Human Gene Module / Chromosome X / LAS1L

LAS1LLAS1 like ribosome biogenesis factor

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
1 / 6
Rare Variants / Common Variants
5 / 0
Aliases
LAS1L, Las1,  Las1-like,  WTS,  dJ475B7.2
Associated Syndromes
Wilson-Turner syndrome
Chromosome Band
Xq12
Associated Disorders
-
Relevance to Autism

De novo missense variants in the LAS1L gene have been identified in probands presenting with intellectual disability or developmental delay (Lelieveld et al., 2016; Deciphering Developmental Disorder Study 2017), while a maternally-inherited in-frame deletion variant in this gene was identified in a male ASD proband from a cohort of 100 Vietnamese children with ASD (Tran et al., 2020). Hemizygous mutations in LAS1L are also responsible for Wilson-Turner syndrome (OMIM 309585), an X-linked recessive neurologic disorder characterized by intellectual disability, dysmorphic facial features, hypogonadism, short stature, and truncal obesity (Hu et al., 2016).

Molecular Function

Involved in the biogenesis of the 60S ribosomal subunit. Required for maturation of the 28S rRNA. Functions as a component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to LAS1L (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes Hu H et al. (2016) No -
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 Primary Genetic landscape of autism spectrum disorder in Vietnamese children Tran KT et al. (2020) Yes -
5 Support - Aguilera C et al. (2021) No -
6 Support - Axel Schmidt et al. (2024) No -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1244G>A p.Arg415Gln missense_variant De novo - Simplex 28135719 et al. (2017)
c.351G>A p.Met117Ile missense_variant Unknown - - 39039281 Axel Schmidt et al. (2024)
c.353C>T p.Ala118Val missense_variant De novo - Simplex 27479843 Lelieveld SH et al. (2016)
c.1237G>A p.Gly413Arg missense_variant Familial Maternal - 34653234 Aguilera C et al. (2021)
c.1558_1566del p.Trp520_Val522del inframe_deletion Familial Maternal Simplex 32193494 Tran KT et al. (2020)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

Score Delta: Score remained at 3

criteria met
See SFARI Gene'scoring criteria
3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

4/1/2022
icon
3

Increased from to 3

Krishnan Probability Score

Score 0.33139765233803

Ranking 24736/25841 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 0.89209559518602

Ranking 3289/18225 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 0.93537350841641

Ranking 12857/18665 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 0.51841452997727

Ranking 387/20870 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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