Human Gene Module / Chromosome 16 / PRR25

PRR25proline rich 25

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
2 / 2
Rare Variants / Common Variants
6 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
16p13.3
Associated Disorders
-
Relevance to Autism

Transmission And De Novo Association (TADA) analysis of whole-genome sequencing data from a cohort of 4,551 individuals in 1,004 multiplex families having two or more autistic children identified PRR25 as a novel ASD risk gene with a false discovery rate (FDR) less than 0.1. A de novo missense variant in this gene has also been observed in a Chinese ASD proband (Wang et al., 2023).

Molecular Function

SFARI Genomic Platforms
Reports related to PRR25 (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support - Wang J et al. (2023) Yes -
2 Primary - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.116C>T p.Pro39Leu missense_variant De novo - Simplex 37393044 Wang J et al. (2023)
c.7C>T p.Arg3Ter stop_gained Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.644-2A>T - splice_site_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.305del p.Asn102MetfsTer98 frameshift_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.523_541del p.Glu175ArgfsTer19 frameshift_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.1102_1105dup p.Pro369LeufsTer? frameshift_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

Score Delta: Score remained at 3

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.

7/1/2023
icon
3

Increased from to 3

Krishnan Probability Score

Score 0.42404725432899

Ranking 21052/25841 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.
ExAC Score

Score 3.128965692874E-6

Ranking 14656/18225 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
Sanders TADA Score

Score 0.53519810164607

Ranking 528/18665 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).
CNVs associated with PRR25(1 CNVs)
16p13.3 73 Deletion-Duplication 103  /  544
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