ATXN2L

Chr 16

ataxin 2 like

Also known as: A2D, A2LG, A2LP, A2RP

NCBI Gene: 11273 ENSG00000168488 UniProt: Q8WWM7 OMIM: 607931

The protein regulates stress granule and P-body formation, which are cellular structures involved in RNA metabolism and stress response. This gene is extremely intolerant to loss-of-function variants (pLI ~1.0, LOEUF 0.143), suggesting that mutations would likely cause severe developmental consequences, though specific disease associations have not yet been established in humans. The protein belongs to the spinocerebellar ataxia family, indicating potential involvement in neurodegenerative processes affecting cerebellar function.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.14

Clinical Summary— ATXN2L

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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.

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ClinVar Variants

141 VUS of 188 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

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?

LoF OE?0.06 (0.02–0.14)

0≤0.351.4

Missense OE?0.75 (0.69–0.81)

0≤0.61.4

Synonymous OE?1.22

0≤1.21.6

LoF obs/exp: 3 / 54.4Missense obs/exp: 471 / 629.5Syn Z: -2.80

This gene — mechanism propensity

0.2099th %ile

GOF

0.2597th %ile

LOF

0.86top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.14

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

188 submitted variants in ClinVar

ClinVar

Classification Summary

VUS141

Likely Benign4

Benign3

Conflicting1

141

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	3	138	0	0	141
Likely Benign	0	1	0	3	4
Benign	0	0	2	1	3
Conflicting	—				1
Total	3	139	2	4	149

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

View in ClinVar →

113 pathogenic / likely-pathogenic (of 153) ClinVar copy-number / structural variants overlap ATXN2L — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →