Target intelligence / Profile preview

Transmembrane protein 16 family (TMEM16 (also called ANO for Anoctamin))

Target
TMEM16 (also called ANO for Anoctamin)
Molecular classification
Ion channel (Ca2+-activated chloride channel, e.g., TMEM16A/B), Phospholipid scramblase (e.g., TMEM16F, TMEM16D), Intracellular ion channel (some isoforms, e.g., ANO3–7), Membrane protein
01

Overview

The Transmembrane protein 16 (TMEM16) family, also officially known as the Anoctamin family (ANO), consists of ten evolutionarily conserved eukaryotic membrane proteins (TMEM16A–K, ANO1–10). Most notably, TMEM16A (ANO1) and TMEM16B (ANO2) act as **calcium-activated chloride channels** crucial in epithelial secretion, sensory neuron activity, and smooth muscle contraction. Other members, such as TMEM16F, serve as **calcium-dependent phospholipid scramblases** critical for processes such as blood coagulation. Members of this family are structurally characterized by 10 transmembrane domains arranged as homodimers. TMEM16 proteins are widely expressed in the body and are implicated in cancer, neuromuscular disorders, bleeding syndromes, neurodegeneration, and fluid secretion pathologies. They are considered significant therapeutic targets, and both pharmacological inhibitors and genetic manipulation affect diverse physiological and pathological processes[1][2][3][4][5][6][7].

Other names
Anoctamin (ANO family; members include ANO1-ANO10)TMEM16A–K (in literature, e.g., TMEM16A/ANO1, TMEM16B/ANO2, TMEM16F, etc.)Ca2+-activated chloride channel (for TMEM16A/B specifically)Calcium-activated chloride channel (CaCC, specifically for TMEM16A/B)Phospholipid scramblase (for some family members, e.g., TMEM16F)
02

Mechanism of action

Channel blocking (e.g., TMEM16A/B antagonism inhibits Ca2+-activated Cl− flow and downstream effects) Disruption of phospholipid translocation (for scramblase family members) Downregulation of epithelial secretion (e.g., pilocarpine-induced saliva reduction by siRNA knockdown)

03

Biological functions

Ion transport (Cl−, Ca2+-activated; primarily TMEM16A/B)Signal transduction (in sensory neurons and various epithelia)Regulation of epithelial secretion (saliva, bile, etc.)Cell proliferation and apoptosis signaling (notably TMEM16A)Neuromodulation and sensory processing (TMEM16B, TMEM16C)Phospholipid scrambling (e.g., TMEM16F promotes membrane phospholipid redistribution)
04

Disease associations

Cancer (TMEM16A is overexpressed/amplified in multiple tumors)Muscular dystrophies (mutations in TMEM16E/ANO5)Bleeding disorders (Scott syndrome, TMEM16F/ANO6)Neurodegenerative disease (e.g., TMEM16C in dystonia, TMEM16B in multiple sclerosis and schizophrenia, TMEM16D in Alzheimer’s)Cardiovascular disease (blood pressure, aldosterone secretion)Diabetes/nephropathy (TMEM16A in podocyte injury)Spinocerebellar ataxia (TMEM16K/ANO10)Inflammatory and pain processes
05

Safety considerations

Targeting broadly expressed ion channels or scramblases may interfere with essential physiological secretion, neuronal, or muscle functionsGenetic deficiencies associate with severe disease phenotypes (e.g., bleeding, muscular degeneration, neurodegeneration)
06

Interacting drugs

Niflumic acid (TMEM16A inhibitor)

2 more in the full profile.

07

Biomarkers

Overexpression in tumors (TMEM16A/ANO1 as a cancer marker)Genetic mutations in muscular dystrophies, Scott syndrome, spinocerebellar ataxia, dystoniaExpression in kidney podocytes, sensory neurons, and specific epithelium

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