ANO6 (Anoctamin 6) - A Multifunctional Phospholipid Scramblase and Ion Channel
Comprehensive gene overview of ANO6, its role in Scott syndrome, blood coagulation, and potential implications in cancer and neurological disorders.
Gene Information Card
| Symbol | ANO6 |
|---|---|
| Full Name | Anoctamin 6 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q12 |
| NCBI Gene ID | 196527 ncbi.nlm.nih.gov/gene/196527 |
| Ensembl ID | ENSG00000134333 |
| UniProt ID | Q4KMQ2 |
| OMIM ID | 608663 |
| HGNC ID | 25240 |
| Aliases | TMEM16F, FLJ32115 |
Description
ANO6 (Anoctamin 6), also known as TMEM16F, encodes a member of the anoctamin (TMEM16) family of calcium-activated chloride channels and phospholipid scramblases. The protein is a multi-pass transmembrane protein that plays a critical role in calcium-dependent exposure of phosphatidylserine on the cell surface, a key event in blood coagulation, apoptotic cell clearance, and bone mineralization. ANO6 also functions as a calcium-activated cation channel and a regulator of cell volume. Mutations in ANO6 are associated with Scott syndrome, a rare bleeding disorder, and have been implicated in various cancers and neurological conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Scott Syndrome | Loss-of-function mutations in ANO6 impair calcium-induced phospholipid scrambling, leading to defective phosphatidylserine exposure on platelets and reduced thrombin generation. | ClinVar, OMIM |
| Cancer (various types) | Altered ANO6 expression or mutations may affect cell migration, invasion, and apoptosis via scramblase activity and ion channel function; implicated in glioblastoma, breast, and colorectal cancers. | COSMIC, PubMed (via NCBI) |
| Neurological disorders (e.g., epilepsy) | ANO6 variants may affect neuronal calcium signaling and membrane dynamics, potentially contributing to seizure susceptibility. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Blood | High | High |
| Bone marrow | High | High |
| Lung | Medium | Medium |
| Brain | Medium | Medium |
| Liver | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | High | Commonly used for functional studies |
| HeLa | Medium | Endogenous expression; used in knockdown studies |
| K562 | High | Leukemia cell line; relevant for blood disorders |
| A549 | Medium | Lung carcinoma; used in cancer studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.506G>A (p.Arg169His) | Missense | Rare | Reported in Scott syndrome; impairs scramblase activity |
| c.1210C>T (p.Arg404Ter) | Nonsense | Rare | Truncating mutation; loss of function in Scott syndrome |
| c.1472T>C (p.Leu491Pro) | Missense | Rare | Associated with neurological phenotypes; functional impact under investigation |
| c.2000A>G (p.Asn667Ser) | Missense | Somatic | Found in cancer; potential gain-of-function effect on ion channel activity |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., nonsense, frameshift, or missense affecting scramblase domain) lead to Scott syndrome, characterized by defective phospholipid scrambling and bleeding diathesis.
Gain of Function (GOF)
Gain-of-function mutations may enhance calcium-activated ion channel activity or scramblase function, potentially promoting cancer cell invasion or altered neuronal excitability.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by forming non-functional heterodimers with wild-type ANO6, reducing overall scramblase activity.
View complete mutation data：
Gene Ontology (GO)
| • Calcium-activated phospholipid scramblase activity | • Calcium-activated cation channel activity |
| • Chloride channel activity | • Plasma membrane |
| • Integral component of membrane | • Phosphatidylserine exposure |
| • Blood coagulation | • Apoptotic cell clearance |
| • Bone mineralization | • Cell volume homeostasis |
Pathways
• Calcium-dependent phospholipid scrambling
• Blood coagulation cascade
• Apoptotic signaling
• Ion transport (calcium-activated chloride/cation channels)
Protein Summary
The ANO6 protein is a 911-amino acid multi-pass transmembrane protein with eight transmembrane domains and a C-terminal cytoplasmic domain. It functions as a calcium-activated phospholipid scramblase, mediating the bidirectional movement of phospholipids across the plasma membrane, and also as a calcium-activated cation channel. ANO6 is widely expressed, with high levels in blood cells and bone marrow. It plays a crucial role in platelet procoagulant activity, osteoblast function, and cell volume regulation. Structural studies reveal a dimeric architecture with a hydrophilic cavity for lipid translocation. Post-translational modifications include N-glycosylation, which may affect trafficking and function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ANO6 Knockout HEK293 Cell Line | EDJ-KQ228 | Human | 196527 | Details Get a Quote |
| ANO6 Knockout A-549 Cell Line | EDJ-KQ23649 | Human | 196527 | Details Get a Quote |
| ANO6 Knockout HCT 116 Cell Line | EDJ-KQ23650 | Human | 196527 | Details Get a Quote |
| ANO6 Knockout HeLa Cell Line | EDJ-KQ23651 | Human | 196527 | Details Get a Quote |
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