ANO3

Summary

ANO3 (anoctamin 3, HGNC:14004) is a protein-coding gene on chromosome 11p14.2, encoding Anoctamin-3 (Q9BYT9). Has calcium-dependent phospholipid scramblase activity; scrambles phosphatidylcholine and galactosylceramide.

The protein encoded by this gene belongs to the TMEM16 family of predicted membrane proteins, that are also known as anoctamins. While little is known about the function of this gene, mutations in this gene have been associated with some cases of autosomal dominant craniocervical dystonia. Cells from individuals with a mutation in this gene exhibited abnormalities in endoplasmic reticulum-dependent calcium signaling. Studies in rat show that the rat ortholog of this protein interacts with, and modulates the activity of a sodium-activated potassium channel. Deletion of this gene caused increased pain sensitivity in the rat model system. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 63982 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dystonia 24 (Strong, GenCC)
• GWAS associations: 21
• Clinical variants (ClinVar): 727 total — 10 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 16
• MANE Select transcript: NM_031418

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14004
Approved symbol	ANO3
Name	anoctamin 3
Location	11p14.2
Locus type	gene with protein product
Status	Approved
Aliases	GENX-3947, DYT23
Ensembl gene	ENSG00000134343
Ensembl biotype	protein_coding
OMIM	610110
Entrez	63982

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000256737, ENST00000525139, ENST00000529242, ENST00000531568, ENST00000531646, ENST00000531798, ENST00000672621

RefSeq mRNA: 3 — MANE Select: NM_031418 NM_001313726, NM_001313727, NM_031418

CCDS: CCDS31447, CCDS81557, CCDS91452

Canonical transcript exons

ENST00000256737 — 27 exons

Exon	Start	End
ENSE00000914897	26531205	26531336
ENSE00000914899	26534456	26534562
ENSE00000914902	26537406	26537461
ENSE00000914904	26541947	26542068
ENSE00000988235	26635013	26635070
ENSE00000988236	26639144	26639241
ENSE00000988237	26641896	26642029
ENSE00000988238	26643182	26643334
ENSE00000988239	26647709	26647856
ENSE00000988240	26656125	26656205
ENSE00000988241	26656376	26656481
ENSE00000996608	26525635	26525679
ENSE00000996609	26443765	26443836
ENSE00000996610	26463030	26463148
ENSE00000996611	26516827	26516927
ENSE00001098173	26598858	26598998
ENSE00001098174	26598365	26598447
ENSE00001098188	26624462	26624498
ENSE00001098189	26599550	26599714
ENSE00001227209	26660262	26663289
ENSE00001359524	26332130	26332321
ENSE00001697263	26634204	26634315
ENSE00003497669	26553249	26553345
ENSE00003622175	26441918	26442112
ENSE00003658210	26559719	26559779
ENSE00003661816	26547416	26547550
ENSE00003674585	26508104	26508262

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 98.71.

FANTOM5 (CAGE): breadth broad, TPM avg 4.8924 / max 797.8667, expressed in 318 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
113519	1.3025	116
113523	1.2230	34
113524	0.6890	33
113525	0.6403	35
113514	0.4949	162
113521	0.2034	21
113515	0.0885	42
113518	0.0813	50
113522	0.0638	17
113520	0.0632	31

Top tissues by expression

285 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	98.71	gold quality
lateral globus pallidus	UBERON:0002476	98.50	gold quality
putamen	UBERON:0001874	94.75	gold quality
middle temporal gyrus	UBERON:0002771	94.60	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.33	gold quality
caudate nucleus	UBERON:0001873	93.74	gold quality
CA1 field of hippocampus	UBERON:0003881	93.00	gold quality
nucleus accumbens	UBERON:0001882	91.76	gold quality
Brodmann (1909) area 46	UBERON:0006483	91.71	gold quality
entorhinal cortex	UBERON:0002728	90.13	gold quality
superior frontal gyrus	UBERON:0002661	89.48	gold quality
orbitofrontal cortex	UBERON:0004167	89.19	gold quality
endothelial cell	CL:0000115	86.63	gold quality
cauda epididymis	UBERON:0004360	86.53	gold quality
postcentral gyrus	UBERON:0002581	85.74	gold quality
parietal lobe	UBERON:0001872	84.53	gold quality
telencephalon	UBERON:0001893	81.43	gold quality
middle frontal gyrus	UBERON:0002702	80.99	gold quality
prefrontal cortex	UBERON:0000451	80.79	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.66	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.06	gold quality
temporal lobe	UBERON:0001871	79.42	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.28	gold quality
frontal cortex	UBERON:0001870	78.77	gold quality
cerebral cortex	UBERON:0000956	78.13	gold quality
Ammon’s horn	UBERON:0001954	77.13	gold quality
neocortex	UBERON:0001950	76.98	gold quality
forebrain	UBERON:0001890	76.65	gold quality
Brodmann (1909) area 10	UBERON:0013541	75.24	gold quality
secondary oocyte	CL:0000655	75.22	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	912.78
E-CURD-119	yes	15.44
E-ANND-3	yes	5.49

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

145 targeting ANO3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616

Literature-anchored findings (GeneRIF, showing 16)

• C11orf25, FLJ10261 (ORAOV2), C12orf3 and FLJ34272 constitute a family of eight-transmembrane proteins with N- and C-terminal tails facing the cytoplasm. (PMID:12739008)
• The significant single nucleotide polymorphisms are located within the overlapping anoctamin 3 (ANO3) and mucin 15 (MUC15) genes. (PMID:22657408)
• Mutations in ANO3 are a cause of autosomal-dominant craniocervical dystonia. (PMID:23200863)
• rat Ano3 (also known as Tmem16c) interacts with, and alters the activity of the sodium-activated potassium channel Slack. Reduced expression of Ano3 in rat models results in increased pain sensitivity. (PMID:23872594)
• Our findings indicate that rare exonic variants in ANO3 do not play a major role in the development of essentail tremor (PMID:24094724)
• Low frequency missense variants in ANO3 occur in both cases and controls, warranting further assessment of this gene in primary torsion dystonia pathogenesis. (PMID:24151159)
• ANO3 causes a varied phenotype of young-onset or adult-onset craniocervical dystonia with tremor and/or myoclonic jerks (PMID:24442708)
• This study demonstrated that Mutations in ANO3 may cause Dystonia. (PMID:25847575)
• Study reports a novel c.1969G>A mutation in the ANO3 gene in a family presenting with a typical dystonia phenotype consistent with previous reports: onset mainly after the fourth decade, begins as cervical dystonia, but evolves to segmental dystonia, without leg involvement or any generalized dystonia. (PMID:27392807)
• This study demonstrated that whole-exome sequencing show reveled ANO3 mutation with early-onset generalized dystonia. (PMID:27666935)
• HTRA2 and ANO3 mutations are not common causes of essential tremor (PMID:27881096)
• De-novo genetic variants in childhood-onset, generalized dystonia represent underestimated phenotypic expression changes in ANO3. (PMID:30712998)
• The expanding clinical and genetic spectrum of ANO3 dystonia. (PMID:33388357)
• A novel ANO3 variant in two siblings with different phenotypes. (PMID:37116293)
• Broadening the clinical spectrum: molecular mechanisms and new phenotypes of ANO3-dystonia. (PMID:38079528)
• The Clinical Spectrum of ANO3-Report of a New Family and Literature Review. (PMID:38284143)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ano3	ENSDARG00000058015
mus_musculus	Ano3	ENSMUSG00000074968
rattus_norvegicus	Ano3	ENSRNOG00000004731

Paralogs (10): ANO2 (ENSG00000047617), ANO8 (ENSG00000074855), PPP1R7 (ENSG00000115685), ANO1 (ENSG00000131620), ANO7 (ENSG00000146205), ANO4 (ENSG00000151572), ANO10 (ENSG00000160746), ANO5 (ENSG00000171714), ANO6 (ENSG00000177119), ANO9 (ENSG00000185101)

