Genetic Variation in Bruton Tyrosine Kinase

Schaafsma, Gerard C. P.; Vihinen, Mauno

doi:10.1007/978-3-319-22714-6_5

Cited by 6 publications

(7 citation statements)

References 40 publications

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“…The distributions of the predicted harmful and benign variants are qualitatively similar to those published previously, for the 1000 Genomes project (de Beer et al., ), those annotated in UniProt (Petukh, Kucukkal, & Alexov, ), and variants in BTK (Schaafsma & Vihinen, ).…”

Section: Resultssupporting

confidence: 82%

Large differences in proportions of harmful and benign amino acid substitutions between proteins and diseases

Schaafsma

Vihinen²

2017

Human Mutation

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Genes and proteins are known to have differences in their sensitivity to alterations. Despite numerous sequencing studies, proportions of harmful and harmless substitutions are not known for proteins and groups of proteins. To address this question, we predicted the outcome for all possible single amino acid substitutions (AASs) in nine representative protein groups by using the PON-P2 method. The effects on 996 proteins were studied and vast differences were noticed. Proteins in the cancer group harbor the largest proportion of harmful variants (42.1%), whereas the non-disease group of proteins not known to have a disease association and not involved in the housekeeping functions had the lowest number of harmful variants (4.2%). Differences in the proportions of the harmful and benign variants are wide within each group, but they still show clear differences between the groups. Frequently appearing protein domains show a wide spectrum of variant frequencies, whereas no major protein structural class-specific differences were noticed. AAS types in the original and variant residues showed distinctive patterns, which are shared by all the protein groups. The observations are relevant for understanding genetic bases of diseases, variation interpretation, and for the development of methods for that purpose.

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Section: Resultssupporting

confidence: 82%

Large differences in proportions of harmful and benign amino acid substitutions between proteins and diseases

Schaafsma

Vihinen²

2017

Human Mutation

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“…BTKbase (http://structure.bmc.lu.se/idbase/BTKbase/) is an LSDB for Bruton agammablobulinemia tyrosine kinase (BTK) variations causing X-linked agammaglobulinemia (XLA) originally released 1995 [Vihinen et al, 1995] and then maintained ever since the last reports being [Väliaho et al, 2006; Schaafsma and Vihinen, 2015]. There are currently 1,357 public entries.…”

Section: Case Study: Btkbasementioning

confidence: 99%

Human Variome Project Quality Assessment Criteria for Variation Databases

et al. 2016

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Numerous databases containing information about DNA, RNA, and protein variations are available. Gene-specific variant databases (locus-specific variation databases, LSDBs) are typically curated and maintained for single genes or groups of genes for a certain disease(s). These databases are widely considered as the most reliable information source for a particular gene/protein/disease, but it should also be made clear they may have widely varying contents, infrastructure, and quality. Quality is very important to evaluate because these databases may affect health decision-making, research, and clinical practice. The Human Variome Project (HVP) established a Working Group for Variant Database Quality Assessment. The basic principle was to develop a simple system that nevertheless provides a good overview of the quality of a database. The HVP quality evaluation criteria that resulted are divided into four main components: data quality, technical quality, accessibility, and timeliness. This report elaborates on the developed quality criteria and how implementation of the quality scheme can be achieved.

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“…An example of the use of VariO in an LSDB can be found at http://databases.lovd.nl/shared/genes/BTK. BTKbase [Väliaho et al., ; Schaafsma and Vihinen, ] is a database for Bruton agammaglobulinemia tyrosine kinase (BTK) variants causing X‐linked agammaglobulinemia, a rare primary immunodeficiency [Tsukada et al., ; Vetrie et al., ]. BTKbase has been previously maintained with MUTbase software [Riikonen and Vihinen, ; Väliaho et al., ].…”

Section: Discussionmentioning

confidence: 99%