ATXN2

Summary

ATXN2 (ataxin 2, HGNC:10555) is a protein-coding gene on chromosome 12q24.12, encoding Ataxin-2 (Q99700). Involved in EGFR trafficking, acting as negative regulator of endocytic EGFR internalization at the plasma membrane.

This gene belongs to a group of genes that is associated with microsatellite-expansion diseases, a class of neurological and neuromuscular disorders caused by expansion of short stretches of repetitive DNA. The protein encoded by this gene has two globular domains near the N-terminus, one of which contains a clathrin-mediated trans-Golgi signal and an endoplasmic reticulum exit signal. The encoded cytoplasmic protein localizes to the endoplasmic reticulum and plasma membrane, is involved in endocytosis, and modulates mTOR signals, modifying ribosomal translation and mitochondrial function. The N-terminal region of the protein contains a polyglutamine tract of 14-31 residues that can be expanded in the pathogenic state to 32-200 residues. Intermediate length expansions of this tract increase susceptibility to amyotrophic lateral sclerosis, while long expansions of this tract result in spinocerebellar ataxia-2, an autosomal-dominantly inherited, neurodegenerative disorder. Genome-wide association studies indicate that loss-of-function mutations in this gene may be associated with susceptibility to type I diabetes, obesity and hypertension. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 6311 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spinocerebellar ataxia type 2 (Definitive, ClinGen)
• GWAS associations: 144
• Clinical variants (ClinVar): 243 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 117
• Druggable target: yes
• MANE Select transcript: NM_001372574

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10555
Approved symbol	ATXN2
Name	ataxin 2
Location	12q24.12
Locus type	gene with protein product
Status	Approved
Aliases	ATX2
Ensembl gene	ENSG00000204842
Ensembl biotype	protein_coding
OMIM	601517
Entrez	6311

Gene structure

Transcript identifiers

Ensembl transcripts: 80 — 59 protein_coding, 11 retained_intron, 5 protein_coding_CDS_not_defined, 5 nonsense_mediated_decay

ENST00000389153, ENST00000389154, ENST00000392645, ENST00000468920, ENST00000471866, ENST00000475132, ENST00000481331, ENST00000482777, ENST00000483311, ENST00000484991, ENST00000492467, ENST00000495342, ENST00000535949, ENST00000542287, ENST00000546483, ENST00000548492, ENST00000549455, ENST00000550104, ENST00000550236, ENST00000550844, ENST00000550889, ENST00000551551, ENST00000551755, ENST00000552323, ENST00000608853, ENST00000616825, ENST00000642389, ENST00000643474, ENST00000643669, ENST00000643694, ENST00000644883, ENST00000645162, ENST00000647305, ENST00000647445, ENST00000671792, ENST00000672105, ENST00000672335, ENST00000672613, ENST00000673273, ENST00000673283, ENST00000673436, ENST00000673449, ENST00000673557, ENST00000890889, ENST00000890890, ENST00000890891, ENST00000890892, ENST00000890893, ENST00000890894, ENST00000890895, ENST00000890896, ENST00000890897, ENST00000890898, ENST00000890899, ENST00000890900, ENST00000890901, ENST00000890902, ENST00000890903, ENST00000890904, ENST00000890905, ENST00000890906, ENST00000890907, ENST00000890908, ENST00000890909, ENST00000890910, ENST00000890911, ENST00000890912, ENST00000918148, ENST00000918149, ENST00000918150, ENST00000918151, ENST00000918152, ENST00000918153, ENST00000959513, ENST00000959514, ENST00000959515, ENST00000959516, ENST00000959517, ENST00000959518, ENST00000959519

RefSeq mRNA: 4 — MANE Select: NM_001372574 NM_001310121, NM_001310123, NM_001372574, NM_002973

CCDS: CCDS31902, CCDS81738, CCDS81739, CCDS91750

Canonical transcript exons

ENST00000673436 — 25 exons

Exon	Start	End
ENSE00002380895	111488476	111488780
ENSE00002387366	111513357	111513539
ENSE00002401831	111510385	111510582
ENSE00003465995	111552906	111552977
ENSE00003467778	111509891	111509998
ENSE00003471940	111519879	111520076
ENSE00003493266	111453677	111453845
ENSE00003506188	111554158	111554217
ENSE00003523834	111516154	111516363
ENSE00003526504	111456029	111456256
ENSE00003541896	111457214	111457359
ENSE00003551992	111470558	111470742
ENSE00003552925	111452214	111452840
ENSE00003565905	111518249	111518427
ENSE00003572230	111552280	111552430
ENSE00003594823	111486761	111486824
ENSE00003609750	111464662	111464715
ENSE00003623717	111485713	111485865
ENSE00003627297	111470108	111470240
ENSE00003635668	111509549	111509619
ENSE00003641899	111520882	111520973
ENSE00003642411	111485265	111485331
ENSE00003667178	111555883	111555919
ENSE00003686278	111525192	111525316
ENSE00003893678	111598784	111599315

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 97.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.0751 / max 513.3541, expressed in 1818 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133307	28.8122	1817
133308	2.2738	1270
133309	2.1807	1189
133300	0.6553	385
133301	0.3910	157
133306	0.3278	147
133305	0.2489	98
133299	0.1854	61

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	97.39	gold quality
colonic epithelium	UBERON:0000397	97.39	gold quality
olfactory bulb	UBERON:0002264	96.09	gold quality
sural nerve	UBERON:0015488	95.86	gold quality
ventricular zone	UBERON:0003053	95.77	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.53	gold quality
right uterine tube	UBERON:0001302	94.44	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.16	gold quality
adrenal tissue	UBERON:0018303	94.07	gold quality
cortical plate	UBERON:0005343	93.98	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.97	gold quality
right ovary	UBERON:0002118	93.95	gold quality
right frontal lobe	UBERON:0002810	93.85	gold quality
adenohypophysis	UBERON:0002196	93.66	gold quality
left ovary	UBERON:0002119	93.65	gold quality
endocervix	UBERON:0000458	93.64	gold quality
stromal cell of endometrium	CL:0002255	93.63	gold quality
ganglionic eminence	UBERON:0004023	93.61	gold quality
calcaneal tendon	UBERON:0003701	93.59	gold quality
secondary oocyte	CL:0000655	93.57	gold quality
cerebellar cortex	UBERON:0002129	93.53	gold quality
oocyte	CL:0000023	93.52	gold quality
cerebellar hemisphere	UBERON:0002245	93.52	gold quality
prefrontal cortex	UBERON:0000451	93.41	gold quality
right adrenal gland cortex	UBERON:0035827	93.30	gold quality
tibial nerve	UBERON:0001323	93.21	gold quality
right adrenal gland	UBERON:0001233	93.19	gold quality
spinal cord	UBERON:0002240	93.19	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.15	gold quality
left adrenal gland cortex	UBERON:0035825	93.11	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.51
E-CURD-46	no	5.43

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETS1, NR1I2, ZNF350

miRNA regulators (miRDB)

81 targeting ATXN2, 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-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-145-5P	99.92	71.13	1836

Literature-anchored findings (GeneRIF, showing 40)

• Identification of two novel single nucleotide polymorphisms (SNPs) in exon 1 of the SCA2 gene. The two biallelic SNPs distinguished two haplotypes, GT and CC. (PMID:11689490)
• The SCA2 gene maps to chromosome 12q24 and the causative mutation involves the expansion of a CAG repeat within the coding region of the gene. (PMID:11872620)
• dysregulation of actin cytoskeletal structure resulting from altered ataxin-2 activity may be responsible for neurodegeneration in SCA2 (PMID:12524342)
• ataxin-2 has an important role in regulating the susceptibility of neuroblastoma cells to apoptotic stimuli in vitro and in vivo (PMID:12545161)
• SCA2 mutations may be responsible for a subset of familial parkinsonism. (PMID:12671950)
• The significance of SCA2 mutation in either sporadic or familial young-onset dopa-responsive parkinsonism suggestive of Parkinson’s disease is not proven in a population of 85 Serbian patients. (PMID:12940846)
• This study observed significant volume loss in the cerebellar hemispheres, vermis, pons, mesencephalon and thalamus. also affected the right orbito-frontal cortex, right temporo-mesial cortex and the primary sensorimotor cortex bilaterally. (PMID:14534423)
• no significant difference when APOE and SCA2 allele frequencies of cases and controls were compared for multiple sclerosis (PMID:15124760)
• exploration of protein architectures of ataxin-2 and ataxin-3 (PMID:15265035)
• SCA2 genotypes in a Polish population are significantly different in allele spectra & frequencies from other populations. The dynamic mutation of SCA2 may begin from the expansion of long pure repeat tracts without the prior loss of interruptions. (PMID:15300851)
• the properties of the CAA interruptions are major determinants of the CAG repeat folding in the normal SCA2 transcripts. (PMID:15533937)
• ATX2 and poly(A)-binding protein (PABC) co-localize in mammalian cells, remarkably, even under conditions in which PABP accumulates in distinct cytoplasmic foci representing sites of mRNA triage (PMID:15663938)
• presence of significant floccular atrophy compared with controls in both ataxin-2 and Ca(V)2.1 mutations (PMID:15826995)
• our analysis showed that all SCA2 mutations carriers had the same ataxin 2 haplotype: haplotype B, which accounts for only 15% of control haplotypes, implying that there is a common founder for all Taiwanese SCA2 patients (PMID:16078202)
• There is an interplay between ataxin-2, endophilin proteins and huntingtin in plastin-associated cellular pathways. (PMID:16115810)
• A recent positive selection of the pre-expansion SCA2 CAG repeat has occurred in Utah residents with European ancestry. (PMID:16205789)
• ATX2 plays a direct role in translational regulation, and polyglutamine expansions within ataxin-2 may cause neurodegeneration by interfering with the translational regulation of particular mRNAs. (PMID:16835262)
• the molecular intrinsic structure of the expanded allele may modulate the phenotypic expression of the SCA2 mutation. (PMID:17149720)
• To investigate the role of SCA2 and SCA3 mutations in Chinese familial and early-onset Parkinson’s disease (PD) patients, CAG triplet repeat expansions of SCA2 and SCA3 genes in 73 Taiwanese/Ethnic Chinese PD patients was analyzed. (PMID:17440947)
• We determined the prevalence of SCA2 and SCA3 mutations in a cohort of ET and atypical Parkinsonism patients. (PMID:17712857)
• Molecular testing for spinocerebellar ataxia type 2 revealed abnormal “cytosineadenine-guanosine” expansion in all affected family members. (PMID:17715286)
• SCA2 gene dosage influences the age of onset for Spinocerebellar Ataxia Type 2 [case report] (PMID:17850638)
• SCA2 is one of the genetic causes of Parkinson disease and multiple system atrophy (PMID:17923635)
• Data show that SCA1, 2 and 3 accounted for more than one third of the ataxia cases seen in the clinic, and in cases with established family history and autosomal dominant inheritance SCA1 was most prevalent followed by SCA2 and SCA3. (PMID:18160752)
• Homozygous SCA2 patients develop levodopa responsive Parkinsonism and dyskinesia and motor fluctuations suggesting a pre-synaptic lesion and eventually progress to dementia with psychosis and ataxia. Slow eye movements are absent at onset but appear later (PMID:18265007)
• These data implicate ataxin-2 to play a role in endocytic receptor cycling. (PMID:18602463)
• rate of clinical disease progression at presentation, especially in SCA2, is dependent on the CAG repeat size, and may commence linearly from birth (PMID:19049837)
• although motor learning capabilities are intact, motor performance deficits are present even years before the clinical manifestation of spinocerebellar ataxia type 2 gene carriers (PMID:19401771)
• analysis of the common origin of pure and interrupted repeat expansions in spinocerebellar ataxia type 2 (PMID:19676102)
• To elucidate a potential role for ATXN2 in human obesity, the coding region of ATXN2 in 92 patients with severe obesity of early onset, was examined. (PMID:20016785)
• Structural basis of binding of P-body-associated proteins GW182 and ataxin-2 by the Mlle domain of poly(A)-binding protein.( (PMID:20181956)
• data establish ATXN2 as a relatively common ALS susceptibility gene (PMID:20740007)
• ataxin-2 acts as a co-regulator of ZBRK1 activating its own transcription, thereby representing the first identified ZBRK1 co-activator. (PMID:20926453)
• Polyglutamine expansions in ataxin 2 are a risk factor for amyotrophic lateral sclerosis. (PMID:21292779)
• In Korean population, the mutation frequencies of SCA2 and SCA17 were similar. SCA2 was a more significant cause of ataxia. (PMID:21334959)
• The expansions in ATXN2 associated with amyotrophic lateral sclerosis were determined to be pure or interrupted CAG repeats. (PMID:21479228)
• the six ethnic groups had their own distribution characterizations of allelic frequencies of ATXN2 STR, and the potential cause of frequency changes in rare alleles could be the consequence of positive selection. (PMID:21482525)
• ATXN-2 CAG repeat expansions are interrupted in amyotrophic lateral sclerosis. (PMID:21537950)
• Data reveal a novel genetic overlap between ALS and SCA2, based on expanded ATXN2 CAG repeat size. (PMID:21562247)
• Expanded ATXN2 repeats may predispose to other neurodegenerative diseases, including progressive supranuclear palsy. (PMID:21610160)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	atxn2	ENSDARG00000052897
mus_musculus	Atxn2	ENSMUSG00000042605
rattus_norvegicus	Atxn2	ENSRNOG00000001256
caenorhabditis_elegans		WBGENE00000231