Protein

Protein identifiers

Anoctamin-3 — Q9BYT9 (reviewed: Q9BYT9)

Alternative names: Transmembrane protein 16C

All UniProt accessions (4): A0A5F9ZHL6, Q9BYT9, E9PKW2, E9PQ79

UniProt curated annotations — full annotation on UniProt →

Function. Has calcium-dependent phospholipid scramblase activity; scrambles phosphatidylcholine and galactosylceramide. Seems to act as potassium channel regulator and may inhibit pain signaling; can facilitate KCNT1/Slack channel activity by promoting its full single-channel conductance at very low sodium concentrations and by increasing its sodium sensitivity. Does not exhibit calcium-activated chloride channel (CaCC) activity.

Subunit / interactions. Interacts with KCNT1/Slack.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in the forebrain striatum.

Disease relevance. Dystonia 24 (DYT24) [MIM:615034] A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT24 is an autosomal dominant focal dystonia affecting the neck, laryngeal muscles, and muscles of the upper limbs. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. The term ‘anoctamin’ was coined because these channels are anion selective and have eight (OCT) transmembrane segments. There is some dissatisfaction in the field with the Ano nomenclature because it is not certain that all the members of this family are anion channels or have the 8-transmembrane topology.

Similarity. Belongs to the anoctamin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BYT9-1	1	yes
Q9BYT9-2	2

RefSeq proteins (3): NP_001300655, NP_001300656, NP_113606* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007632	Anoctamin	Family
IPR032394	Anoct_dimer	Domain
IPR049452	Anoctamin_TM	Domain

Pfam: PF04547, PF16178

Catalyzed reactions (Rhea), 2 shown:

• a 1,2-diacyl-sn-glycero-3-phosphocholine(in) = a 1,2-diacyl-sn-glycero-3-phosphocholine(out) (RHEA:38571)
• a beta-D-galactosyl-(1<->1’)-N-acylsphing-4-enine(out) = a beta-D-galactosyl-(1<->1’)-N-acylsphing-4-enine(in) (RHEA:38899)

UniProt features (33 total): topological domain 9, transmembrane region 8, sequence variant 5, glycosylation site 4, sequence conflict 3, chain 1, region of interest 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYT9-F1	76.30	0.34

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (4): 425, 448, 455, 866

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-2672351	Stimuli-sensing channels
R-HSA-9733458	Induction of Cell-Cell Fusion
R-HSA-1643685	Disease
R-HSA-382551	Transport of small molecules
R-HSA-5663205	Infectious disease
R-HSA-9679506	SARS-CoV Infections
R-HSA-9694516	SARS-CoV-2 Infection
R-HSA-9772573	Late SARS-CoV-2 Infection Events
R-HSA-9824446	Viral Infection Pathways
R-HSA-983712	Ion channel transport

MSigDB gene sets: 190 (showing top): TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_REGULATION_OF_MEMBRANE_LIPID_DISTRIBUTION, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, GOBP_DETECTION_OF_MECHANICAL_STIMULUS, GOBP_DETECTION_OF_TEMPERATURE_STIMULUS, GOBP_CHLORIDE_TRANSPORT, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, GOBP_DETECTION_OF_ABIOTIC_STIMULUS, GOBP_DETECTION_OF_STIMULUS, GOBP_PHOSPHOLIPID_TRANSPORT, GOBP_MEMBRANE_ORGANIZATION, MODULE_48

GO Biological Process (8): detection of temperature stimulus (GO:0016048), monoatomic ion transmembrane transport (GO:0034220), detection of mechanical stimulus (GO:0050982), establishment of localization in cell (GO:0051649), calcium activated phosphatidylcholine scrambling (GO:0061590), calcium activated galactosylceramide scrambling (GO:0061591), chloride transmembrane transport (GO:1902476), lipid transport (GO:0006869)

