ArticleMolecular systems biology2019
Paralog dependency indirectly affects the robustness of human cells.
Article in Molecular systems biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- Context-dependent synthetic lethality - an emerging precision therapeutic approach.Nature reviews. Cancer · 2026Review
- Evolutionary causes and consequences of gene duplication.Nature reviews. Genetics · 2026Review
- Computational prediction of human genetic variants in the mouse genome.Nature biotechnology · 2025Article
- Unraveling cooperative and competitive interactions within protein triplets in the human interactome.Scientific reports · 2025Article
- Sarcospan protects against LGMD R5 via remodeling of the sarcoglycan complex composition in dystrophic mice.The Journal of clinical investigation · 2025Article
- Proteomic compensation by paralogs preserves protein interaction networks after gene loss in cancer.Molecular systems biology · 2025Article
- Computational modeling of human genetic variants in mice.bioRxiv : the preprint server for biology · 2025Article
- Single-cell imaging of protein dynamics of paralogs reveals sources of gene retention.iScience · 2025Article
- The synthetic lethal interaction between CDS1 and CDS2 is a vulnerability in uveal melanoma and across multiple tumor types.Nature genetics · 2025Article
- Incomplete paralog compensation generates selective dependency on TRA2A in cancer.PLoS genetics · 2025Article
- Frequent loss ofiScience · 2024Article
- Mutational biases favor complexity increases in protein interaction networks after gene duplication.Molecular systems biology · 2024Article
- Paralog dispensability shapes homozygous deletion patterns in tumor genomes.Molecular systems biology · 2023Article
- Promoter evolution of mammalian gene duplicates.BMC biology · 2023Article
- Alternative splicing mediates the compensatory upregulation of MBNL2 upon MBNL1 loss-of-function.Nucleic acids research · 2023Article
- Paralog-based synthetic lethality: rationales and applications.Frontiers in oncology · 2023Review
- Paralogous Genes Involved in Embryonic Development: Lessons from the Eye and Other Tissues.Genes · 2022Review
- Mendelian gene identification through mouse embryo viability screening.Genome medicine · 2022Article
- How gene duplication diversifies the landscape of protein oligomeric state and function.Current opinion in genetics & development · 2022Review
- Article
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2 authors.
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Abstract
The protective redundancy of paralogous genes partly relies on the fact that they carry their functions independently. However, a significant fraction of paralogous proteins may form functionally dependent pairs, for instance, through heteromerization. As a consequence, one could expect these heteromeric paralogs to be less protective against deleterious mutations. To test this hypothesis, we examined the robustness landscape of gene loss-of-function by CRISPR-Cas9 in more than 450 human cell lines. This landscape shows regions of greater deleteriousness to gene inactivation as a function of key paralog properties. Heteromeric paralogs are more likely to occupy such regions owing to their high expression and large number of protein-protein interaction partners. Further investigation revealed that heteromers may also be under stricter dosage balance, which may also contribute to the higher deleteriousness upon gene inactivation. Finally, we suggest that physical dependency may contribute to the deleteriousness upon loss-of-function as revealed by the correlation between the strength of interactions between paralogs and their higher deleteriousness upon loss of function.
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