Human Gene Module / Chromosome 20 / PREX1

PREX1Phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
6 / 6
Rare Variants / Common Variants
5 / 6
Aliases
PREX1, P-REX1
Associated Syndromes
-
Chromosome Band
20q13.13
Associated Disorders
-
Relevance to Autism

Common genetic variants and rare deletions in the PREX1 gene were found to associate with autism in a Han Chinese cohort; PREX1 mRNA levels were also significantly lower in peripheral blood cells from autistic individuals compared to controls (Li et al., 2015). In the same report, genetic deletion or knockdown of PREX1 in the CA1 region of the hippocampus in mice resulted in autism-like social behavior.

Molecular Function

The protein encoded by this gene acts as a guanine nucleotide exchange factor for the RHO family of small GTP-binding proteins (RACs). It has been shown to bind to and activate RAC1 by exchanging bound GDP for free GTP. The encoded protein, which is found mainly in the cytoplasm, is activated by phosphatidylinositol-3,4,5-trisphosphate and the beta-gamma subunits of heterotrimeric G proteins.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PREX1 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Synaptic P-Rex1 signaling regulates hippocampal long-term depression and autism-like social behavior Li J , et al. (2015) Yes -
2 Support Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes Feliciano P et al. (2019) Yes -
3 Support - Alonso-Gonzalez A et al. (2021) Yes -
4 Support - Zhou X et al. (2022) Yes -
5 Support - More RP et al. (2023) Yes -
6 Recent Recommendation - et al. () Yes -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss Unknown - Unknown 26621702 Li J , et al. (2015)
c.4095C>T p.Arg1365%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.1036G>C p.Ala346Pro missense_variant De novo - - 31452935 Feliciano P et al. (2019)
c.964G>A p.Gly322Ser missense_variant Familial - Multiplex 36702863 More RP et al. (2023)
c.1579C>T p.Pro527Ser missense_variant De novo - Simplex 33431980 Alonso-Gonzalez A et al. (2021)
Common Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
- - intergenic_variant - - - 26621702 Li J , et al. (2015)
c.415-3822A>G - intron_variant - - - 26621702 Li J , et al. (2015)
c.621+7810T>C;c.621+7811T>C - intron_variant - - - 26621702 Li J , et al. (2015)
c.2159-278A>C;c.3068-278A>C;c.2405-278A>C - intron_variant - - - 26621702 Li J , et al. (2015)
c.2657+226C>T;c.3566+226C>T;c.2903+226C>T - intron_variant - - - 26621702 Li J , et al. (2015)
c.2829-699G>A;c.3738-699G>A;c.3075-699G>A - intron_variant - - - 26621702 Li J , et al. (2015)
SFARI Gene score
2

Strong Candidate

Common genetic variants and rare deletions in the PREX1 gene were found to associate with autism in a Han Chinese cohort; PREX1 mRNA levels were also significantly lower in peripheral blood cells from autistic individuals compared to controls (Li et al., 2015). In the same report, genetic deletion or knockdown of PREX1 in the CA1 region of the hippocampus in mice resulted in autism-like social behavior.

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.

1/1/2021
2
icon
2

Score remained at 2

Description

Common genetic variants and rare deletions in the PREX1 gene were found to associate with autism in a Han Chinese cohort; PREX1 mRNA levels were also significantly lower in peripheral blood cells from autistic individuals compared to controls (Li et al., 2015). In the same report, genetic deletion or knockdown of PREX1 in the CA1 region of the hippocampus in mice resulted in autism-like social behavior.

Reports Added
[Exploring the biological role of postzygotic and germinal de novo mutations in ASD2021]
10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

Common genetic variants and rare deletions in the PREX1 gene were found to associate with autism in a Han Chinese cohort; PREX1 mRNA levels were also significantly lower in peripheral blood cells from autistic individuals compared to controls (Li et al., 2015). In the same report, genetic deletion or knockdown of PREX1 in the CA1 region of the hippocampus in mice resulted in autism-like social behavior.

Reports Added
[Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes2019] [New Scoring Scheme]
10/1/2015
icon
3

Increased from to 3

Description

Common genetic variants and rare deletions in the PREX1 gene were found to associate with autism in a Han Chinese cohort; PREX1 mRNA levels were also significantly lower in peripheral blood cells from autistic individuals compared to controls (Li et al., 2015). In the same report, genetic deletion or knockdown of PREX1 in the CA1 region of the hippocampus in mice resulted in autism-like social behavior.

Krishnan Probability Score

Score 0.49873615383699

Ranking 2219/25841 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 0.99999962189815

Ranking 247/18225 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 0.9458171368785

Ranking 16621/18665 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 0.009398010805336

Ranking 8379/20870 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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