ATXN7

Summary

ATXN7 (ataxin 7, HGNC:10560) is a protein-coding gene on chromosome 3p14.1, encoding Ataxin-7 (O15265). Acts as a component of the SAGA (aka STAGA) transcription coactivator-HAT complex.

The autosomal dominant cerebellar ataxias (ADCA) are a heterogeneous group of neurodegenerative disorders characterized by progressive degeneration of the cerebellum, brain stem and spinal cord. Clinically, ADCA has been divided into three groups: ADCA types I-III. ADCAI is genetically heterogeneous, with five genetic loci, designated spinocerebellar ataxia (SCA) 1, 2, 3, 4 and 6, being assigned to five different chromosomes. ADCAII, which always presents with retinal degeneration (SCA7), and ADCAIII often referred to as the ‘pure’ cerebellar syndrome (SCA5), are most likely homogeneous disorders. Several SCA genes have been cloned and shown to contain CAG repeats in their coding regions. ADCA is caused by the expansion of the CAG repeats, producing an elongated polyglutamine tract in the corresponding protein. The expanded repeats are variable in size and unstable, usually increasing in size when transmitted to successive generations. This locus has been mapped to chromosome 3, and it has been determined that the diseased allele associated with spinocerebellar ataxia-7 contains 37-306 CAG repeats (near the N-terminus), compared to 4-35 in the normal allele. The encoded protein is a component of the SPT3/TAF9/GCN5 acetyltransferase (STAGA) and TBP-free TAF-containing (TFTC) chromatin remodeling complexes, and it thus plays a role in transcriptional regulation. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 6314 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spinocerebellar ataxia 7 (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 15
• Clinical variants (ClinVar): 254 total — 2 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 45
• Druggable target: yes
• MANE Select transcript: NM_001377405

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10560
Approved symbol	ATXN7
Name	ataxin 7
Location	3p14.1
Locus type	gene with protein product
Status	Approved
Aliases	OPCA3, ADCAII, SGF73
Ensembl gene	ENSG00000163635
Ensembl biotype	protein_coding
OMIM	607640
Entrez	6314

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 9 protein_coding, 7 protein_coding_CDS_not_defined, 6 retained_intron

ENST00000295900, ENST00000466529, ENST00000472569, ENST00000474112, ENST00000474513, ENST00000475897, ENST00000477516, ENST00000484332, ENST00000484668, ENST00000487717, ENST00000488239, ENST00000522345, ENST00000642539, ENST00000643453, ENST00000643464, ENST00000646942, ENST00000647117, ENST00000650280, ENST00000674254, ENST00000674280, ENST00000905354, ENST00000938974

RefSeq mRNA: 5 — MANE Select: NM_001377405 NM_000333, NM_001128149, NM_001177387, NM_001377405, NM_001377406

CCDS: CCDS43102, CCDS46861, CCDS54603

Canonical transcript exons

ENST00000674280 — 13 exons

Exon	Start	End
ENSE00001698494	63999450	64003462
ENSE00003898126	63979915	63980167
ENSE00003898195	63990176	63990374
ENSE00003898204	63982939	63983021
ENSE00003898310	63982186	63982445
ENSE00003898328	63995505	63996483
ENSE00003898352	63990738	63990859
ENSE00003898371	63912588	63912923
ENSE00003898554	63988059	63988324
ENSE00003898586	63952379	63952483
ENSE00003898605	63863867	63864158
ENSE00003898789	63913157	63913225
ENSE00003899513	63898399	63898497

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 96.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.4694 / max 417.5045, expressed in 1796 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37145	8.1148	1733
37146	3.7744	1304
37151	3.7056	289
37147	2.8829	928
37144	0.7693	329
37148	0.1130	51
37150	0.1095	62

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of paranasal sinus	UBERON:0005030	96.37	gold quality
jejunal mucosa	UBERON:0000399	94.71	gold quality
superficial temporal artery	UBERON:0001614	93.80	gold quality
epithelium of nasopharynx	UBERON:0001951	93.79	gold quality
trabecular bone tissue	UBERON:0002483	93.78	gold quality
lower lobe of lung	UBERON:0008949	93.40	gold quality
pigmented layer of retina	UBERON:0001782	93.21	gold quality
bone marrow	UBERON:0002371	93.20	gold quality
retina	UBERON:0000966	93.19	gold quality
skin of hip	UBERON:0001554	93.14	gold quality
bone marrow cell	CL:0002092	93.10	gold quality
nipple	UBERON:0002030	93.07	gold quality
jejunum	UBERON:0002115	92.96	gold quality
visceral pleura	UBERON:0002401	92.74	gold quality
sural nerve	UBERON:0015488	92.39	gold quality
upper leg skin	UBERON:0004262	92.36	gold quality
colonic epithelium	UBERON:0000397	92.29	gold quality
tonsil	UBERON:0002372	92.21	gold quality
penis	UBERON:0000989	91.90	gold quality
oral cavity	UBERON:0000167	91.89	gold quality
blood	UBERON:0000178	91.33	gold quality
adrenal tissue	UBERON:0018303	91.13	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.05	gold quality
cauda epididymis	UBERON:0004360	90.96	gold quality
pylorus	UBERON:0001166	90.95	gold quality
tendon of biceps brachii	UBERON:0008188	90.79	gold quality
parietal pleura	UBERON:0002400	90.44	gold quality
mammalian vulva	UBERON:0000997	90.39	gold quality
pleura	UBERON:0000977	90.26	gold quality
sperm	CL:0000019	89.87	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.42
E-GEOD-99795	no	25.76

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CRX, CTCF, TP53

miRNA regulators (miRDB)

376 targeting ATXN7, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-373-5P	99.98	75.36	4753

Literature-anchored findings (GeneRIF, showing 40)

• CAG expansion in SCA7 locus is associated with Machado-Joseph disease (PMID:11697524)
• Activated caspase-3 was recruited into the inclusions in both the cell models and human SCA7 brain and its expression was upregulated in cortical neurones. (PMID:11709544)
• Expression of ataxin-7 in CNS and non-CNS tissue of normal and SCA7 individuals (PMID:12070661)
• identification of a novel ataxin-7 protein enriched in the central nervous system suggests that expression of multiple polyglutamine-containing proteins may play a role in the neurodegeneration patterns characteristic of SCA7 (PMID:12533095)
• Ataxin-7 is the human orthologue of SGF73, which is a subunit of the yeast SAGA complex, a coactivator required for transcription of a subset of RNA Pol II-dependent genes. Ataxin-7 is a new subunit of the mammalian SAGA-like complexes, TFTC/STAGA. (PMID:15115762)
• Demonstrate here that ataxin-7 is the human orthologue of the yeast SAGA SGF73 subunit and is a bona fide subunit of the human TFTC-like transcriptional complexes. (PMID:15115762)
• This patient with Spinocerebellar Ataxia 7 due to unique instability of the CAG repeat. (PMID:15316811)
• Polyglutamine-expanded ataxin-7 inhibits STAGA histone acetyltransferase activity to produce retinal degeneration in Spinocerebellar ataxia type 7. (PMID:15932940)
• We show that transcription mediated by both CBP and RORalpha1 was repressed by expanded ataxin-7. Ataxin-7 may act as a repressor of transcription by inhibiting the acetylation activity of TFTC and STAGA. (PMID:15936949)
• Ataxin-90A aggregates differed morphologically from ataxin7 - 100Q aggregatesand were more toxic to mesencephalic neurons, suggesting that toxicity was determined by the type of aggregate rather than the cellular misfolding response. (PMID:16325416)
• Trinucleotide repeat expansions of ataxin 7 may be involved in neurodegenerative diseases such as cerebellar ataxia. (PMID:16962040)
• Origin of the SCA7 gene mutation in South Africa and the possibility of a founder effect in the Black population (PMID:17026624)
• Massive SCA7 expansion detected in a 7-month-old male with hypotonia, cardiomegaly, and renal failure. (PMID:17254003)
• We present a pediatric patient with 13 and 70 trinucleotide CAG repeats within SCA7 gene and no family history, whose presentation mimicked Kearns-Sayre syndrome (KSS). (PMID:17720198)
• One common pathogenic response in transgenic SCA1 and SCA7 mice reveals the importance of intercellular mechanisms in the pathogenesis of spinocerebellar ataxias. (PMID:18216249)
• expanded CAG-repeats in the SCA7 gene within members of a large Chinese family with spinocerebellar ataxia (PMID:18325672)
• The patients with genetically confirmed SCA 7 presented an early macular dysfunction, preceding any signs of abnormalities in fundus appearance (PMID:19172503)
• analysis of RNA hairpins selective for silencing the mutant ataxin-7 transcript (PMID:19789634)
• These results demonstrate an influence of SUMOylation on the multistep aggregation process of ATXN7 and implicate a role for ATXN7 SUMOylation in SCA7 pathogenesis. (PMID:19843541)
• In response to polyglutamine toxicity, transgenic murine SCA7 rods go through a range of radically different cell fates correlating with the nature, level and ratio of mutant transgene ATXN7 species. (PMID:20600911)
• The solution structures of the SCA7 domain of both ATXN7 and ATXN7L3 reveal a new, common zinc-finger motif at the heart of two distinct folds, providing a molecular basis for the observed functional differences. (PMID:20634802)
• The interaction between APLP2 and ataxin-7 and proteolytic processing of APLP2 may contribute to the pathogenesis of spinocerebellar ataxia type 7. (PMID:20732423)
• This study suggested that the SCA7 gene alternation in SCA7 patient in Chinese Han family. (PMID:20739808)
• identified 118 protein interactions for CACNA1A and ATXN7 linking them to other ataxia-causing proteins and the ataxia network; ataxia network is significantly enriched for proteins that interact with known macular degeneration-causing proteins (PMID:21078624)
• The Trinucleotide Repeat Expansion mutation in ATXN7 related to Spinocerebellar ataxia type 7. (PMID:21827908)
• The results of this study indicated that SCA7 disease pathogenesis involves a convergence of alterations in a variety of different cell types to fully recapitulate the cerebellar degeneration. (PMID:22072678)
• ATXN7 distribution frequently shifts from the nucleus to the cytoplasm; cytoplasmic ATXN7 associates with microtubules (MTs); expression of ATXN7 stabilizes MTs; findings provide a novel physiological function of ATXN7 in regulation of cytoskeletal dynamics and suggest that abnormal cytoskeletal regulation may contribute to SCA7 disease pathology (PMID:22100762)
• Full-length and cleaved fragments of the SCA7 disease protein ataxin-7 (ATXN7) are differentially degraded in a spinocerebellar ataxia type 7 rat model. (PMID:22367614)
• The results of this study demonstrated that oxidative stress contributes to ATXN7 aggregation as well as toxicity. (PMID:22827889)
• Critical nuclear events lead to transcriptional alterations in polyglutamine diseases such as spinocerebellar ataxia type 7 (SCA7) and Huntington’s disease (HD). (PMID:22917585)
• The results demonstrated that a common genetic variant in the ataxia-causing gene ATXN7 influences cerebellar grey matter volume in healthy young adults. (PMID:23100044)
• role of ataxin-7 in differentiation of photoreceptors and cerebellar neurons (PMID:23226359)
• Polyglutamine expansion decreased ATXN7 occupancy, which correlated with increased levels of histone H2B monoubiquitination, at the reelin promoter. (PMID:23236151)
• Epidemiological evidence of a SCA7 founder effect in a Mexican population with spinocerebellar ataxia. (PMID:23368522)
• Haplotype and phylogenetic analyses provide evidence showing that the relatively high frequency of SCA7 in Mexican population is the result of a founder mutation and that Mexican SCA7 carriers possess the Western European ancestry. (PMID:23828024)
• Sequestration of the ponsin splice variant R85FL by the polyglutamine-expanded Atx7 in cell is mediated by the specific SH3C-PRR interaction, which is implicated in the pathogenesis of spinocerebellar ataxia 7. (PMID:23892081)
• polyQ-expanded ataxin-7 directly bound the Gcn5 catalytic core of SAGA while in association with its regulatory proteins, Ada2 and Ada3. (PMID:24129567)
• analysis of the founder effect and ancestral origin of the spinocerebellar ataxia type 7 mutation in Mexican families (PMID:24374739)
• This study shown evidence in vivo, in the SCA7 KI mouse model, that progressive accumulation of mutant ataxin-7 impairs autophagy. (PMID:24859968)
• The proband exhibited a typical phenotype of SCA7, which includes cone dystrophy and spinocerebellar ataxia. (PMID:25643591)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	atxn7	ENSDARG00000074804
mus_musculus	Atxn7	ENSMUSG00000021738
rattus_norvegicus	Atxn7	ENSRNOG00000007246

Paralogs (4): ATXN7L3 (ENSG00000087152), ATXN7L1 (ENSG00000146776), ATXN7L2 (ENSG00000162650), ATXN7L3B (ENSG00000253719)

Protein

Protein identifiers

Ataxin-7 — O15265 (reviewed: O15265)

Alternative names: Spinocerebellar ataxia type 7 protein

All UniProt accessions (3): A0A1B0GX67, A0A2R8YDD6, O15265

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a component of the SAGA (aka STAGA) transcription coactivator-HAT complex. Mediates the interaction of SAGA complex with the CRX and is involved in CRX-dependent gene activation. Probably involved in tethering the deubiquitination module within the SAGA complex. Necessary for microtubule cytoskeleton stabilization. Involved in neurodegeneration.

Subunit / interactions. Component of the SAGA transcription coactivator-HAT complex, at least composed of SUPT3H, GCN5L2, TAF5L, TAF6L, SUPT7L, TADA3L, TAD1L, TAF10, TAF12, TRRAP, TAF9 and ATXN7. The STAGA core complex is associated with a subcomplex required for histone deubiquitination composed of ATXN7L3, ENY2 and USP22. Interacts with SORBS1, PSMC1 and CRX. Interacts with TRRAP, GCN5L2 and TAF10. Interacts with alpha tubulin.

Subcellular location. Nucleus. Nucleolus. Nucleus matrix. Cytoplasm. Cytoskeleton Cytoplasm.

Tissue specificity. Isoform a is expressed in CNS, but is expressed predominantly in the peripherical tissues. Isoform b is expressed in CNS. Also highly expressed in the frontal lobe, skeletal muscle and spinal cord and is expressed at a lower level in the lung, lymphoblast and intestine.

Post-translational modifications. Proteolytically cleaved by caspase-7 (CASP7). The cleavage may be involved in SCA7 degeneration: the isoform fragments may exert distinct toxic influences that could contribute to selective neurodegeneration. Sumoylation decreases the aggregation propensity and cellular toxicity of forms with an expanded poly-Gln region but has no effect on subcellular location or interaction with components of the STAGA complex.

Disease relevance. Spinocerebellar ataxia 7 (SCA7) [MIM:164500] 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. SCA7 belongs to the autosomal dominant cerebellar ataxias type II (ADCA II) which are characterized by cerebellar ataxia with retinal degeneration and pigmentary macular dystrophy. The disease is caused by variants affecting the gene represented in this entry.

Polymorphism. The poly-Gln region of ATXN7 is highly polymorphic (4 to 18 repeats) in the normal population and is expanded to about 38-130 repeats in SCA7 patients. Intermediate alleles with 28 to 35 repeats are prone to further expansion.

Similarity. Belongs to the ataxin-7 family.

