ArticleInvestigative ophthalmology & visual science2026
βA4-Crystallin Mutations Disrupt Structural Stability and Crystallin Interactions in Congenital Cataract Pathogenesis.
Article in Investigative ophthalmology & visual science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: Mutations in the crystallin beta A4 (CRYBA4) gene, which encodes βA4-crystallin, are associated with congenital cataract; yet, the underlying pathogenic mechanisms remain elusive. We systematically investigated four cataract-associated βA4-crystallin mutants (βA4-Y67N, βA4-L69P, βA4-F94S, and βA4-G147V), each representing distinct structural contexts, to assess their effects on structural destabilization and interactions with key crystallins. Methods: We employed a comprehensive approach, including protein expression and purification, size-exclusion chromatography, crosslinking, and circular dichroism spectroscopy, to evaluate the polymerization propensity, structural integrity, and stability of the proteins. Additionally, antibiotic resistance screening and yeast two-hybrid assays were used to examine the impact of these mutations on protein folding and interactions between proteins. Results: Our findings reveal that core mutations (βA4-L69P/βA4-F94S) induce severe aggregation and disrupt interactions with βB1- and βB2-crystallin, the inter-motif mutation (βA4-G147V) reduces protein flexibility, and the surface mutation (βA4-Y67N) results in mild disruption of protein interactions. Notably, αA-crystallin preferentially stabilizes core mutants but exhibits limited effects on others. Conclusions: The present study revealed mutations in βA4-crystallin-driven cataractogenesis via distinct mechanisms according to their distinct structural contexts. αA-crystallin functions as a primary mitigator of severe misfolding, preferentially stabilizing aggregation-prone conformers. These findings suggest that mutation-specific stabilization via small-molecule chaperones or enhanced αA-crystallin activity may represent potential precision therapeutic strategies for βA4-crystallin-associated congenital cataracts.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.