DIP2ADIP2 disco-interacting protein 2 homolog A (Drosophila)
Autism Reports / Total Reports
13 / 14Rare Variants / Common Variants
18 / 0Chromosome Band
21q22.3Associated Disorders
-Genetic Category
Rare Single Gene Mutation, FunctionalRelevance to Autism
Two de novo loss-of-function variants in the DIP2A gene have been identified in ASD probands from the Simons Simplex Collection (refs).
Molecular Function
The protein encoded by this gene may be involved in axon patterning in the central nervous system.
External Links
SFARI Genomic Platforms
Reports related to DIP2A (14 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Primary | De novo gene disruptions in children on the autistic spectrum | Iossifov I , et al. (2012) | Yes | - |
| 2 | Recent Recommendation | The contribution of de novo coding mutations to autism spectrum disorder | Iossifov I et al. (2014) | Yes | - |
| 3 | Recent Recommendation | Low load for disruptive mutations in autism genes and their biased transmission | Iossifov I , et al. (2015) | Yes | - |
| 4 | Support | Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci | Sanders SJ , et al. (2015) | Yes | - |
| 5 | Support | De novo genic mutations among a Chinese autism spectrum disorder cohort | Wang T , et al. (2016) | Yes | - |
| 6 | Support | Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model | Guo H , et al. (2018) | Yes | - |
| 7 | Support | Autism candidate gene DIP2A regulates spine morphogenesis via acetylation of cortactin | Ma J , et al. (2019) | Yes | - |
| 8 | Support | Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism | Satterstrom FK et al. (2020) | Yes | - |
| 9 | Support | Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use | Husson T , et al. (2020) | Yes | - |
| 10 | Support | - | Mahjani B et al. (2021) | Yes | - |
| 11 | Support | - | Zhou X et al. (2022) | Yes | - |
| 12 | Support | - | Ma J et al. (2022) | Yes | Anxiety |
| 13 | Support | - | Wang J et al. (2023) | Yes | - |
| 14 | Support | - | et al. () | No | - |
Rare Variants (18)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | - | missense_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.2953-6G>A | - | splice_region_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.3501+2T>C | - | splice_site_variant | Unknown | - | - | 34615535 | Mahjani B et al. (2021) | |
| - | - | synonymous_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.4202A>C | p.Tyr1401Ser | missense_variant | Unknown | - | - | 34615535 | Mahjani B et al. (2021) | |
| c.3197-41A>G | - | intron_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.1775G>A | p.Trp592Ter | stop_gained | De novo | - | Simplex | 25363768 | Iossifov I et al. (2014) | |
| c.260C>T | p.Ser87Leu | missense_variant | De novo | - | Multiplex | 35982159 | Zhou X et al. (2022) | |
| c.3262G>A | p.Val1088Ile | missense_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| c.3427G>A | p.Asp1143Asn | missense_variant | De novo | - | Simplex | 37393044 | Wang J et al. (2023) | |
| c.1505G>A | p.Gly502Asp | missense_variant | Familial | Maternal | - | 27824329 | Wang T , et al. (2016) | |
| c.1697G>A | p.Gly566Asp | missense_variant | Familial | Paternal | - | 27824329 | Wang T , et al. (2016) | |
| c.2445+6C>T | - | splice_region_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.1300+2T>G | - | splice_site_variant | Familial | Maternal | Simplex | 32094338 | Husson T , et al. (2020) | |
| c.2716G>A | p.Gly906Arg | missense_variant | Familial | Paternal | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.3997G>A | p.Val1333Ile | missense_variant | Familial | Paternal | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.2758G>A | p.Gly920Arg | missense_variant | Unknown | Not maternal | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.1643_1644insCTGGTCT | p.Glu549TrpfsTer3 | frameshift_variant | De novo | - | Simplex | 25363768 | Iossifov I et al. (2014) |
Common Variants
No common variants reported.
SFARI Gene score
1
High Confidence
Score Delta: Score remained at 1
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
2
1
Decreased from 2 to 1
1/1/2020
2
2
Decreased from 2 to 2
Description
Two de novo LoF variants in the DIP2A gene (one frameshift, one nonsense) were identified in ASD probands from the Simons Simplex Collection (PMIDs 22542183, 25363768). However, a de novo LoF variant (splice-site) in this gene was also observed in an unaffected sibling from the Simons Simplex Collection (PMID 25217958).
