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EHD3 and Major Depressive Disorder

Evidence from two independent case‑control studies suggests a potential, albeit limited, association between EHD3 and major depressive disorder (MDD) in a gender‑specific manner. One study, analyzing 517 MDD patients (PMID:24607927), reported that specific EHD3 single nucleotide polymorphisms (SNPs) were exclusively associated with female MDD, with p‑values of 0.0045, 0.0074, and 0.0029 for distinct clinical features. A second multi‑gene study in a Chinese Han cohort comprised 1,062 patients and 992 controls (PMID:22337703) and further implicated EHD3 through combined gene effects in patients when analyzed alongside FREM3. Although these studies provide statistically significant findings in gender‑stratified comparisons, the lack of consistent replication in broader populations limits the overall confidence in this gene‑disease association.

Functional studies of the EHD protein family add biological plausibility to the observed associations. Research focusing on structure–function relationships in EHD proteins demonstrated that alterations in PF motif sequences can disrupt protein dimerization, binding, and subcellular localization (PMID:25875965). However, while these assays support the critical role of endocytic trafficking in neuronal function, no study has yet directly confirmed a functional impact for EHD3 variants in major depressive disorder. This preliminary evidence encourages the inclusion of EHD3 in diagnostic panels and further research to clarify its role in female‐specific MDD risk.

References

  • Neuroscience letters • 2014 • The gender‑specific association of EHD3 polymorphisms with major depressive disorder PMID:24607927
  • American journal of medical genetics. Part B, Neuropsychiatric genetics • 2012 • A study of the combined effects of the EHD3 and FREM3 genes in patients with major depressive disorder PMID:22337703
  • PloS one • 2015 • Role of the EHD2 unstructured loop in dimerization, protein binding and subcellular localization PMID:25875965

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Two studies reporting female‑specific associations in cohorts of 517 (PMID:24607927) and 1,062 (PMID:22337703) MDD patients support an association, but lack of broad replication restricts confidence.

Genetic Evidence

Moderate

Case–control analyses using gender stratification have identified significant SNP associations in EHD3 with MDD, indicating a possible risk factor (PMID:24607927, PMID:22337703).

Functional Evidence

Limited

Functional analyses of EHD family members underscore the importance of PF motifs in endocytic trafficking, yet direct functional data linking EHD3 to MDD pathogenesis is lacking (PMID:25875965).