Paralogs (1): ATXN2L (ENSG00000168488)

Protein

Protein identifiers

Ataxin-2 — Q99700 (reviewed: Q99700)

Alternative names: Spinocerebellar ataxia type 2 protein, Trinucleotide repeat-containing gene 13 protein

All UniProt accessions (24): A0A2R8Y5A6, A0A2R8Y6W7, A0A2R8Y7E6, A0A2R8Y7P6, A0A2R8YCG6, A0A2R8YDM9, A0A2R8YGV1, A0A5F9ZH85, A0A5F9ZHG6, A0A5F9ZHH4, A0A5F9ZHW5, A0A5F9ZHX3, A0A5F9ZI57, Q99700, F8VQP2, F8VRK6, F8VZC1, F8W0B5, F8WB05, F8WB06, H0YH87, S4R3J6, S4R3R6, V9GY86

UniProt curated annotations — full annotation on UniProt →

Function. Involved in EGFR trafficking, acting as negative regulator of endocytic EGFR internalization at the plasma membrane.

Subunit / interactions. Monomer. Can also form homodimers. Interacts with TARDBP; the interaction is RNA-dependent. Interacts with RBFOX1. Interacts with polyribosomes. Interacts with SH3GL2 and SH3GL3. Interacts with SH3KBP1 and CBL. Interacts with EGFR. Interacts with ATXN2L.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in the brain, heart, liver, skeletal muscle, pancreas and placenta. Isoform 1 is predominant in the brain and spinal cord. Isoform 4 is more abundant in the cerebellum. In the brain, broadly expressed in the amygdala, caudate nucleus, corpus callosum, hippocampus, hypothalamus, substantia nigra, subthalamic nucleus and thalamus.

Disease relevance. Spinocerebellar ataxia 2 (SCA2) [MIM:183090] 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 cerebellum degeneration with variable involvement of the brainstem and spinal cord. SCA2 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. SCA2 is characterized by hyporeflexia, myoclonus and action tremor and dopamine-responsive parkinsonism. In some patients, SCA2 presents as pure familial parkinsonism without cerebellar signs. The disease is caused by variants affecting the gene represented in this entry. SCA2 is caused by expansion of a CAG repeat resulting in about 36 to 52 repeats in some patients. Longer expansions result in earlier the expansion, onset of the disease. Amyotrophic lateral sclerosis 13 (ALS13) [MIM:183090] A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. Disease susceptibility is associated with variants affecting the gene represented in this entry. An increased risk for developing amyotrophic lateral sclerosis seems to be conferred by CAG repeat intermediate expansions greater than 23 but below the threshold for developing spinocerebellar ataxia.

Polymorphism. The poly-Gln region of ATXN2 is polymorphic: 17 to 29 repeats are found in the normal population. Higher numbers of repeats result in different disease phenotypes depending on the length of the expansion.

