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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
ANO3
anoctamin 3
Chromosome 11 Β· 11p14.3-p14.2
NCBI Gene: 63982Ensembl: ENSG00000134343.14HGNC: HGNC:14004UniProt: A0A5F9ZHL6
36PubMed Papers
21Diseases
0Drugs
12Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
intracellularly calcium-gated chloride channel activityciliumphospholipid translocationphospholipid scramblase activityCranio-cervical dystonia with laryngeal and upper-limb involvementcervical dystoniaDystoniadystonic disorder
✦AI Summary

ANO3 (anoctamin 3) is a calcium-dependent phospholipid scramblase that primarily functions in regulating potassium channel activity, particularly by modulating KCNT1/Slack channel conductance 1. Unlike other anoctamins, ANO3 does not exhibit calcium-activated chloride channel activity. The protein localizes to the plasma membrane and cilium, where it facilitates phospholipid translocation and monoatomic ion transport. ANO3 mutations cause dystonia-24 (DYT24), a rare autosomal dominant isolated or combined dystonia typically presenting in adulthood 2. The disease mechanism involves calcium homeostasis dysfunction within broader network abnormalities affecting the basal ganglia, cerebellum, thalamus, and cortex 3. Clinical presentation varies with age of onset and variant location; younger patients with variants near the scrambling domain show more severe phenotypes including tremor, dystonic movements, and cognitive difficulties 2. Tremor is particularly prevalent in ANO3-dystonia, representing one of the highest prevalence rates among isolated dystonias 4. Clinically, ANO3-dystonia diagnosis remains challenging due to overlapping neurological symptoms 5. Recent findings suggest ANO3 variants may also contribute to neuronal excitability abnormalities in all-cause dementia pathogenesis 6, though functional studies are needed to clarify the relationship between phospholipid scrambling activity and disease phenotypes.

Sources cited
1
ANO3 is associated with DYT24 isolated dystonia and does not exhibit calcium-activated chloride channel activity; functions in ion transmembrane transport
PMID: 24092288
2
ANO3 mutations cause autosomal dominant dystonia mainly presenting in adulthood; younger patients show more severe phenotypes; variants near scrambling domain correlate with severity
PMID: 38284143
3
ANO3 pathogenic variants linked to calcium homeostasis dysfunction in dystonia pathophysiology involving basal ganglia, cerebellum, thalamus, and cortex networks
PMID: 37738511
4
ANO3 shows high prevalence of tremor in isolated dystonia, second only to HPCA among isolated dystonia genes
PMID: 34264428
5
ANO3 is among genes with pathogenic variations linked to genetic dystonias; dystonia diagnosis complicated by overlapping symptoms with other neurological conditions
PMID: 38612382
6
ANO3 identified as novel locus associated with neuronal excitability in all-cause dementia genome-wide association study
PMID: 39046104
Disease Associationsβ“˜21
Cranio-cervical dystonia with laryngeal and upper-limb involvementOpen Targets
0.77Strong
cervical dystoniaOpen Targets
0.53Moderate
DystoniaOpen Targets
0.51Moderate
dystonic disorderOpen Targets
0.50Moderate
Febrile seizure (within the age range of 3 months to 6 years)Open Targets
0.42Moderate
COVID-19Open Targets
0.37Weak
ovarian neoplasmOpen Targets
0.35Weak
genetic disorderOpen Targets
0.34Weak
MMR-related febrile seizuresOpen Targets
0.33Weak
food allergyOpen Targets
0.32Weak
hypothyroidismOpen Targets
0.30Weak
DNA methylationOpen Targets
0.29Weak
poisoningOpen Targets
0.28Weak
response to antibioticOpen Targets
0.28Weak
liver diseaseOpen Targets
0.28Weak
osteoarthritis, kneeOpen Targets
0.28Weak
sinoatrial node disorderOpen Targets
0.28Weak
osteoarthritisOpen Targets
0.27Weak
heart diseaseOpen Targets
0.27Weak
hemangiomaOpen Targets
0.26Weak
Dystonia 24UniProt
Pathogenic Variants12
NM_031418.4(ANO3):c.1943A>G (p.Asn648Ser)Pathogenic
Dystonic disorder|Dystonia 24|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 648
NM_031418.4(ANO3):c.1969G>A (p.Ala657Thr)Likely pathogenic
Dystonia 24|Dystonic disorder
β˜…β˜…β˜†β˜†2024β†’ Residue 657
NM_031418.4(ANO3):c.1528G>A (p.Glu510Lys)Pathogenic
Dystonic disorder|Dystonia 24|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 510
NM_031418.4(ANO3):c.1819A>T (p.Ile607Phe)Pathogenic
Inborn genetic diseases|not provided|Dystonia 24
β˜…β˜…β˜†β˜†2023β†’ Residue 607
NM_031418.4(ANO3):c.1942A>G (p.Asn648Asp)Likely pathogenic
Dystonic disorder
β˜…β˜†β˜†β˜†2026β†’ Residue 648
NM_031418.4(ANO3):c.1699G>C (p.Gly567Arg)Pathogenic
Dystonic disorder
β˜…β˜†β˜†β˜†2023β†’ Residue 567
NM_031418.4(ANO3):c.1952G>A (p.Ser651Asn)Pathogenic
Dystonic disorder
β˜…β˜†β˜†β˜†2022β†’ Residue 651
NM_031418.4(ANO3):c.922A>C (p.Ile308Leu)Likely pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2013β†’ Residue 308
NM_031418.4(ANO3):c.2586G>T (p.Lys862Asn)Pathogenic
Dystonia 24
β˜†β˜†β˜†β˜†2012β†’ Residue 862
NM_031418.4(ANO3):c.2053A>G (p.Ser685Gly)Pathogenic
Dystonia 24
β˜†β˜†β˜†β˜†2012β†’ Residue 685
NM_031418.4(ANO3):c.1470G>T (p.Trp490Cys)Pathogenic
Dystonia 24
β˜†β˜†β˜†β˜†2012β†’ Residue 490
NM_031418.4(ANO3):c.1480A>T (p.Arg494Trp)Pathogenic
Dystonia 24
β˜†β˜†β˜†β˜†2012β†’ Residue 494
View on ClinVar β†—
Related Genes
ANO4Shared pathway80%GNALProtein interaction76%THAP1Protein interaction67%TOR1AProtein interaction61%CIZ1Protein interaction61%ANO5Shared pathway50%
Tissue Expression6 tissues
Brain
100%
Liver
16%
Heart
6%
Lung
5%
Ovary
2%
Bone Marrow
1%
Gene Interaction Network
Click a node to explore
ANO3ANO4GNALTHAP1TOR1ACIZ1ANO5
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q9BYT9
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.91LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.75 [0.61–0.91]
RankingsWhere ANO3 stands among ~20K protein-coding genes
  • #10,732of 20,598
    Most Researched36
  • #2,704of 5,498
    Most Pathogenic Variants12
  • #8,312of 17,882
    Most Constrained (LOEUF)0.91
Genes detectedANO3
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Genetics and Pathogenesis of Dystonia.
PMID: 37738511
Annu Rev Pathol Β· 2024
1.00
2
Genetic Update and Treatment for Dystonia.
PMID: 38612382
Int J Mol Sci Β· 2024
0.90
3
A genome-wide association meta-analysis of all-cause and vascular dementia.
PMID: 39046104
Alzheimers Dement Β· 2024
0.80
4
Genetics in dystonia.
PMID: 24262166
Parkinsonism Relat Disord Β· 2014
0.70
5
Dystonia.
PMID: 24092288
Continuum (Minneap Minn) Β· 2013
0.60