Human Gene Module / Chromosome 21 / SYNJ1

SYNJ1synaptojanin 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
2 / 3
Rare Variants / Common Variants
7 / 0
Aliases
SYNJ1, EIEE53,  INPP5G,  PARK20
Associated Syndromes
-
Chromosome Band
21q22.11
Associated Disorders
-
Relevance to Autism

Two non-synonymous postzygotic mosaic mutations (PZMs) in the SYNJ1 gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 8/84,448 expected; hypergeometric P-value of 1.2E-03).

Molecular Function

This gene encodes a phosphoinositide phosphatase that regulates levels of membrane phosphatidylinositol-4,5-bisphosphate. As such, expression of this enzyme may affect synaptic transmission and membrane trafficking.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to SYNJ1 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder Lim ET , et al. (2017) Yes -
2 Support - Zhou X et al. (2022) Yes -
3 Support - Karthika Ajit Valaparambil et al. () No -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.*185T>C - missense_variant De novo - - 28714951 Lim ET , et al. (2017)
c.124+1G>A - splice_site_variant De novo - - 28714951 Lim ET , et al. (2017)
c.2288A>G p.Tyr763Cys missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.*782C>T - missense_variant Unknown - - 37943464 Karthika Ajit Valaparambil et al. ()
c.1507C>T p.Gln503Ter missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.475C>T p.Arg159Trp missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.2466A>G p.Thr822%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Two non-synonymous postzygotic mosaic mutations (PZMs) in the SYNJ1 gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 8/84,448 expected; hypergeometric P-value of 1.2E-03).

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

Two non-synonymous postzygotic mosaic mutations (PZMs) in the SYNJ1 gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 8/84,448 expected; hypergeometric P-value of 1.2E-03).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Two non-synonymous postzygotic mosaic mutations (PZMs) in the SYNJ1 gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 8/84,448 expected; hypergeometric P-value of 1.2E-03).

Reports Added
[New Scoring Scheme]
7/1/2017
icon
4

Increased from to 4

Description

Two non-synonymous postzygotic mosaic mutations (PZMs) in the SYNJ1 gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 8/84,448 expected; hypergeometric P-value of 1.2E-03).

Krishnan Probability Score

Score 0.61215372635132

Ranking 178/25841 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 0.2142951462835

Ranking 6971/18225 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 0.94061690526899

Ranking 14632/18665 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 0.37474356473291

Ranking 1731/20870 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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