DPYSL2dihydropyrimidinase like 2
Autism Reports / Total Reports
6 / 17Rare Variants / Common Variants
6 / 0Aliases
DPYSL2, CRMP-2, CRMP2, DHPRP2, DRP-2, DRP2, N2A3, ULIP-2, ULIP2Associated Syndromes
-Chromosome Band
8p21.2Associated Disorders
-Genetic Category
Rare Single Gene Mutation, Syndromic, Genetic Association, FunctionalRelevance to Autism
De novo missense variants that were predicted in silico to be damaging were identified in the DPYSL2 gene in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014) and the Simons Simplex Collection (Iossifov et al., 2014). TADA-Denovo analysis using a combined dataset of previously published cohorts from the Simons Simplex Collection and the Autism Sequencing Consortium, as well as a novel cohort of 262 Japanese ASD trios, in Takata et al., 2018 identified DPYSL2 as a gene significantly enriched in damaging de novo mutations in ASD cases (pBH < 0.05). Multiple studies have reported an association between the DPYSL2 gene and schizophrenia (Nakata et al., 2003; Fallin et al., 2005; Fallin et al., 2011; Liu et al., 2014; Lee et al., 2015), as well as evidence suggesting that the DPYSL2 gene links mTOR signaling and schizophrenia (Liu et al., 2014; Pham et al., 2016).
Molecular Function
This gene encodes a member of the collapsin response mediator protein family. Collapsin response mediator proteins form homo- and hetero-tetramers and facilitate neuron guidance, growth and polarity. The encoded protein promotes microtubule assembly and is required for Sema3A-mediated growth cone collapse, and also plays a role in synaptic signaling through interactions with calcium channels. This gene has been implicated in multiple neurological disorders, and hyperphosphorylation of the encoded protein may play a key role in the development of Alzheimer's disease.
External Links
SFARI Genomic Platforms
Reports related to DPYSL2 (17 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Positive Association | The human dihydropyrimidinase-related protein 2 gene on chromosome 8p21 is associated with paranoid-type schizophrenia | Nakata K , et al. (2003) | No | - |
2 | Negative Association | An investigation of the dihydropyrimidinase-like 2 (DPYSL2) gene in schizophrenia: genetic association study and expression analysis | Zhao X , et al. (2005) | No | - |
3 | Positive Association | Bipolar I disorder and schizophrenia: a 440-single-nucleotide polymorphism screen of 64 candidate genes among Ashkenazi Jewish case-parent trios | Fallin MD , et al. (2005) | No | - |
4 | Negative Association | A two-stage case-control association study of the dihydropyrimidinase-like 2 gene (DPYSL2) with schizophrenia in Japanese subjects | Koide T , et al. (2010) | No | - |
5 | Positive Association | Linkage and association on 8p21.2-p21.1 in schizophrenia | Fallin MD , et al. (2011) | No | - |
6 | Primary | Synaptic, transcriptional and chromatin genes disrupted in autism | De Rubeis S , et al. (2014) | Yes | - |
7 | Support | The contribution of de novo coding mutations to autism spectrum disorder | Iossifov I et al. (2014) | Yes | - |
8 | Positive Association | Functional variants in DPYSL2 sequence increase risk of schizophrenia and suggest a link to mTOR signaling | Liu Y , et al. (2014) | No | - |
9 | Positive Association | Changes in Dpysl2 expression are associated with prenatally stressed rat offspring and susceptibility to schizophrenia in humans | Lee H , et al. (2015) | No | - |
10 | Support | The DPYSL2 gene connects mTOR and schizophrenia | Pham X , et al. (2016) | No | - |
11 | Recent Recommendation | Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder | Takata A , et al. (2018) | Yes | - |
12 | Recent Recommendation | An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders | Chen S , et al. (2018) | No | - |
13 | Support | CRMP2 mediates Sema3F-dependent axon pruning and dendritic spine remodeling | Ziak J , et al. (2020) | Yes | - |
14 | Support | Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism | Satterstrom FK et al. (2020) | Yes | - |
15 | Support | - | Suzuki H et al. (2022) | No | ID, epilepsy/seizures |
16 | Support | - | Zhou X et al. (2022) | Yes | - |
17 | Support | - | Feuer KL et al. (2023) | No | - |
Rare Variants (6)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
c.42C>A | p.Ser14Arg | missense_variant | De novo | - | - | 35861646 | Suzuki H et al. (2022) | |
c.606C>T | p.Gly202%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.1312C>A | p.His438Asn | missense_variant | De novo | - | - | 25363760 | De Rubeis S , et al. (2014) | |
c.1693C>T | p.His565Tyr | missense_variant | De novo | - | Simplex | 35861646 | Suzuki H et al. (2022) | |
c.1801C>T | p.Arg601Cys | missense_variant | De novo | - | Simplex | 25363768 | Iossifov I et al. (2014) | |
c.1028G>A | p.Arg343His | missense_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) |
Common Variants
No common variants reported.
