ATXN10

Summary

ATXN10 (ataxin 10, HGNC:10549) is a protein-coding gene on chromosome 22q13.31, encoding Ataxin-10 (Q9UBB4). May play a role in the regulation of cytokinesis. It is a selective cancer dependency (DepMap: 29.8% of cell lines).

This gene encodes a protein that may function in neuron survival, neuron differentiation, and neuritogenesis. These roles may be carried out via activation of the mitogen-activated protein kinase cascade. Expansion of an ATTCT repeat from 9-32 copies to 800-4500 copies in an intronic region of this locus has been associated with spinocerebellar ataxia, type 10. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 25814 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spinocerebellar ataxia type 10 (Strong, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 68 total — 4 pathogenic
• Phenotypes (HPO): 49
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 29.8% of screened cell lines
• MANE Select transcript: NM_013236

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10549
Approved symbol	ATXN10
Name	ataxin 10
Location	22q13.31
Locus type	gene with protein product
Status	Approved
Aliases	E46L, FLJ37990, ATX10
Ensembl gene	ENSG00000130638
Ensembl biotype	protein_coding
OMIM	611150
Entrez	25814

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding_CDS_not_defined, 4 protein_coding, 1 retained_intron

ENST00000252934, ENST00000381061, ENST00000402380, ENST00000435026, ENST00000451241, ENST00000464482, ENST00000470722, ENST00000476998, ENST00000483549, ENST00000493643, ENST00000498009

RefSeq mRNA: 2 — MANE Select: NM_013236 NM_001167621, NM_013236

CCDS: CCDS14070, CCDS54540

Canonical transcript exons

ENST00000252934 — 12 exons

Exon	Start	End
ENSE00001332462	45843669	45845307
ENSE00001487386	45671834	45672179
ENSE00003463854	45740369	45740538
ENSE00003476531	45702689	45702847
ENSE00003485380	45729425	45729590
ENSE00003526130	45718413	45718493
ENSE00003569372	45806959	45807022
ENSE00003572337	45692996	45693078
ENSE00003629763	45842991	45843178
ENSE00003662543	45700282	45700378
ENSE00003686635	45689712	45689903
ENSE00003687295	45738731	45738839

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 99.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 109.0045 / max 653.0904, expressed in 1823 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192756	93.4869	1819
192758	13.3590	1769
192757	1.4158	816
192759	0.7428	385

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.44	gold quality
ventricular zone	UBERON:0003053	99.40	gold quality
ganglionic eminence	UBERON:0004023	99.33	gold quality
embryo	UBERON:0000922	99.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.93	gold quality
prefrontal cortex	UBERON:0000451	98.83	gold quality
stromal cell of endometrium	CL:0002255	98.82	gold quality
islet of Langerhans	UBERON:0000006	98.48	gold quality
heart right ventricle	UBERON:0002080	98.47	gold quality
postcentral gyrus	UBERON:0002581	98.42	gold quality
pons	UBERON:0000988	98.41	gold quality
adult organism	UBERON:0007023	98.37	gold quality
pigmented layer of retina	UBERON:0001782	98.35	gold quality
parietal lobe	UBERON:0001872	98.33	gold quality
retina	UBERON:0000966	98.32	gold quality
superior frontal gyrus	UBERON:0002661	98.14	gold quality
frontal cortex	UBERON:0001870	98.13	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.13	gold quality
superior vestibular nucleus	UBERON:0007227	98.13	gold quality
parotid gland	UBERON:0001831	98.10	gold quality
bronchial epithelial cell	CL:0002328	97.99	gold quality
corpus callosum	UBERON:0002336	97.96	gold quality
entorhinal cortex	UBERON:0002728	97.95	gold quality
dorsal root ganglion	UBERON:0000044	97.86	gold quality
inferior olivary complex	UBERON:0002127	97.86	gold quality
neocortex	UBERON:0001950	97.81	gold quality
myocardium	UBERON:0002349	97.81	gold quality
substantia nigra pars compacta	UBERON:0001965	97.79	gold quality
epithelium of bronchus	UBERON:0002031	97.78	gold quality
nasal cavity epithelium	UBERON:0005384	97.78	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	11.61
E-GEOD-100618	no	1392.14
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA3, YY1

miRNA regulators (miRDB)

