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…

ADLOEUF 0.171 OMIM phenotype

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

8 unique Pathogenic / Likely Pathogenic· 111 VUS of 178 total submissions

Explore recent and relevant literature in Research Assistant →

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

ClinVar Variant Classifications

178 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5

Likely Pathogenic3

VUS111

Likely Benign31

Benign10

Conflicting1

Pathogenic

Likely Pathogenic

111

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	5	0	0	0	5
Likely Pathogenic	3	0	0	0	3
VUS	9	102	0	0	111
Likely Benign	0	10	2	19	31
Benign	0	3	1	6	10
Conflicting	—				1
Total	17	115	3	25	161

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap DAGLA — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →