Human Gene Module / Chromosome 1 / UBAP2L

UBAP2Lubiquitin associated protein 2 like

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
1 / 5
Rare Variants / Common Variants
15 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
1q21.3
Associated Disorders
-
Relevance to Autism

A de novo frameshift variant in the UBAP2L gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014. Jia et al., 2022 reported detailed genotypic and phenotypic information for a cohort of 12 individuals with de novo UBAP2L variants, including the ASD proband originally reported in Iossifov et al., 2014; all affected individuals presented with a neurodevelopmental disorder characterized by speech and language problems, intellectual disability, childhood motor delay/hypotonia, and various behavioral issues, including a formal diagnosis of autism spectrum disorder in 4 individuals. In the same report, the authors found that Ubap2l-haploinsufficient mice exhibited social and cognitive impairments accompanied by disrupted neurogenesis and reduced stress granule formation during early brain development. Lastly, enrichment analysis for de novo protein-altering variants in 40,853 probands with neurodevelopmental disorders, including 9,228 individuals with a primary diagnosis of ASD, in this report determined that UBAP2L showed an excess of de novo likely gene-disruptive (LGD) variants with a false discovery rate (FDR) less than or equal to 0.01.

Molecular Function

Enables RNA binding activity. Involved in binding activity of sperm to zona pellucida and stress granule assembly. Acts upstream of or within hematopoietic stem cell homeostasis. Part of PcG protein complex.

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 UBAP2L (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Support Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability Lelieveld SH et al. (2016) No -
3 Support Prevalence and architecture of de novo mutations in developmental disorders et al. (2017) No -
4 Support - Kaplanis J et al. (2020) No -
5 Recent Recommendation - Jia X et al. (2022) No ASD, ADHD, epilepsy/seizures, stereotypy
Rare Variants   (15)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.130G>T p.Asp44Tyr missense_variant De novo - - 28135719 et al. (2017)
c.88C>T p.Gln30Ter stop_gained De novo - Simplex 35977029 Jia X et al. (2022)
c.370C>T p.Arg124Ter stop_gained De novo - Simplex 35977029 Jia X et al. (2022)
c.562G>T p.Gly188Ter stop_gained De novo - Simplex 35977029 Jia X et al. (2022)
c.1714C>T p.Gln572Ter stop_gained De novo - Simplex 35977029 Jia X et al. (2022)
c.1846C>T p.Gln616Ter stop_gained De novo - Simplex 35977029 Jia X et al. (2022)
c.2724C>A p.Phe908Leu stop_gained De novo - Simplex 35977029 Jia X et al. (2022)
c.3198+3A>G - splice_region_variant De novo - Simplex 35977029 Jia X et al. (2022)
c.326A>T p.Lys109Met missense_variant De novo - - 33057194 Kaplanis J et al. (2020)
c.2432A>C p.His811Pro missense_variant De novo - - 27479843 Lelieveld SH et al. (2016)
c.558G>A p.Arg186%3D splice_site_variant De novo - Simplex 35977029 Jia X et al. (2022)
c.1965del p.Lys655AsnfsTer23 frameshift_variant De novo - Simplex 35977029 Jia X et al. (2022)
c.673dup p.Thr225AsnfsTer5 splice_region_variant De novo - Simplex 35977029 Jia X et al. (2022)
c.1964dup p.Leu656SerfsTer3 frameshift_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.2158_2165del p.Ser720AlafsTer15 frameshift_variant De novo - Simplex 35977029 Jia X et al. (2022)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

Score Delta: Score remained at 1

criteria met
See SFARI Gene'scoring criteria
1

High Confidence

See all Category 1 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.

1/1/2023
icon
1

Increased from to 1

Krishnan Probability Score

Score 0.49359516429322

Ranking 4064/25841 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 0.99999987312642

Ranking 206/18225 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
Iossifov Probability Score

Score 0.943

Ranking 93/239 scored genes


[Show Scoring Methodology]
Supplementary dataset S2 in the paper by Iossifov et al. (PNAS 112, E5600-E5607 (2015)) lists 239 genes with a probability of at least 0.8 of being associated with autism risk (column I). This probability metric combines the evidence from de novo likely-gene- disrupting and missense mutations and assesses it against the background mutation rate in unaffected individuals from the University of Washington’s Exome Variant Sequence database (evs.gs.washington.edu/EVS/). The list of probability scores can be found here: www.pnas.org/lookup/suppl/doi:10.1073/pnas.1516376112/- /DCSupplemental/pnas.1516376112.sd02.xlsx
Original Source
Sanders TADA Score

Score 0.62000148765064

Ranking 778/18665 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 0.28531381081484

Ranking 2948/20870 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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