DLGAP2discs, large (Drosophila) homolog-associated protein 2
Autism Reports / Total Reports
15 / 18Rare Variants / Common Variants
34 / 2Chromosome Band
8p23.3Associated Disorders
-Genetic Category
Rare Single Gene MutationRelevance to Autism
Rare mutations in the DLGAP2 gene have been identified with autism. In separate studies, de novo duplications were found in patients with ASD (Marshall et al., 2008; Pinto et al., 2010).
Molecular Function
The encoded protein is a membrane-associated guanylate kinase localized at the post-synaptic density in neuronal cells.
External Links
SFARI Genomic Platforms
Reports related to DLGAP2 (18 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Highly Cited | Distinct spatiotemporal expression of SAPAP transcripts in the developing rat brain: a novel dendritically localized mRNA | Kindler S , et al. (2004) | No | - |
| 2 | Recent Recommendation | Computational and experimental identification of novel human imprinted genes | Luedi PP , et al. (2007) | No | - |
| 3 | Primary | Structural variation of chromosomes in autism spectrum disorder | Marshall CR , et al. (2008) | Yes | - |
| 4 | Recent Recommendation | Fragile X mental retardation protein regulates the levels of scaffold proteins and glutamate receptors in postsynaptic densities | Schtt J , et al. (2009) | No | - |
| 5 | Support | Functional impact of global rare copy number variation in autism spectrum disorders | Pinto D , et al. (2010) | Yes | - |
| 6 | Support | Deep exon resequencing of DLGAP2 as a candidate gene of autism spectrum disorders | Chien WH , et al. (2013) | Yes | - |
| 7 | Support | Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders | Cukier HN , et al. (2014) | Yes | - |
| 8 | Support | Synaptic, transcriptional and chromatin genes disrupted in autism | De Rubeis S , et al. (2014) | Yes | - |
| 9 | Support | The contribution of de novo coding mutations to autism spectrum disorder | Iossifov I et al. (2014) | Yes | - |
| 10 | Recent Recommendation | Low load for disruptive mutations in autism genes and their biased transmission | Iossifov I , et al. (2015) | Yes | - |
| 11 | Support | Comprehensive molecular testing in patients with high functioning autism spectrum disorder | Alvarez-Mora MI , et al. (2016) | Yes | - |
| 12 | Support | Resequencing and Association Analysis of Six PSD-95-Related Genes as Possible Susceptibility Genes for Schizophrenia and Autism Spectrum Disorders | Xing J , et al. (2016) | Yes | - |
| 13 | Support | Segregating patterns of copy number variations in extended autism spectrum disorder (ASD) pedigrees | Woodbury-Smith M et al. (2020) | Yes | - |
| 14 | Support | Next-Generation Sequencing in Korean Children With Autism Spectrum Disorder and Comorbid Epilepsy | Lee J et al. (2020) | Yes | - |
| 15 | Support | - | Catusi I et al. (2021) | Yes | - |
| 16 | Support | - | Woodbury-Smith M et al. (2022) | Yes | - |
| 17 | Support | - | Zhou X et al. (2022) | Yes | - |
| 18 | Support | - | Hu C et al. (2023) | Yes | - |
Rare Variants (34)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | - | copy_number_gain | Unknown | - | - | 32477112 | Lee J et al. (2020) | |
| - | - | copy_number_gain | De novo | - | - | 20531469 | Pinto D , et al. (2010) | |
| - | - | copy_number_loss | De novo | - | - | 33925474 | Catusi I et al. (2021) | |
| - | - | copy_number_loss | Unknown | - | - | 26845707 | Alvarez-Mora MI , et al. (2016) | |
| - | - | copy_number_gain | De novo | - | Simplex | 18252227 | Marshall CR , et al. (2008) | |