SFARI Gene score
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
Decreased from 2 to 1
1/1/2020
Decreased from 2 to 2
Description
De novo missense variants that were predicted in silico to be damaging were identified in the DPYSL2 gene in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014) and the Simons Simplex Collection (Iossifov et al., 2014). TADA-Denovo analysis using a combined dataset of previously published cohorts from the Simons Simplex Collection and the Autism Sequencing Consortium, as well as a novel cohort of 262 Japanese ASD trios, in Takata et al., 2018 identified DPYSL2 as a gene significantly enriched in damaging de novo mutations in ASD cases (pBH < 0.05). Multiple studies have reported an association between the DPYSL2 gene and schizophrenia (Nakata et al., 2003; Fallin et al., 2005; Fallin et al., 2011; Liu et al., 2014; Lee et al., 2015), as well as evidence suggesting that the DPYSL2 gene links mTOR signaling and schizophrenia (Liu et al., 2014; Pham et al., 2016).
10/1/2019
Decreased from 3 to 2
New Scoring Scheme
Description
De novo missense variants that were predicted in silico to be damaging were identified in the DPYSL2 gene in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014) and the Simons Simplex Collection (Iossifov et al., 2014). TADA-Denovo analysis using a combined dataset of previously published cohorts from the Simons Simplex Collection and the Autism Sequencing Consortium, as well as a novel cohort of 262 Japanese ASD trios, in Takata et al., 2018 identified DPYSL2 as a gene significantly enriched in damaging de novo mutations in ASD cases (pBH < 0.05). Multiple studies have reported an association between the DPYSL2 gene and schizophrenia (Nakata et al., 2003; Fallin et al., 2005; Fallin et al., 2011; Liu et al., 2014; Lee et al., 2015), as well as evidence suggesting that the DPYSL2 gene links mTOR signaling and schizophrenia (Liu et al., 2014; Pham et al., 2016).
Reports Added
[New Scoring Scheme]7/1/2018
Increased from to 3
Description
De novo missense variants that were predicted in silico to be damaging were identified in the DPYSL2 gene in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014) and the Simons Simplex Collection (Iossifov et al., 2014). TADA-Denovo analysis using a combined dataset of previously published cohorts from the Simons Simplex Collection and the Autism Sequencing Consortium, as well as a novel cohort of 262 Japanese ASD trios, in Takata et al., 2018 identified DPYSL2 as a gene significantly enriched in damaging de novo mutations in ASD cases (pBH < 0.05). Multiple studies have reported an association between the DPYSL2 gene and schizophrenia (Nakata et al., 2003; Fallin et al., 2005; Fallin et al., 2011; Liu et al., 2014; Lee et al., 2015), as well as evidence suggesting that the DPYSL2 gene links mTOR signaling and schizophrenia (Liu et al., 2014; Pham et al., 2016).
Krishnan Probability Score
Score 0.49980804518459
Ranking 2131/25841 scored genes
[Show Scoring Methodology]
ExAC Score
Score 0.9955582887691
Ranking 1485/18225 scored genes
[Show Scoring Methodology]
Iossifov Probability Score
Score 0.817
Ranking 220/239 scored genes
[Show Scoring Methodology]
Sanders TADA Score
Score 0.44687204718797
Ranking 347/18665 scored genes
[Show Scoring Methodology]
Zhang D Score
Score 0.38912946624899
Ranking 1571/20870 scored genes
[Show Scoring Methodology]