GO Molecular Function (3): chloride channel activity (GO:0005254), phospholipid scramblase activity (GO:0017128), protein dimerization activity (GO:0046983)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Ion channel transport	1
Late SARS-CoV-2 Infection Events	1
Disease	1
Viral Infection Pathways	1
SARS-CoV Infections	1
SARS-CoV-2 Infection	1
Infectious disease	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
detection of external stimulus	2
detection of abiotic stimulus	2
calcium activated phospholipid scrambling	2
response to temperature stimulus	1
monoatomic ion transport	1
transmembrane transport	1
response to mechanical stimulus	1
establishment of localization	1
cellular localization	1
chloride transport	1
monoatomic anion transmembrane transport	1
transport	1
lipid localization	1
monoatomic anion channel activity	1
chloride transmembrane transporter activity	1
plasma membrane phospholipid scrambling	1
intramembrane lipid carrier activity	1
protein binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1054 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANO3	GNAL	P38405	801
ANO3	CIZ1	Q9ULV3	787
ANO3	THAP1	Q9NVV9	777
ANO3	TOR1A	O14656	707
ANO3	SGCE	O43556	646
ANO3	TUBB4A	P04350	597
ANO3	PRKRA	O75569	570
ANO3	KCTD17	Q8N5Z5	563
ANO3	ANO10	Q9NW15	556
ANO3	PRRT2	Q7Z6L0	537
ANO3	ATP1A3	P13637	528
ANO3	TAF1	P21675	506
ANO3	PNKD	Q8N490	475
ANO3	HPCA	P32076	474
ANO3	CLCA4	Q14CN2	473
ANO3	CLCA2	Q9UQC9	473

IntAct

10 interactions, top by confidence:

A	B	Type	Score
CTR9	POLR2B	psi-mi:“MI:0914”(association)	0.350
Tsc1	SLU7	psi-mi:“MI:0914”(association)	0.350
ASPM		psi-mi:“MI:0914”(association)	0.350
RAPGEF2	BDP1	psi-mi:“MI:0914”(association)	0.350
RGMA	BDP1	psi-mi:“MI:0914”(association)	0.350
SNX3	MPDZ	psi-mi:“MI:0914”(association)	0.350
Hsph1	USP9Y	psi-mi:“MI:0914”(association)	0.350
HSPA5	NCOR2	psi-mi:“MI:0914”(association)	0.350
HA	P4HB	psi-mi:“MI:0914”(association)	0.350

BioGRID (14): ANO3 (Affinity Capture-MS), ANO3 (Affinity Capture-MS), ANO3 (Affinity Capture-MS), ANO3 (Affinity Capture-MS), ANO3 (Affinity Capture-MS), ANO3 (Affinity Capture-MS), ANO3 (Affinity Capture-MS), ANO3 (Affinity Capture-MS), ANO3 (Proximity Label-MS), ANO3 (Positive Genetic), ANO3 (Affinity Capture-MS), ANO3 (Cross-Linking-MS (XL-MS)), TOP2A (Cross-Linking-MS (XL-MS)), ANO3 (Affinity Capture-MS)

ESM2 similar proteins: A0JPH4, A2AHL1, A8DZH4, D3ZWZ9, E7FFT2, F1QFU0, F1QZE9, P48763, P50482, P86044, Q28CV2, Q32NZ6, Q3TPR7, Q3ZAS0, Q4R7U0, Q4V8U5, Q5F3F5, Q5M7W4, Q5RH73, Q5YCC5, Q5ZKN3, Q68DH5, Q6GQE1, Q6P4P2, Q6UXY8, Q7L1W4, Q7Z2W7, Q7Z402, Q7ZYA0, Q810F5, Q8BH79, Q8C428, Q8C561, Q8CB19, Q8IZK6, Q8N3S3, Q8R455, Q8R4D5, Q8R4P4, Q8R4P5

