KIF2B – Obesity Disorder

KIF2B has been implicated in obesity disorder based on multi‑patient studies evaluating copy number variations in childhood obesity cohorts. The association has emerged from analyses of European American and African American cohorts, where duplication events involving KIF2B were observed in a subset of obesity cases (PMID:20950786).

In the first genome‑wide CNV survey, 17 unique CNV loci were identified in at least three European American childhood obesity probands. Among these loci, KIF2B was identified as part of the replicated duplication events, suggesting an alteration in gene dosage that may contribute to obesity predisposition (PMID:20950786).

A follow‑up study further investigated rare genomic structural variants in obesity. Although associations with variants near KIF2B achieved nominal significance, they did not withstand correction for multiple testing. This mixed result underscores the complexity of rare variant replication in common disorders (PMID:23554873).

The genetic evidence is primarily derived from structural variant analyses, with CNV duplications in KIF2B observed against a background of multi‑ethnic cohorts. No single nucleotide variant meeting HGVS criteria was reported for obesity disorder; hence, the evidence relies on the observation of CNVs rather than sequence‐level variants. Segregation data within affected families remain limited.

Given the nature of the reported CNVs and the observed patterns across independent studies, the inheritance mode for this association is inferred to be autosomal dominant. However, detailed familial segregation evidence is sparse, with no additional affected relatives systematically documented beyond the probands in these studies.

Functional studies that directly assess the impact of KIF2B alterations on obesity phenotypes are currently lacking. Although KIF2B plays roles in cellular processes, its mechanistic involvement in obesity remains to be elucidated by targeted functional assays, leaving the experimental evidence within this context limited.

In summary, the association between KIF2B and obesity disorder is supported by replicated structural variant data across diverse cohorts, despite modest segregation information and a lack of direct functional validation. This evidence emphasizes a moderate but clinically relevant contribution of KIF2B duplications to obesity predisposition, warranting further investigation to clarify its utility in diagnostic decision‑making.

References

• American journal of human genetics • 2010 • A genome‑wide study reveals copy number variants exclusive to childhood obesity cases PMID:20950786
• PloS one • 2013 • Rare genomic structural variants in complex disease: lessons from the replication of associations with obesity PMID:23554873

Evidence Based Scoring (AI generated)