DAGLA

Chr 11AD

diacylglycerol lipase alpha

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

NCBI Gene: 747 ENSG00000134780 UniProt: Q9Y4D2 OMIM: 614015

The protein is a diacylglycerol lipase that synthesizes 2-arachidonoylglycerol, the principal endocannabinoid involved in synaptic signaling and neuronal development in the central nervous system. Mutations cause neuroocular syndrome 2, paroxysmal type, inherited in an autosomal dominant pattern. This gene is highly constrained against loss-of-function mutations (pLI = 1.0, LOEUF = 0.17), indicating that complete loss of protein function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neuroocular syndrome 2, paroxysmal typeMIM #168885

UniProtSpinocerebellar ataxia 20

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Neuroocular syndrome 2, paroxysmal type; no ClinGen or GenCC tier

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.17

LOEUF· LoF intol.

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

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?

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?

LoF OE?0.07 (0.03–0.17)

0≤0.351.4

Missense OE?0.57 (0.53–0.62)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 3 / 45.4Missense obs/exp: 402 / 700.4Syn Z: -0.09

Background carrier burden — how many people carry a rare variant somewhere in DAGLA?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 92

980 rare PASS variants

Rare truncating (LoF)

1 in 6,500

50 rare PASS variants

Rare synonymous (reference)

1 in 62

605 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DAGLA. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 100	1 in 6,300
South Asian	~43k	1 in 66	≈ 1 in 43,000
Remaining (unassigned)	~30k	1 in 84	≈ 1 in 7,400
European (Finnish)	~27k	1 in 210	1 in 2,400
Admixed American	~22k	1 in 82	≈ 1 in 11,000
African / African American	~21k	1 in 61	≈ 1 in 5,600
East Asian	~20k	1 in 64	1 in 1,900
Ashkenazi Jewish	~13k	1 in 390	none seen
Middle Eastern	~2,884	1 in 64	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 19 coding exons well covered in gnomAD exomes and genomes.? see exons ↓