Similarity. Belongs to the ataxin-2 family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q99700-1	1	yes
Q99700-2	2
Q99700-3	3
Q99700-4	4
Q99700-5	5

RefSeq proteins (4): NP_001297050, NP_001297052, NP_001359503, NP_002964 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009604	LsmAD_domain	Domain
IPR009818	PAM2_motif	Conserved_site
IPR010920	LSM_dom_sf	Homologous_superfamily
IPR025852	SM_dom_ATX	Domain
IPR045117	ATXN2-like	Family
IPR047575	Sm	Domain

Pfam: PF06741, PF07145, PF14438

UniProt features (69 total): compositionally biased region 26, modified residue 22, splice variant 12, region of interest 3, sequence variant 2, chain 1, domain 1, cross-link 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3KTR	X-RAY DIFFRACTION	1.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99700-F1	46.41	0.06

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 (23): 248, 393, 466, 478, 508, 554, 624, 640, 640, 642, 684, 728, 741, 772, 784, 856, 857, 861, 865, 867 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 421 (showing top): BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, GOBP_P_BODY_ASSEMBLY, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, TTTGTAG_MIR520D, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_NEGATIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, GOCC_TRANS_GOLGI_NETWORK, UEDA_PERIFERAL_CLOCK, GOBP_REGULATION_OF_RECEPTOR_INTERNALIZATION

GO Biological Process (6): negative regulation of receptor internalization (GO:0002091), regulation of translation (GO:0006417), RNA metabolic process (GO:0016070), P-body assembly (GO:0033962), stress granule assembly (GO:0034063), RNA transport (GO:0050658)

GO Molecular Function (4): RNA binding (GO:0003723), mRNA binding (GO:0003729), epidermal growth factor receptor binding (GO:0005154), protein binding (GO:0005515)

GO Cellular Component (8): cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), trans-Golgi network (GO:0005802), cytosol (GO:0005829), cytoplasmic stress granule (GO:0010494), membrane (GO:0016020), perinuclear region of cytoplasm (GO:0048471), ribonucleoprotein complex (GO:1990904)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
membraneless organelle assembly	2
regulation of receptor internalization	1
receptor internalization	1
negative regulation of receptor-mediated endocytosis	1
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
nucleic acid metabolic process	1
nucleic acid transport	1
establishment of RNA localization	1
nucleic acid binding	1
RNA binding	1
growth factor receptor binding	1
binding	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
Golgi apparatus subcompartment	1
cytoplasmic ribonucleoprotein granule	1
protein-containing complex	1

Protein interactions and networks

STRING

2716 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATXN2	RBFOX1	Q9NWB1	995
ATXN2	TARDBP	Q13148	984
ATXN2	ITPR1	Q14643	969
ATXN2	ATXN1	P54253	955
ATXN2	ATXN3	P54252	939
ATXN2	DDX6	P26196	934
ATXN2	FUS	P35637	918
ATXN2	ATXN7	O15265	912
ATXN2	TIA1	P31483	887
ATXN2	PABPC1	P11940	876
ATXN2	FMR1	Q06787	871
ATXN2	C9orf72	Q96LT7	857
ATXN2	CACNA1A	P78510	855
ATXN2	G3BP1	Q13283	838
ATXN2	ATN1	P54259	831

IntAct

224 interactions, top by confidence:

A	B	Type	Score
DDX6	ATXN2	psi-mi:“MI:0915”(physical association)	0.890
DDX6	ATXN2	psi-mi:“MI:0403”(colocalization)	0.890
ATXN2	PABPC1	psi-mi:“MI:0915”(physical association)	0.820
ATXN2	PABPC1	psi-mi:“MI:0403”(colocalization)	0.820
PABPC1	ATXN2	psi-mi:“MI:0407”(direct interaction)	0.820
PABPC1	ATXN2	psi-mi:“MI:0403”(colocalization)	0.820
OAZ3	AZIN1	psi-mi:“MI:0914”(association)	0.800
CCNDBP1	RPLP0	psi-mi:“MI:0914”(association)	0.800
ATXN2	SH3GL2	psi-mi:“MI:0915”(physical association)	0.780
SH3GL2	ATXN2	psi-mi:“MI:0915”(physical association)	0.780
ATXN2	SH3GL3	psi-mi:“MI:0915”(physical association)	0.760
SH3GL3	ATXN2	psi-mi:“MI:0915”(physical association)	0.760

BioGRID (420): ATXN2 (Affinity Capture-RNA), ATXN2 (Affinity Capture-RNA), ATXN2 (Affinity Capture-MS), ATXN2 (Affinity Capture-MS), ATXN2 (Affinity Capture-MS), ATXN2 (Affinity Capture-MS), ATXN2 (Affinity Capture-MS), ATXN2 (Affinity Capture-MS), ATXN2 (Affinity Capture-MS), ATXN2 (Affinity Capture-MS), ATXN2 (Affinity Capture-MS), ATXN2 (Co-fractionation), ATXN2 (Co-fractionation), ATXN2 (Co-fractionation), ATXN2 (Co-fractionation)

ESM2 similar proteins: A0A087WPF7, A0A0R4IBL7, O09000, O54972, O70305, O75081, O75376, P15806, P15881, P15884, P15923, P21677, P30985, P51514, P98180, Q05AQ8, Q14157, Q14687, Q1LY51, Q2VPM4, Q3U3C9, Q4KKX4, Q4VCS5, Q566L4, Q5F3B1, Q5SFM8, Q5T6F2, Q60722, Q60974, Q61286, Q62655, Q6DIH5, Q7ZWN6, Q7ZXS3, Q80X50, Q86YP4, Q8BZ47, Q8CHY6, Q8IXK0, Q8VHG2

Diamond homologs: O70305, Q29A33, Q7TQH0, Q8SWR8, Q8WWM7, Q99700, P53297, Q55DE7, Q94AM9, Q8L793

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ATXN2	unknown	DDX6	binding
FUS	“down-regulates quantity by repression”	ATXN2	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 200 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Translation initiation complex formation	10	14.8×	1e-07
Formation of the ternary complex, and subsequently, the 43S complex	8	13.4×	7e-06
Ribosomal scanning and start codon recognition	9	13.3×	1e-06
L13a-mediated translational silencing of Ceruloplasmin expression	16	12.5×	8e-11
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	13	11.9×	8e-09
GTP hydrolysis and joining of the 60S ribosomal subunit	15	11.7×	7e-10
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	15	11.3×	7e-10
Formation of a pool of free 40S subunits	13	11.3×	1e-08

GO biological processes:

GO term	Partners	Fold	FDR
formation of cytoplasmic translation initiation complex	5	31.4×	8e-05
translational initiation	9	18.0×	5e-07
stress granule assembly	5	16.8×	2e-03
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	6	15.7×	4e-04
cytoplasmic translation	12	12.4×	1e-07
regulation of mRNA stability	5	11.8×	5e-03
negative regulation of translation	10	10.9×	7e-06
regulation of alternative mRNA splicing, via spliceosome	7	9.6×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	162
Likely benign	28
Benign	15

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3238749	NM_001372574.1(ATXN2):c.18GCA[43] (p.Gln28_Pro29insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln)	Pathogenic
3775779	NM_001372574.1(ATXN2):c.18GCA[38] (p.Gln28_Pro29insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln)	Likely pathogenic
3779390	NM_001372574.1(ATXN2):c.30_58del (p.Gln11fs)	Likely pathogenic

SpliceAI

5596 predictions. Top by Δscore:

Variant	Effect	Δscore
12:111446203:G:GT	donor_gain	1.0000
12:111447032:GG:G	donor_gain	1.0000
12:111447033:GG:G	donor_gain	1.0000
12:111447327:CAGG:C	acceptor_loss	1.0000
12:111447328:AGGTG:A	acceptor_loss	1.0000
12:111447505:GGAA:G	donor_gain	1.0000
12:111447506:GAA:G	donor_gain	1.0000
12:111447540:CCAAG:C	donor_loss	1.0000
12:111447541:CAAGG:C	donor_loss	1.0000
12:111447542:AAGG:A	donor_loss	1.0000
12:111447543:AGG:A	donor_loss	1.0000
12:111447545:G:C	donor_loss	1.0000
12:111447546:T:G	donor_loss	1.0000
12:111447654:A:AG	acceptor_gain	1.0000
12:111447655:G:GG	acceptor_gain	1.0000
12:111447655:GC:G	acceptor_gain	1.0000
12:111447655:GCA:G	acceptor_gain	1.0000
12:111447799:C:G	donor_gain	1.0000
12:111457360:C:CC	acceptor_gain	1.0000
12:111470738:TGGTA:T	acceptor_gain	1.0000
12:111470741:TA:T	acceptor_gain	1.0000
12:111470743:C:CC	acceptor_gain	1.0000
12:111485333:T:C	acceptor_gain	1.0000
12:111485706:GACTT:G	donor_loss	1.0000
12:111485707:ACTT:A	donor_loss	1.0000
12:111485708:CTTAC:C	donor_loss	1.0000
12:111485709:TTA:T	donor_loss	1.0000
12:111485710:T:TC	donor_loss	1.0000
12:111485711:A:AC	donor_gain	1.0000
12:111485712:C:CC	donor_gain	1.0000

AlphaMissense

7562 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:111486782:G:C	F921L	1.000
12:111486782:G:T	F921L	1.000
12:111486783:A:C	F921C	1.000
12:111486783:A:G	F921S	1.000
12:111486784:A:G	F921L	1.000
12:111486800:A:C	N915K	1.000
12:111486800:A:T	N915K	1.000
12:111486804:A:G	L914S	1.000
12:111509565:A:G	F800S	1.000
12:111519975:C:G	R457P	1.000
12:111520002:A:C	I448S	1.000
12:111520002:A:T	I448N	1.000
12:111520012:C:G	A445P	1.000
12:111520024:C:G	A441P	1.000
12:111520030:C:G	A439P	1.000
12:111520035:C:G	R437P	1.000
12:111520043:A:C	F434L	1.000
12:111520043:A:T	F434L	1.000
12:111520045:A:G	F434L	1.000
12:111520068:A:G	L426S	1.000
12:111520907:A:C	Y415D	1.000
12:111520912:G:A	S413F	1.000
12:111520935:A:C	N405K	1.000
12:111520935:A:T	N405K	1.000
12:111520944:A:C	F402L	1.000
12:111520944:A:T	F402L	1.000
12:111520945:A:C	F402C	1.000
12:111520945:A:G	F402S	1.000
12:111520946:A:G	F402L	1.000
12:111520962:C:A	W396C	1.000

dbSNP variants (sampled 300 via entrez): RS1000036918 (12:111591077 A>C), RS1000053462 (12:111492623 G>A), RS1000057956 (12:111453982 G>A,C,T), RS1000101851 (12:111499664 A>C,T), RS1000106179 (12:111537787 A>G), RS1000108651 (12:111543214 T>A,C,G), RS1000118856 (12:111544228 T>C), RS1000133414 (12:111585188 G>A), RS1000176428 (12:111585958 C>T), RS1000198874 (12:111563399 G>A,T), RS1000217801 (12:111567588 C>A,T), RS1000218366 (12:111480118 A>T), RS1000240670 (12:111569619 G>A), RS1000246914 (12:111550024 T>C), RS1000288508 (12:111557140 A>T)

Disease associations

OMIM: gene MIM:601517 | disease phenotypes: MIM:183090, MIM:168600, MIM:609056

GenCC curated gene-disease

Disease	Classification	Inheritance
spinocerebellar ataxia type 2	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
spinocerebellar ataxia type 2	Definitive	AD

Mondo (5): spinocerebellar ataxia type 2 (MONDO:0008458), late-onset Parkinson disease (MONDO:0008199), GM3 synthase deficiency (MONDO:0018274), amyotrophic lateral sclerosis, susceptibility to, 13 (MONDO:0800224), amyotrophic lateral sclerosis (MONDO:0004976)

