Human Gene Module / Chromosome 15 / CGNL1

CGNL1Cingulin-like 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
7 / 7
Rare Variants / Common Variants
8 / 0
Aliases
CGNL1, JACOP
Associated Syndromes
-
Chromosome Band
15q21.3
Associated Disorders
-
Relevance to Autism

Two de novo missense variants in the CGNL1 gene have been identified in ASD probands from the Simons Simplex Collection, with no de novo events in this gene observed in 1,786 unaffected siblings (P=0.04) (Iossifov et al., 2014; Krumm et al., 2015).

Molecular Function

This gene encodes a member of the cingulin family that localizes to both adherens and tight cell-cell junctions and mediates junction assembly and maintenance by regulating the activity of the small GTPases RhoA and Rac1.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CGNL1 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Primary Excess of rare, inherited truncating mutations in autism Krumm N , et al. (2015) Yes -
3 Support Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder Takata A , et al. (2018) Yes -
4 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
5 Support - Woodbury-Smith M et al. (2022) Yes -
6 Support - Zhou X et al. (2022) Yes -
7 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (8)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.2470G>A p.Val824Met missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.2817G>T p.Met939Ile missense_variant De novo - Simplex 25961944 Krumm N , et al. (2015)
c.964C>T p.His322Tyr missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.2677G>C p.Ala893Pro missense_variant De novo - Simplex 29346770 Takata A , et al. (2018)
c.2920C>A p.Gln974Lys missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.3350G>A p.Cys1117Tyr missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.1455del p.Ser486ProfsTer12 frameshift_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.1804-6_1807del - splice_site_variant Familial Maternal Multiplex (monozygotic twins) 31398340 Ruzzo EK , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Two de novo missense variants in the CGNL1 gene have been identified in ASD probands from the Simons Simplex Collection, with no de novo events in this gene observed in 1,786 unaffected siblings (P=0.04) (Iossifov et al., 2014; Krumm et al., 2015).

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.

10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

Two de novo missense variants in the CGNL1 gene have been identified in ASD probands from the Simons Simplex Collection, with no de novo events in this gene observed in 1,786 unaffected siblings (P=0.04) (Iossifov et al., 2014; Krumm et al., 2015).

Reports Added
[New Scoring Scheme]
7/1/2019
3
icon
3

Decreased from 3 to 3

Description

Two de novo missense variants in the CGNL1 gene have been identified in ASD probands from the Simons Simplex Collection, with no de novo events in this gene observed in 1,786 unaffected siblings (P=0.04) (Iossifov et al., 2014; Krumm et al., 2015).

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
7/1/2015
icon
3

Increased from to 3

Description

Two de novo missense variants in the CGNL1 gene have been identified in ASD probands from the Simons Simplex Collection, with no de novo events in this gene observed in 1,786 unaffected siblings (P=0.04) (Iossifov et al., 2014; Krumm et al., 2015).

Krishnan Probability Score

Score 0.44732440116016

Ranking 12731/25841 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 9.0493749988863E-14

Ranking 17507/18225 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 0.92713574374741

Ranking 10599/18665 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 -0.34695647611461

Ranking 17798/20870 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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