Affinage

ANO5

Anoctamin-5 · UniProt Q75V66

Length
913 aa
Mass
107.2 kDa
Annotated
2026-06-09
70 papers in source corpus 21 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ANO5 (TMEM16E) is an intracellular Ca2+-activated phospholipid scramblase of the TMEM16 family that governs membrane remodeling in muscle, bone, germ cells, and endothelium (PMID:26667038, PMID:30257928). The protein is an integral membrane glycoprotein residing in intracellular vesicles and the sarcoplasmic/endoplasmic reticulum rather than the plasma membrane (PMID:17418107, PMID:29665321), and it carries a discrete scrambling domain homologous to TMEM16F that, when transplanted into TMEM16A, is sufficient to confer Ca2+-dependent phospholipid scrambling (PMID:26667038). In reconstituted systems and ANO5-null muscle precursor cells, ANO5 produces Ca2+-dependent phosphatidylserine exposure and nonselective ionic currents, and these activities are required for muscle precursor cell fusion, with viral re-introduction rescuing both scrambling and fusion (PMID:30257928). Beyond myogenesis, ANO5 supports plasma membrane repair by enabling ER-mediated clearance of cytosolic Ca2+ after focal injury, a function lost in patient myoblasts and restored by wild-type ANO5 or by limiting Ca2+ overload (PMID:31341644). Recessive loss-of-function ANO5 mutations cause limb-girdle muscular dystrophy 2L and distal Miyoshi myopathy MMD3 through protein destabilization and defective membrane resealing (PMID:20096397, PMID:28489263), whereas gain-of-function gnathodiaphyseal dysplasia mutations constitutively activate scrambling at low cytosolic Ca2+ — opposite functional consequences depending on mutation class (PMID:29124309, PMID:32112655). ANO5 also interacts through its N-terminus with the C-terminus of BVES at the ER membrane to drive myoblast differentiation (PMID:34963485), localizes to the sperm tail to support motility and fertilization (PMID:26667038), drives endothelial procoagulant phosphatidylserine externalization that promotes vessel-wall fibrin formation (PMID:36951953), and engages EGFR in a ligand-independent manner to stimulate PI3K and macropinocytosis during membrane repair (PMID:39794444).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2007 Medium

    Established where the ANO5 protein resides, distinguishing it from plasma-membrane TMEM16 channels and framing its function as intracellular.

    Evidence Biochemical fractionation and immunohistochemistry with a GDD1-specific antibody

    PMID:17418107

    Open questions at the time
    • Identity of the specific intracellular compartment beyond 'vesicles' not resolved
    • No functional activity assayed
  2. 2010 High

    Linked ANO5 to human disease and to a cellular defect, showing recessive loss-of-function mutations cause LGMD2L/MMD3 with impaired membrane resealing.

    Evidence Genetic analysis, NMD assays, membrane-resealing assays, and EM of sarcolemmal lesions in patient fibroblasts

    PMID:20096397

    Open questions at the time
    • Molecular activity of ANO5 underlying repair not defined
    • Mechanism connecting mutation to repair failure unknown
  3. 2014 Medium

    Showed ANO5 is unstable and proteasomally degraded and lacks surface chloride-channel activity, attributing absent CaCC behavior to its intracellular distribution.

    Evidence Proteasome and PI3K-inhibitor rescue, domain-swap experiments, and CaCC electrophysiology

    PMID:23843187

    Open questions at the time
    • Did not establish the genuine physiological activity of ANO5
    • Domain-swap effects on TMEM16A indirect
  4. 2015 High

    Defined the molecular activity by demonstrating ANO5 contains a functional Ca2+-dependent phospholipid scrambling domain, and uncovered a reproductive role in sperm.

    Evidence Chimeric TMEM16A/E proteins with scrambling assay; TMEM16E-deficient mice with sperm motility and IVF analysis

    PMID:26667038

    Open questions at the time
    • Scrambling shown for chimera, not full-length native ANO5 in this study
    • Molecular target of ANO5 in sperm tail unknown
  5. 2015 Medium

    Tested whether ANO5 loss alone produces muscle disease in mice, finding no overt myopathy but altered lipid/complement gene expression.

