Human Gene Module / Chromosome 11 / HNRNPUL2

HNRNPUL2heterogeneous nuclear ribonucleoprotein U like 2

SFARI Gene Score
2S
Strong Candidate, Syndromic Criteria 2.1, Syndromic
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
8 / 0
Aliases
HNRNPUL2, HNRPUL2,  SAF-A2
Associated Syndromes
-
Chromosome Band
11q12.3
Associated Disorders
ADHD, EPS
Relevance to Autism

Gillentine et al., 2021 reported six previously unpublished individuals with likely gene-disruptive (LGD) variants in the HNRNPUL2 gene, including three ASD probands from the SPARK cohort with de novo LGD variants; neurodevelopmental abnormalities (developmental delay, intellectual disability, and/or specific learning disability), motor delay, delayed speech and language development or speech articulation difficulties, behavioral abnormalities, and autism spectrum disorder were frequently observed in this cohort. A de novo missense variant in this gene had previously been identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014).

Molecular Function

SFARI Genomic Platforms
Reports related to HNRNPUL2 (3 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 - Gillentine MA et al. (2021) Yes ADHD, epilepsy/seizures
3 Support - Woodbury-Smith M et al. (2022) Yes -
Rare Variants   (8)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1522C>T p.Arg508Ter stop_gained Unknown - - 33874999 Gillentine MA et al. (2021)
c.642C>A p.Tyr214Ter stop_gained De novo NA - 33874999 Gillentine MA et al. (2021)
c.343G>A p.Glu115Lys missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.1001dup p.Tyr334Ter frameshift_variant De novo NA - 33874999 Gillentine MA et al. (2021)
c.971G>A p.Arg324His missense_variant De novo NA Simplex 25363768 Iossifov I et al. (2014)
c.1716del p.Arg572SerfsTer4 frameshift_variant De novo NA - 33874999 Gillentine MA et al. (2021)
c.1906del p.Ser636ProfsTer123 frameshift_variant De novo NA - 33874999 Gillentine MA et al. (2021)
c.2141_2142del p.Tyr714LeufsTer70 frameshift_variant De novo NA - 33874999 Gillentine MA et al. (2021)
Common Variants  

No common variants reported.

SFARI Gene score
2S

Strong Candidate, Syndromic

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.

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

4/1/2022
2S

Initial score established: 2S

Krishnan Probability Score

Score 0.40852723004453

Ranking 22929/25841 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.
ExAC Score

Score 0.99992539468351

Ranking 637/18225 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
Sanders TADA Score

Score 0.93764165547847

Ranking 13593/18665 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).
Zhang D Score

Score 0.50827915985306

Ranking 461/20870 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.
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