ATXN1L

Summary

ATXN1L (ataxin 1 like, HGNC:33279) is a protein-coding gene on chromosome 16q22.2, encoding Ataxin-1-like (P0C7T5). Chromatin-binding factor that repress Notch signaling in the absence of Notch intracellular domain by acting as a CBF1 corepressor.

Predicted to enable RNA binding activity and chromatin binding activity. Predicted to be involved in several processes, including learning or memory; negative regulation of transcription by RNA polymerase II; and social behavior. Predicted to act upstream of or within extracellular matrix organization; lung alveolus development; and positive regulation of hematopoietic stem cell proliferation. Located in nucleolus and nucleoplasm.

Source: NCBI Gene 342371 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 114 total
• MANE Select transcript: NM_001137675

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33279
Approved symbol	ATXN1L
Name	ataxin 1 like
Location	16q22.2
Locus type	gene with protein product
Status	Approved
Aliases	BOAT1
Ensembl gene	ENSG00000224470
Ensembl biotype	protein_coding
OMIM	614301
Entrez	342371

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000427980, ENST00000565676, ENST00000569119, ENST00000683775, ENST00000914247, ENST00000914248, ENST00000956037

RefSeq mRNA: 1 — MANE Select: NM_001137675 NM_001137675

CCDS: CCDS45523

Canonical transcript exons

ENST00000427980 — 3 exons

Exon	Start	End
ENSE00001625053	71849624	71857328
ENSE00002607150	71845976	71846104
ENSE00003706486	71848010	71848071

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 98.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.0629 / max 237.9970, expressed in 1780 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154933	11.0629	1780

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	98.21	gold quality
epithelial cell of pancreas	CL:0000083	97.18	gold quality
pancreatic ductal cell	CL:0002079	97.13	gold quality
kidney epithelium	UBERON:0004819	96.15	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.71	gold quality
oocyte	CL:0000023	95.03	gold quality
left ventricle myocardium	UBERON:0006566	95.03	gold quality
tibialis anterior	UBERON:0001385	95.02	gold quality
ileal mucosa	UBERON:0000331	94.85	gold quality
parotid gland	UBERON:0001831	94.71	gold quality
oviduct epithelium	UBERON:0004804	94.42	gold quality
adult organism	UBERON:0007023	93.85	gold quality
secondary oocyte	CL:0000655	93.60	gold quality
skin of hip	UBERON:0001554	93.42	gold quality
nasal cavity epithelium	UBERON:0005384	93.09	gold quality
cauda epididymis	UBERON:0004360	93.01	gold quality
germinal epithelium of ovary	UBERON:0001304	92.87	gold quality
seminal vesicle	UBERON:0000998	92.86	gold quality
upper arm skin	UBERON:0004263	92.62	gold quality
myocardium	UBERON:0002349	92.60	gold quality
deltoid	UBERON:0001476	92.38	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.24	gold quality
caput epididymis	UBERON:0004358	92.00	gold quality
amniotic fluid	UBERON:0000173	91.98	gold quality
upper leg skin	UBERON:0004262	91.97	gold quality
biceps brachii	UBERON:0001507	91.32	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.31	gold quality
sperm	CL:0000019	91.29	gold quality
layer of synovial tissue	UBERON:0007616	91.28	gold quality
corpus epididymis	UBERON:0004359	91.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.92

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HEY1

Literature-anchored findings (GeneRIF, showing 5)

• Boat is an in vivo binding partner of ataxin-1 whose altered expression in Purkinje cells may contribute to their degeneration in causes spinocerebellar ataxia type 1 animals (PMID:16121196)
• Both ATXN1 and BOAT1 bind to the promoter region of Hey1 and inhibit the transcriptional output of Notch through direct interactions with CBF1, a transcription factor that is crucial for the Notch pathway. (PMID:21475249)
• The ATXN1L-CIC-ETS transcription factor axis as a mediator of resistance to MAPKi. (PMID:28178529)
• This study highlights the CIC-ATXN1-ATXN1L axis as a more potent regulator of the cell cycle than previously appreciated (PMID:30093628)
• TRIM25 promotes Capicua degradation independently of ERK in the absence of ATXN1L. (PMID:33115448)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	atxn1l	ENSDARG00000086977
mus_musculus	Atxn1l	ENSMUSG00000069895
rattus_norvegicus	Atxn1l	ENSRNOG00000038766
drosophila_melanogaster	Atx-1	FBGN0029907
caenorhabditis_elegans	K04F10.1	WBGENE00019394

Paralogs (1): ATXN1 (ENSG00000124788)

Protein

Protein identifiers

Ataxin-1-like — P0C7T5 (reviewed: P0C7T5)

Alternative names: Brother of ataxin-1

All UniProt accessions (1): P0C7T5

UniProt curated annotations — full annotation on UniProt →

Function. Chromatin-binding factor that repress Notch signaling in the absence of Notch intracellular domain by acting as a CBF1 corepressor. Binds to the HEY promoter and might assist, along with NCOR2, RBPJ-mediated repression. Can suppress ATXN1 cytotoxicity in spinocerebellar ataxia type 1 (SCA1). In concert with CIC and ATXN1, involved in brain development.