Diamond homologs: A1A5B4, A2AHL1, A6QLE6, P86044, Q14AT5, Q32M45, Q4KMQ2, Q5XXA6, Q6IFT6, Q6IWH7, Q6P9J9, Q75UR0, Q75V66, Q8BHY3, Q8C5H1, Q8CFW1, Q9BYT9, Q9NQ90, Q6PB70, Q9HCE9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

727 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	4
Uncertain significance	344
Likely benign	192
Benign	135

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
145522	GRCh38/hg38 11p14.3-13(chr11:24595399-31096539)x3	Pathogenic
2159492	NM_031418.4(ANO3):c.1952G>A (p.Ser651Asn)	Pathogenic
2829570	NM_031418.4(ANO3):c.1699G>C (p.Gly567Arg)	Pathogenic
3391911	GRCh37/hg19 11p14.3-13(chr11:24192701-32455527)x1	Pathogenic
376757	GRCh37/hg19 11p15.1-13(chr11:18536224-31923308)x1	Pathogenic
376759	GRCh37/hg19 11p15.1-13(chr11:21586131-33168232)x1	Pathogenic
39496	NM_031418.4(ANO3):c.1480A>T (p.Arg494Trp)	Pathogenic
39497	NM_031418.4(ANO3):c.1470G>T (p.Trp490Cys)	Pathogenic
39498	NM_031418.4(ANO3):c.2053A>G (p.Ser685Gly)	Pathogenic
39499	NM_031418.4(ANO3):c.2586G>T (p.Lys862Asn)	Pathogenic
148655	GRCh38/hg38 11p14.3-14.1(chr11:23024064-27978597)x1	Likely pathogenic
225071	NM_031418.4(ANO3):c.922A>C (p.Ile308Leu)	Likely pathogenic
4709728	NM_031418.4(ANO3):c.1942A>G (p.Asn648Asp)	Likely pathogenic
807374	NM_031418.4(ANO3):c.1969G>A (p.Ala657Thr)	Likely pathogenic

SpliceAI

5412 predictions. Top by Δscore:

Variant	Effect	Δscore
11:26441912:TTGCA:T	acceptor_loss	1.0000
11:26441913:TGCAG:T	acceptor_loss	1.0000
11:26441914:GCAG:G	acceptor_loss	1.0000
11:26441915:CAG:C	acceptor_loss	1.0000
11:26441916:A:T	acceptor_loss	1.0000
11:26441917:G:GT	acceptor_loss	1.0000
11:26441917:GGT:G	acceptor_gain	1.0000
11:26441917:GGTAT:G	acceptor_gain	1.0000
11:26442111:AGG:A	donor_loss	1.0000
11:26442112:GGTG:G	donor_loss	1.0000
11:26442113:G:GA	donor_loss	1.0000
11:26443763:A:AG	acceptor_gain	1.0000
11:26443764:G:GA	acceptor_gain	1.0000
11:26443764:GTT:G	acceptor_gain	1.0000
11:26443764:GTTA:G	acceptor_gain	1.0000
11:26463026:A:AG	acceptor_gain	1.0000
11:26463028:A:AG	acceptor_gain	1.0000
11:26463029:G:GA	acceptor_gain	1.0000
11:26463029:GC:G	acceptor_gain	1.0000
11:26463029:GCC:G	acceptor_gain	1.0000
11:26463029:GCCC:G	acceptor_gain	1.0000
11:26463029:GCCCT:G	acceptor_gain	1.0000
11:26463144:CTAAG:C	donor_loss	1.0000
11:26463145:TAAGG:T	donor_loss	1.0000
11:26463146:AAGGT:A	donor_loss	1.0000
11:26463147:AG:A	donor_loss	1.0000
11:26463148:G:GC	donor_loss	1.0000
11:26463150:T:C	donor_loss	1.0000
11:26508096:A:AG	acceptor_gain	1.0000
11:26508097:T:G	acceptor_gain	1.0000

AlphaMissense

6540 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:26508231:T:C	L187P	1.000
11:26534457:T:C	F291L	1.000
11:26534459:C:A	F291L	1.000
11:26534459:C:G	F291L	1.000
11:26534500:G:C	R305P	1.000
11:26541999:G:C	R362T	1.000
11:26542000:A:C	R362S	1.000
11:26542000:A:T	R362S	1.000
11:26542008:T:C	L365S	1.000
11:26542019:T:A	W369R	1.000
11:26542019:T:C	W369R	1.000
11:26547427:G:T	G389V	1.000
11:26547447:T:C	F396L	1.000
11:26547449:T:A	F396L	1.000
11:26547449:T:G	F396L	1.000
11:26547453:T:A	W398R	1.000
11:26547453:T:C	W398R	1.000
11:26547457:T:C	L399P	1.000
11:26547478:T:G	L406W	1.000
11:26547498:G:C	G413R	1.000
11:26598418:T:A	W501R	1.000
11:26598418:T:C	W501R	1.000
11:26643208:T:C	F768L	1.000
11:26643210:T:A	F768L	1.000
11:26643210:T:G	F768L	1.000
11:26643233:C:A	P776H	1.000
11:26643233:C:G	P776R	1.000
11:26643255:T:A	N783K	1.000
11:26643255:T:G	N783K	1.000
11:26643268:A:G	R788G	1.000

dbSNP variants (sampled 300 via entrez): RS1000001685 (11:26364414 C>T), RS1000006004 (11:26598633 A>G), RS1000006286 (11:26238836 A>C,G), RS1000007494 (11:26338574 T>G), RS1000013562 (11:26472686 T>C,G), RS1000014161 (11:26385986 C>T), RS1000020649 (11:26549419 T>C), RS1000023124 (11:26428743 G>A,C), RS1000025013 (11:26277715 T>C), RS1000051744 (11:26452379 G>A,T), RS1000053794 (11:26301103 C>G,T), RS1000056656 (11:26598209 G>A,T), RS1000064830 (11:26203611 T>C), RS1000067354 (11:26510764 G>A), RS1000071860 (11:26489246 C>A)

Disease associations

OMIM: gene MIM:610110 | disease phenotypes: MIM:615034, MIM:106210, MIM:612469, MIM:213000

GenCC curated gene-disease

Disease	Classification	Inheritance
dystonia 24	Strong	Autosomal dominant

Mondo (6): dystonic disorder (MONDO:0003441), dystonia 24 (MONDO:0014019), hereditary ataxia (MONDO:0100309), aniridia 1 (MONDO:0024507), Wilms tumor, aniridia, genitourinary anomalies, intellectual disability, and obesity syndrome (MONDO:0012913), isolated cerebellar hypoplasia/agenesis (MONDO:0008939)

Orphanet (6): Cranio-cervical dystonia with laryngeal and upper-limb involvement (Orphanet:420485), Hereditary ataxia (Orphanet:183518), Isolated aniridia (Orphanet:250923), WAGR syndrome (Orphanet:893), Isolated cerebellar agenesis (Orphanet:1398), Cerebellar hypoplasia-tapetoretinal degeneration syndrome (Orphanet:2246)

HPO phenotypes

16 total (17 of 16 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000473	Torticollis
HP:0000643	Blepharospasm
HP:0001336	Myoclonus
HP:0001600	Abnormality of the larynx
HP:0002346	Head tremor
HP:0002378	Hand tremor
HP:0002451	Limb dystonia
HP:0003621	Juvenile onset
HP:0003829	Typified by incomplete penetrance
HP:0007351	Upper limb postural tremor
HP:0011462	Young adult onset
HP:0012048	Oromandibular dystonia
HP:0012477	Vocal tremor
HP:0031960	Arm dystonia
HP:0200085	Limb tremor
HP:0001332	Dystonia

