Amino acid residues 860-876 in the C-terminal part of RB1 constitute a bipartite nuclear localization signal (NLS). An NLS deletion mutant of RB1, generated by directed mutagenesis, shows impaired nuclear localization (Zacksenhaus et al. 1993). RB1 R830_G887 mutant (also known as RB1 delEx24-25), reported in low-penetrance familial retinoblastoma, similarly lacks the NLS and shows primarily cytosolic localization (Bremner et al. 1997). Many loss-of-function mutations in RB1, such as nonsense and frameshift mutations, lead to premature termination of translation and formation of truncated proteins that lack the NLS. Although the subcellular localization has not been examined for these mutants, it is expected for their translocation to the nucleus to be impaired and for them to predominantly localize to the cytosol.The RB1 nonsense and frameshift mutants reported in cancer that are listed below have been annotated as candidate mutants for impaired translocation to the nucleus based on the absence of the NLS. Please note that some of these nonsense mutants lack more than 90% of their amino acid sequence and are likely to be null mutants, with no protein detectable. Even frameshift mutations that happen close to the 3’ end of the RB1 gene have been shown to produce mRNAs that are prone to nonsense-mediated decay (Mitter et al. 2009).These are the nonsense mutants annotated as candidates for impaired translocation to the nucleus:RB1 K4*RB1 Q35*RB1 E48*RB1 E54*RB1 K63*RB1 E72*RB1 W75*RB1 W78*RB1 E79*RB1 K80*RB1 G86*RB1 K95*RB1 K96*RB1 E97*RB1 W99*RB1 G100*RB1 S114*RB1 Q121*RB1 E125*RB1 E137*RB1 S149*RB1 L158*RB1 E166*RB1 Q176*RB1 E184*RB1 W195*RB1 L199*RB1 L206*RB1 E209*RB1 S215*RB1 Q217*RB1 C221*RB1 S230*RB1 K240*RB1 R251*RB1 R255*RB1 Q257*RB1 Q266*RB1 E275*RB1 E280*RB1 E282*RB1 K289*RB1 G304*RB1 G310*RB1 E313*RB1 E315*RB1 R320*RB1 E322*RB1 E323*RB1 K329*RB1 L335*RB1 Q344*RB1 E364*RB1 Q384*RB1 L389*RB1 S391*RB1 Q395*RB1 S397*RB1 K412*RB1 K429*RB1 G435*RB1 Q436*RB1 E440*RB1 S443*RB1 Q444*RB1 R445*RB1 Y446*RB1 Y454*RB1 R455*RB1 S463*RB1 E464*RB1 E465*RB1 R467*RB1 Q471*RB1 C489*RB1 E492*RB1 Y498*RB1 Q504*RB1 L512*RB1 W516*RB1 L523*RB1 E533*RB1 E539*RB1 R544*RB1 L550*RB1 E551*RB1 R552*RB1 R556*RB1 W563*RB1 S565*RB1 S567*RB1 S576*RB1 E580*RB1 G581*RB1 Q597*RB1 Y606*RB1 K615*RB1 S618*RB1 Q631*RB1 S634*RB1 Q637*RB1 Q639*RB1 S648*RB1 K652*RB1 Y655*RB1 E672*RB1 E675*RB1 E677*RB1 W681*RB1 Q685*RB1 Q689*RB1 E691*RB1 E693*RB1 Q702*RB1 Y709*RB1 K715*RB1 K720*RB1 Y728*RB1 Q736*RB1 E737*RB1 K745*RB1 E747*RB1 E748*RB1 Y749*RB1 Y756*RB1 S758*RB1 Q762*RB1 R763*RB1 K765*RB1 Q770*RB1 L779*RB1 R787*RB1 Y790*RB1 K791*RB1 G801*RB1 S807*RB1 E817*RB1 S829*RB1 L832*RB1 S834*RB1 E837*RB1 S838*RB1 E843*RB1 Q846*RB1 Q850*These are the frameshift mutants annotated as candidates for impaired translocation to the nucleus:RB1 R7Efs*58RB1 R7Pfs*24RB1 T9Rfs*56RB1 A11Rfs*20RB1 A15Pfs*3RB1 A17Pfs*3RB1 P28Lfs*37RB1 D32Tfs*33RB1 P39Rfs*26RB1 P39Sfs*10RB1 L44Rfs*4RB1 T58Yfs*52RB1 C61Vfs*4RB1 