Human Gene Module / Chromosome 2 / MEMO1

MEMO1mediator of cell motility 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
1 / 2
Rare Variants / Common Variants
1 / 0
Aliases
MEMO1, C2orf4,  CGI-27,  MEMO,  NS5ATP7
Associated Syndromes
-
Chromosome Band
2p22.3
Associated Disorders
-
Relevance to Autism

Nakagawa et al., 2019 demonstrated that deletion or knockdown of the Memo1 gene in mice resulted in hyperbranching of radial glial cell (RGC) basal processes and disrupted RGC tiling, which in turn resulted in aberrant radial unit assembly and neuronal layering. Furthermore, the authors showed that MEMO1 containing an ASD-associated splice-site variant (originally identified in Iossifov et al., 2014) failed to rescue RG tiling defects in Memo1 conditional knockout mice compared to wild-type MEMO1.

Molecular Function

May control cell migration by relaying extracellular chemotactic signals to the microtubule cytoskeleton. Mediator of ERBB2 signaling. The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to MEMO1 (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Recent Recommendation Memo1-Mediated Tiling of Radial Glial Cells Facilitates Cerebral Cortical Development Nakagawa N , et al. (2019) No -
Rare Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.143+1G>A - splice_site_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Nakagawa et al., 2019 demonstrated that deletion or knockdown of the Memo1 gene in mice resulted in hyperbranching of radial glial cell (RGC) basal processes and disrupted RGC tiling, which in turn resulted in aberrant radial unit assembly and neuronal layering. Furthermore, the authors showed that MEMO1 containing an ASD-associated splice-site variant (originally identified in Iossifov et al., 2014) failed to rescue RG tiling defects in Memo1 conditional knockout mice compared to wild-type MEMO1.

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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

Nakagawa et al., 2019 demonstrated that deletion or knockdown of the Memo1 gene in mice resulted in hyperbranching of radial glial cell (RGC) basal processes and disrupted RGC tiling, which in turn resulted in aberrant radial unit assembly and neuronal layering. Furthermore, the authors showed that MEMO1 containing an ASD-associated splice-site variant (originally identified in Iossifov et al., 2014) failed to rescue RG tiling defects in Memo1 conditional knockout mice compared to wild-type MEMO1.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Nakagawa et al., 2019 demonstrated that deletion or knockdown of the Memo1 gene in mice resulted in hyperbranching of radial glial cell (RGC) basal processes and disrupted RGC tiling, which in turn resulted in aberrant radial unit assembly and neuronal layering. Furthermore, the authors showed that MEMO1 containing an ASD-associated splice-site variant (originally identified in Iossifov et al., 2014) failed to rescue RG tiling defects in Memo1 conditional knockout mice compared to wild-type MEMO1.

Reports Added
[New Scoring Scheme]
7/1/2019
icon
4

Increased from to 4

Description

Nakagawa et al., 2019 demonstrated that deletion or knockdown of the Memo1 gene in mice resulted in hyperbranching of radial glial cell (RGC) basal processes and disrupted RGC tiling, which in turn resulted in aberrant radial unit assembly and neuronal layering. Furthermore, the authors showed that MEMO1 containing an ASD-associated splice-site variant (originally identified in Iossifov et al., 2014) failed to rescue RG tiling defects in Memo1 conditional knockout mice compared to wild-type MEMO1.

Krishnan Probability Score

Score 0.4473919159085

Ranking 12506/25841 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
Krishnan Probability Score

Score 0.44256022043815

Ranking 17358/25841 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 0.87615669386783

Ranking 3420/18225 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 0.22323051276161

Ranking 125/18665 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 -0.60677901736099

Ranking 19925/20870 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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