Isoforms (3)

UniProt ID	Names	Canonical?
O15265-1	a, Ataxin-7a	yes
O15265-2	b, Ataxin-7b, SCA7b
O15265-3	3

RefSeq proteins (5): NP_000324, NP_001121621, NP_001170858, NP_001364334, NP_001364335 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013243	SCA7_dom	Domain
IPR052237	Ataxin-7-like_regulator	Family

Pfam: PF08313

UniProt features (50 total): compositionally biased region 16, region of interest 6, sequence variant 4, mutagenesis site 4, strand 4, sequence conflict 3, helix 3, site 2, cross-link 2, splice variant 2, turn 2, chain 1, domain 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9RDK	ELECTRON MICROSCOPY	2.41
7KTR	ELECTRON MICROSCOPY	2.93
8H7G	ELECTRON MICROSCOPY	3.7
7KTS	ELECTRON MICROSCOPY	19.09
2KKR	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15265-F1	51.92	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.

Catalytic / active sites (2): 266–267 (cleavage; by caspase-7); 344–345 (cleavage; by caspase-7)

Post-translational modifications (2): 257, 257

Mutagenesis-validated functional residues (4):

Position	Phenotype
257	almost completely abolishes sumoylation.
266	abolished cleavage by caspase-7 and attenuates formation of protein aggregates in sca7 degeneration; when associated wit
344	abolished cleavage by caspase-7 and attenuates formation of protein aggregates in sca7 degeneration; when associated wit
858	no effect on sumoylation.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-3214847	HATs acetylate histones
R-HSA-5689880	Ub-specific processing proteases
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-392499	Metabolism of proteins
R-HSA-4839726	Chromatin organization
R-HSA-5688426	Deubiquitination
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 397 (showing top): GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, NAGY_STAGA_COMPONENTS_HUMAN, MODULE_255, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MODULE_317, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_DN, GOBP_MICROTUBULE_DEPOLYMERIZATION, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_NUCLEUS_ORGANIZATION, TGTGTGA_MIR377

GO Biological Process (8): microtubule cytoskeleton organization (GO:0000226), regulation of DNA repair (GO:0006282), regulation of transcription by RNA polymerase II (GO:0006357), nucleus organization (GO:0006997), negative regulation of microtubule depolymerization (GO:0007026), visual perception (GO:0007601), regulation of RNA splicing (GO:0043484), positive regulation of DNA-templated transcription (GO:0045893)

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

GO Cellular Component (10): SAGA complex (GO:0000124), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), microtubule cytoskeleton (GO:0015630), nuclear matrix (GO:0016363), transcription factor TFTC complex (GO:0033276), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Chromatin modifying enzymes	1
Deubiquitination	1
Chromatin organization	1
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
nuclear lumen	3
regulation of DNA-templated transcription	2
SAGA-type complex	2
intracellular membraneless organelle	2
cytoskeleton organization	1
microtubule-based process	1
DNA repair	1
regulation of DNA metabolic process	1
regulation of cellular response to stress	1
transcription by RNA polymerase II	1
organelle organization	1
microtubule depolymerization	1
negative regulation of microtubule polymerization or depolymerization	1
regulation of microtubule depolymerization	1
negative regulation of protein depolymerization	1
negative regulation of supramolecular fiber organization	1
sensory perception of light stimulus	1
RNA splicing	1
regulation of gene expression	1
regulation of primary metabolic process	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
binding	1
DUBm complex	1
peptidase complex	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cytoskeleton	1
RNA polymerase II, holoenzyme	1
RNA polymerase II transcription regulator complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1480 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATXN7	ENY2	Q9NPA8	997
ATXN7	ATXN7L3	Q14CW9	994
ATXN7	USP22	Q9UPT9	972
ATXN7	CACNA1A	P78510	964
ATXN7	PPP2R2B	Q00005	923
ATXN7	ATXN2	Q99700	912
ATXN7	ATXN1	P54253	898
ATXN7	ATXN3	P54252	895
ATXN7	SGF29	Q96ES7	894
ATXN7	KAT2A	Q92830	888
ATXN7	TADA3	O75528	887
ATXN7	KAT2B	Q92831	879
ATXN7	TBP	P20226	856
ATXN7	ATXN10	Q9UBB4	856
ATXN7	CRX	O43186	847

IntAct

114 interactions, top by confidence:

