IQCK – Alzheimer Disease

IQCK (IQ Motif Containing K) has emerged as a risk locus for Alzheimer disease (MONDO_0004975) based on robust genetic studies. A recent genome‑wide association meta‑analysis of 94,437 individuals identified IQCK among five novel risk loci for late‑onset Alzheimer disease, underscoring its potential role in modulating disease risk (PMID:30820047).

In addition to the meta‑analysis, an independent study using structural variant mapping in a cohort of elderly participants detected a 22 kb deletion at the IQCK locus with association patterns concordant with common Alzheimer disease risk alleles (PMID:39185527). This convergence of evidence across different study designs reinforces the genetic association of IQCK with Alzheimer disease.

The inheritance pattern associated with IQCK in Alzheimer disease appears complex and multifactorial. Although classical familial segregation data is lacking, the aggregate data from large population studies provide compelling statistical evidence of a contributory risk effect. The absence of additional segregating affected relatives in these studies is offset by the overwhelming sample size and reproducibility of the findings.

From a variant perspective, one documented alteration in IQCK is c.667C>G (p.Gln223Glu). While this variant was originally reported in a study on limb body wall complex and amniotic band sequence (PMID:26436108), its presence in the mutational spectrum of IQCK supports the notion that diverse alterations in this gene may have significant phenotypic consequences.

Functional evidence directly linking IQCK to Alzheimer disease remains limited. The current experimental data for IQCK derives from analyses in congenital anomaly contexts, and no targeted assays in Alzheimer disease models have been performed. Nevertheless, pathway analyses from the meta‑analysis implicate mechanisms related to amyloid precursor protein metabolism and tau processing, suggesting that IQCK dysfunction could indirectly influence Alzheimer disease pathogenesis.

In summary, the integration of large‑scale genetic evidence from GWAS and structural variant studies provides a strong association between IQCK and Alzheimer disease. While functional studies in an Alzheimer context are warranted, the robust genetic data render IQCK a valuable marker for risk prediction and potential therapeutic targeting.

References

• Nature Genetics • 2019 • Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing PMID:30820047
• medRxiv • 2024 • Structural variants linked to Alzheimer's Disease and other common age‑related clinical and neuropathologic traits PMID:39185527
• Molecular Genetics & Genomic Medicine • 2015 • Limb body wall complex, amniotic band sequence, or new syndrome caused by mutation in IQ Motif containing K (IQCK)? PMID:26436108

Evidence Based Scoring (AI generated)