ATXN2L

Chr 16

ataxin 2 like

Also known as: A2D, A2LG, A2LP, A2RP

NCBI Gene: 11273ENSG00000168488UniProt: Q8WWM7

This gene encodes an ataxin type 2 related protein of unknown function. This protein is a member of the spinocerebellar ataxia (SCAs) family, which is associated with a complex group of neurodegenerative disorders. Several alternatively spliced transcripts encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

339
ClinVar variants
113
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— ATXN2L
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
113 Pathogenic / Likely Pathogenic· 174 VUS of 339 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.14LOEUF
pLI 1.000
Z-score 6.45
OE 0.06 (0.02–0.14)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.25Z-score
OE missense 0.75 (0.69–0.81)
471 obs / 629.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.06 (0.02–0.14)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.69–0.81)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.22
0≤1.21.6
LoF obs/exp: 3 / 54.4Missense obs/exp: 471 / 629.5Syn Z: -2.80

ClinVar Variant Classifications

339 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic103
Likely Pathogenic10
VUS174
Likely Benign5
Benign3
Conflicting3
103
Pathogenic
10
Likely Pathogenic
174
VUS
5
Likely Benign
3
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
103
0
103
Likely Pathogenic
0
0
10
0
10
VUS
1
138
35
0
174
Likely Benign
0
1
1
3
5
Benign
0
0
2
1
3
Conflicting
—3
Total11391514298

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ATXN2L · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
ATAXIN 2-LIKE; ATXN2L
MIM #607931 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Time-dependent regulation of cytokine production by RNA binding proteins defines T cell effector function.
Popović B et al.·Cell Rep
2023
Genetic architecture and biology of youth-onset type 2 diabetes.
Kwak SH et al.·Nat Metab
2024
ATXN2L upregulated by epidermal growth factor promotes gastric cancer cell invasiveness and oxaliplatin resistance.
Lin L et al.·Cell Death Dis
2019
Prognostic Alternative mRNA Splicing in Adrenocortical Carcinoma.
Liang W et al.·Front Endocrinol (Lausanne)
2021
A de novo ATXN2L variant in a child with developmental delay and macrocephaly.
Alzahrani F et al.·Am J Med Genet A
2021
Single-cell RNA sequencing identifies macrophage signatures correlated with clinical features and tumour microenvironment in meningiomas.
Zhang X·IET Syst Biol
2023
Repurposing metformin as a potential anticancer agent using in silico technique.
Mahfauz M et al.·Daru
2024
SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function.
Li M et al.·J Am Soc Nephrol
2017Meta-analysis
Identification of ferroptosis genes in immune infiltration and prognosis in thyroid papillary carcinoma using network analysis.
Lin R et al.·BMC Genomics
2021
[Effect of leukapheresis on gene expression profiles of donor's peripheral blood mononuclear cells].
Shin JW et al.·Korean J Lab Med
2008
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Complete remission of relapsed ATXN2L::JAK2 fusion positive anaplastic large cell lymphoma following ruxolitinib monotherapy in a child.
Cohen T et al.·NPJ Precis Oncol
2026
Liquid-liquid phase separation of ATXN2L enhances mRNA translation in hepatocellular carcinoma.
Wang S et al.·Cell Rep
2025
Conditional ATXN2L-Null in Adult Frontal Cortex CamK2a+ Neurons Does Not Cause Cell Death but Restricts Spontaneous Mobility and Affects the Alternative Splicing Pathway.
Key J et al.·Cells
2025🔓 Open Access
Exosomal FOXL1 from bone marrow mesenchymal stem cells activates the METTL3/ATXN2L pathway to ameliorate high glucose-induced human retinal microvascular endothelial cell injury.
Niu C et al.·Diabetol Metab Syndr
2025🔓 Open Access
ATXN2L primarily interacts with NUFIP2, the absence of ATXN2L results in NUFIP2 depletion, and the ATXN2-polyQ expansion triggers NUFIP2 accumulation.
Key J et al.·Neurobiol Dis
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools