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ANO2 – Panic Disorder

The association between ANO2 and panic disorder (MONDO_0005383) is supported by two independent genetic association studies conducted in Japanese cohorts. In one study involving 200 cases (PMID:19165232), a genome‑wide association approach identified several SNPs near candidate genes including ANO2. A second study evaluating 351 patients (PMID:23018769) further implicated ANO2, although neither study provided evidence of familial segregation or specific causative variants. As such, the genetic evidence is derived solely from common variant association, rendering the overall gene–disease association limited.

Functional assessments of ANO2 have elucidated its role as a calcium‑activated chloride channel with multiple alternatively spliced isoforms that modulate neuronal excitability. Experimental studies have demonstrated that differences in splicing affect both the channel’s Ca(2+)-sensitivity and activation kinetics (PMID:23669718, PMID:37403222, PMID:28046119). Although these studies do not directly model panic disorder, their mechanistic insights support a functional context relevant to the pathophysiology of anxiety disorders. Collectively, while the genetic evidence remains limited, the functional data contribute moderate support to ANO2’s role in panic disorder. This integrated evidence aids diagnostic decision‑making and informs the development of potential multi‑gene risk assessments.

References

  • Journal of Human Genetics • 2009 • Genome-wide association study of panic disorder in the Japanese population PMID:19165232
  • Psychiatric Genetics • 2012 • A survey of putative anxiety-associated genes in panic disorder patients with and without bladder symptoms PMID:23018769
  • The Journal of General Physiology • 2013 • Channel properties of the splicing isoforms of the olfactory calcium-activated chloride channel Anoctamin 2 PMID:23669718
  • Experimental Neurobiology • 2023 • Intracellular Loop in the Brain Isoforms of Anoctamin 2 Channels Regulates Calcium-dependent Activation PMID:37403222
  • PloS One • 2017 • Permeation Mechanisms in the TMEM16B Calcium-Activated Chloride Channels PMID:28046119

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Association observed in two independent GWAS studies involving 200 cases (PMID:19165232) and 351 cases (PMID:23018769); however, the lack of familial segregation and specific pathogenic variants limits the overall strength.

Genetic Evidence

Limited

Multiple association studies implicate ANO2 in panic disorder but do not report specific causative variants or segregation data.

Functional Evidence

Moderate

Functional assays demonstrate that alternative splicing of ANO2 modulates calcium-dependent chloride channel activity in neuronal cells, supporting a potential mechanistic role in panic disorder (PMID:23669718, PMID:37403222, PMID:28046119).