GNGT2 and Glaucoma

In a large‐scale whole exome sequencing study of 51,624 participants (PMID:35022715), GNGT2 (HGNC:4412) was statistically implicated as a candidate gene for glaucoma (MONDO_0005041). The study identified its association through a genome‐wide analysis of ocular phenotypes, including refractive error and glaucoma, although no specific rare coding variants in GNGT2 were directly reported. There is an absence of detailed segregation data, as no affected relatives have been documented to segregate a variant in GNGT2 with the glaucoma phenotype. The genetic signal is derived from cohort-level analyses rather than discrete familial case studies. This limitation in genetic evidence is compounded by the lack of independent replication studies or functional assays directly relevant to the glaucoma phenotype. Overall, the current evidence supports a limited gene‑disease association for GNGT2 in glaucoma.

The genetic evidence for GNGT2 is primarily based on statistical associations from a well-powered study, without specific variant-level confirmation or segregation analysis in affected families (PMID:35022715). Although functional assessment studies have examined GNGT2 in the context of Alzheimer disease (PMID:35897046), these experiments do not directly validate its role in glaucoma. In addition, there is no clear evidence of recurrent or founder variants for GNGT2 in patients with glaucoma. Further investigations, including targeted segregation studies and functional assays in ocular models, are required to substantiate its pathogenic role. Key take‑home sentence: While GNGT2 represents a promising candidate for glaucoma risk, its clinical utility remains limited until further validation studies are conducted.

References

• Human molecular genetics • 2022 • Whole exome sequence analysis in 51,624 participants identifies novel genes and variants associated with refractive error and myopi PMID:35022715
• Alzheimer's research & therapy • 2022 • Deletion of Abi3/Gngt2 influences age-progressive amyloid β and tau pathologies in distinctive ways PMID:35897046

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