Human Gene Module / Chromosome 11 / PRPF19

PRPF19pre-mRNA processing factor 19

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
9 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
11q12.2
Associated Disorders
-
Relevance to Autism

Li et al., 2023 reported six unrelated individuals with de novo heterozygous PRPF19 variants, four of whom had a formal diagnosis of autism; subsequent functional analysis of two PRPF19 missense variants identified in individuals with autism (p.Gly404Ser and p.Leu499Phe) in Drosophila rescue assays demonstrated that both variants led to social behavior deficits in flies. Additional de novo coding variants in this gene, including two de novo missense variants, had previously been identiifed in ASD probands (Lim et al., 2017; Zhou et al., 2022).

Molecular Function

Enables identical protein binding activity and ubiquitin-ubiquitin ligase activity. Involved in several processes, including DNA damage checkpoint signaling; cellular protein metabolic process; and mRNA splicing, via spliceosome. Acts upstream of or within protein polyubiquitination. Located in cytoplasm; nuclear speck; and site of double-strand break. Part of Prp19 complex and U2-type catalytic step 2 spliceosome. Colocalizes with DNA replication factor A complex.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PRPF19 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder Lim ET , et al. (2017) Yes -
2 Support - Zhou X et al. (2022) Yes -
3 Primary - Dong Li et al. (2024) Yes ID
Rare Variants   (9)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain De novo - Simplex 37962958 Dong Li et al. (2024)
c.52T>C p.Ser18Pro missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.567G>A p.Lys189= synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.859A>C p.Thr287Pro missense_variant De novo - - 28714951 Lim ET , et al. (2017)
c.383G>A p.Arg128Gln missense_variant De novo - Simplex 37962958 Dong Li et al. (2024)
c.1210G>A p.Gly404Ser missense_variant De novo - Simplex 37962958 Dong Li et al. (2024)
c.1264C>T p.Arg422Cys missense_variant De novo - Simplex 37962958 Dong Li et al. (2024)
c.1495C>T p.Leu499Phe missense_variant De novo - Simplex 37962958 Dong Li et al. (2024)
c.816del p.His273ThrfsTer37 frameshift_variant De novo - Simplex 37962958 Dong Li 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.

1/1/2024
icon
3

Increased from to 3

Krishnan Probability Score

Score 0.41369331826961

Ranking 21797/25841 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 0.99856669586423

Ranking 1165/18225 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 0.93054689424135

Ranking 11458/18665 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 -0.17421134674597

Ranking 14815/20870 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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