Orphanet (6): Spinocerebellar ataxia type 2 (Orphanet:98756), Hereditary late-onset Parkinson disease (Orphanet:411602), Amish infantile epilepsy syndrome (Orphanet:171714), GM3 synthase deficiency (Orphanet:370933), Amyotrophic lateral sclerosis (Orphanet:803), Salt-and-pepper syndrome (Orphanet:370938)

HPO phenotypes

117 total (30 of 117 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000012	Urinary urgency
HP:0000020	Urinary incontinence
HP:0000217	Xerostomia
HP:0000298	Mask-like facies
HP:0000510	Rod-cone dystrophy
HP:0000514	Slow saccadic eye movements
HP:0000597	Ophthalmoparesis
HP:0000602	Ophthalmoplegia
HP:0000623	Supranuclear ophthalmoplegia
HP:0000639	Nystagmus
HP:0000640	Gaze-evoked nystagmus
HP:0000641	Dysmetric saccades
HP:0000657	Oculomotor apraxia
HP:0000708	Atypical behavior
HP:0000712	Emotional lability
HP:0000716	Depression
HP:0000726	Dementia
HP:0000738	Hallucinations
HP:0000739	Anxiety
HP:0000751	Personality changes
HP:0001151	Impaired horizontal smooth pursuit
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001265	Hyporeflexia
HP:0001272	Cerebellar atrophy
HP:0001290	Generalized hypotonia
HP:0001300	Parkinsonism

GWAS associations

144 associations (top):

Study	Trait	p-value
GCST000157_7	Celiac disease	8.000000e-08
GCST000394_4	Diastolic blood pressure	3.000000e-18
GCST000502_1	Hematocrit	1.000000e-12
GCST000649_24	Chronic kidney disease	4.000000e-11
GCST000847_3	Retinal vascular caliber	2.000000e-13
GCST001236_6	Blood pressure	7.000000e-20
GCST001474_12	Hypothyroidism	3.000000e-12
GCST001765_12	Red blood cell traits	4.000000e-19
GCST001791_45	Urate levels	7.000000e-12
GCST001863_1	Beta-2 microglubulin plasma levels	3.000000e-08
GCST002186_6	Platelet count	5.000000e-11
GCST002373_2	Thyroid peroxidase antibody levels	1.000000e-07
GCST002378_2	Thyroid peroxidase antibody positivity	1.000000e-09
GCST002504_1	Peripheral artery disease	6.000000e-07
GCST003043_77	Inflammatory bowel disease	1.000000e-08
GCST003044_55	Crohn’s disease	7.000000e-08
GCST003129_17	Primary biliary cholangitis	3.000000e-08
GCST003155_15	Systemic lupus erythematosus	4.000000e-09
GCST003273_1	Diastolic blood pressure	5.000000e-07
GCST003273_13	Diastolic blood pressure	1.000000e-08
GCST003342_3	Glaucoma (primary open-angle)	9.000000e-10
GCST003988_7	Hypothyroidism	1.000000e-26
GCST004131_54	Inflammatory bowel disease	2.000000e-09
GCST004132_84	Crohn’s disease	7.000000e-07
GCST004267_5	Blood osmolality (transformed sodium)	2.000000e-06
GCST004293_3	Glomerular filtration rate (cystatin C)	2.000000e-08
GCST004600_9	Eosinophil percentage of white cells	3.000000e-120
GCST004602_162	Mean corpuscular volume	1.000000e-09
GCST004603_117	Platelet count	3.000000e-34
GCST004606_73	Eosinophil count	1.000000e-180

EFO canonical traits (45, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0004348	hematocrit
EFO:0004617	cystatin C measurement
EFO:0004731	eye measurement
EFO:0006340	mean arterial pressure
EFO:0004509	hemoglobin measurement
EFO:0004531	urate measurement
EFO:0005197	beta-2 microglobulin measurement
EFO:0004309	platelet count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007985	platelet crit
EFO:0007986	reticulocyte count
EFO:0007984	platelet component distribution width
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0005091	monocyte count
EFO:0008205	left ventricular structural measurement
EFO:0004340	body mass index
EFO:0004329	alcohol drinking
EFO:0006527	smoking status measurement
EFO:0006335	systolic blood pressure
EFO:0008393	reaction time measurement
EFO:0004695	intraocular pressure measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0007796	parental longevity
EFO:0004318	smoking behavior

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D000690	Amyotrophic Lateral Sclerosis	C10.228.854.139; C10.574.562.250; C10.574.950.050; C10.668.467.250; C18.452.845.800.050

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1795085 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

26 measured of 26 human assays (26 total across all organisms); most potent 26 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEM-US-00055	IC50	4 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors
CHEM-US-00046	IC50	5 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors
6-((3aR,6aR)-octahydropyrrolo[3,4-	IC50	5 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors
CHEM-US-00042	IC50	6 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors
6-[(3aR,6aR)-5-[2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridine-4-carbonyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-2-carbonyl]pyridine-3-sulfonamide	IC50	6 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors
(3aS,8aR)-6-[2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridine-4-carbonyl]-N-[(3-oxo-1,2-oxazol-5-yl)methyl]-1,3,3a,4,5,7,8,8a-octahydropyrrolo[3,4-d]azepine-2-carboxamide	IC50	6 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors
CHEM-US-00043	IC50	7 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors
CHEM-US-00056	IC50	7 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors
CHEM-US-00041	IC50	8 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors
CHEM-US-00040	IC50	9 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors
6-[(3aR,6aR)-5-[2-cyclopropyl-6-(oxan-3-ylmethoxy)pyridine-4-carbonyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-2-carbonyl]pyridine-3-sulfonamide	IC50	9 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors
6-[(3aR,6aR)-5-[5-cyclopropyl-6-(oxan-3-yloxy)pyridine-3-carbonyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-2-carbonyl]pyridine-3-sulfonamide	IC50	10 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors
6-[(3aS,8aR)-6-[2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridine-4-carbonyl]-1,3,3a,4,5,7,8,8a-octahydropyrrolo[3,4-d]azepine-2-carbonyl]-5,7-dihydro-4H-[1,2]oxazolo[5,4-c]pyridin-3-one	IC50	10 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors
6-((3aS,6aS)-5-(5-Cyclopropyl-6-(tetrahydro-2H-pyran-4-yloxy)nicotinoyl)octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)benzo[d]oxazol-2(3H)-one	IC50	12 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors
CHEM-US-00060	IC50	13 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors
BDBM352333	IC50	14 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors
1-[(3aR,6aR)-2-[2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridine-4-carbonyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carbonyl]piperidine-4-sulfonamide	IC50	16 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors
CHEM-US-00038	IC50	17 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors
CHEM-US-00054	IC50	19 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors
4-[(3aS,6aR)-5-[2-cyclopropyl-6-(oxan-4-ylmethoxy)pyridine-4-carbonyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-2-carbonyl]benzenesulfonamide	IC50	19 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors
CHEM-US-00045	IC50	20 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors
[(3aS,6aS)-5-[5-cyclopropyl-6-(oxan-4-yloxy)pyridine-3-carbonyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-(2,3,3a,4,5,6,7,7a-octahydro-1H-benzotriazol-5-yl)methanone	IC50	20 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors
CHEM-US-00039	IC50	22 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors
5-((3aS,6aS)-5-(5-Cyclopropyl-6-(tetrahydro-2H-pyran-4-yloxy)nicotinoyl)octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)pyridine-2-sulfonamide	IC50	29 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors
6-(((3aS,6aS)-5-(5-Cyclopropyl-6-(tetrahydro-2H-pyran-4-yloxy)nicotinoyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)methyl)benzo[d]oxazol-2(3H)-one	IC50	39 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors
4-((3aR,6aS)-5-(5-Cyclopropyl-6-(tetrahydro-2H-pyran-4-yloxy)nicotinoyl)octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)benzenesulfonamide	IC50	91 nM	US-9802944: Bicyclic compounds as autotaxin (ATX) and lysophosphatidic acid (LPA) production inhibitors

ChEMBL bioactivities

183 potent at pChembl≥5 of 183 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	IC50	1	nM	CHEMBL5853724
9.00	IC50	1	nM	CHEMBL5742822
9.00	IC50	1	nM	CHEMBL5942504
9.00	IC50	1	nM	CHEMBL5891838
9.00	IC50	1	nM	CHEMBL6045323
9.00	IC50	1	nM	CHEMBL6056368
9.00	IC50	1	nM	CHEMBL5864526
8.70	IC50	2	nM	CHEMBL5838559
8.60	IC50	2.5	nM	CHEMBL6007231
8.60	IC50	2.5	nM	CHEMBL5936761
8.52	IC50	3	nM	CHEMBL5933692
8.52	IC50	3	nM	CHEMBL5820330
8.52	IC50	3	nM	CHEMBL5958918
8.52	IC50	3	nM	CHEMBL5905590
8.40	IC50	4	nM	CHEMBL5933692
8.35	IC50	4.5	nM	CHEMBL5763641
8.35	IC50	4.5	nM	CHEMBL5838015
8.30	IC50	5	nM	CHEMBL5933692
8.30	IC50	5	nM	CHEMBL5990103
8.30	IC50	5	nM	CHEMBL5958918
8.30	IC50	5	nM	CHEMBL5886430
8.30	IC50	5	nM	CHEMBL5800521
8.22	IC50	6	nM	CHEMBL5933692
8.22	IC50	6	nM	CHEMBL5843544
8.22	IC50	6	nM	CHEMBL6017850
8.22	IC50	6	nM	CHEMBL6052537
8.22	IC50	6	nM	CHEMBL5994085
8.22	IC50	6	nM	CHEMBL6035974
8.15	IC50	7	nM	CHEMBL5933692
8.15	IC50	7	nM	CHEMBL6015917
8.15	IC50	7	nM	CHEMBL6036191
8.15	IC50	7	nM	CHEMBL6052537
8.15	IC50	7	nM	CHEMBL5990906
8.10	IC50	8	nM	CHEMBL5933692
8.10	IC50	8	nM	CHEMBL5955789
8.10	IC50	8	nM	CHEMBL5826249
8.05	IC50	9	nM	CHEMBL5933692
8.05	IC50	9	nM	CHEMBL5880994
8.05	IC50	9	nM	CHEMBL5755832
8.05	IC50	9	nM	CHEMBL5966115
8.00	IC50	10	nM	CHEMBL5990463
8.00	IC50	10	nM	CHEMBL5884918
8.00	IC50	10	nM	CHEMBL5860665
8.00	IC50	10	nM	CHEMBL5927896
8.00	IC50	10	nM	CHEMBL5879507
8.00	IC50	10	nM	CHEMBL5823546
8.00	IC50	10	nM	CHEMBL6052537
8.00	IC50	10	nM	CHEMBL5875314
7.98	IC50	10.5	nM	CHEMBL5870399
7.96	IC50	11	nM	CHEMBL5988012

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases reaction, increases expression, increases abundance, affects binding, affects reaction	3
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	3
bisphenol A	affects cotreatment, decreases expression, decreases methylation	2
cadmium sulfate	increases expression	2
Arsenic	affects methylation, increases abundance, increases expression	2
Cisplatin	affects cotreatment, decreases expression	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
beta-lapachone	decreases expression, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	affects phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
bisphenol B	increases expression	1
abrine	increases expression	1
perfluorobutanesulfonic acid	decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Fulvestrant	increases methylation	1
Vehicle Emissions	decreases expression, increases abundance	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Gallic Acid	increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, decreases expression	1

ChEMBL screening assays

5 unique, capped per target: 3 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1794367	Functional	PUBCHEM_BIOASSAY: qHTS for Inhibitors of ATXN expression: Validation. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID588349, AID588380]	PubChem BioAssay data set
CHEMBL5650971	Binding	Binding affinity to human ATXN2 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

Cellosaurus cell lines

24 cell lines: 18 induced pluripotent stem cell, 5 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_9U78	H271 C1	Induced pluripotent stem cell	Male
CVCL_AB81	H196 C7	Induced pluripotent stem cell	Male
CVCL_AB82	H266 C10	Induced pluripotent stem cell	Female
CVCL_D1LL	Abcam K-562 ATXN2 KO	Cancer cell line	Female
CVCL_D2I7	Abcam Raji ATXN2 KO	Cancer cell line	Male
CVCL_D8ZT	Ubigene HEK293 ATXN2 KO	Transformed cell line	Female
CVCL_DQ63	H196 C7 GC	Induced pluripotent stem cell	Male
CVCL_DQ64	H266 C10 GC	Induced pluripotent stem cell	Female
CVCL_DQ65	H271 C1 GC	Induced pluripotent stem cell	Male
CVCL_SE30	HAP1 ATXN2 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00455143	PHASE4	TERMINATED	Cognitive Protection - Dexmedetomidine and Cognitive Reserve
NCT00561678	PHASE4	COMPLETED	Perioperative Cognitive Function - Dexmedetomidine and Cognitive Reserve
NCT01807481	PHASE4	UNKNOWN	Phase IV Study to Evaluate the Efficacy and Safety of Mircera in PD
NCT00542412	PHASE4	COMPLETED	CARE Canadian ALS Riluzole Evaluation
NCT00560287	PHASE4	UNKNOWN	Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis
NCT00613899	PHASE4	COMPLETED	Feasibility of Telesurveillance and Home Cough Assistance for Amyotrophic Lateral Patients (ALS)
NCT04997954	PHASE4	UNKNOWN	EMERALD TRIAL Open Label Extension Study
NCT06849115	PHASE4	COMPLETED	Effects of L-Carnitine in Amyotrophic Lateral Sclerosis Patients With CHCHD10 Mutations
NCT07223723	PHASE4	RECRUITING	A Study to Learn More About the Long-Term Safety of Tofersen (Qalsody) in Chinese Participants With SOD-1 Amyotrophic Lateral Sclerosis (ALS)
NCT03347344	PHASE3	COMPLETED	Clinical Trial With Riluzole in Spinocerebellar Ataxia Type 2 (ATRIL)
NCT03408080	PHASE3	ACTIVE_NOT_RECRUITING	Open Pilot Trial of BHV-4157
NCT03701399	PHASE3	ACTIVE_NOT_RECRUITING	Troriluzole in Adult Participants With Spinocerebellar Ataxia
NCT07015671	PHASE3	COMPLETED	Bioavailability and Bioequivalence Study of ER Torsemide and Spironolactone FDC Tablet in Healthy Subjects
NCT00021697	PHASE3	COMPLETED	Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS
NCT00035815	PHASE3	COMPLETED	Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial
NCT00047723	PHASE3	COMPLETED	Minocycline to Treat Amyotrophic Lateral Sclerosis
NCT00069186	PHASE3	UNKNOWN	Study of Creatine Monohydrate in Patients With Amyotrophic Lateral Sclerosis
NCT00136110	PHASE3	COMPLETED	Trial of Sodium Valproate in Amyotrophic Lateral Sclerosis
NCT00330681	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS)
NCT00349622	PHASE3	COMPLETED	Clinical Trial Ceftriaxone in Subjects With ALS
NCT00372879	PHASE3	COMPLETED	Clinical Trial of Vitamin E to Treat Muscular Cramps in Patients With ALS
NCT00415519	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS) Who Met Severity Classification III
NCT00424463	PHASE3	COMPLETED	Expanded Controlled Study of Safety and Efficacy of MCI-186 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT00839033	PHASE3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT00868166	PHASE3	COMPLETED	Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From ALS
NCT00965497	PHASE3	COMPLETED	Escitalopram (Lexapro) for Depression MS or ALS
NCT01016522	PHASE3	TERMINATED	Safety and Tolerability of the Ketogenic Diet in Amyotrophic Lateral Sclerosis (ALS)
NCT01160263	PHASE3	COMPLETED	Study of Dopamine and Serotonin Transporters in Patients With Amyotrophic Lateral Sclerosis and Controls
NCT01281189	PHASE3	COMPLETED	Phase 3 Study of Dexpramipexole in ALS
NCT01492686	PHASE3	COMPLETED	Phase 3 Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis
NCT01583088	PHASE3	TERMINATED	Early Stage Amyotrophic Lateral Sclerosis Phrenic Stimulation
NCT01622088	PHASE3	TERMINATED	Phase 3 Extension Study of Dexpramipexole in ALS
NCT02496767	PHASE3	COMPLETED	Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year
NCT02623699	PHASE3	COMPLETED	An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS)
NCT02936635	PHASE3	COMPLETED	A Study for Patients Who Completed VITALITY-ALS (CY 4031)
NCT03127267	PHASE3	RECRUITING	Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients
NCT03280056	PHASE3	COMPLETED	Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients
NCT03491462	PHASE3	COMPLETED	Arimoclomol in Amyotropic Lateral Sclerosis
NCT03505021	PHASE3	COMPLETED	Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS
NCT03548311	PHASE3	COMPLETED	Clinical Trial of Ultra-high Dose Methylcobalamin for ALS