Human Gene Module / Chromosome 15 / CELF6

CELF6CUGBP, Elav-like family member 6

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 5
Rare Variants / Common Variants
6 / 1
Aliases
CELF6, BRUNOL6
Associated Syndromes
-
Chromosome Band
15q23
Associated Disorders
-
Relevance to Autism

A SNP located in the 5'UTR of an alternative first exon of the CELF6 gene (rs2959930) associated with autism in male probands from AGRE using the transmission disequilibrium test (TDT). Screening for rare variants in the alternative first exon and exons 11-13 of the CELF6 gene in 384 male white ASD probands from AGRE identified a paternally-inherited nonsense variant in a male proband that showed incomplete penetrance with ASD. Disruption of CELF6 in mice resulted in animals exhibiting resistance to change and decreased ultrasonic vocalization as well as abnormal levels of serotonin in the brain (Dougherty et al., 2013).

Molecular Function

RNA-binding protein implicated in the regulation of pre-mRNA alternative splicing. Mediates exon inclusion and/or exclusion in pre-mRNA that are subject to tissue-specific and developmentally regulated alternative splicing.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CELF6 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary The disruption of Celf6, a gene identified by translational profiling of serotonergic neurons, results in autism-related behaviors Dougherty JD , et al. (2013) Yes -
2 Support Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders Li J , et al. (2017) Yes -
3 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
4 Support Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes Feliciano P et al. (2019) Yes -
5 Support - Zhou X et al. (2022) Yes -
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.748-6T>G - splice_region_variant De novo - - 35982159 Zhou X et al. (2022)
c.1237+2T>C - splice_site_variant De novo - - 31452935 Feliciano P et al. (2019)
c.881-1G>A - splice_site_variant Familial - Simplex 28831199 Li J , et al. (2017)
C>G - stop_gained Familial Paternal Multiplex 23407934 Dougherty JD , et al. (2013)
c.734_747del p.Ala245AspfsTer34 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.1089C>G p.Tyr363Ter stop_gained Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.346-1479C>T;c.-133C>T;c.67-1479C>T;c.-62-1479C>T;c.-195C>T;c.-24+9572C>T - intron_variant, 5_prime_UTR_variant - - - 23407934 Dougherty JD , et al. (2013)
SFARI Gene score
2

Strong Candidate

A SNP located in the 5'UTR of an alternative first exon of the CELF6 gene (rs2959930) associated with autism in male probands from AGRE using the transmission disequilibrium test (TDT) in Dougherty et al., 2013. Screening for rare variants in the alternative first exon and exons 11-13 of the CELF6 gene in 384 male white ASD probands from AGRE in this report identified a paternally-inherited nonsense variant in a male proband that showed incomplete penetrance with ASD. Disruption of CELF6 in mice resulted in animals exhibiting resistance to change and decreased ultrasonic vocalization as well as abnormal levels of serotonin in the brain. An inherited splice-site variant in CELF6 was identified in a Chinese ASD proband in Li et al., 2017.

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

A SNP located in the 5'UTR of an alternative first exon of the CELF6 gene (rs2959930) associated with autism in male probands from AGRE using the transmission disequilibrium test (TDT) in Dougherty et al., 2013. Screening for rare variants in the alternative first exon and exons 11-13 of the CELF6 gene in 384 male white ASD probands from AGRE in this report identified a paternally-inherited nonsense variant in a male proband that showed incomplete penetrance with ASD. Disruption of CELF6 in mice resulted in animals exhibiting resistance to change and decreased ultrasonic vocalization as well as abnormal levels of serotonin in the brain. An inherited splice-site variant in CELF6 was identified in a Chinese ASD proband in Li et al., 2017.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A SNP located in the 5'UTR of an alternative first exon of the CELF6 gene (rs2959930) associated with autism in male probands from AGRE using the transmission disequilibrium test (TDT) in Dougherty et al., 2013. Screening for rare variants in the alternative first exon and exons 11-13 of the CELF6 gene in 384 male white ASD probands from AGRE in this report identified a paternally-inherited nonsense variant in a male proband that showed incomplete penetrance with ASD. Disruption of CELF6 in mice resulted in animals exhibiting resistance to change and decreased ultrasonic vocalization as well as abnormal levels of serotonin in the brain. An inherited splice-site variant in CELF6 was identified in a Chinese ASD proband in Li et al., 2017.

Reports Added
[Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes2019] [New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

A SNP located in the 5'UTR of an alternative first exon of the CELF6 gene (rs2959930) associated with autism in male probands from AGRE using the transmission disequilibrium test (TDT) in Dougherty et al., 2013. Screening for rare variants in the alternative first exon and exons 11-13 of the CELF6 gene in 384 male white ASD probands from AGRE in this report identified a paternally-inherited nonsense variant in a male proband that showed incomplete penetrance with ASD. Disruption of CELF6 in mice resulted in animals exhibiting resistance to change and decreased ultrasonic vocalization as well as abnormal levels of serotonin in the brain. An inherited splice-site variant in CELF6 was identified in a Chinese ASD proband in Li et al., 2017.

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
10/1/2017
icon
4

Increased from to 4

Description

A SNP located in the 5'UTR of an alternative first exon of the CELF6 gene (rs2959930) associated with autism in male probands from AGRE using the transmission disequilibrium test (TDT) in Dougherty et al., 2013. Screening for rare variants in the alternative first exon and exons 11-13 of the CELF6 gene in 384 male white ASD probands from AGRE in this report identified a paternally-inherited nonsense variant in a male proband that showed incomplete penetrance with ASD. Disruption of CELF6 in mice resulted in animals exhibiting resistance to change and decreased ultrasonic vocalization as well as abnormal levels of serotonin in the brain. An inherited splice-site variant in CELF6 was identified in a Chinese ASD proband in Li et al., 2017.

Reports Added
[Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders.2017]
Krishnan Probability Score

Score 0.49503505739233

Ranking 3255/25841 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 0.37680700127607

Ranking 6083/18225 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 0.92366954936149

Ranking 9826/18665 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
Larsen Cumulative Evidence Score

Score 5

Ranking 277/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Zhang D Score

Score -0.005857223738841

Ranking 8869/20870 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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