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST002672_1	Febrile seizures	4.000000e-20
GCST002673_1	Febrile seizures (MMR vaccine-unrelated)	5.000000e-14
GCST002674_8	Febrile seizures (MMR vaccine-related)	2.000000e-12
GCST002740_82	Inflammatory skin disease	2.000000e-06
GCST002875_88	Diisocyanate-induced asthma	1.000000e-06
GCST003056_3	Gait variability	4.000000e-07
GCST003992_38	Photic sneeze reflex	1.000000e-18
GCST004059_1	Exhaled nitric oxide levels	2.000000e-06
GCST004060_4	Exhaled nitric oxide output	2.000000e-07
GCST005411_5	Thrombin-activatable fibrinolysis inhibitor activation peptide	9.000000e-07
GCST006916_11	Attention deficit hyperactivity disorder	3.000000e-06
GCST006956_1	Erectile dysfunction	9.000000e-07
GCST006992_2	Cerebrospinal fluid p-tau levels in Alzheimer’s disease dementia	5.000000e-07
GCST008764_4	Perceived intensity of neohesperidin dihydrochalcone	8.000000e-06
GCST009391_1233	Metabolite levels	1.000000e-06
GCST009391_305	Metabolite levels	6.000000e-06
GCST012336_8	Alcohol use disorder (consumption score)	1.000000e-06
GCST90020025_928	Waist-to-hip ratio adjusted for BMI	3.000000e-10
GCST90020025_929	Waist-to-hip ratio adjusted for BMI	6.000000e-10
GCST90020027_1453	Waist-hip index	2.000000e-10
GCST90020027_1454	Waist-hip index	8.000000e-10

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0006519	MMR-related febrile seizures
EFO:0006995	response to diisocyanate
EFO:0007887	autosomal dominant compelling helio-ophthalmic outburst syndrome
EFO:0005536	nitric oxide exhalation measurement
EFO:0004763	p-tau measurement
EFO:0010422	triacylglycerol 54:4 measurement
EFO:0010429	triacylglycerol 56:2 measurement
EFO:0007645	longitudinal alcohol consumption measurement
EFO:0009458	alcohol use disorder measurement
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D020821	Dystonic Disorders	C10.228.662.300
C562568	Cerebellar Hypoplasia (supp.)
C531684	Hereditary spinal ataxia (supp.)
C567292	Wilms Tumor, Aniridia, Genitourinary Anomalies, Mental Retardation, and Obesity Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs293983	ANO3		0.00	0

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Aflatoxin B1	decreases methylation, decreases expression	2
bisphenol A	increases methylation	1
trichostatin A	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases methylation	1
(+)-JQ1 compound	decreases expression	1
Arsenic Trioxide	decreases expression	1
Vorinostat	increases expression	1
Panobinostat	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Daunorubicin	affects response to substance	1
Formaldehyde	increases expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Methapyrilene	increases methylation	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1

Clinical trials (associated diseases)