K63Rfs*38RB1 I66Dfs*44RB1 I66Yfs*11RB1 R71Efs*39RB1 E72Vfs*34RB1 R73Sfs*36RB1 A74Efs*4RB1 L76*RB1 T77Lfs*34RB1 E97Gfs*13RB1 E97Nfs*14RB1 W99Lfs*11RB1 W99Yfs*5RB1 G100Efs*11RB1 C102Yfs*7RB1 F104Lfs*7RB1 E112Dfs*6RB1 T116Lfs*8RB1 N123Tfs*2RB1 I124*RB1 I124Rfs*6RB1 E125Kfs*11RB1 N133*RB1 N133Tfs*3RB1 L134*RB1 L135Tfs*5RB1 E137Rfs*3RB1 T140Nfs*6RB1 K143Mfs*19RB1 D145Ifs*8RB1 M148Hfs*9RB1 M148Ifs*8RB1 M148Vfs*8RB1 R150Kfs*7RB1 D156Mfs*19RB1 D156Vfs*19RB1 L158Mfs*19RB1 Y173Ffs*11RB1 S182Ifs*3RB1 S182Yfs*2RB1 N186Ifs*6RB1 S194Ffs*7RB1 W195*RB1 L199Ffs*4RB1 L199Yfs*2RB1 Q207Tfs*5RB1 E209Vfs*3RB1 D224Afs*40RB1 P232Rfs*4RB1 Y239Lfs*25RB1 S249Ffs*22RB1 P250Afs*16RB1 P250Sfs*20RB1 P253Gfs*5RB1 N258Efs*11RB1 Q266Hfs*2RB1 N269*RB1 L277Pfs*9RB1 C278*RB1 H281Qfs*6RB1 H281Sfs*2RB1 E287Rfs*2RB1 N290Kfs*20RB1 V291Ifs*9RB1 F299Lfs*4RB1 G310Dfs*22RB1 L317*RB1 S318*RB1 S318Nfs*13RB1 R320Dfs*12RB1 E323Kfs*9RB1 I324Mfs*17RB1 L326*RB1 N328*RB1 N328Ifs*4RB1 A333Ffs*13RB1 R334*RB1 L337Wfs*12RB1 D340Yfs*5RB1 L343Sfs*3RB1 D346Rfs*4RB1 D346Vfs*17RB1 S360Pfs*2RB1 N367*RB1 P370Lfs*10RB1 Q383Nfs*3RB1 Q384Tfs*11RB1 L385*RB1 M386Ifs*11RB1 L389Ffs*3RB1 Q395Pfs*11RB1 N406Kfs*4RB1 E413Kfs*4RB1 S414Kfs*14RB1 I415Nfs*13RB1 K417Wfs*23RB1 R418Sfs*9RB1 V419*RB1 C438Vfs*19RB1 G442Dfs*15RB1 G449Efs*8RB1 V450Sfs*13RB1 Y453*RB1 M460Ifs*3RB1 N472Ifs*6RB1 L477Mfs*17RB1 D479Efs*16RB1 D479Vfs*14RB1 N480Kfs*13RB1 F482Sfs*10RB1 H483Ifs*12RB1 H483Sfs*10RB1 H483Yfs*9RB1 M484Vfs*8RB1 L486Ifs*6RB1 C489Lfs*5RB1 E492Lfs*4RB1 T497Hfs*22RB1 T502Nfs*17RB1 F514Pfs*8RB1 N522Ifs*2RB1 K524Rfs*28RB1 A525Pfs*7RB1 Y529Lfs*26RB1 Y529Tfs*3RB1 I532Nfs*57RB1 K537Nfs*14RB1 G540Afs*3RB1 L542Kfs*11RB1 K548Nfs*3RB1 C553Vfs*58RB1 C553Wfs*53RB1 A562Hfs*49RB1 L564Sfs*47RB1 S565*RB1 D571Lfs*41RB1 K574*RB1 S576Rfs*34RB1 K577Rfs*34RB1 R579Qfs*29RB1 D584Nfs*2RB1 S588Ffs*6RB1 N593Sfs*5RB1 N593Tfs*11RB1 P595Lfs*16RB1 Y606Lfs*47RB1 P609Cfs*43RB1 R611Lfs*43RB1 G617Rfs*36RB1 N623Qfs*15RB1 N627Mfs*16RB1 A635Gfs*6RB1 P641Afs*12RB1 L647Ffs*5RB1 S648Tfs*4RB1 L649Ffs*11RB1 F650Lfs*5RB1 Y651Ifs*7RB1 V654Cfs*4RB1 V654Sfs*14RB1 Y655Ifs*3RB1 Y655Lfs*13RB1 Y655Lfs*4RB1 Y659Ifs*4RB1 R661*RB1 T664Nfs*4RB1 C666*RB1 L670Cfs*7RB1 L676Ffs*16RB1 E677Dfs*19RB1 I679*RB1 E693Nfs*3RB1 M695Rfs*10RB1 D697Qfs*23RB1 R698Afs*22RB1 I723Nfs*28RB1 T726Nfs*25RB1 P732Lfs*12RB1 K740Tfs*10RB1 L743*RB1 E747Gfs*3RB1 E748Dfs*6RB1 V754Sfs*4RB1 M761Nfs*21RB1 I768Cfs*23RB1 L769Cfs*41RB1 Y771Cfs*23RB1 Y771Lfs*24RB1 R775Gfs*35RB1 P777Lfs*33RB1 L797*RB1 L797Ffs*14RB1 L797Ffs*18RB1 R798Qfs*4RB1 R798Tfs*17RB1 I799Ffs*11RB1 N803Tfs*7RB1 I806Lfs*10RB1 P808Kfs*12RB1 L809Rfs*17RB1 Y813Kfs*12RB1 Y813Qfs*10RB1 S816Qfs*10RB1 P822Qfs*4RB1 M825*RB1 M825Ifs*13RB1 R828Kfs*10RB1 L832Ffs*5RB1 E837Dfs*12RB1 S842*RB1 K844Sfs*5RB1 N854*RB1 D856Efs*17
Dunn, JM, Ahmad, KF, Bridge, P, Gallie, BL, Du, DC, Bremner, R, Connolly-Wilson, MJ, Rushlow, D, Mostachfi, H
Loss of function and partial loss of function of RB1 mutants (localization) [cytosol]
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