ANO10

Summary

ANO10 (anoctamin 10, HGNC:25519) is a protein-coding gene on chromosome 3p22.1-p21.33, encoding Anoctamin-10 (Q9NW15). Does not exhibit calcium-activated chloride channel (CaCC) activity.

The transmembrane protein encoded by this gene belongs to the anoctamin family of calcium-activated chloride channels, also known as the transmembrane 16 family. The encoded protein contains eight transmembrane domains with cytosolic N- and C-termini. Defects in this gene may cause autosomal recessive spinocerebellar ataxia-10. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 55129 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive spinocerebellar ataxia 10 (Definitive, ClinGen)
• GWAS associations: 6
• Clinical variants (ClinVar): 581 total — 54 pathogenic, 20 likely-pathogenic
• Phenotypes (HPO): 41
• MANE Select transcript: NM_018075

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25519
Approved symbol	ANO10
Name	anoctamin 10
Location	3p22.1-p21.33
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10375, MGC47890, SCAR10
Ensembl gene	ENSG00000160746
Ensembl biotype	protein_coding
OMIM	613726
Entrez	55129

Gene structure

Transcript identifiers

Ensembl transcripts: 52 — 49 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000292246, ENST00000350459, ENST00000396091, ENST00000413397, ENST00000414522, ENST00000427171, ENST00000428472, ENST00000428831, ENST00000436073, ENST00000439141, ENST00000444344, ENST00000448045, ENST00000451430, ENST00000456438, ENST00000466658, ENST00000486959, ENST00000495772, ENST00000910680, ENST00000910681, ENST00000910682, ENST00000910683, ENST00000910684, ENST00000910685, ENST00000910686, ENST00000910687, ENST00000910688, ENST00000910689, ENST00000910690, ENST00000910691, ENST00000910692, ENST00000910693, ENST00000910694, ENST00000920381, ENST00000920382, ENST00000920383, ENST00000920384, ENST00000920385, ENST00000920386, ENST00000920387, ENST00000920388, ENST00000920389, ENST00000920390, ENST00000920391, ENST00000970565, ENST00000970566, ENST00000970567, ENST00000970568, ENST00000970569, ENST00000970570, ENST00000970571, ENST00000970572, ENST00000970573

RefSeq mRNA: 12 — MANE Select: NM_018075 NM_001204831, NM_001204832, NM_001204833, NM_001204834, NM_001346463, NM_001346464, NM_001346465, NM_001346466, NM_001346467, NM_001346468, NM_001346469, NM_018075

CCDS: CCDS2710, CCDS56247, CCDS56248, CCDS56249, CCDS56250

Canonical transcript exons

ENST00000292246 — 13 exons

Exon	Start	End
ENSE00001054139	43555278	43555469
ENSE00001054140	43580353	43580472
ENSE00001054142	43598532	43598666
ENSE00001054143	43574809	43574864
ENSE00001054144	43549720	43549848
ENSE00001054145	43576692	43577261
ENSE00001054147	43561220	43561402
ENSE00001078236	43432611	43432727
ENSE00001634290	43605714	43605863
ENSE00001781202	43621909	43622011
ENSE00001943103	43365848	43366974
ENSE00003607958	43565653	43565727
ENSE00003789243	43600384	43600581

Expression profiles

Bgee: expression breadth ubiquitous, 271 present calls, max score 95.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.6047 / max 289.5386, expressed in 1804 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41842	20.5188	1801
41843	1.0860	758

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	95.89	gold quality
mucosa of transverse colon	UBERON:0004991	95.08	gold quality
duodenum	UBERON:0002114	93.50	gold quality
jejunal mucosa	UBERON:0000399	92.82	gold quality
rectum	UBERON:0001052	92.75	gold quality
popliteal artery	UBERON:0002250	91.71	gold quality
tibial artery	UBERON:0007610	91.70	gold quality
smooth muscle tissue	UBERON:0001135	91.52	gold quality
islet of Langerhans	UBERON:0000006	91.40	gold quality
lower esophagus mucosa	UBERON:0035834	91.35	gold quality
aorta	UBERON:0000947	91.31	gold quality
skin of leg	UBERON:0001511	91.06	gold quality
ascending aorta	UBERON:0001496	90.90	gold quality
thoracic aorta	UBERON:0001515	90.87	gold quality
gingival epithelium	UBERON:0001949	90.81	gold quality
descending thoracic aorta	UBERON:0002345	90.76	gold quality
colonic epithelium	UBERON:0000397	90.71	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.71	gold quality
calcaneal tendon	UBERON:0003701	90.52	gold quality
skin of abdomen	UBERON:0001416	90.39	gold quality
right lobe of thyroid gland	UBERON:0001119	90.35	gold quality
left lobe of thyroid gland	UBERON:0001120	90.34	gold quality
left coronary artery	UBERON:0001626	90.25	gold quality
transverse colon	UBERON:0001157	90.24	gold quality
adult mammalian kidney	UBERON:0000082	90.20	gold quality
thyroid gland	UBERON:0002046	90.12	gold quality
spinal cord	UBERON:0002240	90.12	gold quality
coronary artery	UBERON:0001621	89.99	gold quality
small intestine	UBERON:0002108	89.94	gold quality
ectocervix	UBERON:0012249	89.93	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.17

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting ANO10, 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-4533	100.00	69.48	2758
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-569	99.42	66.32	1009
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-935	98.82	69.36	1072
HSA-MIR-589-5P	98.72	66.96	927
HSA-MIR-7705	98.69	67.47	543
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-6854-5P	96.77	65.96	848
HSA-MIR-5702	96.68	68.21	958
HSA-MIR-132-5P	96.61	65.79	115
HSA-MIR-1182	96.41	64.89	336
HSA-MIR-4423-5P	95.24	64.42	454

Literature-anchored findings (GeneRIF, showing 14)

• This study report Gypsy family with autosomal recessive ataxia caused by the same truncating ANO10 defect. (PMID:22008874)
• New DNA sequencing technologies are enabling us to investigate the whole or large targeted proportions of the genome in a rapid, affordable, and comprehensive way. Exome and targeted sequencing ANO10 genes causing ataxia. (PMID:22527681)
• Whole-exome and targeted sequencing have defined the genetic basis of dizziness including new genes causing ataxia: GBA2, TGM6, ANO10 and SYT14 (PMID:24275721)
• An ANO10 mutation is responsible for autosomal recessive cerebellar ataxia that is mainly characterized by cerebellar atrophy and lack of peripheral neuropathy. (PMID:25089919)
• The detection of mutations in ANO10 indicate that ANO10 defects cause secondary low coenzyme Q10. (PMID:25182700)
• ANO10 has a central role in innate immune defense against Borrelia infection. (PMID:25730773)
• results suggest that executive and attentional disorders are impaired in ANO10 mutation (PMID:27045840)
• This study describe 2 Romani families from Serbia presenting with seemingly dominant (multiple affected individuals in successive generations) cerebellar ataxia, both harboring the same homozygous (recessive) mutation in ANO10, identified by whole-exome sequencing. (PMID:27787937)
• mutations in ANO10 cause cellular defects and genetic disorders through deranged local Ca(2+) signaling. (PMID:27838374)
• ANO10 mutations cause recessive ataxias. (PMID:30515630)
• Cognitive impairment seems to be a characteristic of the SCAR10 produced by an ANO10 gene mutation, with a range from mild impairment, especially involving prefrontal systems, to a severe cognitive impairment suggesting widespread cerebral involvement. (PMID:31423897)
• Data show that transmembrane protein 16K (TMEM16K) is an endoplasmic reticulum (ER)-resident lipid scramblase with a requirement for short chain lipids and calcium for robust activity. (PMID:31477691)
• TMEM16K is an interorganelle regulator of endosomal sorting. (PMID:32620747)
• [Rare forms of autosomal recessive spinocerebellar ataxia associated with mutations in the ANO10 (ATX-ANO10) and SYNE1 (ATX-SYNE1) genes]. (PMID:39269294)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ano10a	ENSDARG00000057736
mus_musculus	Ano10	ENSMUSG00000037949
rattus_norvegicus	Ano10	ENSRNOG00000000219

Paralogs (10): ANO2 (ENSG00000047617), ANO8 (ENSG00000074855), PPP1R7 (ENSG00000115685), ANO1 (ENSG00000131620), ANO3 (ENSG00000134343), ANO7 (ENSG00000146205), ANO4 (ENSG00000151572), ANO5 (ENSG00000171714), ANO6 (ENSG00000177119), ANO9 (ENSG00000185101)

Protein

Protein identifiers

Anoctamin-10 — Q9NW15 (reviewed: Q9NW15)

Alternative names: Transmembrane protein 16K

All UniProt accessions (10): Q9NW15, C9IYD3, C9IZD0, C9J670, C9JA49, C9JH90, C9JJS5, C9JPY2, C9JQC9, H7C3N6

UniProt curated annotations — full annotation on UniProt →

Function. Does not exhibit calcium-activated chloride channel (CaCC) activity. Can inhibit the activity of ANO1.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in the brain. Intermediate levels in the retina and heart and low levels in the placenta, liver, lung, duodenum, kidney, testis and spleen. In brain areas, highest expression in the frontal and occipital cortices and in the cerebellum. Lower expression in the fetal brain than in the adult brain.

Disease relevance. Spinocerebellar ataxia, autosomal recessive, 10 (SCAR10) [MIM:613728] A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR10 is characterized by onset in the teenage or young adult years of gait and limb ataxia, dysarthria, and nystagmus associated with marked cerebellar atrophy on brain imaging. 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 (5)

UniProt ID	Names	Canonical?
Q9NW15-1	1	yes
Q9NW15-2	2
Q9NW15-3	3
Q9NW15-4	4
Q9NW15-5	5

RefSeq proteins (12): NP_001191760, NP_001191761, NP_001191762, NP_001191763, NP_001333392, NP_001333393, NP_001333394, NP_001333395, NP_001333396, NP_001333397, NP_001333398, NP_060545* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007632	Anoctamin	Family
IPR049452	Anoctamin_TM	Domain

Pfam: PF04547

UniProt features (72 total): helix 28, strand 14, topological domain 9, transmembrane region 8, splice variant 4, sequence variant 4, turn 3, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
5OC9	X-RAY DIFFRACTION	3.2
6R7X	ELECTRON MICROSCOPY	3.47
6R65	X-RAY DIFFRACTION	3.5
6R7Y	ELECTRON MICROSCOPY	4.2
6R7Z	ELECTRON MICROSCOPY	5.14

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NW15-F1	86.26	0.55

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: 205 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CHLORIDE_TRANSPORT, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, MODULE_95, GOBP_TRANSMEMBRANE_TRANSPORT, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, PARENT_MTOR_SIGNALING_UP, GOMF_GATED_CHANNEL_ACTIVITY, GOMF_PASSIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_MONOATOMIC_CATION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_MONOATOMIC_ANION_CHANNEL_ACTIVITY

GO Biological Process (3): monoatomic ion transmembrane transport (GO:0034220), chloride transmembrane transport (GO:1902476), monoatomic cation transmembrane transport (GO:0098655)

GO Molecular Function (3): calcium-activated cation channel activity (GO:0005227), intracellularly calcium-gated chloride channel activity (GO:0005229), chloride channel activity (GO:0005254)

GO Cellular Component (3): plasma membrane (GO:0005886), cilium (GO:0005929), 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
monoatomic ion transport	1
transmembrane transport	1
chloride transport	1
monoatomic anion transmembrane transport	1
monoatomic cation transport	1
monoatomic ion transmembrane transport	1
monoatomic ion-gated channel activity	1
ligand-gated monoatomic cation channel activity	1
chloride channel activity	1
ligand-gated monoatomic anion channel activity	1
intracellularly calcium-gated channel activity	1
monoatomic anion channel activity	1
chloride transmembrane transporter activity	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cellular anatomical structure	1

Protein interactions and networks

STRING

656 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANO10	COQ8A	Q8NI60	608
ANO10	CLCA4	Q14CN2	605
ANO10	CLCA2	Q9UQC9	602
ANO10	SYT14	Q8NB59	584
ANO10	CLCA1	A8K7I4	576
ANO10	ANO3	Q9BYT9	556
ANO10	APTX	Q7Z2E3	543
ANO10	ANO1	Q5XXA6	529
ANO10	CIMIP7	H3BNL1	476
ANO10	SPG7	Q9UQ90	474
ANO10	SETX	Q7Z333	450
ANO10	CACNA1A	P78510	440
ANO10	CLDN23	Q96B33	435
ANO10	SYNE1	Q8NF91	424
ANO10	KCNV2	Q8TDN2	422

IntAct

33 interactions, top by confidence:

A	B	Type	Score
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
ANO10	HTR4	psi-mi:“MI:0915”(physical association)	0.370
ANO10	SMARCA2	psi-mi:“MI:0915”(physical association)	0.370
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
ORF16	CUL3	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC17A2	ABCD4	psi-mi:“MI:0914”(association)	0.350
MFSD10	NDUFS8	psi-mi:“MI:0914”(association)	0.350
MFSD3	NME4	psi-mi:“MI:0914”(association)	0.350
MFSD5	ILVBL	psi-mi:“MI:0914”(association)	0.350
SLC16A6	RER1	psi-mi:“MI:0914”(association)	0.350
SLC18A2	LGALS8	psi-mi:“MI:0914”(association)	0.350
SLC19A2	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC22A9	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC23A1	NEMP1	psi-mi:“MI:0914”(association)	0.350
SLC2A7	GPR89A	psi-mi:“MI:0914”(association)	0.350
SLC30A5	NBAS	psi-mi:“MI:0914”(association)	0.350
SLC35B2	NDUFS8	psi-mi:“MI:0914”(association)	0.350
SLC35C2	PGRMC1	psi-mi:“MI:0914”(association)	0.350
SLC35E3	TP53I11	psi-mi:“MI:0914”(association)	0.350
SLC35F3	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC7A1	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC7A3	ILVBL	psi-mi:“MI:0914”(association)	0.350
TMEM241	FAAH	psi-mi:“MI:0914”(association)	0.350
TCTN2	TMEM120B	psi-mi:“MI:2364”(proximity)	0.270
TMEM216	GPR89A	psi-mi:“MI:2364”(proximity)	0.270
KRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
HRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
sseG	SLC33A1	psi-mi:“MI:2364”(proximity)	0.270
SBDS	RPSA2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (77): ANO10 (Proximity Label-MS), ANO10 (Proximity Label-MS), ANO10 (Affinity Capture-MS), ANO10 (Affinity Capture-MS), ANO10 (Affinity Capture-MS), ANO10 (Proximity Label-MS), ANO10 (Proximity Label-MS), ANO10 (Synthetic Lethality), ANO10 (Proximity Label-MS), ANO10 (Proximity Label-MS), ANO10 (Proximity Label-MS), ANO10 (Proximity Label-MS), ANO10 (Proximity Label-MS), ANO10 (Proximity Label-MS), ANO10 (Proximity Label-MS)

ESM2 similar proteins: A0A452G813, A0A8V0ZB02, A2AJN7, A2AWR3, A9LIW2, B1WB39, B6HTR9, D3ZNF5, F4I248, F4JCY2, O23693, O57428, O77761, O94886, Q06538, Q0VGV9, Q12791, Q17JQ7, Q3KTM2, Q3TWI9, Q4R7U0, Q4V8U5, Q5GH60, Q5GH68, Q5R826, Q5R9A7, Q5T3F8, Q5YCC5, Q62976, Q6NP91, Q6PP77, Q7SYR6, Q7Z3F1, Q7Z402, Q7ZYA0, Q8BH79, Q8C428, Q8CBX0, Q8GUH7, Q8NBS3

Diamond homologs: A0MFS9, Q0JJZ6, Q6PB70, Q9HCE9, Q9NW15, Q4V8U5, Q8BH79

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	54
Likely pathogenic	20
Uncertain significance	162
Likely benign	219
Benign	49

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1027440	NM_018075.5(ANO10):c.206T>A (p.Leu69Ter)	Pathogenic
1335511	NM_018075.5(ANO10):c.131_132dup (p.Asp45fs)	Pathogenic
162018	NM_018075.5(ANO10):c.1144G>T (p.Glu382Ter)	Pathogenic
1675913	NM_018075.5(ANO10):c.1219-1G>T	Pathogenic
1807057	NM_018075.5(ANO10):c.1585G>T (p.Glu529Ter)	Pathogenic
2692976	NM_018075.5(ANO10):c.1029del (p.Leu344fs)	Pathogenic
2699838	NM_018075.5(ANO10):c.440del (p.Pro147fs)	Pathogenic
2726709	NM_018075.5(ANO10):c.243del (p.Ala83fs)	Pathogenic
2753708	NM_018075.5(ANO10):c.312del (p.Arg105fs)	Pathogenic
2771365	NM_018075.5(ANO10):c.616dup (p.Glu206fs)	Pathogenic
2772348	NM_018075.5(ANO10):c.1063del (p.Thr355fs)	Pathogenic
2809084	NM_018075.5(ANO10):c.710G>A (p.Trp237Ter)	Pathogenic
2821448	NM_018075.5(ANO10):c.470T>A (p.Leu157Ter)	Pathogenic
2830725	NM_018075.5(ANO10):c.269_270del (p.Lys90fs)	Pathogenic
2831610	NM_018075.5(ANO10):c.1349_1350del (p.Phe450fs)	Pathogenic
2835782	NM_018075.5(ANO10):c.993T>G (p.Tyr331Ter)	Pathogenic
2838973	NM_018075.5(ANO10):c.31del (p.Ser11fs)	Pathogenic
2846174	NM_018075.5(ANO10):c.132del (p.Asp45fs)	Pathogenic
2846516	NM_018075.5(ANO10):c.818_819dup (p.Thr274fs)	Pathogenic
2852336	NM_018075.5(ANO10):c.758G>A (p.Trp253Ter)	Pathogenic
2856009	NM_018075.5(ANO10):c.1264del (p.Val422fs)	Pathogenic
2858109	NM_018075.5(ANO10):c.1646C>G (p.Ser549Ter)	Pathogenic
2858407	NM_018075.5(ANO10):c.12del (p.Leu5fs)	Pathogenic
2865911	NM_018075.5(ANO10):c.1321del (p.Gln441fs)	Pathogenic
2867864	NM_018075.5(ANO10):c.432_439del (p.Gly145fs)	Pathogenic
2878503	NM_018075.5(ANO10):c.38del (p.Ser13fs)	Pathogenic
2881856	NM_018075.5(ANO10):c.1350del (p.Leu451fs)	Pathogenic
2957244	NM_018075.5(ANO10):c.1132C>T (p.Arg378Ter)	Pathogenic
2982219	NM_018075.5(ANO10):c.1244C>G (p.Ser415Ter)	Pathogenic
2984107	NM_018075.5(ANO10):c.1248_1249del (p.Phe417fs)	Pathogenic

SpliceAI

3324 predictions. Top by Δscore:

Variant	Effect	Δscore
3:43549716:TTA:T	donor_loss	1.0000
3:43549717:TA:T	donor_loss	1.0000
3:43549718:A:AC	donor_gain	1.0000
3:43549718:AC:A	donor_gain	1.0000
3:43549718:ACCT:A	donor_gain	1.0000
3:43549718:ACCTC:A	donor_gain	1.0000
3:43549719:C:CC	donor_gain	1.0000
3:43549719:CC:C	donor_gain	1.0000
3:43549719:CCT:C	donor_gain	1.0000
3:43549719:CCTC:C	donor_gain	1.0000
3:43549719:CCTCC:C	donor_gain	1.0000
3:43549844:GCCAA:G	acceptor_gain	1.0000
3:43549845:CCAA:C	acceptor_gain	1.0000
3:43549845:CCAAC:C	acceptor_gain	1.0000
3:43549846:CAA:C	acceptor_gain	1.0000
3:43549846:CAAC:C	acceptor_gain	1.0000
3:43549847:AA:A	acceptor_gain	1.0000
3:43549847:AACT:A	acceptor_loss	1.0000
3:43549848:ACTA:A	acceptor_loss	1.0000
3:43549849:C:A	acceptor_loss	1.0000
3:43549849:C:CC	acceptor_gain	1.0000
3:43549850:T:C	acceptor_loss	1.0000
3:43561335:C:CT	acceptor_gain	1.0000
3:43561336:A:T	acceptor_gain	1.0000
3:43565728:C:CC	acceptor_gain	1.0000
3:43565732:C:CT	acceptor_gain	1.0000
3:43565733:A:T	acceptor_gain	1.0000
3:43577258:CTGT:C	acceptor_gain	1.0000
3:43577259:TGT:T	acceptor_gain	1.0000
3:43577262:C:CC	acceptor_gain	1.0000

AlphaMissense

4345 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:43555283:A:G	W555R	1.000
3:43555283:A:T	W555R	1.000
3:43549807:G:C	N570K	0.999
3:43549807:G:T	N570K	0.999
3:43555413:G:C	F511L	0.999
3:43555413:G:T	F511L	0.999
3:43555415:A:G	F511L	0.999
3:43555419:G:C	S509R	0.999
3:43555419:G:T	S509R	0.999
3:43555421:T:G	S509R	0.999
3:43555429:C:T	G506D	0.999
3:43555430:C:G	G506R	0.999
3:43561386:A:G	L437P	0.999
3:43565707:A:C	F413L	0.999
3:43565707:A:T	F413L	0.999
3:43565709:A:G	F413L	0.999
3:43574828:A:G	L400P	0.999
3:43576881:A:G	C325R	0.999
3:43549799:A:G	L573P	0.998
3:43555281:C:A	W555C	0.998
3:43555281:C:G	W555C	0.998
3:43555319:G:T	R543S	0.998
3:43555368:G:C	N526K	0.998
3:43555368:G:T	N526K	0.998
3:43555390:G:T	A519D	0.998
3:43561389:A:G	L436P	0.998
3:43565660:A:C	L429W	0.998
3:43574818:T:A	K403N	0.998
3:43574818:T:G	K403N	0.998
3:43576712:G:T	A381D	0.998