72 targeting ATXN10, 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-4668-3P	100.00	68.74	2635
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-3618	99.69	68.57	1012
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-3682-3P	99.58	67.63	865

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 29.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 26)

• frequency of SCA10 in spinocerebellar ataxia in France (PMID:11891842)
• Interruptions in the expanded ATTCT repeat of spinocerebellar ataxia type 10 suggest that the purity of the expanded repeat element may be a disease modifier. (PMID:16385455)
• These results implicate replication origin activity as one molecular mechanism associated with the instability of ataxin 10(ATTCT)n tracts that are longer than normal length. (PMID:17846122)
• cause Spinocerebellar ataxia type 10 by expansion of the ATTCT pentanucleotide repeat in intron 9 of the gene (PMID:18386626)
• The normal reference standard for ATXN10 gene’s ATTCT pentanucleotide repeat of 9-32 is verified in the Chinese Han group. (PMID:19147916)
• Nucleosome formation on pure and interrupted ATTCT pentanucleotides associated with spinocerebellar ataxia type 10 (SCA10), is reported. (PMID:19171184)
• evidence for an ancestral common origin for SCA10 in Latin America, which might have arisen in an ancestral Amerindian population and later have been spread into the mixed populations of Mexico and Brazil. (PMID:19234597)
• Ataxin 10 and eukaryotic initiation factors interacts with M2 protein of influenza A virus. (PMID:19835171)
• Data suggest that SCA10 could be related to chromatin structure abnormalities caused by the expansion and not to an abnormal or abnormally expressed ATXN10. (PMID:19936807)
• suggesting that the loss of function of hnRNP K plays a key role in cell death of SCA10. (PMID:20548952)
• Network building strategy led to the proposal of candidates for new ciliopathy disease genes, leading to the identification of the first human mutations in the Nephronophthisis gene Ataxin10 (ATXN10) and Joubert syndrome gene Tectonic2 (TCTN2). (PMID:21565611)
• The expansion of the attct repeat in intron 9 of atxn10 is may caused Spinocerebellar ataxia type 10. (PMID:21827910)
• Plk1 phosphorylates Ataxin-10 on Ser 77 and Thr 82. (PMID:21857149)
• The SCA10 pentanucleotide repeat expansion was not found among a group of Cypriot ataxia patients. All had 10-19 ATTCT repeats. Controls had 11-20 repeats, with 14 being the most common number. (PMID:23026538)
• the presence of repeat interruptions in SCA10 repeat expansion may have a role in epilepsy phenotype (PMID:24318420)
• This is the first description of a family with two SCA mutations with affected subjects having a combined SCA2 and SCA10 phenotype. (PMID:25630585)
• Inhibition of Aurora B or expression of the S12A mutant renders reduced interaction between Ataxin-10 and polo-like kinase 1 (Plk1), a kinase previously identified to regulate Ataxin-10 in cytokinesis. (PMID:25666058)
• Data suggest precursor mRNA for SCA10 (crystalized using two model AUUCU SCA10 repeats) exhibits the following conformation: the two asymmetric RNA molecules are antiparallel to each other and the interaction is stabilized by multiple hydrogen bonds. (PMID:26039897)
• Single molecule real time sequencing of long tandem nucleotide repeats in spinocerebellar ataxia ATXN10 reveals unique insight of repeat expansion structure in three unrelated patients. (PMID:26295943)
• Inheritance patterns of ATCCT repeat interruptions in spinocerebellar ataxia type 10 expansions of ataxin-10 has been reported. (PMID:28423040)
• Polymorphism in ATXN10 gene is associated with spinocerebellar ataxia type 10. (PMID:28542277)
• The 19-CGGC-14 shared haplotype was found in 47% of Brazilian and in 63% of Peruvian families. Frequencies from both are statistically different from Brazilian controls but not Quechua controls. The most frequent haplotype in Quechuas, 19-15-CGGC-14-10, is found in 50% of Brazilian and in 65% of Peruvian patients. The ATTCT expansion may have arisen in a Native American chromosome. (PMID:28905220)
• Ataxin-10 is involved in Golgi membrane dynamics (PMID:29169923)
• ATXN10 allele distribution in a healthy Amerindian population from Peru does not differ from that of other populations. (PMID:31342269)
• The most common clinical presentation of SCA10 in Brazilian families was pure cerebellar ataxia. (PMID:31377949)
• Extended haplotype with rs41524547-G defines the ancestral origin of SCA10. (PMID:38832639)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	atxn10	ENSDARG00000008439
mus_musculus	Atxn10	ENSMUSG00000016541
rattus_norvegicus	Atxn10	ENSRNOG00000014637

