Human Gene Module / Chromosome 18 / DLGAP1

DLGAP1DLG associated protein 1

Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
5 / 7
Rare Variants / Common Variants
12 / 0
Associated Syndromes
Genetic Category
Rare Single Gene Mutation, Functional
Chromosome Band
Associated Disorders
Relevance to Autism

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module; sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism (Li et al., 2014).

Molecular Function

The protein encoded by this gene is expressed in the brain, localizes to the postsynaptic density, and interacts with a number of ASD-associated proteins, including DLG1, DLG4, SHANK1, SHANK2 and SHANK3.

Reports related to DLGAP1 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Large-scale discovery of novel genetic causes of developmental disorders. Deciphering Developmental Disorders Study (2014) No -
2 Primary Integrated systems analysis reveals a molecular network underlying autism spectrum disorders. Li J , et al. (2015) Yes -
3 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 -
4 Support De novo genic mutations among a Chinese autism spectrum disorder cohort. Wang T , et al. (2016) Yes -
5 Support Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases. Stessman HA , et al. (2017) Yes -
6 Support Dlgap1 knockout mice exhibit alterations of the postsynaptic density and selective reductions in sociability. Coba MP , et al. (2018) No -
7 Support Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model. Guo H , et al. (2018) Yes -
Rare Variants   (12)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.22C>A p.Arg8Ser missense_variant Unknown - - 27271353 Xing J , et al. (2016)
c.215G>A p.Arg72His missense_variant Unknown - - 27271353 Xing J , et al. (2016)
c.497G>A p.Gly166Asp missense_variant Unknown - - 27271353 Xing J , et al. (2016)
c.1175T>C p.Ile392Thr missense_variant Unknown - - 27271353 Xing J , et al. (2016)
c.1273G>A p.Asp703Asn missense_variant Unknown - - 27271353 Xing J , et al. (2016)
c.2260G>A p.Asp754Asn missense_variant Unknown - - 27271353 Xing J , et al. (2016)
c.230C>T p.Ser77Leu missense_variant Unknown - Unknown 25549968 Li J , et al. (2015)
c.215G>A p.Arg72His missense_variant De novo - - 28191889 Stessman HA , et al. (2017)
c.424G>T p.Val142Leu missense_variant Unknown Not maternal - 27824329 Wang T , et al. (2016)
c.293G>A p.Arg98His missense_variant Familial Maternal Simplex 30564305 Guo H , et al. (2018)
C>T R/Gln missense_variant De novo - Unknown 25533962 Deciphering Developmental Disorders Study (2014)
C>T p.(=) synonymous_variant De novo - Unknown 25533962 Deciphering Developmental Disorders Study (2014)
Common Variants  

No common variants reported.

SFARI Gene score

Suggestive Evidence



Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

4.4 + acc3

Initial score established: 4.4 + acc3



Krishnan Probability Score

Score 0.60353762061072

Ranking 363/25841 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: A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at
ExAC Score

Score 0.99304551428356

Ranking 1659/18225 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 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: aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score

Score 0.95004101463091

Ranking 18334/18665 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
Zhang D Score

Score 0.59611276742204

Ranking 91/20870 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.
CNVs associated with DLGAP1(1 CNVs)
18p11.31 11 Deletion-Duplication 19  /  48
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