| c.136G>A | p.Gly46Ser | missense_variant | Unknown | - | - | 27271353 | Xing J , et al. (2016) | |
| c.1330G>T | p.Asp444Tyr | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.2117C>T | p.Ala706Val | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.520G>A | p.Asp174Asn | missense_variant | Unknown | - | - | 27271353 | Xing J , et al. (2016) | |
| c.371G>T | p.Arg124Leu | missense_variant | Familial | - | - | 27271353 | Xing J , et al. (2016) | |
| c.1225A>G | p.Ser409Gly | missense_variant | Unknown | - | - | 27271353 | Xing J , et al. (2016) | |
| c.1289C>T | p.Ser430Phe | missense_variant | Unknown | - | - | 27271353 | Xing J , et al. (2016) | |
| c.1997G>A | p.Ser666Asn | missense_variant | Unknown | - | - | 27271353 | Xing J , et al. (2016) | |
| c.2044G>A | p.Ala682Thr | missense_variant | Unknown | - | - | 27271353 | Xing J , et al. (2016) | |
| c.2219C>A | p.Thr740Asn | missense_variant | Unknown | - | - | 27271353 | Xing J , et al. (2016) | |
| c.2284G>A | p.Val762Ile | missense_variant | Unknown | - | - | 27271353 | Xing J , et al. (2016) | |
| c.232C>T | p.Pro78Ser | missense_variant | Familial | Maternal | - | 37007974 | Hu C et al. (2023) | |
| c.637A>G | p.Met213Val | missense_variant | De novo | - | - | 25363760 | De Rubeis S , et al. (2014) | |
| c.1289G>T | p.Cys430Phe | missense_variant | Familial | Maternal | - | 37007974 | Hu C et al. (2023) | |
| c.2153G>A | p.Gly718Glu | missense_variant | Familial | Maternal | - | 37007974 | Hu C et al. (2023) | |
| - | - | copy_number_gain | Familial | Paternal | Multiplex | 32372567 | Woodbury-Smith M et al. (2020) | |
| c.1330G>T | p.Asp444Tyr | missense_variant | De novo | - | Multiplex | 35982159 | Zhou X et al. (2022) | |
| c.2710G>A | p.Gly904Ser | missense_variant | De novo | - | Multiplex | 35982159 | Zhou X et al. (2022) | |
| c.574G>T | p.Ala192Ser | missense_variant | Unknown | - | Unknown | 23915500 | Chien WH , et al. (2013) | |
| c.425A>C | p.His142Pro | missense_variant | De novo | - | - | 35205252 | Woodbury-Smith M et al. (2022) | |
| c.2216G>C | p.Arg739Thr | missense_variant | De novo | - | Simplex | 25363768 | Iossifov I et al. (2014) | |
| c.44C>T | p.Ser15Phe | missense_variant | Familial | Maternal | Simplex | 23915500 | Chien WH , et al. (2013) | |
| c.1810C>T | p.Arg604Cys | missense_variant | Familial | Paternal | Simplex | 27271353 | Xing J , et al. (2016) | |
| c.277C>A | p.Leu93Met | missense_variant | Familial | Maternal | Simplex | 23915500 | Chien WH , et al. (2013) | |
| c.545G>A | p.Gly182Asp | missense_variant | Familial | Paternal | Simplex | 23915500 | Chien WH , et al. (2013) | |
| c.970A>T | p.Arg324Trp | missense_variant | Familial | Paternal | Simplex | 23915500 | Chien WH , et al. (2013) | |
| c.1516T>C | p.Cys506Arg | missense_variant | Familial | Paternal | Simplex | 23915500 | Chien WH , et al. (2013) | |
| c.2392G>C | p.Glu798Gln | missense_variant | Familial | Maternal | Simplex | 23915500 | Chien WH , et al. (2013) | |
| c.2209G>C | p.Ala737Pro | missense_variant | Familial | - | Extended multiplex (at least one pair of ASD affec | 24410847 | Cukier HN , et al. (2014) |
Common Variants (2)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Paternal Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.-68-4A>G;c.242-4A>G | - | intron_variant | - | - | - | 23915500 | Chien WH , et al. (2013) | |
| c.1151C>A;c.1460C>A | p.Pro384Gln | missense_variant | - | - | - | 23915500 | Chien WH , et al. (2013) |
SFARI Gene score
2
Strong Candidate
In ASD-associated CNVs (Pinto et al., 2010) for which at present there is not independent evidence.
