Protein-truncating variants

Protein-truncating variants (PTVs) are genetic variants predicted to shorten the coding sequence of genes,^[1] through ways like a stop-gain mutation.^[2]^[3]^[4]^[5] PTV is sometime categorized under the umbrella term frameshift or truncating variants (FTVs), which includes both PTVs and DNA variants caused by frameshift mutation.

Implication in diseases/disorders

It was believed that protein-truncating variants are not associated with human diseases.^[2] Recent studies have implied the involvement of PTVs in autism spectrum disorder.^[6]

References

^ Rivas, M. A.; Pirinen, M.; Conrad, D. F.; Lek, M.; Tsang, E. K.; Karczewski, K. J.; Maller, J. B.; Kukurba, K. R.; DeLuca, D. S. (2015-05-08). "Effect of predicted protein-truncating genetic variants on the human transcriptome". Science. 348 (6235): 666–669. Bibcode:2015Sci...348..666R. doi:10.1126/science.1261877. ISSN 0036-8075. PMC 4537935. PMID 25954003.
^ ^a ^b Stenson, Peter D.; Mort, Matthew; Ball, Edward V.; Shaw, Katy; Phillips, Andrew D.; Cooper, David N. (January 2014). "The Human Gene Mutation Database: building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine". Human Genetics. 133 (1): 1–9. doi:10.1007/s00439-013-1358-4. ISSN 0340-6717. PMC 3898141. PMID 24077912.
^ Easton, Douglas F.; Dunning, Alison M.; Pharoah, Paul DP; Ostrander, Elaine A.; Luben, Robert; Brown, Judith; Conroy, Don M.; Baynes, Caroline; Ahmed, Shahana (2017-11-01). "Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks". Journal of Medical Genetics. 54 (11). Journal of Medical Genetics, The BMJ: 732–741. doi:10.1136/jmedgenet-2017-104588. PMC 5740532. PMID 28779002.
^ pubmeddev; al, DeBoever C., et (2018). "Medical relevance of protein-truncating variants across 337,205 individuals in the UK Biobank study. - PubMed - NCBI". Nature Communications. 9 (1): 1612. doi:10.1038/s41467-018-03910-9. PMC 5915386. PMID 29691392.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ MacArthur, Daniel G.; Lappalainen, Tuuli; Montgomery, Stephen B.; McCarthy, Mark I.; Dermitzakis, Emmanouil T.; Sammeth, Michael; Ardlie, Kristin; Donnelly, Peter; Guigo, Roderic (2015-05-08). "Effect of predicted protein-truncating genetic variants on the human transcriptome". Science. 348 (6235): 666–669. Bibcode:2015Sci...348..666R. doi:10.1126/science.1261877. PMC 4537935. PMID 25954003.
^ De Rubeis, S He, X Goldberg, AP Poultney, CS Samocha, K Cicek, AE Kou, Y Liu, L Fromer, M Walker, S Singh, T Klei, L Kosmicki, J Shih-Chen, F Aleksic, B Biscaldi, M Bolton, PF Brownfeld, JM Cai, J Campbell, NG Carracedo, A Chahrour, MH Chiocchetti, AG Coon, H Crawford, EL Curran, SR Dawson, G Duketis, E Fernandez, BA Gallagher, L Geller, E Guter, SJ Hill, RS Ioniță-Laza, J Jimenz Gonzalez, P Kilpinen, H Klauck, SM Kolevzon, A Lee, I Lei, I Lei, J Lehtimäki, T Lin, C-F Ma'ayan, A Marshall, CR McInnes, AL Neale, B Owen, MJ Ozaki, N Parellada, M Parr, JR Purcell, S Puura, K Rajagopalan, D Rehnström, K Reichenberg, A Sabo, A Sachse, M Sanders, SJ Schafer, C Schulte-Rüther, M Skuse, D Stevens, C Szatmari, P Tammimies, K Valladares, O Voran, A Li-San, W Weiss, LA Willsey, AJ Yu, TW Yuen, RKC DDD Study, Homozygosity Mapping Collaborative for Autism, UK10K Consortium, Cook, EH Freitag, CM Gill, M Hultman, CM Lehner, T Palotie, A Schellenberg, GD Sklar, P State, MW Sutcliffe, JS Walsh, CA Scherer, SW Zwick, ME Barett, JC Cutler, DJ Roeder, K Devlin, B Daly, MJ Buxbaum, JD (2014-11-13). Synaptic, transcriptional and chromatin genes disrupted in autism. OCLC 1031073384.{{cite book}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)