    Evidence Ano5 knockout mouse with histology, force assays, echocardiography, and microarray

    PMID:26693275

    Open questions at the time
    • Species/strain differences from human disease unexplained
    • Functional meaning of transcriptional changes not pursued
  6. 2017 High

    Confirmed native human ANO5 scrambling and current activity and demonstrated that a GDD mutation is gain-of-function, activating scrambling at low Ca2+.

    Evidence Mammalian overexpression with scrambling assay, patch-clamp, and site-directed mutagenesis (T513I)

    PMID:29124309

    Open questions at the time
    • Only partial plasma-membrane localization on overexpression complicates physiological interpretation
  7. 2017 Medium

    Connected pathogenic mutations to protein loss in patient muscle, showing truncating mutations abolish and point mutations destabilize ANO5.

    Evidence Western blot with validated monoclonal antibody on fractionated patient muscle biopsies

    PMID:28489263

    Open questions at the time
    • Degradation pathway in vivo not dissected
    • Residual function of destabilized mutants unquantified
  8. 2018 High

    Causally tied ANO5 scrambling/current activity to muscle precursor cell fusion via knockout and viral rescue.

    Evidence HEK293 reconstitution, Ano5-/- MPC fusion and PS-exposure assays, electrophysiology, and viral rescue

    PMID:30257928

    Open questions at the time
    • How scrambling mechanistically drives fusion not resolved
    • Subcellular site of fusion-relevant scrambling unclear
  9. 2018 Medium

    Refined localization to the sarcoplasmic reticulum and showed truncated ANO5 forms aggregates.

    Evidence Immunofluorescence with validated antibody on muscle cryosections; truncated construct expression in C2C12 cells

    PMID:29665321

    Open questions at the time
    • Aggregation pathogenicity not tested in vivo
  10. 2018 Medium

    Established a rabbit model recapitulating human dystrophy, providing an animal system where ANO5 loss reproduces disease unlike the mouse.

    Evidence CRISPR/Cas9 frame-disrupting indels in rabbits with CK, histology, and imaging

    PMID:29789544

    Open questions at the time
    • Cellular mechanism not interrogated in this model
  11. 2019 High

    Defined the membrane-repair mechanism, showing ANO5 enables ER-mediated cytosolic Ca2+ clearance after injury.

    Evidence Patient myoblasts, focal laser injury repair assays, Ca2+ imaging, genetic and pharmacological rescue

    PMID:31341644

    Open questions at the time
    • Molecular link between scrambling activity and ER Ca2+ handling not delineated
  12. 2019 Medium

    Implicated ANO5 in SR Ca2+ handling and nuclear positioning in myotubes, broadening its muscle role beyond repair.

    Evidence shRNA knockdown in C2C12 with immunofluorescence, western blot (Kif5b/DHPR/SERCA1), Ca2+ imaging, co-localization

    PMID:31680776

    Open questions at the time
    • Whether protein-expression changes are direct or secondary unknown
    • Single knockdown system
  13. 2020 High

    Systematically partitioned disease alleles, showing MD mutations cause loss-of-function and GDD mutations gain-of-function scrambling.

    Evidence HEK293 scrambling assays across multiple site-directed patient variants

    PMID:32112655

    Open questions at the time
    • Tissue-specific consequences of opposite activities not addressed
  14. 2021 High

    Identified BVES as a direct ER-membrane partner of ANO5 required for myoblast differentiation, adding a protein-interaction dimension.

    Evidence BioID2 proximity labeling, reciprocal Co-IP, domain mapping, co-localization, and CRISPR differentiation assays

    PMID:34963485

    Open questions at the time
    • Functional consequence of the interaction on scrambling activity not tested
  15. 2021 Medium

    Produced a mouse out-of-frame deletion model reproducing mild-to-moderate LGMD2L independent of sarcolemmal chloride-channel activity.

    Evidence Knockout mouse with histology, force measures, chloride electrophysiology, and regeneration assays

    PMID:34633328

    Open questions at the time
    • Cellular driver of progressive muscle loss not isolated
  16. 2021 Medium

    Demonstrated that a GDD gain-of-function knock-in recapitulates skeletal dysplasia with opposing osteoblast/osteoclast phenotypes.

    Evidence Cys360Tyr knock-in mouse with skeletal phenotyping and osteoblast/osteoclast cultures

    PMID:34841576

    Open questions at the time
    • Mechanistic link between scrambling gain-of-function and bone cell behavior unresolved
  17. 2022 Medium

    Extended ANO5 function to bone homeostasis through Ca2+-dependent osteoblast and osteoclast differentiation.

