Human Gene Module / Chromosome 11 / CAPRIN1

CAPRIN1Cell cycle associated protein 1

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
3 / 6
Rare Variants / Common Variants
17 / 0
EAGLE Score
5.5
Limited Learn More
Aliases
CAPRIN1, GPIAP1,  GPIP137,  M11S1,  RNG105,  p137GPI
Associated Syndromes
-
Chromosome Band
11p13
Associated Disorders
-
Genetic Category
Rare Single Gene Mutation, Syndromic, Functional
Relevance to Autism

CAPRIN1 interacts with Fragile X Mental Retardation Protein (FMRP) at the level of the translation machinery as well as in trafficking neuronal granules (El Fatimay et al., 2012). A de novo nonsense variant in CAPRIN1 was identified in a male ASD proband (Jiang et al., 2013). Pavinato et al., 2022 identified 12 cases with loss-of-function variants in the CAPRIN1 gene presenting with a neurodevelopmental phenotype characterized by language impairment/speech delay (100%), intellectual disability (83%), ADHD (82%), and autism spectrum disorder (67%); patient-derived lymphoblasts and fibroblasts showed monoallelic expression of the wild-type allele and a reduction of the transcript and protein compatible with haploinsufficiency, and studies assessing CAPRIN1-/- human iPSCs generated by CRISPR/Cas9 demonstrated that loss of CAPRIN1 resulted in reduced neuronal processes, overall disruption of neuronal organization, increased neuronal degeneration, altered RNA translation, and impaired calcium signalling and increased oxidative stress.

Molecular Function

May regulate the transport and translation of mRNAs of proteins involved in synaptic plasticity in neurons and cell proliferation and migration in multiple cell types. In neuronal cells, directly binds to several mRNAs associated with RNA granules, including BDNF, CAMK2A, CREB1, MAP2, NTRK2 mRNAs, as well as to GRIN1 and KPNB1 mRNAs, but not to rRNAs .

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CAPRIN1 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Recent Recommendation Fragile X mental retardation protein interacts with the RNA-binding protein Caprin1 in neuronal RiboNucleoProtein complexes [corrected] El Fatimy R , et al. (2012) No -
2 Primary Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing Jiang YH , et al. (2013) Yes -
3 Support Comprehensive behavioral analysis of RNG105 (Caprin1) heterozygous mice: Reduced social interaction and attenuated response to novelty Ohashi R , et al. (2016) No -
4 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
5 Recent Recommendation - Pavinato L et al. (2022) No ASD, ADHD, epilepsy/seizures
6 Support - Zhou X et al. (2022) Yes -
Rare Variants   (17)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - Simplex 35979925 Pavinato L et al. (2022)
c.118C>T p.Gln40Ter stop_gained De novo - - 35982159 Zhou X et al. (2022)
c.1195C>T p.Gln399Ter stop_gained De novo - - 35982159 Zhou X et al. (2022)
c.892C>T p.Gln298Ter stop_gained De novo - - 35979925 Pavinato L et al. (2022)
c.1072C>T p.Arg358Ter stop_gained De novo - - 35979925 Pavinato L et al. (2022)
c.1744C>T p.Gln582Ter stop_gained De novo - - 35979925 Pavinato L et al. (2022)
c.1195C>T p.Gln399Ter stop_gained De novo - Simplex 23849776 Jiang YH , et al. (2013)
c.928A>T p.Lys310Ter stop_gained De novo - Simplex 35979925 Pavinato L et al. (2022)
c.1195C>T p.Gln399Ter stop_gained De novo - Simplex 35979925 Pavinato L et al. (2022)
c.1024dup p.His342ProfsTer30 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.1002A>G p.Ala334%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.279+1G>T - splice_site_variant Familial Maternal Simplex 35979925 Pavinato L et al. (2022)
c.879G>A p.Glu293%3D splice_region_variant De novo - Simplex 35979925 Pavinato L et al. (2022)
c.1372C>T p.Arg458Ter stop_gained Familial Paternal Multiplex 35979925 Pavinato L et al. (2022)
c.1493_1496del p.Ser498AsnfsTer10 frameshift_variant De novo - Simplex 35979925 Pavinato L et al. (2022)
c.1103delinsTATGT p.Gly368ValfsTer5 frameshift_variant De novo - Simplex 35979925 Pavinato L et al. (2022)
c.377_380del p.Thr126LysfsTer11 frameshift_variant Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
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.

10/1/2019
3
icon
1

Decreased from 3 to 1

New Scoring Scheme
Description

A de novo nonsense variant in CAPRIN1 was identified in a male ASD proband; this variant was not present in dbSNP135, 1000 Genomes, or ESP6500 (PMID 23849776). CAPRIN1 interacts with Fragile X Mental Retardation Protein (FMRP) at the level of the translation machinery as well as in trafficking neuronal granules (PMID 22737234).

Reports Added
[New Scoring Scheme]
7/1/2019
3
icon
3

Decreased from 3 to 3

Description

A de novo nonsense variant in CAPRIN1 was identified in a male ASD proband; this variant was not present in dbSNP135, 1000 Genomes, or ESP6500 (PMID 23849776). CAPRIN1 interacts with Fragile X Mental Retardation Protein (FMRP) at the level of the translation machinery as well as in trafficking neuronal granules (PMID 22737234).

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
1/1/2016
3
icon
3

Decreased from 3 to 3

Description

A de novo nonsense variant in CAPRIN1 was identified in a male ASD proband; this variant was not present in dbSNP135, 1000 Genomes, or ESP6500 (PMID 23849776). CAPRIN1 interacts with Fragile X Mental Retardation Protein (FMRP) at the level of the translation machinery as well as in trafficking neuronal granules (PMID 22737234).

Reports Added
[Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.2013] [Fragile X mental retardation protein interacts with the RNA-binding protein Caprin1 in neuronal RiboNucleoProtein complexes [corrected].2012] [Comprehensive behavioral analysis of RNG105 (Caprin1) heterozygous mice: Reduced social interaction and attenuated response to novelty.2016]
7/1/2015
icon
3

Increased from to 3

Description

A de novo nonsense variant in CAPRIN1 was identified in a male ASD proband; this variant was not present in dbSNP135, 1000 Genomes, or ESP6500 (PMID 23849776). CAPRIN1 interacts with Fragile X Mental Retardation Protein (FMRP) at the level of the translation machinery as well as in trafficking neuronal granules (PMID 22737234).

Krishnan Probability Score

Score 0.44686544718121

Ranking 14379/25841 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 0.9997676618087

Ranking 798/18225 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 0.93066640588775

Ranking 11490/18665 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 9

Ranking 196/461 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 0.39953012821414

Ranking 1472/20870 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
G3BP1 GTPase activating protein (SH3 domain) binding protein 1 Human Protein Binding 10146 Q13283
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