Reports Added
[Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci.2015] [Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism2020] [Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use.2020]10/1/2019
3
2
Decreased from 3 to 2
New Scoring Scheme
Description
Two de novo LoF variants in the DIP2A gene (one frameshift, one nonsense) were identified in ASD probands from the Simons Simplex Collection (PMIDs 22542183, 25363768). However, a de novo LoF variant (splice-site) in this gene was also observed in an unaffected sibling from the Simons Simplex Collection (PMID 25217958).
1/1/2019
3
3
Decreased from 3 to 3
Description
Two de novo LoF variants in the DIP2A gene (one frameshift, one nonsense) were identified in ASD probands from the Simons Simplex Collection (PMIDs 22542183, 25363768). However, a de novo LoF variant (splice-site) in this gene was also observed in an unaffected sibling from the Simons Simplex Collection (PMID 25217958).
10/1/2016
3
3
Decreased from 3 to 3
Description
Two de novo LoF variants in the DIP2A gene (one frameshift, one nonsense) were identified in ASD probands from the Simons Simplex Collection (PMIDs 22542183, 25363768). However, a de novo LoF variant (splice-site) in this gene was also observed in an unaffected sibling from the Simons Simplex Collection (PMID 25217958).
1/1/2016
3
3
Decreased from 3 to 3
Description
Two de novo LoF variants in the DIP2A gene (one frameshift, one nonsense) were identified in ASD probands from the Simons Simplex Collection (PMIDs 22542183, 25363768). However, a de novo LoF variant (splice-site) in this gene was also observed in an unaffected sibling from the Simons Simplex Collection (PMID 25217958).
10/1/2014
3
Increased from to 3
Description
Two de novo LoF variants in the DIP2A gene (one frameshift, one nonsense) were identified in ASD probands from the Simons Simplex Collection (PMIDs 22542183, 25363768). However, a de novo LoF variant (splice-site) in this gene was also observed in an unaffected sibling from the Simons Simplex Collection (PMID 25217958).
Krishnan Probability Score
Score 0.44571733907595
Ranking 15245/25841 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 0.7260990736083
Ranking 4340/18225 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 0.892
Ranking 155/239 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 0.075330466337625
Ranking 56/18665 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 12
Ranking 156/461 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 0.094877340060148
Ranking 6246/20870 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 |
|---|---|---|---|---|---|
| C1ORF186 | Uncharacterized protein C1orf186 | Human | Protein Binding | 440712 | Q6ZWK4 |
| C20orf20 | MRG/MORF4L binding protein | Human | Protein Binding | 55257 | A8C4L5 |
| CEP44 | centrosomal protein 44kDa | Human | Protein Binding | 80817 | Q9C0F1 |
| FAM214B | family with sequence similarity 214, member B | Human | Protein Binding | 80256 | Q7L5A3 |
| GPATCH2L | G patch domain containing 2-like | Human | Protein Binding | 55668 | Q9NWQ4 |
| HAVCR2 | Hepatitis A virus cellular receptor 2 | Human | Protein Binding | 84868 | Q8TDQ0 |
| IL20RA | Interleukin-20 receptor subunit alpha | Human | Protein Binding | 53832 | Q9UHF4 |
| JMJD6 | jumonji domain containing 6 | Human | Protein Binding | 23210 | Q6NYC1 |
| LPCAT1 | lysophosphatidylcholine acyltransferase 1 | Human | Protein Binding | 79888 | Q8NF37 |
| MANSC1 | Human | Protein Binding | |||
| PTGER3 | prostaglandin E receptor 3 (subtype EP3) | Human | Protein Binding | 5733 | P43115 |
| PTPN3 | protein tyrosine phosphatase, non-receptor type 3 | Human | Protein Binding | 5774 | B7Z9V1 |
| SELE | E-selectin | Human | Protein Binding | 6401 | P16581 |
| STAC3 | SH3 and cysteine rich domain 3 | Human | Protein Binding | 246329 | Q96MF2 |
| TPCN2 | two pore segment channel 2 | Human | Protein Binding | 219931 | Q59G56 |
| ZBTB43 | zinc finger and BTB domain containing 43 | Human | Protein Binding | 23099 | O43298 |