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IGDCC4 – Age‑related Macular Degeneration

This summary outlines the current association evidence between IGDCC4 (HGNC:13770) and age‑related macular degeneration (MONDO_0005150). Two independent genome‑wide association studies in Israeli cohorts contributed to this finding. In the discovery study, 403 cases (PMID:37732190) and 256 controls were analyzed, with a replication set including an additional 155 cases (PMID:37732190). Although IGDCC4 was one of four loci reaching suggestive significance in the discovery phase, the replication did not provide robust gene‑specific corroboration, and no familial segregation data were available.

Genetic evidence is limited to a single reported missense variant, c.3188G>T (p.Trp1063Leu), identified in one of the studies. Functional data specific to IGDCC4 remain scarce, with no targeted assays demonstrating a clear pathogenic mechanism. Consequently, while the GWAS signals indicate a possible role in AMD susceptibility, the overall evidence does not yet support a strong causal link. Further functional and segregation analyses are required to define the clinical utility of IGDCC4 testing in AMD.

References

  • medRxiv • 2023 • Genome‑wide association study and genomic risk prediction of age‑related macular degeneration in Israel PMID:37732190
  • medRxiv • 2023 • Study replicating AMD association signals in Israel PMID:38844476

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Suggestive association based on two independent GWAS cohorts (403 cases [PMID:37732190] and 155 replication cases [PMID:37732190]) with nominal statistical significance and lacking segregation and extensive functional validation.

Genetic Evidence

Limited

A single missense variant, c.3188G>T (p.Trp1063Leu), has been reported in IGDCC4, with insufficient additional variant or segregation data to confer strong genetic evidence.

Functional Evidence

Limited

There are no robust functional studies or experimental assays specifically confirming a pathogenic mechanism for IGDCC4 in age‑related macular degeneration.