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25 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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ATXN2L
ataxin 2 like
Chromosome 16 · 16p11.2
NCBI Gene: 11273Ensembl: ENSG00000168488.19HGNC: HGNC:31326UniProt: H3BUF6
187PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
RNA bindingcytoplasmic stress granulecytosolmembraneneurodegenerative diseaseCrohn's diseaseobesityMacrocephaly
✦AI Summary

ATXN2L (ataxin-2-like) is an RNA-binding protein with critical roles in post-transcriptional gene regulation and stress granule biology. Structurally, ATXN2L contains Lsm, LsmAD, and PAM2 domains 1 and functions primarily as a perinuclear regulator of mRNA metabolism 2. Its primary mechanism involves liquid-liquid phase separation (LLPS) to form RNA granules that recruit translation initiation factors and regulate mRNA translation 3. ATXN2L interacts with multiple RNA-binding proteins including NUFIP2, PABPN1, and HNRNPK, and is essential for embryonic survival 2. In immune regulation, ATXN2L dampens cytokine production in T cells through binding to 3' UTRs of IFNG, TNF, and IL2 4, while promoting translation of nonpolyadenylated reovirus mRNA 5. ATXN2L participates in alternative splicing regulation via its Sm domains 1. Disease relevance includes upregulation in hepatocellular carcinoma and gastric cancer, where it promotes invasiveness and chemoresistance through EGF/PI3K/Akt signaling 63. In youth-onset type 2 diabetes, rare ATXN2L variants show exome-wide significance 7. ATXN2L may also be sequestered in ATXN2 aggregates in spinocerebellar ataxia type 2, contributing to neurodegeneration 2. ATXN2L modulates fibrinogen production through post-transcriptional mechanisms under inflammatory conditions 8.

Sources cited
1
ATXN2L interacts with NUFIP2 and other RNA-binding proteins; is perinuclear and essential for embryonic life; may be sequestered in ATXN2 aggregates in disease
PMID: 40220918
2
ATXN2L dampens and shortens T cell cytokine production by binding to 3' UTRs of IFNG, TNF, and IL2
PMID: 37074914
3
ATXN2L undergoes liquid-liquid phase separation to form granules that recruit translation initiation factors and promote mRNA translation in hepatocellular carcinoma
PMID: 41273724
4
ATXN2L promotes translation of nonpolyadenylated reovirus mRNA through binding to the 3' terminus
PMID: 41408047
5
ATXN2L regulates fibrinogen production through post-transcriptional mechanisms under IL-6 stimulation
PMID: 36696182
6
ATXN2L shows exome-wide significant rare variant association with youth-onset type 2 diabetes
PMID: 38278947
7
ATXN2L contains Lsm and PAM2 domains; is required for embryonic development; participates in alternative splicing regulation
PMID: 41090760
8
ATXN2L is upregulated in gastric cancer by EGF/PI3K/Akt signaling; promotes invasiveness and oxaliplatin chemoresistance
PMID: 30787271
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.28Weak
Crohn's diseaseOpen Targets
0.26Weak
obesityOpen Targets
0.21Weak
Intellectual disabilityOpen Targets
0.18Weak
MacrocephalyOpen Targets
0.18Weak
atrial fibrillationOpen Targets
0.16Weak
Neurodevelopmental disorderOpen Targets
0.12Weak
marfanoid habitus and intellectual disabilityOpen Targets
0.12Weak
intelligenceOpen Targets
0.10Suggestive
overnutritionOpen Targets
0.09Suggestive
type 2 diabetes mellitusOpen Targets
0.09Suggestive
diabetes mellitusOpen Targets
0.08Suggestive
smoking behaviorOpen Targets
0.07Suggestive
mathematical abilityOpen Targets
0.06Suggestive
hypogonadismOpen Targets
0.06Suggestive
bipolar disorderOpen Targets
0.06Suggestive
gastric cancerOpen Targets
0.05Suggestive
schizophreniaOpen Targets
0.05Suggestive
rheumatoid arthritisOpen Targets
0.05Suggestive
autism spectrum disorderOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ATXN3LProtein interaction100%DCP1AProtein interaction99%PABPC4Protein interaction92%PABPC1Protein interaction92%FAM98AProtein interaction92%DDX6Protein interaction91%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
58%
Ovary
51%
Liver
48%
Brain
37%
Heart
20%
Gene Interaction Network
Click a node to explore
ATXN2LATXN3LDCP1APABPC4PABPC1FAM98ADDX6
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8WWM7
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.30Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.21 [0.15–0.30]
RankingsWhere ATXN2L stands among ~20K protein-coding genes
  • #2,286of 20,598
    Most Researched187 · top quartile
  • #1,113of 17,882
    Most Constrained (LOEUF)0.30 · top 10%
Genes detectedATXN2L
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
ATXN2L primarily interacts with NUFIP2, the absence of ATXN2L results in NUFIP2 depletion, and the ATXN2-polyQ expansion triggers NUFIP2 accumulation.
PMID: 40220918
Neurobiol Dis · 2025
1.00
2
Time-dependent regulation of cytokine production by RNA binding proteins defines T cell effector function.
PMID: 37074914
Cell Rep · 2023
0.90
3
Mid-Gestation lethality of
PMID: 32698485
Int J Mol Sci · 2020
0.84
4
Liquid-liquid phase separation of ATXN2L enhances mRNA translation in hepatocellular carcinoma.
PMID: 41273724
Cell Rep · 2025
0.80
5
Ataxin-2-like promotes translation of nonpolyadenylated reovirus mRNA.
PMID: 41408047
Nat Commun · 2025
0.70