Human Gene Module / Chromosome 8 / PABPC1

PABPC1poly(A) binding protein cytoplasmic 1

SFARI Gene Score
3S
Suggestive Evidence, Syndromic Criteria 3.1, Syndromic
Autism Reports / Total Reports
4 / 6
Rare Variants / Common Variants
10 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
8q22.3
Associated Disorders
-
Relevance to Autism

De novo missense variants in the PABPC1 gene have been identified in three ASD probands (De Rubeis et al., 2014; Krupp et al., 2017; Guo et al., 2019), as well as in two individuals with unspecified developmental disorders (Kaplanis et al., 2020). Wegler et al., 2022 described four probands with an overlapping phenotype of developmental delay with expressive speech delay, seizures, and behavioral issues including autistic features and heterozygous de novo variants that clustered in the PABP domain of PABPC1; functional analysis of the three missense variants identified in this report demonstrated reduced interaction between PABPC1 and PAIP2 and a failure to rescue the decrease of neural progenitor cells caused by Pabpc1 knockdown in the mouse brain.

Molecular Function

This gene encodes a poly(A) binding protein. The protein shuttles between the nucleus and cytoplasm and binds to the 3' poly(A) tail of eukaryotic messenger RNAs via RNA-recognition motifs. The binding of this protein to poly(A) promotes ribosome recruitment and translation initiation; it is also required for poly(A) shortening which is the first step in mRNA decay.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PABPC1 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
3 Support Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder Krupp DR , et al. (2017) Yes -
4 Support Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes Guo H , et al. (2018) Yes -
5 Support - Kaplanis J et al. (2020) No -
6 Recent Recommendation - Wegler M et al. (2022) No ASD or autistic features, ADHD
Rare Variants   (10)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.503+917T>G - intron_variant De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.1367C>T p.Pro456Leu missense_variant De novo - - 33057194 Kaplanis J et al. (2020)
c.1442G>A p.Arg481His missense_variant De novo - - 33057194 Kaplanis J et al. (2020)
c.412A>G p.Lys138Glu missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.611A>T p.Asp204Val missense_variant De novo - Multiplex 30504930 Guo H , et al. (2018)
c.1687G>A p.Gly563Ser missense_variant De novo - Simplex 35511136 Wegler M et al. (2022)
c.1691A>G p.Glu564Gly missense_variant De novo - Simplex 35511136 Wegler M et al. (2022)
c.1709T>C p.Ile570Thr missense_variant De novo - Simplex 35511136 Wegler M et al. (2022)
c.1417G>A p.Val473Ile missense_variant De novo - Simplex 28867142 Krupp DR , et al. (2017)
c.1664_1666del p.Pro555del inframe_deletion De novo - Simplex 35511136 Wegler M et al. (2022)
Common Variants  

No common variants reported.

SFARI Gene score
3S

Suggestive Evidence, Syndromic

Score Delta: Score remained at 3S

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.

S

Syndromic

See all Category S Genes

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
icon
3

Increased from to 3

Krishnan Probability Score

Score 0.4471536183309

Ranking 13951/25841 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 0.99969244288815

Ranking 844/18225 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 0.74380346048178

Ranking 1495/18665 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 0.15517236695096

Ranking 5074/20870 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
Submit New Gene

Report an Error