Subunit / interactions. Homodimer. Interacts with CIC. Interacts (via AXH domain) with NCOR2. Interacts with ATXN1. Directly interacts with RBPJ; this interaction is disrupted in the presence of Notch intracellular domain. Competes with ATXN1 for RBPJ-binding. Found in a complex with CIC and ATXN1.

Subcellular location. Nucleus. Cell projection. Dendrite.

Tissue specificity. Expressed in cerebellum and cerebral cortex.

Similarity. Belongs to the ATXN1 family.

RefSeq proteins (1): NP_001131147* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003652	Ataxin_AXH_dom	Domain
IPR020997	Ataxin-1_N	Domain
IPR036096	Ataxin_AXH_dom_sf	Homologous_superfamily
IPR043404	ATAXIN1-like	Family

Pfam: PF08517, PF12547

UniProt features (19 total): region of interest 7, compositionally biased region 5, modified residue 4, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0C7T5-F1	50.97	0.16

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 (4): 284, 330, 361, 615

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 199 (showing top): GOBP_MEMORY, GOBP_COGNITION, GOBP_BEHAVIOR, chr16q22, GOBP_STEM_CELL_PROLIFERATION, GOBP_LEARNING, GOBP_HEMATOPOIETIC_STEM_CELL_PROLIFERATION, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTRASPECIES_INTERACTION_BETWEEN_ORGANISMS, GOBP_HEAD_DEVELOPMENT, GOBP_REGULATION_OF_STEM_CELL_PROLIFERATION, GOCC_NEURON_PROJECTION, GOBP_RESPIRATORY_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_STEM_CELL_PROLIFERATION, GOBP_LUNG_ALVEOLUS_DEVELOPMENT, GOMF_CHROMATIN_BINDING

GO Biological Process (10): negative regulation of transcription by RNA polymerase II (GO:0000122), transcription by RNA polymerase II (GO:0006366), brain development (GO:0007420), learning (GO:0007612), memory (GO:0007613), extracellular matrix organization (GO:0030198), social behavior (GO:0035176), lung alveolus development (GO:0048286), positive regulation of hematopoietic stem cell proliferation (GO:1902035), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (5): DNA binding (GO:0003677), chromatin binding (GO:0003682), RNA binding (GO:0003723), POZ domain binding (GO:0031208), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), dendrite (GO:0030425), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	2
learning or memory	2
nucleic acid binding	2
binding	2
nuclear lumen	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
central nervous system development	1
animal organ development	1
head development	1
extracellular structure organization	1
external encapsulating structure organization	1
behavior	1
biological process involved in intraspecies interaction between organisms	1
lung development	1
anatomical structure development	1
hematopoietic stem cell proliferation	1
regulation of hematopoietic stem cell proliferation	1
positive regulation of stem cell proliferation	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
protein domain specific binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
neuron projection	1
dendritic tree	1

Protein interactions and networks

STRING

1052 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATXN1L	ACE2	Q9BYF1	881
ATXN1L	CIC	Q96RK0	808
ATXN1L	RBM17	Q96I25	698
ATXN1L	PQBP1	O60828	688
ATXN1L	ETV5	P41161	625
ATXN1L	ZNF821	O75541	597
ATXN1L	ATXN1	P54253	572
ATXN1L	ANP32A	P39687	559
ATXN1L	NCOR2	Q9Y618	545
ATXN1L	DUX4L2	P0CJ85	528
ATXN1L	RORA	P35397	489
ATXN1L	UBQLN4	Q9NRR5	488
ATXN1L	GFI1	Q99684	481
ATXN1L	RBPJ	Q06330	480
ATXN1L	KAT5	Q92993	459

IntAct

153 interactions, top by confidence:

A	B	Type	Score
NFIC	NFIB	psi-mi:“MI:2364”(proximity)	0.690
RBPJ	ATXN1L	psi-mi:“MI:0914”(association)	0.640
ATXN1L	RBPJ	psi-mi:“MI:0915”(physical association)	0.640
RBPJ	ATXN1L	psi-mi:“MI:0915”(physical association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
ATXN1L		psi-mi:“MI:0915”(physical association)	0.560
ATXN1L	USP54	psi-mi:“MI:0915”(physical association)	0.560
ATXN1L	PICALM	psi-mi:“MI:0915”(physical association)	0.560
FAM22F	ATXN1L	psi-mi:“MI:0915”(physical association)	0.560
ATXN1L	AGXT	psi-mi:“MI:0915”(physical association)	0.560
ZBTB32	ATXN1L	psi-mi:“MI:0915”(physical association)	0.560
ATXN1L	FAM168A	psi-mi:“MI:0915”(physical association)	0.560
FOXH1	ATXN1L	psi-mi:“MI:0915”(physical association)	0.560
RBFOX2	ATXN1L	psi-mi:“MI:0915”(physical association)	0.560
	ATXN1L	psi-mi:“MI:0915”(physical association)	0.560
ATXN1L	SPMIP9	psi-mi:“MI:0915”(physical association)	0.560
ATXN1L	SHISA2	psi-mi:“MI:0915”(physical association)	0.560
ATXN1L	RBFOX1	psi-mi:“MI:0915”(physical association)	0.560
ATXN1L	KRTAP11-1	psi-mi:“MI:0915”(physical association)	0.560
ATXN1L	UNKL	psi-mi:“MI:0915”(physical association)	0.560
ATXN1L	MYOZ3	psi-mi:“MI:0915”(physical association)	0.560
ATXN1L	KRTAP8-1	psi-mi:“MI:0915”(physical association)	0.560
ATXN1L	ARID5A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (179): ATXN1L (Affinity Capture-MS), ATXN1L (Affinity Capture-MS), ATXN1L (Affinity Capture-MS), ATXN1L (Affinity Capture-MS), ATXN1L (Synthetic Lethality), ATXN1L (Two-hybrid), ATXN1L (Two-hybrid), ATXN1L (Two-hybrid), ATXN1L (Two-hybrid), ATXN1L (Two-hybrid), ATXN1L (Two-hybrid), ATXN1L (Two-hybrid), ATXN1L (Two-hybrid), ATXN1L (Two-hybrid), ATXN1L (Two-hybrid)

ESM2 similar proteins: A4GTP4, A5X7A0, A7XYI6, E1BE02, E7F888, F6W2R2, O35914, O94993, P0C7T5, P0C7T6, P11831, P19419, P41969, P54253, P54254, P70178, Q00417, Q04891, Q0P5V2, Q1RNF8, Q2MJB4, Q32MQ0, Q3U108, Q498S6, Q4G112, Q5ND04, Q5VZB9, Q61321, Q63540, Q69ZB8, Q6PJG2, Q80WT2, Q8BH05, Q8BX22, Q8CFG4, Q8TF72, Q8VIG0, Q8WNV5, Q8WYQ9, Q90WM5

Diamond homologs: P0C7T5, P0C7T6, Q2KJ34, Q63540, P54253, P54254, A0A0G2JTZ2, A4IIJ8, A4QNG3, A5A763, B0ZTE2, B1H349, B3DLD3, B3DM43, B7ZR65, F1LYL9, F1M8W4, O18896, O42569, O55170, O60248, O60381, O94993, O95416, P35710, P35711, P35712, P35713, P40645, P40647, P40649, P43267, P43680, P48430, P48431, P48432, P48434, P48436, P54231, P56693

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 94 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
Deactivation of the beta-catenin transactivating complex	5	20.1×	4e-04
MITF-M-dependent gene expression	5	15.6×	9e-04
MITF-M-regulated melanocyte development	7	13.8×	1e-04
TCF dependent signaling in response to WNT	5	10.2×	2e-03
Signaling by WNT	5	9.7×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
chondrocyte differentiation	5	17.9×	5e-04
cartilage development	5	15.0×	9e-04
somatic stem cell population maintenance	5	14.8×	9e-04
anatomical structure morphogenesis	7	11.6×	2e-04
transcription by RNA polymerase II	12	10.1×	4e-07
gene expression	8	7.6×	6e-04
brain development	7	6.6×	3e-03
nervous system development	8	4.4×	8e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	109
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2213 predictions. Top by Δscore:

Variant	Effect	Δscore
16:71808988:T:C	donor_gain	1.0000
16:71846100:GGCTG:G	donor_gain	1.0000
16:71846101:GCTGG:G	donor_gain	1.0000
16:71847909:G:GT	donor_gain	1.0000
16:71848004:TTCTA:T	acceptor_loss	1.0000
16:71848005:TCTA:T	acceptor_loss	1.0000
16:71848008:A:AG	acceptor_gain	1.0000
16:71848008:AGG:A	acceptor_loss	1.0000
16:71848009:G:GA	acceptor_loss	1.0000
16:71848009:G:GG	acceptor_gain	1.0000
16:71860668:TCTCA:T	acceptor_gain	1.0000
16:71860669:CTCA:C	acceptor_gain	1.0000
16:71860669:CTCAC:C	acceptor_gain	1.0000
16:71860670:TCA:T	acceptor_gain	1.0000
16:71860670:TCACT:T	acceptor_gain	1.0000
16:71860671:CA:C	acceptor_gain	1.0000
16:71860671:CAC:C	acceptor_gain	1.0000
16:71860672:ACTG:A	acceptor_loss	1.0000
16:71860673:C:CC	acceptor_gain	1.0000
16:71860673:C:CG	acceptor_loss	1.0000
16:71864985:T:TA	donor_gain	1.0000
16:71879899:ATACT:A	donor_loss	1.0000
16:71879901:ACT:A	donor_loss	1.0000
16:71879902:CTC:C	donor_loss	1.0000
16:71879904:CA:C	donor_loss	1.0000
16:71879905:A:AC	donor_gain	1.0000
16:71879905:ACA:A	donor_loss	1.0000
16:71879906:C:CG	donor_gain	1.0000
16:71879906:CA:C	donor_gain	1.0000
16:71879906:CAGTG:C	donor_gain	1.0000

AlphaMissense

4423 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:71851145:T:C	F469L	1.000
16:71851146:T:C	F469S	1.000
16:71851146:T:G	F469C	1.000
16:71851147:C:A	F469L	1.000
16:71851147:C:G	F469L	1.000
16:71851164:T:A	I475N	1.000
16:71851164:T:C	I475T	1.000
16:71851164:T:G	I475S	1.000
16:71851170:T:C	L477P	1.000
16:71851185:T:C	L482P	1.000
16:71851189:G:C	K483N	1.000
16:71851189:G:T	K483N	1.000
16:71851203:T:A	L488H	1.000
16:71851203:T:C	L488P	1.000
16:71851215:A:G	D492G	1.000
16:71851215:A:T	D492V	1.000
16:71851217:T:C	F493L	1.000
16:71851218:T:C	F493S	1.000
16:71851218:T:G	F493C	1.000
16:71851219:T:A	F493L	1.000
16:71851219:T:G	F493L	1.000
16:71851230:C:A	A497D	1.000
16:71851248:T:C	L503P	1.000
16:71851262:A:C	S508R	1.000
16:71851264:C:A	S508R	1.000
16:71851264:C:G	S508R	1.000
16:71851269:T:A	V510D	1.000
16:71851311:T:C	L524P	1.000
16:71851316:T:C	F526L	1.000
16:71851317:T:C	F526S	1.000

dbSNP variants (sampled 300 via entrez): RS1000151399 (16:71848255 A>T), RS1000382171 (16:71849683 C>A,T), RS1000480940 (16:71848038 C>G,T), RS1000550586 (16:71845542 GAAAGA>G), RS1000594309 (16:71843985 A>G), RS1000602918 (16:71845277 T>C), RS1000902221 (16:71855598 T>C,G), RS1000933059 (16:71856049 G>T), RS1001164571 (16:71850354 C>T), RS1001368566 (16:71856306 T>G), RS1001564680 (16:71850023 A>G), RS1001595289 (16:71852739 G>T), RS1001756669 (16:71846729 G>A), RS1001777377 (16:71856031 G>A), RS1002021663 (16:71846044 C>A,T)

Disease associations

OMIM: gene MIM:614301 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003329_10	Response to anti-TNF therapy in rheumatoid arthritis	9.000000e-06
GCST90002385_82	High light scatter reticulocyte count	4.000000e-17
GCST90002386_288	High light scatter reticulocyte percentage of red cells	4.000000e-15
GCST90002405_312	Reticulocyte count	5.000000e-19
GCST90002406_437	Reticulocyte fraction of red cells	1.000000e-16

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004653	response to TNF antagonist
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance, affects cotreatment	2
Valproic Acid	affects expression, increases expression	2
FR900359	affects phosphorylation	1
alpha-pinene	decreases expression, increases abundance, affects cotreatment	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	decreases stability	1
butyraldehyde	decreases expression	1
aflatoxin B2	decreases methylation	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Copper	affects binding, decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Disulfiram	affects binding, decreases expression	1
Formaldehyde	decreases expression	1
Ozone	affects cotreatment, decreases expression, increases abundance	1
Smoke	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1
Volatile Organic Compounds	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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