A	B	Type	Score
SGF29	NDC80	psi-mi:“MI:0914”(association)	0.840
TAF12	TAF4	psi-mi:“MI:0914”(association)	0.760
TRRAP	ATXN7	psi-mi:“MI:0914”(association)	0.740
ATXN7	TRRAP	psi-mi:“MI:0915”(physical association)	0.740
ATXN7	TAF10	psi-mi:“MI:0914”(association)	0.690
ATXN7	TAF10	psi-mi:“MI:0915”(physical association)	0.690
TAF10	ATXN7	psi-mi:“MI:0915”(physical association)	0.690
ATXN7L3	USP27X	psi-mi:“MI:0914”(association)	0.640
SORBS1	ATXN7	psi-mi:“MI:0407”(direct interaction)	0.630
ATXN7	SORBS1	psi-mi:“MI:0407”(direct interaction)	0.630

BioGRID (194): GCN5 (Reconstituted Complex), ATXN7 (Reconstituted Complex), ATXN7 (Reconstituted Complex), ATXN7 (Reconstituted Complex), ATXN7 (Co-purification), ATXN7 (Co-purification), ATXN7 (Co-purification), ATXN7 (Affinity Capture-MS), ATXN7 (Affinity Capture-MS), USP22 (Affinity Capture-Western), ATXN7 (Affinity Capture-Western), ATXN7 (Reconstituted Complex), ATXN7 (Affinity Capture-MS), ATXN7 (Affinity Capture-MS), ATXN7 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IYX6, A5X7A0, A7MB40, A7XYH5, A7XYH9, A7XYI6, A7XYJ6, A7XYQ1, E1BE02, E7F888, E9Q2Z1, F6NSX9, F8VPJ6, O15265, O35914, P35547, P59598, P78312, P83758, Q04891, Q0P5V2, Q13029, Q28BT7, Q28EW4, Q2KHR2, Q32N19, Q499E5, Q568E2, Q5ZJ69, Q5ZM88, Q62255, Q63755, Q6ZPI3, Q76L83, Q7YR76, Q8BZ32, Q8C8Y5, Q8CGI1, Q8IZQ8, Q8R4I1

Diamond homologs: O15265, O94397, P0DH66, P0DH68, P53165, Q3T136, Q5T6C5, Q8R4I1, Q9CZ05, Q9ULK2

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ATXN7	“form complex”	“SAGA complex”	binding
ATXN7	“down-regulates activity”	CRX	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 83 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
Molecules associated with elastic fibres	5	24.5×	2e-04
HATs acetylate histones	11	13.8×	1e-07
Non-integrin membrane-ECM interactions	5	12.2×	5e-03
Chromatin organization	8	10.4×	2e-04
Chromatin modifying enzymes	8	9.2×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
regulation of DNA repair	12	43.6×	3e-14
regulation of RNA splicing	11	31.7×	1e-11
RNA polymerase II preinitiation complex assembly	5	17.9×	1e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	198
Likely benign	19
Benign	10

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
562100	NG_008227.1:g.53130CAG[38_130]	Pathogenic
626311	NM_001377405.1(ATXN7):c.89AGC[233] (p.Gln39_Pro40insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln)	Pathogenic
1676280	NM_001377405.1(ATXN7):c.2119C>A (p.Arg707Ser)	Likely pathogenic
4077402	NM_001377405.1(ATXN7):c.1141C>T (p.Arg381Ter)	Likely pathogenic

SpliceAI

3769 predictions. Top by Δscore:

