Human Gene Module / Chromosome X / RPL10

RPL10ribosomal protein L10

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 14
Rare Variants / Common Variants
9 / 0
Aliases
RPL10, QM,  NOV,  DXS648,  DXS648E,  FLJ23544,  FLJ27072,  DKFZp686J1851
Associated Syndromes
-
Chromosome Band
Xq28
Associated Disorders
-
Relevance to Autism

Rare mutations in the RPL10 gene have been identified with autism (Klauck et al., 2006).

Molecular Function

This gene encodes a ribosomal protein that is a component of the 60S subunit. Th e protein belongs to the L10E family of ribosomal proteins.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Zebrafish
Entrez Gene
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to RPL10 (14 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited QM, a putative tumor suppressor, regulates proto-oncogene c-yes Oh HS , et al. (2002) No -
2 Recent Recommendation Loss of heterozygosity and microsatellite instability at the Xq28 and the A/G heterozygosity of the QM gene are associated with ovarian cancer Shen XJ , et al. (2006) No -
3 Recent Recommendation Ribosomal protein L10 interacts with the SH3 domain and regulates GDNF-induced neurite growth in SH-SY-5y cells Park S and Jeong DG (2006) No -
4 Primary Mutations in the ribosomal protein gene RPL10 suggest a novel modulating disease mechanism for autism Klauck SM , et al. (2006) Yes -
5 Recent Recommendation Mutational analysis of the ribosomal protein Rpl10 from yeast Hofer A , et al. (2007) No -
6 Recent Recommendation Saccharomyces cerevisiae HMO1 interacts with TFIID and participates in start site selection by RNA polymerase II Kasahara K , et al. (2008) No -
7 Negative Association An investigation of ribosomal protein L10 gene in autism spectrum disorders Gong X , et al. (2009) No -
8 Support Mutation and expression analyses of the ribosomal protein gene RPL10 in an extended German sample of patients with autism spectrum disorder Chiocchetti A , et al. (2011) Yes -
9 Recent Recommendation Protein signatures of oxidative stress response in a patient specific cell line model for autism Chiocchetti AG , et al. (2014) No -
10 Recent Recommendation A novel ribosomopathy caused by dysfunction of RPL10 disrupts neurodevelopment and causes X-linked microcephaly in humans Brooks SS , et al. (2014) No -
11 Support RPL10 mutation segregating in a family with X-linked syndromic Intellectual Disability Thevenon J , et al. (2015) No Microcephaly
12 Support A Novel Mutation in RPL10 (Ribosomal Protein L10) Causes X-Linked Intellectual Disability, Cerebellar Hypoplasia, and Spondylo-Epiphyseal Dysplasia Zanni G , et al. (2015) No -
13 Support A de novo mutation in RPL10 causes a rare X-linked ribosomopathy characterized by syndromic intellectual disability and epilepsy: A new case and review of the literature Bourque DK , et al. (2017) Yes Hypotonia, ataxia, microcephaly, dysmorphic featur
14 Support - Cappuccio G et al. (2022) No Autistic features, stereotypy
Rare Variants   (9)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.232A>G p.Lys78Glu missense_variant De novo - Simplex 29066376 Bourque DK , et al. (2017)
c.95G>T p.Arg32Leu missense_variant Familial Maternal Simplex 35876338 Cappuccio G et al. (2022)
c.95G>T p.Arg32Leu missense_variant Familial Maternal Multiplex 35876338 Cappuccio G et al. (2022)
c.616C>A p.Leu206Met missense_variant Familial Maternal Multiplex 16940977 Klauck SM , et al. (2006)
c.639C>G p.His213Gln missense_variant Familial Maternal Multiplex 16940977 Klauck SM , et al. (2006)
c.639C>G p.His213Gln missense_variant Familial Maternal Simplex 21567917 Chiocchetti A , et al. (2011)
c.191C>T p.Ala64Val missense_variant Familial Maternal Extended multiplex 26290468 Zanni G , et al. (2015)
c.232A>G p.Lys78Glu missense_variant Familial Maternal Multi-generational 25316788 Brooks SS , et al. (2014)
c.481G>A p.Glu161Lys missense_variant Familial Maternal Multi-generational 25846674 Thevenon J , et al. (2015)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Maternally-inherited missense variants in the RPL10 gene were identified in male ASD probands from two independent families in Klauck et al., 2006; functional analysis of these variants demonstrated that generation of the complete translating ribosome complement, rather than basic translation,was impaired in cells expressing mutant RPL10. Gong et al., 2009 failed to detect any non-synonymous variants in RPL10 in a cohort of 141 ASD cases and found no significant difference in RPL10 transcript levels between ASD cases and controls. Although RPL10 failed to reach statistical significance as an ASD gene in a replication study with a larger cohort of German ASD patients in Chiocchetti et al., 2011, the authors identified another ASD case carrying the previously identified p.His213Gln missense variant. Maternally-inherited missense variants in the RPL10 gene have also been identified in families presenting with an X-linked disorder characterized by intellectual disability, epilepsy, microcephaly, and other syndromic features (Brooks et al., 2014; Thevenon et al., 25846674; Zanni et al., 2015). A de novo missense variant in RPL10 (p.Lys78Glu) was identified in a male patient presenting with ASD, severe intellectual disability, epilepsy, and other syndromic features in Bourque et al., 2017; this missense variant had previously been identified in a multi-generational pedigree in Brooks et al., 2014 and had been shown experimentally in this study to be a loss-of-function variant.

