Human Gene Module / Chromosome 5 / LARP1

LARP1La ribonucleoprotein 1, translational regulator

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
3 / 4
Rare Variants / Common Variants
11 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
5q33.2
Associated Disorders
-
Relevance to Autism

Chettle et al., 2024 reported a case series of seven unrelated probands with de novo heterozygous loss of function or missense variants in the LARP1 gene who presented with a variable neurodevelopmental phenotype that included developmental delay, intellectual disability, hypotonia, and/or behavioral abnormalities including autism spectrum disorder, which was reported in four probands; subsequent studies using immortalized lymphoblasts from a proband with a LARP1 loss of function variant demonstrated reduced LARP1 mRNA and protein levels resulting in reduced rates of aerobic respiration and glycolysis in proband-derived cells. De novo missense variants in the LARP1 gene have also been identified in ASD probands from a cohort of 30 Japanese probands with sporadic ASD, the Autism Sequencing Consortium, and the MSSNG cohort (Hashimoto et al., 2016; Satterstrom et al., 2020; Zhou et al., 2022).

Molecular Function

Enables eukaryotic initiation factor 4E binding activity; nucleic acid binding activity; and ribosomal small subunit binding activity. Involved in several processes, including TORC1 signaling; cellular response to rapamycin; and posttranscriptional regulation of gene expression. Located in cytoplasmic stress granule. Colocalizes with TORC1 complex and polysomal ribosome.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to LARP1 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Whole-exome sequencing and neurite outgrowth analysis in autism spectrum disorder Hashimoto R , et al. (2015) Yes -
2 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
3 Support - Zhou X et al. (2022) Yes -
4 Primary - James Chettle et al. (2024) No ASD, ADHD
Rare Variants   (11)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1267G>C p.Asp423His missense_variant De novo - - 39182167 James Chettle et al. (2024)
c.1378G>C p.Ala460Pro missense_variant De novo - - 39182167 James Chettle et al. (2024)
c.1673T>C p.Ile558Thr missense_variant De novo - - 39182167 James Chettle et al. (2024)
c.2119G>A p.Glu707Lys missense_variant De novo - - 39182167 James Chettle et al. (2024)
c.2287A>T p.Ile763Phe missense_variant De novo - - 39182167 James Chettle et al. (2024)
c.2379C>G p.Asp793Glu missense_variant De novo - - 39182167 James Chettle et al. (2024)
c.2456A>G p.Lys819Arg missense_variant De novo - - 39182167 James Chettle et al. (2024)
c.935A>G p.Asn312Ser missense_variant De novo - - 31981491 Satterstrom FK et al. (2020)
c.1976C>T p.Pro659Leu missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.2858T>G p.Met953Arg missense_variant De novo - Simplex 26582266 Hashimoto R , et al. (2015)
c.2164dup p.Thr722AsnfsTer5 frameshift_variant De novo - - 39182167 James Chettle et al. (2024)
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.

10/1/2024
icon
3

Increased from to 3

Krishnan Probability Score

Score 0.51408477749056

Ranking 1779/25841 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 0.9999521889832

Ranking 581/18225 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 0.94314504723775

Ranking 15575/18665 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 -0.079827754020235

Ranking 11575/20870 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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