Mutation:BRCA1
From Proteopedia
(Difference between revisions)
Sequence
⎈ mutations with manual annotation;pathogenic;benign;not yet reviewed;
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<StructureSection load='' size='340' side='right' caption='' scene=''> | <StructureSection load='' size='340' side='right' caption='' scene=''> | ||
| - | '''Some | + | '''Some interesting mutation exaamples''': |
* [http://proteopedia.org/w/Mutation:BRCA1?res=39&mut=R Cys39Arg] | * [http://proteopedia.org/w/Mutation:BRCA1?res=39&mut=R Cys39Arg] | ||
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* [http://proteopedia.org/w/Mutation:BRCA1?res=1706&mut=A Gly1706Ala] | * [http://proteopedia.org/w/Mutation:BRCA1?res=1706&mut=A Gly1706Ala] | ||
| - | Germline mutations in the BRCA1 tumor suppressor gene often result in a significant increase in susceptibility to breast and ovarian cancers. Although the molecular basis of their effects remains largely obscure, many mutations are known to target the highly conserved C-terminal BRCT repeats that function as a phosphoserine/phosphothreonine-binding module. <ref>PMID: 15133502</ref> | + | Germline mutations in the BRCA1 tumor suppressor gene often result in a very significant increase in susceptibility to breast and ovarian cancers. Although the molecular basis of their effects remains largely obscure, many mutations are known to target the highly conserved C-terminal BRCT repeats that function as a phosphoserine/phosphothreonine-binding module. <ref>PMID: 15133502</ref> |
The most common cause of monogenic disease is a single base DNA variant resulting in an amino acid substitution. A set of structural effects, such as reduction in hydrophobic area, overpacking, backbone strain, and loss of electrostatic interactions, is used to represent the impact of single residue mutations on protein stability. The distinction between disease and non-disease variants, strongly supports the hypothesis that loss of protein stability is a major factor contributing to monogenic disease.<ref>pmid 16169011</ref> | The most common cause of monogenic disease is a single base DNA variant resulting in an amino acid substitution. A set of structural effects, such as reduction in hydrophobic area, overpacking, backbone strain, and loss of electrostatic interactions, is used to represent the impact of single residue mutations on protein stability. The distinction between disease and non-disease variants, strongly supports the hypothesis that loss of protein stability is a major factor contributing to monogenic disease.<ref>pmid 16169011</ref> | ||
Revision as of 08:13, 13 June 2019
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References
- ↑ Clapperton JA, Manke IA, Lowery DM, Ho T, Haire LF, Yaffe MB, Smerdon SJ. Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. Nat Struct Mol Biol. 2004 Jun;11(6):512-8. Epub 2004 May 9. PMID:15133502 doi:10.1038/nsmb775
- ↑ Yue P, Li Z, Moult J. Loss of protein structure stability as a major causative factor in monogenic disease. J Mol Biol. 2005 Oct 21;353(2):459-73. PMID:16169011 doi:http://dx.doi.org/10.1016/j.jmb.2005.08.020
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