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| ==Classification== | | <StructureSection load='' size='350' side='right' caption='' scene=''> |
| '''BRCA Exchange''': Pathogenic, '''ClinVar''': Pathogenic | |
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| == Commentary==
| | Anything in this section will appear adjacent to the 3D structure and will be scrollable. |
| This mutation Cys61Gly disrupts zinc ion binding necessary for stability of the RING structure <ref name='p22172724'>pmid 22172724</ref><ref name='p16403807'>pmid 16403807</ref>. As a consequence, it abolishes interaction with BARD1 and also with E2 conjugate enzymes and thereby reduces its ubiquitin ligase activity. BRCA1 C61G homozygous mice leads to embryonic lethality due to loss of BRCA1 RING function. Drost et al <ref name='p22172724'/> showed that residual activity of this C61G mutant BRCA1 protein with a dysfunctional RING domain triggers acquired resistance to PARP inhibitors and platinum drugs. For these tumors DNA repair process is partially intact, although homologous recombination (HR) reporter activity is very low. According to Sweet et al <ref>pmid: 19543972</ref>, the odds of pathogenicity of this mutation is 5E+05:1, in favor of being deleterious.
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| ==Experimental results==
| | </StructureSection> |
| Heterozygous mutation facilitates tumor development and homozygous mutation is embryonically lethal in a mouse model where p53 is targeted deleted in the mammary gland and BRCA1 deletion is varied according to the required zygosity <ref name='p22172724'/>. High impact in yeast two-hybrid assay <ref name='p16403807'/></ref>.
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| ==Impacted biological activities==
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| E3 Ubiquitin ligase activity Homologous recombination
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| ==Variant==
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| C61G, chr17:g.41258504:A>C, NP_009225.1:p.(Cys61Gly), rs28897672
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| ==Allele Frequency==
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| 2.825e-05 (ExAC minus TCGA)
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| ==References==
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| <references/>
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