Sequence variations of phase-separating proteins and resources for studying biomolecular condensates

Phase separation (PS) is an important mechanism underlying the formation of biomolecular condensates. Physiological condensates are associated with numerous biological processes, such as transcription, immunity, signaling, and synaptic transmission. Changes in particular amino acids or segments can disturb the protein’s phase behavior and interactions with other biomolecules in condensates. It is thus presumed that variations in the phase-separating-prone domains can significantly impact the properties and functions of condensates. The dysfunction of condensates contributes to a number of pathological processes. Pharmacological perturbation of these condensates is proposed as a promising way to restore physiological states. In this review, we characterize the variations observed in PS proteins that lead to aberrant biomolecular compartmentalization. We also showcase recent advancements in bioinformatics of membraneless organelles (MLOs), focusing on available databases useful for screening PS proteins and describing endogenous condensates, guiding researchers to seek the underlying pathogenic mechanisms of biomolecular condensates.