Variant	Effect	Δscore
3:63876201:A:AG	donor_gain	1.0000
3:63898388:T:A	acceptor_gain	1.0000
3:63898395:GCAG:G	acceptor_loss	1.0000
3:63898396:CAG:C	acceptor_loss	1.0000
3:63898397:A:AG	acceptor_gain	1.0000
3:63898397:A:AT	acceptor_loss	1.0000
3:63898398:G:GA	acceptor_gain	1.0000
3:63898398:GA:G	acceptor_gain	1.0000
3:63898398:GAT:G	acceptor_gain	1.0000
3:63898398:GATC:G	acceptor_gain	1.0000
3:63898398:GATCT:G	acceptor_gain	1.0000
3:63898494:AAAG:A	donor_loss	1.0000
3:63898496:AGGT:A	donor_loss	1.0000
3:63898497:GGTA:G	donor_loss	1.0000
3:63898498:G:C	donor_loss	1.0000
3:63912919:GGACG:G	donor_gain	1.0000
3:63912920:GACGG:G	donor_gain	1.0000
3:63913223:AAGGT:A	donor_loss	1.0000
3:63913224:AGG:A	donor_loss	1.0000
3:63913227:T:A	donor_loss	1.0000
3:63917601:TATCA:T	donor_gain	1.0000
3:63917602:ATCAA:A	donor_gain	1.0000
3:63952377:A:AG	acceptor_gain	1.0000
3:63952378:G:GG	acceptor_gain	1.0000
3:63952484:G:GC	donor_loss	1.0000
3:63952485:TAA:T	donor_loss	1.0000
3:63980168:G:GG	donor_gain	1.0000
3:63982935:ACAG:A	acceptor_loss	1.0000
3:63982937:A:AG	acceptor_gain	1.0000
3:63982937:AGA:A	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000014035 (3:64000588 T>C), RS1000022977 (3:63962739 T>C,G), RS1000030195 (3:63873349 C>T), RS1000032797 (3:63897434 G>A,C), RS1000068804 (3:63879560 C>T), RS1000071784 (3:63884913 C>T), RS1000094236 (3:63996573 G>C), RS1000144285 (3:63873669 C>T), RS1000144454 (3:63958951 A>G), RS1000144858 (3:63920881 CATT>C), RS1000156081 (3:63974494 T>C,G), RS1000215530 (3:63919505 A>G), RS1000229916 (3:63916522 C>T), RS1000233410 (3:63974244 A>G), RS1000276661 (3:63936095 C>A)

Disease associations

OMIM: gene MIM:607640 | disease phenotypes: MIM:164500

GenCC curated gene-disease

Disease	Classification	Inheritance
spinocerebellar ataxia 7	Definitive	Autosomal dominant
spinocerebellar ataxia type 7	Moderate	Autosomal dominant

Mondo (3): spinocerebellar ataxia 7 (MONDO:0016163), inherited retinal dystrophy (MONDO:0019118), (MONDO:0008120)

Orphanet (3): Autosomal dominant cerebellar ataxia type II (Orphanet:208508), Spinocerebellar ataxia type 7 (Orphanet:94147), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

45 total (30 of 45 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000514	Slow saccadic eye movements
HP:0000529	Progressive visual loss
HP:0000548	Cone/cone-rod dystrophy
HP:0000572	Visual loss
HP:0000580	Pigmentary retinopathy
HP:0000597	Ophthalmoparesis
HP:0000602	Ophthalmoplegia
HP:0000608	Macular degeneration
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000623	Supranuclear ophthalmoplegia
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000709	Psychosis
HP:0001098	Abnormal fundus morphology
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001268	Mental deterioration
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001310	Dysmetria
HP:0001319	Neonatal hypotonia
HP:0001324	Muscle weakness
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001508	Failure to thrive
HP:0001635	Congestive heart failure