Score Delta: Score remained at 2
criteria met
See SFARI Gene'scoring criteriaWe 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
2
Decreased from 3 to 2
Description
In ASD-associated CNVs (Pinto et al., 2010) for which at present there is not independent evidence.
4/1/2021
3
3
Decreased from 3 to 3
Description
In ASD-associated CNVs (Pinto et al., 2010) for which at present there is not independent evidence.
4/1/2020
3
3
Decreased from 3 to 3
Description
In ASD-associated CNVs (Pinto et al., 2010) for which at present there is not independent evidence.
10/1/2019
4
3
Decreased from 4 to 3
New Scoring Scheme
Description
In ASD-associated CNVs (Pinto et al., 2010) for which at present there is not independent evidence.
Reports Added
[New Scoring Scheme]7/1/2016
4
4
Decreased from 4 to 4
Description
In ASD-associated CNVs (Pinto et al., 2010) for which at present there is not independent evidence.
1/1/2016
4
4
Decreased from 4 to 4
Description
In ASD-associated CNVs (Pinto et al., 2010) for which at present there is not independent evidence.
Reports Added
[Structural variation of chromosomes in autism spectrum disorder.2008] [Functional impact of global rare copy number variation in autism spectrum disorders.2010] [Deep exon resequencing of DLGAP2 as a candidate gene of autism spectrum disorders.2013] [Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders.2014] [Distinct spatiotemporal expression of SAPAP transcripts in the developing rat brain: a novel dendritically localized mRNA.2004] [Computational and experimental identification of novel human imprinted genes.2007] [Fragile X mental retardation protein regulates the levels of scaffold proteins and glutamate receptors in postsynaptic densities.2009] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Comprehensive molecular testing in patients with high functioning autism spectrum disorder.2016]7/1/2014
No data
4
Increased from No data to 4
Description
In ASD-associated CNVs (Pinto et al., 2010) for which at present there is not independent evidence.
4/1/2014
No data
4
Increased from No data to 4
Description
In ASD-associated CNVs (Pinto et al., 2010) for which at present there is not independent evidence.
Krishnan Probability Score
Score 0.62762954543632
Ranking 72/25841 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.
ExAC Score
Score 0.95039732591759
Ranking 2674/18225 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
Iossifov Probability Score
Score 0.929
Ranking 111/239 scored genes
[Show Scoring Methodology]
Supplementary dataset S2 in the paper by Iossifov et al. (PNAS 112, E5600-E5607 (2015)) lists
239 genes with a probability of at least 0.8 of being associated with autism risk (column I). This
probability metric combines the evidence from de novo likely-gene- disrupting and missense
mutations and assesses it against the background mutation rate in unaffected individuals from the
University of Washingtonâs Exome Variant Sequence database (evs.gs.washington.edu/EVS/).
The list of probability scores can be found here:
www.pnas.org/lookup/suppl/doi:10.1073/pnas.1516376112/-
/DCSupplemental/pnas.1516376112.sd02.xlsx
Sanders TADA Score
Score 0.74983049102443
Ranking 1553/18665 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).
Larsen Cumulative Evidence Score
Score 29
Ranking 73/461 scored genes
[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available
ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size,
and variant frequency in the general population. The approach was first presented in Mol Autism
7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from
that paper.
Zhang D Score
Score 0.42599030081976
Ranking 1166/20870 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.
Interactome
- Protein Binding
- DNA Binding
- RNA Binding
- Protein Modification
- Direct Regulation
- ASD-Linked Genes
Interaction Table
| Interactor Symbol | Interactor Name | Interactor Organism | Interactor Type | Entrez ID | Uniprot ID |
|---|---|---|---|---|---|
| KRTAP4-2 | keratin associated protein 4-2 | Human | Protein Binding | 85291 | Q9BYR5 |