Human Gene Module / Chromosome 14 / FBXO33

FBXO33F-box protein 33

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 4
Rare Variants / Common Variants
1 / 2
Aliases
FBXO33, BMND12,  Fbx33,  c14_5247
Associated Syndromes
-
Chromosome Band
14q21.1
Associated Disorders
-
Relevance to Autism

Genetic association has been found between the FBXO33 gene and autism in two large cohorts (AGRE and ACC) of European ancestry and replicated in two other cohorts (CAP and CART) (Wang et al., 2009).

Molecular Function

This locus represents an member of the F-box gene family. The encoded protein contains an F-box motif and a domain that might form a structure similar to a leucine-rich repeat found in placental RNAse inhibitor.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to FBXO33 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Common genetic variants on 5p14.1 associate with autism spectrum disorders Wang K , et al. (2009) Yes -
2 Positive Association A genome-wide association study of autism incorporating autism diagnostic interview-revised, autism diagnostic observation schedule, and social responsiveness scale Connolly JJ , et al. (2012) Yes -
3 Positive Association Case-control genome-wide association study of persistent attention-deficit hyperactivity disorder identifies FBXO33 as a novel susceptibility gene for the disorder Snchez-Mora C , et al. (2014) No -
4 Support - Woodbury-Smith M et al. (2022) Yes -
Rare Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.321G>C p.Leu107%3D synonymous_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
Common Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
- - intergenic_variant - - - 22935194 Connolly JJ , et al. (2012)
- G to A intergenic_variant - - - 19404256 Wang K , et al. (2009)
SFARI Gene score
2

Strong Candidate

FBXO33 is in a region of a de novo translocation in an individual with severe autism and MR (PMID: 20648246). The translocation might actually implicate the nearby gene LRFN5 based on expression data in the region; however, additional individuals with a deletion in this region did not have autism. A suggestive association was reported by Wang et al., 2009 (PMID: 19404256).

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

FBXO33 is in a region of a de novo translocation in an individual with severe autism and MR (PMID: 20648246). The translocation might actually implicate the nearby gene LRFN5 based on expression data in the region; however, additional individuals with a deletion in this region did not have autism. A suggestive association was reported by Wang et al., 2009 (PMID: 19404256).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

FBXO33 is in a region of a de novo translocation in an individual with severe autism and MR (PMID: 20648246). The translocation might actually implicate the nearby gene LRFN5 based on expression data in the region; however, additional individuals with a deletion in this region did not have autism. A suggestive association was reported by Wang et al., 2009 (PMID: 19404256).

Reports Added
[New Scoring Scheme]
10/1/2014
4
icon
4

Decreased from 4 to 4

Description

FBXO33 is in a region of a de novo translocation in an individual with severe autism and MR (PMID: 20648246). The translocation might actually implicate the nearby gene LRFN5 based on expression data in the region; however, additional individuals with a deletion in this region did not have autism. A suggestive association was reported by Wang et al., 2009 (PMID: 19404256).

Reports Added
[Case-control genome-wide association study of persistent attention-deficit hyperactivity disorder identifies FBXO33 as a novel susceptibility gene ...2014]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

FBXO33 is in a region of a de novo translocation in an individual with severe autism and MR (PMID: 20648246). The translocation might actually implicate the nearby gene LRFN5 based on expression data in the region; however, additional individuals with a deletion in this region did not have autism. A suggestive association was reported by Wang et al., 2009 (PMID: 19404256).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

FBXO33 is in a region of a de novo translocation in an individual with severe autism and MR (PMID: 20648246). The translocation might actually implicate the nearby gene LRFN5 based on expression data in the region; however, additional individuals with a deletion in this region did not have autism. A suggestive association was reported by Wang et al., 2009 (PMID: 19404256).

Krishnan Probability Score

Score 0.49478433364375

Ranking 3425/25841 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 0.98607714230671

Ranking 1954/18225 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 0.92800462810817

Ranking 10808/18665 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 10.5

Ranking 177/461 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 0.43959367658647

Ranking 1028/20870 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
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
ARL4C ADP-ribosylation factor-like 4C Human Protein Binding 10123 P56559
VTN vitronectin Human Protein Binding 7448 D9ZGG2
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