Human Gene Module / Chromosome 11 / DAGLA

DAGLAdiacylglycerol lipase alpha

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 7
Rare Variants / Common Variants
29 / 0
Aliases
DAGLA, C11orf11,  DAGL(ALPHA),  DAGLALPHA,  NSDDR
Associated Syndromes
-
Chromosome Band
11q12.2
Associated Disorders
-
Relevance to Autism

A paternally-inherited deletion disrupting seven exons of the DAGLA gene was identified in a male ASD proband and an affected male sibling; however, this deletion was also observed in an unaffected male sibling but was not observed in controls (Prasad et al., 2012).

Molecular Function

This gene encodes a diacylglycerol lipase. The encoded enzyme is involved in the biosynthesis of the endocannabinoid 2-arachidonoyl-glycerol.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to DAGLA (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary A discovery resource of rare copy number variations in individuals with autism spectrum disorder Prasad A , et al. (2013) Yes -
2 Support Transcriptome analysis of cortical tissue reveals shared sets of downregulated genes in autism and schizophrenia Ellis SE , et al. (2016) Yes -
3 Support Rare genetic variants in the endocannabinoid system genes CNR1 and DAGLA are associated with neurological phenotypes in humans Smith DR , et al. (2017) No -
4 Support Role of Striatal Direct Pathway 2-Arachidonoylglycerol Signaling in Sociability and Repetitive Behavior Shonesy BC , et al. (2018) No -
5 Support Mutations in ASH1L confer susceptibility to Tourette syndrome Liu S , et al. (2019) No -
6 Support - Singh T et al. (2022) No -
7 Support - Zhou X et al. (2022) Yes -
Rare Variants   (29)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1613G>A p.Arg538His missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1741C>T p.Arg581Trp missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.263C>T p.Thr88Met missense_variant Unknown - - 29145497 Smith DR , et al. (2017)
- - copy_number_loss Familial Paternal Multiplex 23275889 Prasad A , et al. (2013)
c.589C>T p.Arg197Trp missense_variant Unknown - - 29145497 Smith DR , et al. (2017)
c.757G>T p.Ala253Ser missense_variant Unknown - - 29145497 Smith DR , et al. (2017)
c.940G>A p.Ala314Thr missense_variant Unknown - - 29145497 Smith DR , et al. (2017)
c.992C>T p.Ala331Val missense_variant Unknown - - 29145497 Smith DR , et al. (2017)
c.1213-3A>G - splice_region_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1105G>A p.Val369Ile missense_variant Unknown - - 29145497 Smith DR , et al. (2017)
c.1375C>T p.Arg459Cys missense_variant Unknown - - 29145497 Smith DR , et al. (2017)
c.1742G>A p.Arg581Gln missense_variant Unknown - - 29145497 Smith DR , et al. (2017)
c.2243C>T p.Ala748Val missense_variant Unknown - - 29145497 Smith DR , et al. (2017)
c.2294G>A p.Arg765Gln missense_variant Unknown - - 29145497 Smith DR , et al. (2017)
c.2300C>T p.Ala767Val missense_variant Unknown - - 29145497 Smith DR , et al. (2017)
c.2377G>A p.Asp793Asn missense_variant Unknown - - 29145497 Smith DR , et al. (2017)
c.2430C>A p.His810Gln missense_variant Unknown - - 29145497 Smith DR , et al. (2017)
c.2444G>A p.Arg815His missense_variant Unknown - - 29145497 Smith DR , et al. (2017)
c.2525C>T p.Ala842Val missense_variant Unknown - - 29145497 Smith DR , et al. (2017)
c.2573C>T p.Ala858Val missense_variant Unknown - - 29145497 Smith DR , et al. (2017)
c.2621C>T p.Ala874Val missense_variant Unknown - - 29145497 Smith DR , et al. (2017)
c.2653G>C p.Gly885Arg missense_variant Unknown - - 29145497 Smith DR , et al. (2017)
c.2675G>T p.Arg892Leu missense_variant Unknown - - 29145497 Smith DR , et al. (2017)
c.2909C>A p.Pro970His missense_variant Unknown - - 29145497 Smith DR , et al. (2017)
c.2962C>G p.Leu988Val missense_variant Unknown - - 29145497 Smith DR , et al. (2017)
c.3049G>C p.Asp1017His missense_variant Unknown - - 29145497 Smith DR , et al. (2017)
c.3127T>C p.Ter1043GlnextTer29 stop_lost Unknown - - 29145497 Smith DR , et al. (2017)
c.932G>A p.Arg311Gln missense_variant De novo - Simplex 31673123 Liu S , et al. (2019)
c.2443C>T p.Arg815Cys missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A paternally-inherited deletion disrupting seven exons of the DAGLA gene was identified in a male ASD proband and an affected male sibling, as well as in an unaffected male sibling; this variant was not observed in controls (Prasad et al., 2012). This gene was shown to be differentially expressed (P < 0.05) in both schizophrenia (Z -2.98) and autism (Z -4.22) post-mortem brain samples in Ellis et al., 2016. Screening for rare genetic variants in core endocannabinoid system genes in 6,032 patients with a broad spectrum of neurological disorders determined that heterozygous rare coding variants in DAGLA were significantly associated with seizures and neurodevelopmental disorders, including autism, compared to controls (Smith et al., 2017).