dbSNP variants (sampled 300 via entrez): RS1000002808 (3:43470846 C>G,T), RS1000012039 (3:43656596 G>A), RS1000012213 (3:43471021 A>G,T), RS1000013198 (3:43417730 T>C), RS1000017474 (3:43373968 A>C), RS1000019770 (3:43522917 T>C), RS1000031694 (3:43671371 A>G), RS1000034810 (3:43657098 T>C,G), RS1000035205 (3:43609942 T>C), RS1000052293 (3:43508557 A>G,T), RS1000057332 (3:43426261 C>T), RS1000064635 (3:43471379 T>A,C), RS1000066524 (3:43522532 A>T), RS1000068311 (3:43494433 A>G), RS1000078358 (3:43419311 G>A)

Disease associations

OMIM: gene MIM:613726 | disease phenotypes: MIM:613728, MIM:213200, MIM:209850, MIM:275630

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive spinocerebellar ataxia 10	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
autosomal recessive spinocerebellar ataxia 10	Definitive	AR

Mondo (4): autosomal recessive spinocerebellar ataxia 10 (MONDO:0013392), autosomal recessive cerebellar ataxia (MONDO:0015244), autism (MONDO:0005260), Dorfman-Chanarin disease (MONDO:0010155)

Orphanet (3): Adult-onset autosomal recessive cerebellar ataxia (Orphanet:284289), Autosomal recessive cerebellar ataxia (Orphanet:1172), Neutral lipid storage disease with ichthyosis (Orphanet:98907)

HPO phenotypes

41 total (30 of 41 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000503	Tortuosity of conjunctival vessels
HP:0000508	Ptosis
HP:0000514	Slow saccadic eye movements
HP:0000518	Cataract
HP:0000608	Macular degeneration
HP:0000639	Nystagmus
HP:0000641	Dysmetric saccades
HP:0000651	Diplopia
HP:0000666	Horizontal nystagmus
HP:0001152	Saccadic smooth pursuit interruptions
HP:0001249	Intellectual disability
HP:0001256	Mild intellectual disability
HP:0001260	Dysarthria
HP:0001272	Cerebellar atrophy
HP:0001310	Dysmetria
HP:0001347	Hyperreflexia
HP:0001348	Brisk reflexes
HP:0001350	Slurred speech
HP:0001761	Pes cavus
HP:0002066	Gait ataxia
HP:0002070	Limb ataxia
HP:0002073	Progressive cerebellar ataxia
HP:0002078	Truncal ataxia
HP:0002080	Intention tremor
HP:0002197	Generalized-onset seizure
HP:0002380	Fasciculations
HP:0003457	EMG abnormality
HP:0003487	Babinski sign
HP:0003596	Middle age onset

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001762_789	Obesity-related traits	2.000000e-07
GCST007896_2	Primary central nervous system lymphoma	2.000000e-08
GCST008832_1	Gastroesophageal reflux disease	3.000000e-08
GCST90020024_1140	A body shape index	1.000000e-09
GCST90020025_1939	Waist-to-hip ratio adjusted for BMI	7.000000e-10
GCST90020027_170	Waist-hip index	5.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005188	CCL11 measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	3
bisphenol A	increases expression	2
Calcitriol	increases expression, affects cotreatment	2
Testosterone	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
sodium bichromate	decreases expression	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	decreases expression	1
fenpyroximate	decreases expression	1
bisphenol B	increases expression	1
pyrachlostrobin	decreases expression	1
picoxystrobin	decreases expression	1
NSC 689534	affects binding, increases expression	1
bisphenol AF	increases expression	1
Bortezomib	increases expression	1
Ethanol	increases expression	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	decreases expression	1
Copper	affects binding, increases expression	1
Formaldehyde	decreases expression	1
Pesticides	affects methylation	1
Rotenone	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SC60	HAP1 ANO10 (-) 1	Cancer cell line	Male
CVCL_XL36	HAP1 ANO10 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms