KRT82 – Keratoconus

Keratoconus is a complex corneal ectasia with genetic heterogeneity, and recent candidate gene studies have implicated KRT82 in its etiology. In a case report of a Chinese family with monozygotic twins (PMID:39544142), KRT82 was listed among several candidate genes, suggesting its possible involvement even though detailed mutation data were not provided in that study.

A subsequent multi‐patient study in Chinese KC patients identified a stop‑gain variant in KRT82, specifically c.241C>T (p.Arg81Ter), among other candidate variants. This study, which performed exome sequencing on 28 affected individuals (PMID:32744102), reinforces the potential role of KRT82 in keratoconus through the identification of a truncated protein product that may disrupt normal corneal structure.

Genetic evidence for KRT82 is supported by its recurrence in independent studies. Although only a single candidate variant was reported in the multi‐patient study, the convergence of findings from both isolated case reports and larger cohorts provides moderate support for the gene‑disease association. Limited segregation data were observed in the family study, where the monozygotic twins and an affected (subclinically manifesting) mother strengthen the pathogenic implication of candidate variants (PMID:39544142).

Functional evidence remains sparse; while experimental assessment studies were mentioned in the provided evidence header, no comprehensive mechanistic or rescue data were detailed. As such, the functional concordance with keratoconus pathobiology is currently not robust enough to upgrade the association beyond a moderate level of confidence.

In summary, the genetic findings from both a case report and a multi‐patient exome sequencing study suggest that KRT82 may have a contributory role in keratoconus, although further functional studies and expanded segregation analysis are needed to definitively confirm its pathogenicity. The available evidence indicates a moderate level of clinical validity for the KRT82–keratoconus association.

Key take‑home message: The identification of the candidate stop‑gain variant c.241C>T (p.Arg81Ter) in KRT82 underscores its potential utility in diagnostic pipelines for keratoconus and warrants further validation for clinical and commercial applications.

References

• Ophthalmic Genetics • 2025 • Analysis of candidate variants in a Chinese family with monozygotic twins with keratoconus PMID:39544142
• Ophthalmic Genetics • 2020 • Exome sequencing identification of susceptibility genes in Chinese patients with keratoconus PMID:32744102

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