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

A paternally-inherited deletion disrupting seven exons of the DAGLA gene was identified in a male ASD proband and an affected male sibling, as well as in an unaffected male sibling; this variant was not observed in controls (Prasad et al., 2012). This gene was shown to be differentially expressed (P < 0.05) in both schizophrenia (Z -2.98) and autism (Z -4.22) post-mortem brain samples in Ellis et al., 2016. Screening for rare genetic variants in core endocannabinoid system genes in 6,032 patients with a broad spectrum of neurological disorders determined that heterozygous rare coding variants in DAGLA were significantly associated with seizures and neurodevelopmental disorders, including autism, compared to controls (Smith et al., 2017).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A paternally-inherited deletion disrupting seven exons of the DAGLA gene was identified in a male ASD proband and an affected male sibling, as well as in an unaffected male sibling; this variant was not observed in controls (Prasad et al., 2012). This gene was shown to be differentially expressed (P < 0.05) in both schizophrenia (Z -2.98) and autism (Z -4.22) post-mortem brain samples in Ellis et al., 2016. Screening for rare genetic variants in core endocannabinoid system genes in 6,032 patients with a broad spectrum of neurological disorders determined that heterozygous rare coding variants in DAGLA were significantly associated with seizures and neurodevelopmental disorders, including autism, compared to controls (Smith et al., 2017).

Reports Added
[Mutations in ASH1L confer susceptibility to Tourette syndrome.2019] [New Scoring Scheme]
10/1/2017
icon
4

Increased from to 4

Description

A paternally-inherited deletion disrupting seven exons of the DAGLA gene was identified in a male ASD proband and an affected male sibling, as well as in an unaffected male sibling; this variant was not observed in controls (Prasad et al., 2012). This gene was shown to be differentially expressed (P < 0.05) in both schizophrenia (Z -2.98) and autism (Z -4.22) post-mortem brain samples in Ellis et al., 2016. Screening for rare genetic variants in core endocannabinoid system genes in 6,032 patients with a broad spectrum of neurological disorders determined that heterozygous rare coding variants in DAGLA were significantly associated with seizures and neurodevelopmental disorders, including autism, compared to controls (Smith et al., 2017).

Reports Added
[Rare genetic variants in the endocannabinoid system genes CNR1 and DAGLA are associated with neurological phenotypes in humans.2017]
Krishnan Probability Score

Score 0.49220967727967

Ranking 4670/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.95314834249245

Ranking 2628/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.94621404347514

Ranking 16780/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Zhang D Score

Score 0.27088373981584

Ranking 3176/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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