ARMS2

ARMS2, or Age-related Maculopathy Susceptibility 2, is a human gene located on chromosome 10q26 in a region that also includes the HTRA1 gene. The ARMS2-HTRA1 locus is one of the strongest genetic risk regions linked to age-related macular degeneration (AMD). The ARMS2 gene encodes a protein whose precise function is not well characterized, and the mechanisms by which ARMS2 variants influence AMD risk remain an area of ongoing research.

The most studied variant in this locus is rs10490924, which results in an amino acid change (A69S) in the ARMS2 protein and has been repeatedly associated with AMD risk across diverse populations. However, there is debate about causality: it is unclear whether rs10490924 directly alters ARMS2 function or serves as a marker for other causal variants that affect the nearby HTRA1 gene or regulatory elements in the region. Some studies emphasize regulatory impacts on HTRA1 expression as driving the association, while others support contributions from ARMS2 coding or expression changes. Population data show that risk alleles at this locus modify AMD susceptibility, with effect sizes varying by ancestry and study design.

In summary, ARMS2 is a key gene in a locus strongly linked to AMD risk, but the precise causal variant and mechanism remain unresolved, requiring further genetic and functional studies.