    Evidence Ano5 knockout mice with calcium imaging, differentiation assays, signaling western blots, and PTH treatment

    PMID:35982081

    Open questions at the time
    • How ANO5 controls intracellular Ca2+ transients in bone cells not defined
  18. 2022 Medium

    Revealed sex-dependent tissue involvement, with male mice showing muscle repair defects and females showing cardiomyopathy.

    Evidence Ano5-/- mice with post-exercise CK, laser-injury repair, and echocardiography, sex-stratified

    PMID:35020501

    Open questions at the time
    • Basis of sexual dimorphism unknown
    • Cardiac mechanism not dissected
  19. 2023 High

    Established a vascular function: ANO5-dependent endothelial PS externalization drives vessel-wall procoagulant activity and thrombosis.

    Evidence Genetic screen, in vitro PS assays, intravital laser-injury thrombosis model, TMEM16E-null mice, benzbromarone inhibition

    PMID:36951953

    Open questions at the time
    • Endothelial localization and Ca2+ trigger not detailed
  20. 2023 Medium

    Detailed the osteoclast arm, showing ANO5 loss suppresses RANKL-NF-kB signaling and osteoclastogenesis.

    Evidence Ano5-/- mice with TRAP/phalloidin staining, resorption assays, qRT-PCR, NF-kB western blots and pharmacological rescue

    PMID:36989132

    Open questions at the time
    • Direct connection of scrambling to NF-kB signaling not shown
  21. 2025 Medium

    Connected ANO5 scrambling to a membrane-repair effector pathway via ligand-independent EGFR/PI3K signaling and macropinocytosis.

    Evidence Co-IP (TMEM16E-EGFR), PI3K activity assay, macropinocytosis and annexin-V internalization assays, amiloride inhibition, live imaging

    PMID:39794444

    Open questions at the time
    • How PS externalization triggers EGFR remains unclear
    • Single-lab Co-IP for EGFR interaction

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single intracellular scramblase mechanistically produces such divergent tissue outcomes—muscle repair, sperm motility, bone remodeling, and endothelial coagulation—and the structural basis of its Ca2+-gated scrambling remain unresolved.
  • No structural model of ANO5 scrambling gate
  • Unified mechanism linking scrambling to downstream tissue-specific signaling absent
  • Reasons for mouse vs. rabbit/human disease discordance unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0005215 transporter activity 2
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-1266738 Developmental Biology 2 R-HSA-1643685 Disease 2 R-HSA-109582 Hemostasis 1 R-HSA-8953897 Cellular responses to stimuli 1
Partners
BVESEGFR

