Target intelligence / Profile preview

Transmembrane protein 16A (Anoctamin-1) (TMEM16A (ANO1))

Target
TMEM16A (ANO1)
Molecular classification
Ion channel, Ligand-gated ion channel, Calcium-activated chloride channel
01

Overview

Transmembrane protein 16A (Anoctamin-1), commonly known as **TMEM16A** or **ANO1**, is a calcium-activated chloride channel that forms a homodimeric membrane protein with each subunit independently conducting chloride ions[2][3][4][6]. This channel is activated by increases in intracellular Ca²⁺ concentration, coupling chloride ion conduction to various physiological processes, including epithelial secretion, smooth muscle contraction, and control of neuronal excitability[3][4][6]. TMEM16A is widely expressed in epithelial, neuronal, and smooth muscle tissues and is implicated in diseases such as asthma, cystic fibrosis, hypertension, and multiple cancers—where it is also used as the immunohistochemical marker DOG1 for diagnosing gastrointestinal stromal tumors[4][6]. Pharmacological modulation of TMEM16A is being explored for therapeutic benefits in disorders of fluid secretion and airway hyperresponsiveness, though safety challenges remain due to the channel’s role in multiple organ systems and the structural similarity to other TMEM16 family members[6].

Other names
Anoctamin-1ANO1Calcium-activated chloride channel protein 1CaCCDOG1
02

Mechanism of action

Open-channel blockade (e.g., by 1PBC): direct pore occlusion; Negative allosteric modulation or inhibition of channel gating (e.g., NPPB, niflumic acid, T16Ainh-A01); Attenuation of Ca²⁺-induced channel activation

03

Biological functions

Chloride ion transportEpithelial secretionRegulation of smooth muscle contractionSensory transduction (e.g., nociception)Regulation of neuronal excitability
04

Disease associations

CancerAsthmaCystic fibrosisHypertensionSARS-CoV-2–related lung pathologyOther respiratory and secretory diseases
05

Safety considerations

Potential disturbance of epithelial ion/fluid homeostasis (risk in cystic fibrosis or airway diseases)Smooth muscle contractility effects (possible risk for gastrointestinal, airway, or vascular adverse events)Off-target effects due to family homology with other TMEM16 paralogsLong-term modulation risks not fully characterized in clinical context
06

Interacting drugs

1PBC (TMEM16A channel blocker)[6]

4 more in the full profile.

07

Biomarkers

DOG1 (immunohistochemical marker for gastrointestinal stromal tumors)[4]TMEM16A/ANO1 gene amplification or overexpression in certain cancers (prognostic indicator)

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