Human Gene Module / Chromosome 14 / PRPF39

PRPF39pre-mRNA processing factor 39

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
2 / 3
Rare Variants / Common Variants
4 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
14q21.2
Associated Disorders
-
Relevance to Autism

A de novo nonsense variant, an paternally-inherited splice-site variant, and a paternally-inherited damaging missense variant in the PRPF39 gene were identified in ASD probands from the Autism Sequencing Consortium in De Rubeis et al., 2014. A maternally-inherited splice-site variant in this gene was later observed in an ASD proband from the Simons Simplex Collection in Krumm et al., 2015. Transmission and De Novo Association (TADA) analysis of a combined cohort consisting of 536 Chinese ASD probands and 1457 Chinese controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, in Guo et al., 2017 identified PRPF39 as an ASD candidate gene with a PTADA of 0.003073.

Molecular Function

Involved in pre-mRNA splicing

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PRPF39 (3 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 Excess of rare, inherited truncating mutations in autism Krumm N , et al. (2015) Yes -
3 Recent Recommendation Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders Li J , et al. (2017) No -
Rare Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.644G>A p.Trp215Ter stop_gained De novo - - 25363760 De Rubeis S , et al. (2014)
c.570-2A>G - splice_site_variant Familial - Simplex 25961944 Krumm N , et al. (2015)
c.-19-1G>T - splice_site_variant Familial Paternal - 25363760 De Rubeis S , et al. (2014)
c.142T>C p.Ser48Pro missense_variant Familial Paternal - 25363760 De Rubeis S , et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo nonsense variant, a paternally-inherited splice-site variant, and a paternally-inherited damaging missense variant in the PRPF39 gene were identified in ASD probands from the Autism Sequencing Consortium in De Rubeis et al., 2014. A maternally-inherited splice-site variant in this gene was later observed in an ASD proband from the Simons Simplex Collection in Krumm et al., 2015. Transmission and De Novo Association (TADA) analysis of a combined cohort consisting of 536 Chinese ASD probands and 1457 Chinese controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, in Guo et al., 2017 identified PRPF39 as an ASD candidate gene with a PTADA of 0.003073.

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

A de novo nonsense variant, a paternally-inherited splice-site variant, and a paternally-inherited damaging missense variant in the PRPF39 gene were identified in ASD probands from the Autism Sequencing Consortium in De Rubeis et al., 2014. A maternally-inherited splice-site variant in this gene was later observed in an ASD proband from the Simons Simplex Collection in Krumm et al., 2015. Transmission and De Novo Association (TADA) analysis of a combined cohort consisting of 536 Chinese ASD probands and 1457 Chinese controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, in Guo et al., 2017 identified PRPF39 as an ASD candidate gene with a PTADA of 0.003073.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A de novo nonsense variant, a paternally-inherited splice-site variant, and a paternally-inherited damaging missense variant in the PRPF39 gene were identified in ASD probands from the Autism Sequencing Consortium in De Rubeis et al., 2014. A maternally-inherited splice-site variant in this gene was later observed in an ASD proband from the Simons Simplex Collection in Krumm et al., 2015. Transmission and De Novo Association (TADA) analysis of a combined cohort consisting of 536 Chinese ASD probands and 1457 Chinese controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, in Guo et al., 2017 identified PRPF39 as an ASD candidate gene with a PTADA of 0.003073.

Reports Added
[New Scoring Scheme]
7/1/2017
icon
4

Increased from to 4

Description

A de novo nonsense variant, a paternally-inherited splice-site variant, and a paternally-inherited damaging missense variant in the PRPF39 gene were identified in ASD probands from the Autism Sequencing Consortium in De Rubeis et al., 2014. A maternally-inherited splice-site variant in this gene was later observed in an ASD proband from the Simons Simplex Collection in Krumm et al., 2015. Transmission and De Novo Association (TADA) analysis of a combined cohort consisting of 536 Chinese ASD probands and 1457 Chinese controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, in Guo et al., 2017 identified PRPF39 as an ASD candidate gene with a PTADA of 0.003073.

Krishnan Probability Score

Score 0.42914832533249

Ranking 20862/25841 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 0.99512173227692

Ranking 1520/18225 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 0.24471039838292

Ranking 139/18665 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 0.33103417480585

Ranking 2279/20870 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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