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 GDD1/TMEM16E (ANO5) protein is an integral membrane glycoprotein that resides predominantly in intracellular vesicles, not at the plasma membrane, as determined by biochemical fractionation and immunohistochemistry using a GDD1-specific antibody. Biochemical fractionation, immunohistochemistry, subcellular localization with specific antibody Biochemical and biophysical research communications Medium 17418107
2010 Loss-of-function recessive mutations in ANO5 (splice site, frameshift causing NMD, and missense mutations) cause proximal LGMD2L and distal MMD3 muscular dystrophies, with defective membrane repair documented in patient fibroblasts by membrane-resealing assays. Genetic mutation analysis, nonsense-mediated mRNA decay assessment, membrane-resealing ability assays, electron microscopy of sarcolemmal lesions American journal of human genetics High 20096397
2014 TMEM16E/ANO5 protein is rapidly degraded via the proteasome pathway; degradation is rescued by PI3K pathway inhibition and the chemical chaperone sodium butyrate. The GDD-causing mutant TMEM16E(gdd) exhibits lower stability than wild-type. TMEM16E does not exhibit cell-surface Ca2+-activated Cl- channel (CaCC) activity due to its intracellular vesicle distribution. A putative pore-forming domain of TMEM16E disrupts CaCC activity of TMEM16A via domain swapping. Proteasome inhibitor assays, PI3K inhibitor rescue, domain-swap experiments, electrophysiology (CaCC assay), site-directed mutagenesis Journal of cellular physiology Medium 23843187
2015 TMEM16E carries a 35-amino-acid segment homologous to the scrambling domain in TMEM16F. When this segment replaced the corresponding region of TMEM16A, the chimeric molecule localized to the plasma membrane and supported Ca2+-dependent phospholipid scrambling, demonstrating that TMEM16E harbors a functional scrambling domain. Chimeric protein construction, plasma membrane localization assay, Ca2+-dependent phospholipid scrambling assay Molecular and cellular biology High 26667038
2015 TMEM16E is expressed in germ cells during spermatogenesis and localizes to the sperm tail. TMEM16E-deficient male mice show reduced sperm motility and inefficient fertilization of zona-intact eggs in vitro, while morphology, beating, mitochondrial function, capacitation, and zona pellucida binding are unaffected. TMEM16E-deficient mouse generation, immunolocalization, in vitro fertilization assay, sperm motility analysis Molecular and cellular biology High 26667038
2015 Genetic disruption of Ano5 in C57BL/6J mice does not cause overt skeletal or cardiac muscle pathology up to 18 months, no significant differences in force production or eccentric contraction force deficit, and cardiac hypertrophy after isoproterenol was indistinguishable from wild type. Microarray identified altered lipid metabolism and complement pathway genes in KO skeletal muscle. Ano5 knockout mouse generation, histology, force production assays, eccentric contraction assay, echocardiography, microarray Skeletal muscle Medium 26693275
2017 Human TMEM16E/ANO5 displays Ca2+-dependent phospholipid scrambling (PLS) and non-selective ionic currents when overexpressed in mammalian cells, with partial plasma membrane localization. The GDD-causing T513I mutation confers gain-of-function PLS and large ion currents even at low cytosolic Ca2+, whereas the equivalent mutation in TMEM16B paralog had little effect. Overexpression in mammalian cell lines, phospholipid scrambling assay, patch-clamp electrophysiology, site-directed mutagenesis Cellular and molecular life sciences : CMLS High 29124309
2017 ANO5 protein is expressed as a single 107 kDa polypeptide in human skeletal muscle. Truncating mutations (c.191dupA, c.1261C>T) abolish ANO5 expression entirely; non-truncating pathogenic point mutations reduce ANO5 expression in the membrane fraction, consistent with protein destabilization and degradation. Western blot with validated monoclonal antibody, tissue fractionation of patient muscle biopsies Neuropathology and applied neurobiology Medium 28489263