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[1] Rivas, M. A.; Pirinen, M.; Conrad, D. F.; Lek, M.; Tsang, E. K.; Karczewski, K. J.; Maller, J. B.; Kukurba, K. R.; DeLuca, D. S. (2015-05-08). "Effect of predicted protein-truncating genetic variants on the human transcriptome". Science. 348 (6235): 666–669. Bibcode:2015Sci...348..666R. doi:10.1126/science.1261877. ISSN 0036-8075. PMC 4537935. PMID 25954003.

[:0-2] Stenson, Peter D.; Mort, Matthew; Ball, Edward V.; Shaw, Katy; Phillips, Andrew D.; Cooper, David N. (January 2014). "The Human Gene Mutation Database: building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine". Human Genetics. 133 (1): 1–9. doi:10.1007/s00439-013-1358-4. ISSN 0340-6717. PMC 3898141. PMID 24077912.

[3] Easton, Douglas F.; Dunning, Alison M.; Pharoah, Paul DP; Ostrander, Elaine A.; Luben, Robert; Brown, Judith; Conroy, Don M.; Baynes, Caroline; Ahmed, Shahana (2017-11-01). "Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks". Journal of Medical Genetics. 54 (11). Journal of Medical Genetics, The BMJ: 732–741. doi:10.1136/jmedgenet-2017-104588. PMC 5740532. PMID 28779002.

[4] ubmeddev; al, DeBoever C., et (2018). "Medical relevance of protein-truncating variants across 337,205 individuals in the UK Biobank study. - PubMed - NCBI". Nature Communications. 9 (1): 1612. doi:10.1038/s41467-018-03910-9. PMC 5915386. PMID 29691392.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[5] MacArthur, Daniel G.; Lappalainen, Tuuli; Montgomery, Stephen B.; McCarthy, Mark I.; Dermitzakis, Emmanouil T.; Sammeth, Michael; Ardlie, Kristin; Donnelly, Peter; Guigo, Roderic (2015-05-08). "Effect of predicted protein-truncating genetic variants on the human transcriptome". Science. 348 (6235): 666–669. Bibcode:2015Sci...348..666R. doi:10.1126/science.1261877. PMC 4537935. PMID 25954003.

[6] De Rubeis, S He, X Goldberg, AP Poultney, CS Samocha, K Cicek, AE Kou, Y Liu, L Fromer, M Walker, S Singh, T Klei, L Kosmicki, J Shih-Chen, F Aleksic, B Biscaldi, M Bolton, PF Brownfeld, JM Cai, J Campbell, NG Carracedo, A Chahrour, MH Chiocchetti, AG Coon, H Crawford, EL Curran, SR Dawson, G Duketis, E Fernandez, BA Gallagher, L Geller, E Guter, SJ Hill, RS Ioniță-Laza, J Jimenz Gonzalez, P Kilpinen, H Klauck, SM Kolevzon, A Lee, I Lei, I Lei, J Lehtimäki, T Lin, C-F Ma'ayan, A Marshall, CR McInnes, AL Neale, B Owen, MJ Ozaki, N Parellada, M Parr, JR Purcell, S Puura, K Rajagopalan, D Rehnström, K Reichenberg, A Sabo, A Sachse, M Sanders, SJ Schafer, C Schulte-Rüther, M Skuse, D Stevens, C Szatmari, P Tammimies, K Valladares, O Voran, A Li-San, W Weiss, LA Willsey, AJ Yu, TW Yuen, RKC DDD Study, Homozygosity Mapping Collaborative for Autism, UK10K Consortium, Cook, EH Freitag, CM Gill, M Hultman, CM Lehner, T Palotie, A Schellenberg, GD Sklar, P State, MW Sutcliffe, JS Walsh, CA Scherer, SW Zwick, ME Barett, JC Cutler, DJ Roeder, K Devlin, B Daly, MJ Buxbaum, JD (2014-11-13). Synaptic, transcriptional and chromatin genes disrupted in autism. OCLC 1031073384.{{cite book}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)

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