169 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00142259	PHASE4	UNKNOWN	Efficacy and Safety of DBS of the GPi in Patients With Primary Generalized and Segmental Dystonia
NCT00950196	PHASE4	COMPLETED	Amantadine for Improving Neurologic Symptoms in Ataxia-Telangiectasia
NCT00998660	PHASE4	COMPLETED	RECHARGE Sub-Study to the Implantable Systems Performance Registry (ISPR)
NCT02263417	PHASE4	COMPLETED	A Randomized Controlled Trail Comparing Subthalamic and Pallidal Deep Brain Stimulation for Dystonia
NCT00169403	PHASE3	UNKNOWN	Pallidal Stimulation in Patients With Idiopathic Generalised Dystonia
NCT03232320	PHASE3	COMPLETED	Meditoxin® Treatment in Patients With Cervical Dystonia
NCT00001784	PHASE2	COMPLETED	Mexiletine for the Treatment of Focal Dystonia
NCT00105430	PHASE2	COMPLETED	Deep Brain Stimulation for Cervical Dystonia
NCT00106782	PHASE2	COMPLETED	Transcranial Electrical Polarization to Treat Focal Hand Dystonia
NCT00122044	PHASE2	COMPLETED	Childhood Hypertonia of Central Origin: A Trial of Anticholinergic Treatment Effects
NCT00169338	PHASE2	COMPLETED	Pallidal Stimulation in Patients With Post-anoxic and Idiopathic Dystonia
NCT00331669	PHASE2	UNKNOWN	Efficacy and Safety of Deep Brain Stimulation (DBS) of the Pallidal (GPi) in Patients With Tardive Dystonia
NCT02107261	PHASE2	COMPLETED	Incobotulinum Toxin A (Xeomin®) As A Treatment For Focal Task-Specific Dystonia Of The Musician’s Hand
NCT02470325	PHASE2	UNKNOWN	The Effects of Cannabis on Dystonia and Spasticity on Pediatric Patients
NCT05027997	PHASE2	COMPLETED	Exploratory Study of Dipraglurant (ADX48621) for the Treatment of Patients With Blepharospasm
NCT06412653	PHASE2	COMPLETED	Prospective Pilot Trial to Address Feasibility and Safety of Oral Zinc in GNAO1 Associated Disorders
NCT07304089	PHASE2	RECRUITING	A Study to Evaluate the Efficacy, Safety, and Tolerability of VIM0423 in Individuals With Isolated Dystonia
NCT01433757	PHASE1	COMPLETED	Ampicillin for DYT-1 Dystonia Motor Symptoms
NCT01698450	PHASE1	COMPLETED	Magnetic Resonance (MR) Guided Functional Ultrasound-Neurosurgery for Movement Disorders
NCT02982304	PHASE1	UNKNOWN	Multi-Target Pallidal and Thalamic Deep Brain Stimulation for Hemi-Dystonia
NCT06117020	PHASE1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
NCT06554288	PHASE1	RECRUITING	Pharmacogenomic Contributions to Trihexyphenidyl Biotransformation and Response in Children With Dystonic Cerebral Palsy
NCT00004421	PHASE2/PHASE3	COMPLETED	Deep Brain Stimulation in Treating Patients With Dystonia
NCT00272246	PHASE2/PHASE3	UNKNOWN	Bilateral Internal Pallidum Stimulation in Primary Generalized Dystonia
NCT00608231	PHASE2/PHASE3	WITHDRAWN	Dexmedetomidine Effects on Microelectrode Recording in Deep Brain Stimulation
NCT04277247	PHASE2/PHASE3	UNKNOWN	Botulinum Toxin Type A for Foot Dystonia-associated Pain in Parkinson’s Disease
NCT02015039	PHASE1/PHASE2	COMPLETED	Pilot Trial of Botulinum Toxin and Occupational Therapy for Writer’s Cramp
NCT02911103	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Deep Brain Stimulation Surgery for Focal Hand Dystonia
NCT04727177	EARLY_PHASE1	UNKNOWN	Precision-targeted Transcranial Magnetic Stimulation in the Treatment of Primary Dystonia
NCT00006336	Not specified	COMPLETED	Sensory Training to Treat Focal Dystonia
NCT00017875	Not specified	COMPLETED	Transcranial Magnetic Stimulation (TMS) Studies of Dystonia
NCT00029601	Not specified	COMPLETED	Surround Inhibition in Patients With Dystonia
NCT00031369	Not specified	TERMINATED	Brain Anatomy in Dystonia
NCT00047957	Not specified	COMPLETED	Brain Inhibition of Muscle Movement in Normal Volunteers
NCT00050024	Not specified	COMPLETED	Transcranial Magnetic Stimulation and Electrical Stimulation of Nerves to Study Focal Dystonia
NCT00072956	Not specified	COMPLETED	The Physiology of Tricks
NCT00082615	Not specified	COMPLETED	Neurophysiological Markers in Patients With Craniofacial Dystonia and Their Relatives
NCT00102999	Not specified	COMPLETED	Brain Function in Focal Dystonia
NCT00285870	Not specified	COMPLETED	Quantification of Upper Extremity Hypertonia
NCT00355927	Not specified	UNKNOWN	Sedation During Microelectrode Recordings Before Deep Brain Stimulation for Movement Disorders.