Protein

Protein identifiers

Ataxin-10 — Q9UBB4 (reviewed: Q9UBB4)

Alternative names: Brain protein E46 homolog, Spinocerebellar ataxia type 10 protein

All UniProt accessions (3): Q9UBB4, B1AHE3, B1AHE4

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in the regulation of cytokinesis. May play a role in signaling by stimulating protein glycosylation. Induces neuritogenesis by activating the Ras-MAP kinase pathway and is necessary for the survival of cerebellar neurons. Does not appear to play a major role in ciliogenesis.

Subunit / interactions. Homooligomer. Interacts with GNB2. Interacts with IQCB1. Interacts with OGT.

Subcellular location. Cytoplasm. Perinuclear region. Midbody. Cytoskeleton. Cilium basal body. Microtubule organizing center. Centrosome. Centriole.

Tissue specificity. Expressed in the central nervous system.

Post-translational modifications. Polyubiquitinated. Phosphorylation at Ser-12 by AURKB promotes the association of ATXN10 with PLK1. Phosphorylation at Ser-77 and Thr-82 by PLK1 may play a role in the regulation of cytokinesis and may stimulate the proteasome-mediated degradation of ATXN10.

Disease relevance. Spinocerebellar ataxia 10 (SCA10) [MIM:603516] Spinocerebellar ataxia is 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. SCA10 is an autosomal dominant cerebellar ataxia (ADCA). The disease is caused by variants affecting the gene represented in this entry. Defects in ATXN1 may be a cause of nephronophthisis a chronic tubulo-interstitial nephropathy that leads to anemia, polyuria, polydipsia, isosthenuria and death in uremia.

Similarity. Belongs to the ataxin-10 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UBB4-1	1	yes
Q9UBB4-2	2

RefSeq proteins (2): NP_001161093, NP_037368* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR019156	Ataxin-10_domain	Domain
IPR051374	Ataxin-10/CTR86_families	Family

Pfam: PF09759

UniProt features (7 total): modified residue 5, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBB4-F1	90.03	0.73

Functional residue map

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

Post-translational modifications (5): 10, 12, 77, 82, 430

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 279 (showing top): HORIUCHI_WTAP_TARGETS_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, MORF_UBE2I, MORF_HDAC1, MORF_UBE2N, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_NEUROGENESIS, MORF_HDAC2, GOCC_MICROTUBULE_ORGANIZING_CENTER, PUJANA_CHEK2_PCC_NETWORK, GOBP_CYTOKINESIS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, GOBP_CILIUM_ORGANIZATION, GOBP_REGULATION_OF_CELL_CYCLE, LUI_TARGETS_OF_PAX8_PPARG_FUSION

GO Biological Process (6): nervous system development (GO:0007399), neuron projection development (GO:0031175), regulation of cytokinesis (GO:0032465), cell division (GO:0051301), cilium assembly (GO:0060271), plasma membrane bounded cell projection organization (GO:0120036)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (14): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), centriole (GO:0005814), cytosol (GO:0005829), plasma membrane (GO:0005886), cilium (GO:0005929), membrane (GO:0016020), dendrite (GO:0030425), midbody (GO:0030496), ciliary basal body (GO:0036064), neuronal cell body (GO:0043025), perinuclear region of cytoplasm (GO:0048471), cytoskeleton (GO:0005856), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
microtubule organizing center	2
intracellular membraneless organelle	2
cytoplasm	2
system development	1
neuron development	1
plasma membrane bounded cell projection organization	1
cytokinesis	1
regulation of cell cycle process	1
regulation of cell division	1
cellular process	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
cell projection organization	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
neuron projection	1
dendritic tree	1
cilium	1
somatodendritic compartment	1
cell body	1

Protein interactions and networks

STRING

1128 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATXN10	SPTBN2	O15020	924
ATXN10	CACNA1A	P78510	897
ATXN10	ATXN7	O15265	856
ATXN10	TTBK2	Q6IQ55	837
ATXN10	IQCB1	Q15051	798
ATXN10	PPP2R2B	Q00005	796
ATXN10	KCNC3	Q14003	695
ATXN10	NOP56	O00567	669
ATXN10	ATXN2	Q99700	665
ATXN10	PLEKHG4	Q58EX7	663
ATXN10	TBP	P20226	611
ATXN10	DAB1	O75553	610
ATXN10	ATXN1	P54253	607
ATXN10	TGM6	O95932	604
ATXN10	BEAN1	Q3B7T3	598

IntAct

276 interactions, top by confidence:

A	B	Type	Score
APP	APBB1	psi-mi:“MI:0914”(association)	0.740
L3MBTL2	E2F6	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
MYC	ATXN10	psi-mi:“MI:0915”(physical association)	0.670
PPP1R12A	ATXN10	psi-mi:“MI:0915”(physical association)	0.670
AP2B1	ATXN10	psi-mi:“MI:0915”(physical association)	0.560
ATXN10	BAK1	psi-mi:“MI:0915”(physical association)	0.560
CD1C	ATXN10	psi-mi:“MI:0915”(physical association)	0.560
HNRNPK	ATXN10	psi-mi:“MI:0915”(physical association)	0.560
MLLT6	ATXN10	psi-mi:“MI:0915”(physical association)	0.560
TLE1	ATXN10	psi-mi:“MI:0915”(physical association)	0.560
VIM	ATXN10	psi-mi:“MI:0915”(physical association)	0.560
ZNF232	ATXN10	psi-mi:“MI:0915”(physical association)	0.560
NCOA4	ATXN10	psi-mi:“MI:0915”(physical association)	0.560
	ATXN10	psi-mi:“MI:0915”(physical association)	0.560
COPS3	ATXN10	psi-mi:“MI:0915”(physical association)	0.560
ATXN10	API5	psi-mi:“MI:0915”(physical association)	0.560
PIAS1	ATXN10	psi-mi:“MI:0915”(physical association)	0.560
HYAL2	ATXN10	psi-mi:“MI:0915”(physical association)	0.560
CDC23	ATXN10	psi-mi:“MI:0915”(physical association)	0.560
MICAL2	ATXN10	psi-mi:“MI:0915”(physical association)	0.560
SLU7	ATXN10	psi-mi:“MI:0915”(physical association)	0.560
UTP14A	ATXN10	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (185): ATXN10 (Affinity Capture-MS), ATXN10 (Affinity Capture-MS), ATXN10 (Affinity Capture-MS), ATXN10 (Two-hybrid), ATXN10 (Proximity Label-MS), ATXN10 (Proximity Label-MS), ATXN10 (Proximity Label-MS), ATXN10 (Proximity Label-MS), ATXN10 (Proximity Label-MS), ATXN10 (Affinity Capture-MS), ATXN10 (Affinity Capture-MS), ATXN10 (Affinity Capture-MS), ATXN10 (Affinity Capture-MS), ATXN10 (Affinity Capture-MS), ATXN10 (Affinity Capture-MS)

ESM2 similar proteins: A2AU72, A7MBJ5, E9Q912, O43028, O75602, O93614, P28658, P39968, P52306, P97536, Q04173, Q05AL1, Q0P5A6, Q16401, Q2KI54, Q2TBW0, Q4R4Y2, Q59MN0, Q5EFZ4, Q5IFJ8, Q5PPZ9, Q5R6L5, Q5R6S3, Q5RD03, Q5RE06, Q5W041, Q68FK4, Q6BTZ4, Q6C5Y8, Q6CX49, Q6FJV1, Q6NXE6, Q6ZQ38, Q757R0, Q84ZC0, Q86VP6, Q8BNU0, Q8BVE3, Q8BW49, Q8IUR7