2018 ANO5 overexpression confers Ca2+-dependent phospholipid scrambling and a nonselective ionic current to HEK-293 cells. Ano5-/- mouse muscle precursor cells (MPCs) exhibit defective cell fusion in culture (fewer nuclei per myotube), decreased Ca2+-dependent phosphatidylserine exposure, and reduced Ca2+-dependent outwardly rectifying ionic currents. Viral re-introduction of ANO5 rescues fusion, scrambling, and ionic currents. HEK-293 overexpression, phospholipid scrambling assay, patch-clamp electrophysiology, Ano5-/- MPC isolation, myotube fusion assay, viral rescue experiment The Journal of general physiology High 30257928
2018 Immunofluorescence staining of healthy muscle cryosections with a validated monoclonal antibody localizes ANO5 to the sarcoplasmic reticulum. A LGMD2L patient with the c.191dupA homozygous mutation showed no ANO5 signal. A truncated ANO5 peptide (first 121 aa) resulting from a novel splice variant forms aggregates when expressed in C2C12 cells. Immunofluorescence with validated monoclonal antibody (N421A/85), transfection of truncated ANO5 constructs into C2C12 cells, observation of aggregate formation The journal of pathology. Clinical research Medium 29665321
2018 CRISPR-mediated frame-disrupting ANO5 mutations in rabbits (exon 12/13 indels) lead to typical muscular dystrophy signs: increased serum CK, muscle necrosis, regeneration, fatty replacement, and fibrosis, establishing a rabbit animal model that recapitulates human disease. CRISPR/Cas9 knock-in in rabbits, serum CK measurement, histology, muscle imaging Cell death & disease Medium 29789544
2019 ANO5-deficient patient myoblasts (carrying c.2272C>T mutation causing protein degradation) show normal myogenesis but defective plasma membrane repair (PMR). The repair deficit is linked to impaired ER-mediated cytosolic Ca2+ clearance after focal injury. Wild-type ANO5 expression or pharmacological prevention of cytosolic Ca2+ overload rescues PMR in patient cells. Patient-derived myoblast lines, plasma membrane repair assay (focal laser injury), Ca2+ imaging, WT ANO5 rescue by transfection, pharmacological Ca2+ modulation Cell death discovery High 31341644
2019 ANO5 knockdown in C2C12 myotubes causes clustered/aggregated nuclei (nuclear positioning defect) associated with reduced Kif5b protein expression. ANO5 knockdown also impairs depolarization-induced Ca2+ transients and reduces SR Ca2+ storage, associated with reduced DHPR and SERCA1 protein expression and disrupted DHPR–RyR1 co-localization. shRNA knockdown in C2C12 myoblasts, immunofluorescence for nuclear positioning, western blot for Kif5b/DHPR/SERCA1, Ca2+ imaging, co-localization analysis The Korean journal of physiology & pharmacology Medium 31680776
2020 Using HEK293-based functional assays, MD-associated ANO5 mutations are associated with loss-of-function phospholipid scrambling, while GDD-associated mutations are associated with gain-of-function scrambling, demonstrating opposite effects on ANO5 activity depending on mutation class. HEK293 overexpression, phospholipid scrambling assay, site-directed mutagenesis of multiple patient-associated variants Human mutation High 32112655
2021 BVES is a novel interacting protein of ANO5 identified by proximity labeling (BioID2) and confirmed by co-immunoprecipitation. The N-terminus of ANO5 mediates interaction with the C-terminus of BVES. ANO5 and BVES co-localize at the endoplasmic reticulum membrane in muscle cells. Genome-editing disruption of either ANO5 or BVES significantly suppresses C2C12 myoblast differentiation. BioID2 proximity labeling, mass spectrometry, co-immunoprecipitation, co-localization by immunofluorescence, CRISPR/Cas9 disruption, myoblast differentiation assay Cell & bioscience High 34963485
2021 A targeted out-of-frame deletion Ano5 mouse model shows progressive muscle loss, increased muscle weakness, and persistent myofiber regeneration without chronic inflammation, recapitulating mild-to-moderate LGMD2L. These features are not associated with changes in calcium-activated sarcolemmal chloride channel activity or impaired in vivo regenerative myogenesis. Knockout mouse generation, histology, grip/force measurements, chloride channel electrophysiology, regeneration assays Journal of neuromuscular diseases Medium 34633328
2022 Ablation of Ano5 in mice reduces intracellular calcium transients in osteoblasts and osteoclasts, leading to defective osteoblast and osteoclast differentiation. Ano5 KO mice exhibit low bone volume, abnormal calcium deposits, and reduced WNT/β-Catenin signaling in osteoblasts and RANKL-NFATc1 signaling in osteoclasts. Parathyroid hormone treatment enhances bone strength in KO mice. Ano5 knockout mouse model, calcium imaging, osteoblast/osteoclast differentiation assays, western blot for signaling pathways, PTH treatment in vivo NPJ genomic medicine Medium 35982081
2022 Male Ano5-/- mice show elevated serum CK after exercise and defective plasma membrane repair after laser injury, while female Ano5-/- mice are indistinguishable from wild type by these measures. Female Ano5-/- mice exhibit features of cardiomyopathy by echocardiography despite normal skeletal muscle repair, demonstrating sex-dependent tissue involvement. Ano5-/- mouse model, serum CK measurement after exercise, laser injury membrane repair assay, echocardiography American journal of physiology. Cell physiology Medium 35020501
2023 TMEM16E (ANO5) is required for endothelial cell procoagulant activity via phosphatidylserine externalization. In an intravital laser-injury thrombosis model, PS externalization is concentrated at the vessel wall. TMEM16E-null mice show reduced vessel-wall-dependent fibrin formation. The TMEM16 inhibitor benzbromarone prevents PS externalization, EC procoagulant activity, and protects mice from thrombosis. Focused genetic screen, in vitro PS externalization assay, intravital laser-injury mouse thrombosis model, TMEM16E-null mice, pharmacological inhibition with benzbromarone The Journal of clinical investigation High 36951953
2023 Ano5 deficiency impairs osteoclastogenesis: Ano5-/- mice exhibit inhibited formation of multinucleated osteoclasts, reduced TRAP activity, decreased expression of Nfatc1, c-Fos, and osteoclast genes, disrupted actin ring formation, and less mineral resorption. RANKL-induced NF-κB signaling is suppressed in Ano5-/- osteoclasts, and this can be partially rescued by NF-κB activator. Ano5-/- mouse model, TRAP staining, phalloidin staining for actin rings, bone resorption assay, qRT-PCR, western blot for NF-κB signaling, pharmacological NF-κB activation Oral diseases Medium 36989132
2025 TMEM16E activation promotes macropinocytosis essential for plasma membrane integrity. TMEM16E externalizes phosphatidylserine associated with resting growth factor receptors, interacts with and signals through EGFR in a ligand-independent manner, stimulates PI3K, and facilitates macropinocytosis and internalization of membrane-bound annexin V. TMEM16E is internalized during this process but returns to the plasma membrane. Co-immunoprecipitation (TMEM16E–EGFR interaction), PI3K activity assay, macropinocytosis assay, annexin V internalization assay, amiloride inhibition, live imaging Communications biology Medium 39794444
2021 Introduction of the GDD-causing p.Cys360Tyr mutation in Ano5 knock-in mice recapitulates GDD skeletal features (massive jawbones, bowing tibia, bone fragility, sclerosis). Knock-in osteoblasts show increased osteoblastogenesis and hypermineralized bone matrix. Knock-in osteoclasts show decreased osteoclastogenesis and disrupted actin ring formation. Knock-in mouse model (Cys360Tyr), skeletal phenotyping, calvaria-derived osteoblast cultures, bone marrow-derived macrophage osteoclast cultures, ALP/TRAP staining, phalloidin staining Journal of bone and mineral research Medium 34841576

Source papers

Stage 0 corpus · 70 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Recessive mutations in the putative calcium-activated chloride channel Anoctamin 5 cause proximal LGMD2L and distal MMD3 muscular dystrophies. American journal of human genetics 205 20096397
2011 Mutation of rice BC12/GDD1, which encodes a kinesin-like protein that binds to a GA biosynthesis gene promoter, leads to dwarfism with impaired cell elongation. The Plant cell 137 21325138
2007 Molecular characterization of GDD1/TMEM16E, the gene product responsible for autosomal dominant gnathodiaphyseal dysplasia. Biochemical and biophysical research communications 88 17418107
2012 Eight new mutations and the expanding phenotype variability in muscular dystrophy caused by ANO5. Neurology 87 22402862
2015 A Role of TMEM16E Carrying a Scrambling Domain in Sperm Motility. Molecular and cellular biology 68 26667038
2018 Anoctamin 5/TMEM16E facilitates muscle precursor cell fusion. The Journal of general physiology 64 30257928
2015 Next generation sequencing on patients with LGMD and nonspecific myopathies: Findings associated with ANO5 mutations. Neuromuscular disorders : NMD 59 25891276
2017 Gain of function of TMEM16E/ANO5 scrambling activity caused by a mutation associated with gnathodiaphyseal dysplasia. Cellular and molecular life sciences : CMLS 57 29124309
2013 ANO5 gene analysis in a large cohort of patients with anoctaminopathy: confirmation of male prevalence and high occurrence of the common exon 5 gene mutation. Human mutation 55 23606453
2012 A novel missense mutation in ANO5/TMEM16E is causative for gnathodiaphyseal dyplasia in a large Italian pedigree. European journal of human genetics : EJHG 51 23047743
2011 Amyloidosis and exercise intolerance in ANO5 muscular dystrophy. Neuromuscular disorders : NMD 47 21820307
2013 ANO5-muscular dystrophy: clinical, pathological and molecular findings. European journal of neurology 46 23663589
2015 Genetic disruption of Ano5 in mice does not recapitulate human ANO5-deficient muscular dystrophy. Skeletal muscle 44 26693275
2004 Identification and characterization of TMEM16E and TMEM16F genes in silico. International journal of oncology 42 15067359
2023 TMEM16E regulates endothelial cell procoagulant activity and thrombosis. The Journal of clinical investigation 41 36951953
2016 A Novel ANO5 Mutation Causing Gnathodiaphyseal Dysplasia With High Bone Turnover Osteosclerosis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 40 27541832
2019 Dysregulated calcium homeostasis prevents plasma membrane repair in Anoctamin 5/TMEM16E-deficient patient muscle cells. Cell death discovery 36 31341644
2012 Novel ANO5 mutations causing hyper-CK-emia, limb girdle muscular weakness and Miyoshi type of muscular dystrophy. Muscle & nerve 35 22499103
2019 Clinical and molecular findings in a cohort of ANO5-related myopathy. Annals of clinical and translational neurology 34 31353849
2005 Molecular cloning and characterization of the murine gnathodiaphyseal dysplasia gene GDD1. Biochemical and biophysical research communications 32 15882990
2017 Three novel ANO5 missense mutations in Caucasian and Chinese families and sporadic cases with gnathodiaphyseal dysplasia. Scientific reports 31 28176803
2016 Whole exome sequencing links dental tumor to an autosomal-dominant mutation in ANO5 gene associated with gnathodiaphyseal dysplasia and muscle dystrophies. Scientific reports 30 27216912
2013 ANO5 mutations in the Dutch limb girdle muscular dystrophy population. Neuromuscular disorders : NMD 30 23607914
2014 Comparing clinical data and muscle imaging of DYSF and ANO5 related muscular dystrophies. Neuromuscular disorders : NMD 28 25176504
2014 TMEM16E (GDD1) exhibits protein instability and distinct characteristics in chloride channel/pore forming ability. Journal of cellular physiology 27 23843187
2014 Novel ANO5 homozygous microdeletion causing myalgia and unprovoked rhabdomyolysis in an Arabic man. Muscle & nerve 27 24889862
2018 Development of muscular dystrophy in a CRISPR-engineered mutant rabbit model with frame-disrupting ANO5 mutations. Cell death & disease 26 29789544
2017 Gnathodiaphyseal dysplasia: Severe atypical presentation with novel heterozygous mutation of the anoctamin gene (ANO5). Bone 26 29175271
2021 Lidocaine Suppresses Gastric Cancer Development Through Circ_ANO5/miR-21-5p/LIFR Axis. Digestive diseases and sciences 24 34050852
2020 TMEM16E/ANO5 mutations related to bone dysplasia or muscular dystrophy cause opposite effects on lipid scrambling. Human mutation 24 32112655
2016 Gnathodiaphyseal dysplasia: report of a family with a novel mutation of the ANO5 gene. Oral surgery, oral medicine, oral pathology and oral radiology 23 27068316
2022 Anoctamin 5 (ANO5) Muscle Disorders: A Narrative Review. Genes 22 36292621
2012 Novel mutations in the Anoctamin 5 gene (ANO5) associated with limb-girdle muscular dystrophy 2L. Muscle & nerve 21 23169617
2022 Ano5 modulates calcium signaling during bone homeostasis in gnathodiaphyseal dysplasia. NPJ genomic medicine 15 35982081
2019 ANO5 mutations in the Polish limb girdle muscular dystrophy patients: Effects on the protein structure. Scientific reports 15 31395899