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST002539_49	Schizophrenia	1.000000e-08
GCST004946_63	Schizophrenia	4.000000e-08
GCST006627_11	Diastolic blood pressure	1.000000e-10
GCST006803_106	Schizophrenia	1.000000e-10
GCST006867_22	Type 2 diabetes	1.000000e-08
GCST008058_129	Estimated glomerular filtration rate	5.000000e-16
GCST009600_13	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	4.000000e-09
GCST010002_428	Refractive error	5.000000e-11
GCST010698_66	Subcortical volume (min-P)	1.000000e-16
GCST010699_21	Brain morphology (min-P)	9.000000e-10
GCST010701_75	Cortical surface area (MOSTest)	4.000000e-09
GCST010702_127	Subcortical volume (MOSTest)	4.000000e-09
GCST010703_71	Brain morphology (MOSTest)	3.000000e-08
GCST90002404_47	Red cell distribution width	3.000000e-11
GCST90014268_12	Cataracts	3.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0004346	neuroimaging measurement
EFO:0009188	Red cell distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6193765 (PROTEIN-PROTEIN INTERACTION)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
sodium arsenite	affects methylation, increases abundance, increases expression	3
Arsenic	increases expression, affects methylation, decreases expression, increases abundance	3
Benzo(a)pyrene	decreases expression, affects methylation	3
Valproic Acid	decreases expression, affects cotreatment	3
Acetaminophen	decreases expression, increases expression	2
Cadmium	decreases expression, increases abundance	2
FR900359	increases phosphorylation	1
bisphenol A	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Oxaliplatin	decreases expression	1
Fulvestrant	decreases methylation	1
Leflunomide	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Ozone	affects expression, increases abundance	1
Selenium	affects cotreatment, decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Vitamin E	affects cotreatment, decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4610590	Binding	Protac activity at C-IAP1/ataxin-7 mutant in fibroblasts derived from SCA7 patient assessed as reduction in mutant ataxin-7 expression after 24 to 48 hrs by Western blot analysis	Application of protein knockdown strategy targeting β-sheet structure to multiple disease-associated polyglutamine proteins. — Bioorg Med Chem

Cellosaurus cell lines

12 cell lines: 9 induced pluripotent stem cell, 1 embryonic stem cell, 1 finite cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_9847	VUB10_SCA7	Embryonic stem cell	Female
CVCL_AX22	GM03561	Finite cell line	Female
CVCL_AX23	GM03562	Transformed cell line	Female
CVCL_D6SI	LUMCi051-A	Induced pluripotent stem cell	Female
CVCL_D6SJ	LUMCi052-A	Induced pluripotent stem cell	Female
CVCL_D6SK	LUMCi052-B	Induced pluripotent stem cell	Female
CVCL_D6SL	LUMCi052-C	Induced pluripotent stem cell	Female
CVCL_D6SM	LUMCi051-B	Induced pluripotent stem cell	Female
CVCL_L661	OPCA-iPSC1	Induced pluripotent stem cell	Female
CVCL_L662	OPCA-iPSC2	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03701399	PHASE3	ACTIVE_NOT_RECRUITING	Troriluzole in Adult Participants With Spinocerebellar Ataxia
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT04301284	PHASE2	WITHDRAWN	Study of CAD-1883 for Spinocerebellar Ataxia
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT03660917	PHASE2/PHASE3	RECRUITING	Riluzole in Patients With Spinocerebellar Ataxia Type 7
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT04288128	Not specified	COMPLETED	Integrated Functional Evaluation of the Cerebellum
NCT05826171	Not specified	ACTIVE_NOT_RECRUITING	Priming Motor Learning Through Exercise in People With Spinocerebellar Ataxia
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT
NCT03853252	Not specified	COMPLETED	iPS Cells of Patients for Models of Retinal Dystrophies
NCT05130385	Not specified	UNKNOWN	High Resolution Optical Coherence Tomography
NCT05294978	Not specified	RECRUITING	EyeConic: Qualification for Cone-Optogenetics
NCT05573984	Not specified	ACTIVE_NOT_RECRUITING	Natural History of PRPF31 Mutation-Associated Retinal Dystrophy
NCT05793515	Not specified	COMPLETED	Mechanisms of Inherited Retinal Dystrophies Using Whole Genome Sequencing and in Vitro and in Vivo Models
NCT05820100	Not specified	COMPLETED	Observational Study to Assess the Reliability and Validity of the MLYMT and MLSDT
NCT05976139	Not specified	RECRUITING	Micropulsed Laser in Patients With Macular Oedema in Retinal Dystrophies
NCT06162585	Not specified	ACTIVE_NOT_RECRUITING	Non-Interventional Long Term Follow-up Study of Participants Previously Enrolled in the RESTORE Study
NCT06177977	Not specified	RECRUITING	SS-HH-OCT as a Novel Diagnostic Modality for Early-Onset Retinal Dystrophies (EORDs)