Diamond homologs: P25355, P28658, Q09888, Q2TBW0, Q4R4Y2, Q55EI6, Q5AGE5, Q5FVB0, Q5RE06, Q6CTY9, Q6FMC0, Q75EM1, Q9ER24, Q9UBB4, Q6BKV2

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PLK1	down-regulates	ATXN10	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 128 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
ubiquitin-dependent protein catabolic process	10	7.1×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	19
Likely benign	9
Benign	18

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
3248117	NC_000022.10:g.(?45958792)(46971995_?)del	Pathogenic
39003	NM_013236.3(ATXN10):c.1173+54822_1173+54826ATTCT(360_370)	Pathogenic
39004	NM_013236.3(ATXN10):c.1173+54822_1173+54826ATTCT(400_760)	Pathogenic
39006	NM_013236.3(ATXN10):c.1173+54822_1173+54826ATTCT[850]	Pathogenic

SpliceAI

3080 predictions. Top by Δscore:

Variant	Effect	Δscore
22:45689710:A:AG	acceptor_gain	1.0000
22:45689710:AG:A	acceptor_loss	1.0000
22:45689711:G:GC	acceptor_loss	1.0000
22:45689711:G:GG	acceptor_gain	1.0000
22:45689711:GA:G	acceptor_gain	1.0000
22:45689711:GAGA:G	acceptor_gain	1.0000
22:45689711:GAGAA:G	acceptor_gain	1.0000
22:45689833:T:G	donor_gain	1.0000
22:45689900:TCAGG:T	donor_loss	1.0000
22:45689901:CAGGT:C	donor_loss	1.0000
22:45689904:G:A	donor_loss	1.0000
22:45689905:T:G	donor_loss	1.0000
22:45692985:A:AG	acceptor_gain	1.0000
22:45692986:A:G	acceptor_gain	1.0000
22:45692988:A:G	acceptor_gain	1.0000
22:45700379:G:GG	donor_gain	1.0000
22:45702683:T:A	acceptor_gain	1.0000
22:45702683:TGGAA:T	acceptor_loss	1.0000
22:45702684:GGAAG:G	acceptor_loss	1.0000
22:45702685:GAAGG:G	acceptor_loss	1.0000
22:45702686:AAGGT:A	acceptor_loss	1.0000
22:45702687:A:T	acceptor_loss	1.0000
22:45702843:TGGCC:T	donor_gain	1.0000
22:45702844:GGCC:G	donor_gain	1.0000
22:45702844:GGCCG:G	donor_gain	1.0000
22:45702845:GCC:G	donor_gain	1.0000
22:45702845:GCCG:G	donor_gain	1.0000
22:45702846:CC:C	donor_gain	1.0000
22:45702847:CGT:C	donor_loss	1.0000
22:45702848:G:C	donor_loss	1.0000

AlphaMissense

3135 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:45689852:G:C	R86T	1.000
22:45689852:G:T	R86M	1.000
22:45689860:C:A	R89S	1.000
22:45689861:G:C	R89P	1.000
22:45689851:A:G	R86G	0.999
22:45689853:G:C	R86S	0.999
22:45689853:G:T	R86S	0.999
22:45689854:T:C	C87R	0.999
22:45689858:T:C	L88P	0.999
22:45689861:G:T	R89L	0.999
22:45689865:T:A	N90K	0.999
22:45689865:T:G	N90K	0.999
22:45689866:G:C	A91P	0.999
22:45689867:C:A	A91D	0.999
22:45700301:G:C	Q137H	0.999
22:45700301:G:T	Q137H	0.999
22:45700308:G:C	G140R	0.999
22:45700309:G:A	G140D	0.999
22:45700311:A:G	N141D	0.999
22:45700313:C:A	N141K	0.999
22:45700313:C:G	N141K	0.999
22:45702843:T:A	W215R	0.999
22:45702843:T:C	W215R	0.999
22:45672149:T:C	L29P	0.998
22:45689756:T:C	L54P	0.998
22:45689845:T:C	C84R	0.998
22:45689860:C:G	R89G	0.998
22:45689871:C:G	C92W	0.998
22:45700288:G:C	R133P	0.998
22:45700293:G:C	G135R	0.998

dbSNP variants (sampled 300 via entrez): RS1000000725 (22:45845141 G>GAGA), RS1000006481 (22:45817630 T>C,G), RS1000029803 (22:45733995 G>T), RS1000040064 (22:45794766 A>G), RS1000070567 (22:45694213 T>A), RS1000091447 (22:45671498 G>A,T), RS1000096475 (22:45714226 T>C), RS1000108617 (22:45811508 C>G,T), RS1000113888 (22:45708334 G>A), RS1000117105 (22:45772776 A>C), RS1000125636 (22:45788274 C>G,T), RS1000133596 (22:45834456 G>A,C), RS1000135471 (22:45746502 G>A), RS1000148017 (22:45673821 C>T), RS1000166104 (22:45784453 C>A,T)

Disease associations

OMIM: gene MIM:611150 | disease phenotypes: MIM:603516

GenCC curated gene-disease

Disease	Classification	Inheritance
spinocerebellar ataxia type 10	Strong	Autosomal dominant

Mondo (1): spinocerebellar ataxia type 10 (MONDO:0011330)

Orphanet (1): Spinocerebellar ataxia type 10 (Orphanet:98761)

HPO phenotypes

49 total (30 of 49 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000012	Urinary urgency
HP:0000020	Urinary incontinence
HP:0000639	Nystagmus
HP:0000640	Gaze-evoked nystagmus
HP:0000716	Depression
HP:0000718	Aggressive behavior
HP:0000726	Dementia
HP:0000741	Apathy
HP:0000762	Decreased nerve conduction velocity
HP:0001250	Seizure
HP:0001260	Dysarthria
HP:0001265	Hyporeflexia
HP:0001271	Polyneuropathy
HP:0001272	Cerebellar atrophy
HP:0001290	Generalized hypotonia
HP:0001310	Dysmetria
HP:0001347	Hyperreflexia
HP:0002015	Dysphagia
HP:0002061	Lower limb spasticity
HP:0002062	Abnormal pyramidal tract morphology
HP:0002066	Gait ataxia
HP:0002067	Bradykinesia
HP:0002070	Limb ataxia
HP:0002071	Abnormality of extrapyramidal motor function
HP:0002073	Progressive cerebellar ataxia
HP:0002075	Dysdiadochokinesis
HP:0002080	Intention tremor
HP:0002133	Status epilepticus
HP:0002141	Gait imbalance

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST005994_7	Hematocrit	2.000000e-09
GCST005995_19	Hemoglobin	3.000000e-08
GCST006979_831	Heel bone mineral density	3.000000e-15
GCST006979_832	Heel bone mineral density	1.000000e-11
GCST006988_43	Blond vs. brown/black hair color	2.000000e-08
GCST008151_87	Waist circumference	5.000000e-07
GCST008160_87	Waist circumference	5.000000e-07
GCST008162_3	Hip circumference	2.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0009270	heel bone mineral density
EFO:0003924	hair color

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566874	Spinocerebellar Ataxia 10 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725023 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.99	Kd	103.2	nM	CHEMBL3752910
6.99	ED50	103.2	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 10 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147928: Binding affinity to human ATXN10 incubated for 45 mins by Kinobead based pull down assay	kd	0.1032	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
Valproic Acid	increases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
uranyl acetate	affects expression	1
bisphenol A	increases expression	1
deoxynivalenol	decreases expression	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, increases reaction	1
sulforaphane	decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benztropine	increases expression	1
Clozapine	increases expression	1
Dimethyl Sulfoxide	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ethyl Methanesulfonate	decreases expression	1
Fluorouracil	affects reaction, decreases expression	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Methyl Methanesulfonate	decreases expression	1
Ribonucleotides	affects binding	1
Tretinoin	decreases expression	1
Uranium	affects expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650970	Binding	Binding affinity to human ATXN10 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03701399	PHASE3	ACTIVE_NOT_RECRUITING	Troriluzole in Adult Participants With Spinocerebellar Ataxia
NCT04301284	PHASE2	WITHDRAWN	Study of CAD-1883 for Spinocerebellar Ataxia
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT04495426	Not specified	UNKNOWN	Genetic Mechanism of Conserved Ancestral Haplotype in SCA10