols · 2026Article
- Insights into the genetic basis of natural selection and domestication from Sorghum.Scientific reports · 2026Article
- A recurrent North African ZP1 variant and a literature review of genotype-phenotype correlations in ZP-related infertility.Journal of assisted reproduction and genetics · 2026Review
1,169 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
As large-scale re-sequencing of genomes reveals many protein mutations, especially in human cancer tissues, prediction of their likely functional impact becomes important practical goal. Here, we introduce a new functional impact score (FIS) for amino acid residue changes using evolutionary conservation patterns. The information in these patterns is derived from aligned families and sub-families of sequence homologs within and between species using combinatorial entropy formalism. The score performs well on a large set of human protein mutations in separating disease-associated variants (∼19 200), assumed to be strongly functional, from common polymorphisms (∼35 600), assumed to be weakly functional (area under the receiver operating characteristic curve of ∼0.86). In cancer, using recurrence, multiplicity and annotation for ∼10 000 mutations in the COSMIC database, the method does well in assigning higher scores to more likely functional mutations ('drivers'). To guide experimental prioritization, we report a list of about 1000 top human cancer genes frequently mutated in one or more cancer types ranked by likely functional impact; and, an additional 1000 candidate cancer genes with rare but likely functional mutations. In addition, we estimate that at least 5% of cancer-relevant mutations involve switch of function, rather than simply loss or gain of function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.