Human Gene Module / Chromosome 3 / FBXO40

FBXO40F-box protein 40

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 6
Rare Variants / Common Variants
4 / 1
Aliases
FBXO40, FBX40,  KIAA1195,  MGC129902,  MGC129903
Associated Syndromes
-
Chromosome Band
3q13.33
Associated Disorders
-
Relevance to Autism

In a genome-wide study, association was found between CNVs in the FBXO40 gene and autism in AGRE and ACC cohorts (European ancestry) (Glessner et al., 2009). In addition, a rare variant in the FBXO40 gene has been identified in two siblings with ASD (Vaags et al., 2012).

Molecular Function

Ubiquitin-protein ligase

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to FBXO40 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Recent Recommendation FBXO40, a gene encoding a novel muscle-specific F-box protein, is upregulated in denervation-related muscle atrophy Ye J , et al. (2007) No -
2 Primary Autism genome-wide copy number variation reveals ubiquitin and neuronal genes Glessner JT , et al. (2009) Yes -
3 Support Rare deletions at the neurexin 3 locus in autism spectrum disorder Vaags AK , et al. (2012) Yes -
4 Support Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders Cukier HN , et al. (2014) Yes -
5 Support - Zhou X et al. (2022) Yes -
6 Support - Wang J et al. (2023) Yes -
Rare Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1445T>A p.Phe482Tyr missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1682A>T p.His561Leu missense_variant De novo - Simplex 37393044 Wang J et al. (2023)
c.344T>G p.Ile115Ser missense_variant Familial Paternal Multiplex 22209245 Vaags AK , et al. (2012)
c.679G>A p.Ala227Thr missense_variant Familial - Extended multiplex (at least one pair of ASD affec 24410847 Cukier HN , et al. (2014)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
- - copy_number_gain - - - 19404257 Glessner JT , et al. (2009)
SFARI Gene score
2

Strong Candidate

Three duplications (unknown inheritance) were seen in a 1000-case discovery cohort but not in a 1000-case replication cohort or ~2500 controls. Two additional genes included in all events were listed (GOLGB1 and HCLS1). Two of the three duplications were confirmed by qPCR.

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

Three duplications (unknown inheritance) were seen in a 1000-case discovery cohort but not in a 1000-case replication cohort or ~2500 controls. Two additional genes included in all events were listed (GOLGB1 and HCLS1). Two of the three duplications were confirmed by qPCR.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Three duplications (unknown inheritance) were seen in a 1000-case discovery cohort but not in a 1000-case replication cohort or ~2500 controls. Two additional genes included in all events were listed (GOLGB1 and HCLS1). Two of the three duplications were confirmed by qPCR.

Reports Added
[New Scoring Scheme]
7/1/2014
No data
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4

Increased from No data to 4

Description

Three duplications (unknown inheritance) were seen in a 1000-case discovery cohort but not in a 1000-case replication cohort or ~2500 controls. Two additional genes included in all events were listed (GOLGB1 and HCLS1). Two of the three duplications were confirmed by qPCR.

4/1/2014
No data
icon
4

Increased from No data to 4

Description

Three duplications (unknown inheritance) were seen in a 1000-case discovery cohort but not in a 1000-case replication cohort or ~2500 controls. Two additional genes included in all events were listed (GOLGB1 and HCLS1). Two of the three duplications were confirmed by qPCR.

Krishnan Probability Score

Score 0.49622498448795

Ranking 2649/25841 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 3.6419894887019E-8

Ranking 15916/18225 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 0.93236495080851

Ranking 11959/18665 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 3

Ranking 338/461 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
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
GSN Gelsolin Human Protein Binding 2934 P06396-2
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