DAGLA

Chr 11AD

diacylglycerol lipase alpha

Also known as: C11orf11, DAGL(ALPHA), DAGLALPHA, NOC2, NSDDR

NCBI Gene: 747ENSG00000134780UniProt: Q9Y4D2

This gene encodes a diacylglycerol lipase. The encoded enzyme is involved in the biosynthesis of the endocannabinoid 2-arachidonoyl-glycerol.[provided by RefSeq, Nov 2010]

Primary Disease Associations & Inheritance

Neuroocular syndrome 2, paroxysmal typeMIM #168885
AD
UniProtSpinocerebellar ataxia 20
190
ClinVar variants
18
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— DAGLA
⚡
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
18 Pathogenic / Likely Pathogenic· 113 VUS of 190 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.17LOEUF
pLI 1.000
Z-score 5.83
OE 0.07 (0.03–0.17)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
4.01Z-score
OE missense 0.57 (0.53–0.62)
402 obs / 700.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.07 (0.03–0.17)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.57 (0.53–0.62)
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.1.01
0≤1.21.6
LoF obs/exp: 3 / 45.4Missense obs/exp: 402 / 700.4Syn Z: -0.09

ClinVar Variant Classifications

190 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic6
VUS113
Likely Benign31
Benign10
Conflicting1
12
Pathogenic
6
Likely Pathogenic
113
VUS
31
Likely Benign
10
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
10
0
12
Likely Pathogenic
2
0
4
0
6
VUS
7
100
6
0
113
Likely Benign
0
9
3
19
31
Benign
0
3
1
6
10
Conflicting
—1
Total111122425173

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

View in ClinVar →

Protein Context — Lollipop Plot

DAGLA · 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

Neuroocular syndrome 2, paroxysmal type

MIM #168885

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Diacylglycerol lipase alpha promotes hepatocellular carcinoma progression and induces lenvatinib resistance by enhancing YAP activity.
Yan YC et al.·Cell Death Dis
2023
Endocannabinoid dysfunction in neurological disease: neuro-ocular DAGLA-related syndrome.
Bainbridge MN et al.·Brain
2022
Systematic analysis of variants escaping nonsense-mediated decay uncovers candidate Mendelian diseases.
Torene RI et al.·Am J Hum Genet
2024
Identification of DAGLA as an autoantibody target in cerebellar ataxia.
Miske R et al.·J Neurol Neurosurg Psychiatry
2024
Chimeric antigen receptor T cells in treatment-refractory DAGLA antibody-associated encephalitis.
Hegelmaier T et al.·Med
2025Case report
Rare genetic variants in the endocannabinoid system genes CNR1 and DAGLA are associated with neurological phenotypes in humans.
Smith DR et al.·PLoS One
2017
Diacylglycerol lipase alpha promotes tumorigenesis in oral cancer by cell-cycle progression.
Okubo Y et al.·Exp Cell Res
2018
Identification of Endocannabinoid Predictors of Treatment Outcomes in Major Depressive Disorder: A Secondary Analysis of the First Canadian Biomarker Integration Network in Depression (CAN-BIND 1) Study.
Kim HK et al.·Pharmacopsychiatry
2022
Genome-wide association studies and fine-mapping identify genomic loci for n-3 and n-6 polyunsaturated fatty acids in Hispanic American and African American cohorts.
Yang C et al.·Commun Biol
2023Cohort
Impact of anesthesia-related genes on prognosis and tumor microenvironment in hepatocellular carcinoma: A comprehensive analysis.
Xu X et al.·Environ Toxicol
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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