2020 Genetic association analysis identifies a role for ANO5 in prostate cancer progression. Cancer medicine 14 32027096
2017 Diagnostic anoctamin-5 protein defect in patients with ANO5-mutated muscular dystrophy. Neuropathology and applied neurobiology 14 28489263
2021 Introduction of a Cys360Tyr Mutation in ANO5 Creates a Mouse Model for Gnathodiaphyseal Dysplasia. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 13 34841576
2022 ANO5-related muscle diseases: From clinics and genetics to pathology and research strategies. Genes & diseases 12 36157496
2018 Novel ANO5 mutation c.1067G>T (p.C356F) identified by whole genome sequencing in a big family with atypical gnathodiaphyseal dysplasia. Head & neck 12 30554457
2021 Muscle biopsy and MRI findings in ANO5-related myopathy. Muscle & nerve 11 34550615
2020 Persistent asymptomatic or mild symptomatic hyperCKemia due to mutations in ANO5: the mildest end of the anoctaminopathies spectrum. Journal of neurology 11 32367299
2018 A novel ANO5 splicing variant in a LGMD2L patient leads to production of a truncated aggregation-prone Ano5 peptide. The journal of pathology. Clinical research 11 29665321
2023 Familial gigantiform cementoma with recurrent ANO5 p.Cys356Tyr mutations: Clinicopathological and genetic study with literature review. Molecular genetics & genomic medicine 9 37649308
2021 Anoctamin 5 Knockout Mouse Model Recapitulates LGMD2L Muscle Pathology and Offers Insight Into in vivo Functional Deficits. Journal of neuromuscular diseases 9 34633328
2021 BVES is a novel interactor of ANO5 and regulates myoblast differentiation. Cell & bioscience 9 34963485
2019 Gnathodiaphyseal dysplasia with a novel R597I mutation of ANO5: Mandibular reconstruction strategies. Journal of stomatology, oral and maxillofacial surgery 8 30641283
2017 A Japanese male with a novel ANO5 mutation with minimal muscle weakness and muscle pain till his late fifties. Neuromuscular disorders : NMD 8 28214267
2023 Genetic disruption of Ano5 leads to impaired osteoclastogenesis for gnathodiaphyseal dysplasia. Oral diseases 7 36989132
2016 Decreased Aerobic Capacity in ANO5-Muscular Dystrophy. Journal of neuromuscular diseases 7 27911336
2020 Anoctamin 5 (ANO5) muscular dystrophy-three different phenotypes and a new histological pattern. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 6 32399949
2019 Deficiency of Anoctamin 5/TMEM16E causes nuclear positioning defect and impairs Ca2+ signaling of differentiated C2C12 myotubes. The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 6 31680776
2023 Integration of metabolomics and transcriptomics provides insights into enhanced osteogenesis in Ano5 knock-in mouse model. Frontiers in endocrinology 5 36742392
2025 Activation of TMEM16E scramblase induces ligand independent growth factor receptor signaling and macropinocytosis for membrane repair. Communications biology 4 39794444
2020 Gnathodiaphyseal dysplasia is not recapitulated in a respective mouse model carrying a mutation of the Ano5 gene. Bone reports 4 32455153
2020 Characterization of a novel allele of bc12/gdd1 indicates a differential leaf color function for BC12/GDD1 in Indica and Japonica backgrounds. Plant science : an international journal of experimental plant biology 4 32771145
2020 Cardiac MRI identifies valvular and myocardial disease in a subset of ANO5-related muscular dystrophy patients. Neuromuscular disorders : NMD 4 32819793
2019 Identification of a novel ANO5 missense mutation in a Chinese family with familial florid osseous dysplasia. Journal of human genetics 4 30996299
2025 Ano5Cys360Tyr mutation leads to bone dysfunction of gnathodiaphyseal dysplasia via disturbing Akt signaling. Bone reports 3 39866532
2022 Sex differences in the involvement of skeletal and cardiac muscles in myopathic Ano5 mice. American journal of physiology. Cell physiology 3 35020501
2025 Ano5 deficiency disturbed bone formation by inducing osteoclast apoptosis in Gnathodiaphyseal dysplasia. Experimental cell research 2 40049314
2025 Ano5 Deficiency Leads to Abnormal Bone Formation via miR-34c-5p/KLF4/β-Catenin in Gnathodiaphyseal Dysplasia. International journal of molecular sciences 2 40508076
2023 Hypertrophic Cardiomyopathy Complicated by Post-COVID-19 Myopericarditis in Patient with ANO5-Related Distal Myopathy. Genes 1 37510237
2021 Novel ANO5 intronic Roma variant alters splicing causing muscular dystrophy. Clinical genetics 1 33818761
2021 ANO5 in membrane repair - Status: "It's complicated". Cell calcium 1 33934044
2026 Long-term clinical and radiological trajectories in ANO5-related myopathies highlight muscle MRI as a predictor of disease progression. Journal of neurology 0 41981189
2026 Ano5 deficiency inhibits osteoclastogenesis and reduces ovariectomy-induced bone loss by regulating the ACSL4-dependent ferroptosis pathway. Tissue & cell 0 42229282
2025 ANO5 p.I616F variant drives florid cemento-osseous dysplasia by disrupting transmembrane domain structure. BMC oral health 0 40841909
2024 Novel Variant in ANO5 Muscular Dystrophy: Identification by Whole Genome Sequencing and Quad Analysis. Genes 0 39457424
2022 Novel Variants of ANO5 in Two Patients With Limb Girdle Muscular Dystrophy: Case Report. Frontiers in neurology 0 35463132

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