The DOI matches its Crossref record; 135 of the 135 references it cites were found in a registry or an index.
Phase Separation as a Missing Mechanism for Interpretation of Disease Mutations
Open accessAbstract
It is unclear how disease mutations impact intrinsically disordered protein regions (IDRs), which lack a stable folded structure. These mutations, while prevalent in disease, are frequently neglected or annotated as variants of unknown significance. Biomolecular phase separation, a physical process often mediated by IDRs, has increasingly appreciated roles in cellular organization and regulation. We find that autism spectrum disorder (ASD)- and cancer-associated proteins are enriched for predicted phase separation propensities, suggesting that IDR mutations disrupt phase separation in key cellular processes. More generally, we hypothesize that combinations of small-effect IDR mutations perturb phase separation, potentially contributing to "missing heritability" in complex disease susceptibility.
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Biomolecular condensates: organizers of cellular biochemistry
Banani, S. F., Lee, H. O., Hyman, A. A., & Rosen, M. K. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.7 · Cited by 6,100
Activation of β-Catenin-Tcf Signaling in Colon Cancer by Mutations in β-Catenin or APC
Morin, P. J., Sparks, A. B., Korinek, V., Barker, N., Clevers, H., Vogelstein, B., & Kinzler, K. W. (1997) · Science · doi:10.1126/science.275.5307.1787 · Cited by 3,942
A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease Mutation
Patel, A., Lee, H. O., Jawerth, L., Maharana, S., Jahnel, M., Hein, M. Y., Stoynov, S., Mahamid, J., Saha, S., Franzmann, T. M., et al. (2015) · Cell · doi:10.1016/j.cell.2015.07.047 · Cited by 3,282
The complexity of NF-κB signaling in inflammation and cancer
Hoesel, B., & Schmid, J. A. (2013) · Molecular Cancer · doi:10.1186/1476-4598-12-86 · Cited by 3,165
Molliex, A., Temirov, J., Lee, J., Coughlin, M., Kanagaraj, A. P., Kim, H. J., Mittag, T., & Taylor, J. P. (2015) · Cell · doi:10.1016/j.cell.2015.09.015 · Cited by 2,893
Coactivator condensation at super-enhancers links phase separation and gene control
Sabari, B. R., Dall’Agnese, A., Boija, A., Klein, I. A., Coffey, E. L., Shrinivas, K., Abraham, B. J., Hannett, N. M., Zamudio, A. V., Manteiga, J. C., et al. (2018) · Science · doi:10.1126/science.aar3958 · Cited by 2,595
Intrinsically disordered proteins in cellular signalling and regulation
Wright, P. E., & Dyson, H. J. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3920 · Cited by 2,401
Satterstrom, F. K., Kosmicki, J. A., Wang, J., Breen, M. S., De Rubeis, S., An, J.-Y., Peng, M., Collins, R., Grove, J., Klei, L., et al. (2020) · Cell · doi:10.1016/j.cell.2019.12.036 · Cited by 2,321 · cited 2×
“Moreover, while a growing fraction of ASD can be explained by penetrant ‘‘loss-of-function’’ mutations typically affecting folded protein regions, these highimpact mutations, in an otherwise complex disorder, explain perhaps 5%–25% of the families depending on the severity of symptoms (Fernandez and Scherer, 2017; Sat…”
BackgroundSelf-citationWang, J., Choi, J.-M., Holehouse, A. S., Lee, H. O., Zhang, X., Jahnel, M., Maharana, S., Lemaitre, R., Pozniakovsky, A., Drechsel, D., et al. (2018) · Cell · doi:10.1016/j.cell.2018.06.006 · Cited by 2,076
Transcriptomic Analysis of Autistic Brain Reveals Convergent Molecular Pathology
Voineagu, I., Wang, X., Johnston, P., Lowe, J. K., Tian, Y., Horvath, S., Mill, J., Cantor, R. M., Blencowe, B. J., & Geschwind, D. H. (2011) · Nature · doi:10.1038/nature10110 · Cited by 1,874 · cited 2×
“Splicing Transcriptome-wide dysregulation of mRNA splicing levels has been observed in post-mortem brains of people with ASD (Gandal et al., 2018; Irimia et al., 2014; Voineagu et al., 2011).”
Background
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Self-citationProtein codes promote selective subcellular compartmentalization
Kilgore, H. R., Chinn, I., Mikhael, P. G., Mitnikov, I., Van Dongen, C., Zylberberg, G., Afeyan, L., Banani, S. F., Wilson-Hawken, S., Lee, T. I., et al. (2025) · Science · doi:10.1126/science.adq2634 · Cited by 99
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Nuclear Protein Condensates and Their Properties in Regulation of Gene Expression
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Metadata
- Authors
- Tsang, B., Pritišanac, I., Scherer, S. W., Moses, A. M., & Forman-Kay, J. D.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2020-12
- Volume
- 183
- Issue
- 7
- Pages
- 1742-1756
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W3114473647
- Cited by
- 281
- References
- 135
- FWCI
- 8.44
- Type
- journal article
- Language
- en
- Open access
- bronze
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