Human Gene Module / Chromosome 11 / CPSF7

CPSF7cleavage and polyadenylation specific factor 7

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
6 / 8
Rare Variants / Common Variants
9 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
11q12.2
Associated Disorders
-
Relevance to Autism

One de novo loss-of-function and two potentially damaging missense variants in the CPSF7 gene have been identified in ASD probands from the Autism Sequencing Consortium, the SPARK cohort, and the MSSNG cohort (Yuen et al., 2017; Satterstrom et al., 2020; Zhou et al., 2022). Transmission and de novo association (TADA) analysis of whole-exome and whole-genome sequencing data from the Autism Sequencing Consortium, the Simons Simplex Collection, the MSSNG cohort, and the SPARK cohort in Trost et al., 2022 identified CPSF7 as an ASD-associated gene with a false discovery rate (FDR) < 0.1. Furthermore, analysis of de novo mutations in the coding regions of 843 stress granule-associated genes from 40,853 NDD probands, including 9228 individuals primarily diagnosed with ASD and 31,625 individuals primarily diagnosed with intellectual disability or developmental delay from 26 published studies, in Jia et al., 2022 identified CPSF7 as an NDD candidate gene with a false discovery rate (FDR) less than 0.05.

Molecular Function

Cleavage factor Im (CFIm) is one of six factors necessary for correct cleavage and polyadenylation of pre-mRNAs. CFIm is composed of three different subunits of 25, 59, and 68 kDa, and it functions as a heterotetramer, with a dimer of the 25 kDa subunit binding to two of the 59 or 68 kDa subunits. The protein encoded by this gene represents the 59 kDa subunit, which can interact with the splicing factor U2 snRNP Auxiliary Factor (U2AF) 65 to link the splicing and polyadenylation complexes.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CPSF7 (8 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Prevalence and architecture of de novo mutations in developmental disorders et al. (2017) No -
2 Primary Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
3 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
4 Support - Kaplanis J et al. (2020) No -
5 Recent Recommendation - Jia X et al. (2022) Yes -
6 Support - Zhou X et al. (2022) Yes -
7 Recent Recommendation - Trost B et al. (2022) Yes -
8 Support - Soo-Whee Kim et al. (2024) Yes -
Rare Variants   (9)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.664C>G p.Arg222Gly missense_variant De novo - - 28135719 et al. (2017)
c.1079A>G p.Tyr360Cys missense_variant De novo - - 28135719 et al. (2017)
c.614G>A p.Arg205Gln missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.680G>A p.Gly227Glu missense_variant De novo - - 33057194 Kaplanis J et al. (2020)
c.692G>A p.Arg231Gln missense_variant De novo - - 33057194 Kaplanis J et al. (2020)
c.787A>C p.Ser263Arg missense_variant De novo - - 33057194 Kaplanis J et al. (2020)
c.703C>T p.Arg235Ter stop_gained De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.646T>A p.Phe216Ile missense_variant De novo - - 31981491 Satterstrom FK et al. (2020)
c.203_220del p.Pro68_Tyr74delinsHis inframe_deletion De novo - - 39334436 Soo-Whee Kim et al. (2024)
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.

1/1/2023
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1

Increased from to 1

Krishnan Probability Score

Score 0.49231635588046

Ranking 4605/25841 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 0.99133017505779

Ranking 1751/18225 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 0.93024597381812

Ranking 11378/18665 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 0.10908801339096

Ranking 5933/20870 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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