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

Maternally-inherited missense variants in the RPL10 gene were identified in male ASD probands from two independent families in Klauck et al., 2006; functional analysis of these variants demonstrated that generation of the complete translating ribosome complement, rather than basic translation,was impaired in cells expressing mutant RPL10. Gong et al., 2009 failed to detect any non-synonymous variants in RPL10 in a cohort of 141 ASD cases and found no significant difference in RPL10 transcript levels between ASD cases and controls. Although RPL10 failed to reach statistical significance as an ASD gene in a replication study with a larger cohort of German ASD patients in Chiocchetti et al., 2011, the authors identified another ASD case carrying the previously identified p.His213Gln missense variant. Maternally-inherited missense variants in the RPL10 gene have also been identified in families presenting with an X-linked disorder characterized by intellectual disability, epilepsy, microcephaly, and other syndromic features (Brooks et al., 2014; Thevenon et al., 25846674; Zanni et al., 2015). A de novo missense variant in RPL10 (p.Lys78Glu) was identified in a male patient presenting with ASD, severe intellectual disability, epilepsy, and other syndromic features in Bourque et al., 2017; this missense variant had previously been identified in a multi-generational pedigree in Brooks et al., 2014 and had been shown experimentally in this study to be a loss-of-function variant.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Maternally-inherited missense variants in the RPL10 gene were identified in male ASD probands from two independent families in Klauck et al., 2006; functional analysis of these variants demonstrated that generation of the complete translating ribosome complement, rather than basic translation,was impaired in cells expressing mutant RPL10. Gong et al., 2009 failed to detect any non-synonymous variants in RPL10 in a cohort of 141 ASD cases and found no significant difference in RPL10 transcript levels between ASD cases and controls. Although RPL10 failed to reach statistical significance as an ASD gene in a replication study with a larger cohort of German ASD patients in Chiocchetti et al., 2011, the authors identified another ASD case carrying the previously identified p.His213Gln missense variant. Maternally-inherited missense variants in the RPL10 gene have also been identified in families presenting with an X-linked disorder characterized by intellectual disability, epilepsy, microcephaly, and other syndromic features (Brooks et al., 2014; Thevenon et al., 25846674; Zanni et al., 2015). A de novo missense variant in RPL10 (p.Lys78Glu) was identified in a male patient presenting with ASD, severe intellectual disability, epilepsy, and other syndromic features in Bourque et al., 2017; this missense variant had previously been identified in a multi-generational pedigree in Brooks et al., 2014 and had been shown experimentally in this study to be a loss-of-function variant.

Reports Added
[New Scoring Scheme]
10/1/2017
4
icon
4

Decreased from 4 to 4

Description

Maternally-inherited missense variants in the RPL10 gene were identified in male ASD probands from two independent families in Klauck et al., 2006; functional analysis of these variants demonstrated that generation of the complete translating ribosome complement, rather than basic translation, was impaired in cells expressing mutant RPL10. Gong et al., 2009 failed to detect any non-synonymous variants in RPL10 in a cohort of 141 ASD cases and found no significant difference in RPL10 transcript levels between ASD cases and controls. Although RPL10 failed to reach statistical significance as an ASD gene in a replication study with a larger cohort of German ASD patients in Chiocchetti et al., 2011, the authors identified another ASD case carrying the previously identified p.His213Gln missense variant. Maternally-inherited missense variants in the RPL10 gene have also been identified in families presenting with an X-linked disorder characterized by intellectual disability, epilepsy, microcephaly, and other syndromic features (Brooks et al., 2014; Thevenon et al., 25846674; Zanni et al., 2015). A de novo missense variant in RPL10 (p.Lys78Glu) was identified in a male patient presenting with ASD, severe intellectual disability, epilepsy, and other syndromic features in Bourque et al., 2017; this missense variant had previously been identified in a multi-generational pedigree in Brooks et al., 2014 and had been shown experimentally in this study to be a loss-of-function variant.

Reports Added
[A de novo mutation in RPL10 causes a rare X-linked ribosomopathy characterized by syndromic intellectual disability and epilepsy: A new case and re...2017] [Mutation and expression analyses of the ribosomal protein gene RPL10 in an extended German sample of patients with autism spectrum disorder.2011]
1/1/2016
4
icon
4

Decreased from 4 to 4

Description

Rare variant without large case-control study (Klauck et al., 2006)

Reports Added
[Mutations in the ribosomal protein gene RPL10 suggest a novel modulating disease mechanism for autism.2006] [A novel ribosomopathy caused by dysfunction of RPL10 disrupts neurodevelopment and causes X-linked microcephaly in humans.2014] [QM, a putative tumor suppressor, regulates proto-oncogene c-yes.2002] [Loss of heterozygosity and microsatellite instability at the Xq28 and the A/G heterozygosity of the QM gene are associated with ovarian cancer.2006] [Ribosomal protein L10 interacts with the SH3 domain and regulates GDNF-induced neurite growth in SH-SY-5y cells.2006] [Mutational analysis of the ribosomal protein Rpl10 from yeast.2007] [Saccharomyces cerevisiae HMO1 interacts with TFIID and participates in start site selection by RNA polymerase II.2008] [An investigation of ribosomal protein L10 gene in autism spectrum disorders.2009] [Protein signatures of oxidative stress response in a patient specific cell line model for autism.2014] [RPL10 mutation segregating in a family with X-linked syndromic Intellectual Disability.2015] [A Novel Mutation in RPL10 (Ribosomal Protein L10) Causes X-Linked Intellectual Disability, Cerebellar Hypoplasia, and Spondylo-Epiphyseal Dysplasia.2015]
4/1/2015
4
icon
4

Decreased from 4 to 4

Description

Rare variant without large case-control study (Klauck et al., 2006)

Reports Added
[RPL10 mutation segregating in a family with X-linked syndromic Intellectual Disability.2015]
10/1/2014
4
icon
4

Decreased from 4 to 4

Description

Rare variant without large case-control study (Klauck et al., 2006)

Reports Added
[A novel ribosomopathy caused by dysfunction of RPL10 disrupts neurodevelopment and causes X-linked microcephaly in humans.2014]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

Rare variant without large case-control study (Klauck et al., 2006)

4/1/2014
No data
icon
4

Increased from No data to 4

Description

Rare variant without large case-control study (Klauck et al., 2006)

Krishnan Probability Score

Score 0.33049324740845

Ranking 24835/25841 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 0.90119329809699

Ranking 3223/18225 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 0.93147524579005

Ranking 11710/18665 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 8

Ranking 234/461 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 -0.28732672748029

Ranking 17016/20870 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
ACS2 Acetyl-coA synthetase isoform Worm Protein Binding 850846 P52910
PLB3 Phospholipase B (lysophospholipase) involved in phospholipid metabolism; hydrolyzes phosphatidylinositol and phosphatidylserine and displays transacylase activity in vitro Worm Protein Binding 854151 Q08108
SED1 Major stress-induced structural GPI-cell wall glycoprotein in stationary-phase cells, associates with translating ribosomes, possible role in mitochondrial genome maintenance; ORF contains two distinct variable minisatellites Worm Protein Binding 851649 Q01589
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