Human Gene Module / Chromosome 11 / PPFIA1

PPFIA1PTPRF interacting protein alpha 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 5
Rare Variants / Common Variants
6 / 0
Aliases
PPFIA1, LIP.1,  LIP1,  LIPRIN
Associated Syndromes
-
Chromosome Band
11q13.3
Associated Disorders
ASD
Relevance to Autism

A de novo complex chromosomal rearrangement with breakpoints disrupting the intronic sequence of the RAB19, PPFIA1, and SHANK2 genes was identified in a 3.5-year-old male patient with moderate ID, speech delay, autistic behavior, and facial dysmorphism (Schluth-Bolard et al., 2013). A rare de novo missense variant that was predicted to be probably damaging was identified in the PPFIA1 gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014; yeast two-hybrid experiments in Chen et al., 2018 demonstrated that this variant disrupted the interaction of PPFIA1 with several genes, including the ASD candidate gene PPP2R5D.

Molecular Function

The protein encoded by this gene is a member of the LAR protein-tyrosine phosphatase-interacting protein (liprin) family. Liprins interact with members of LAR family of transmembrane protein tyrosine phosphatases, which are known to be important for axon guidance and mammary gland development. This protein binds to the intracellular membrane-distal phosphatase domain of tyrosine phosphatase LAR, and appears to localize LAR to cell focal adhesions. This interaction may regulate the disassembly of focal adhesion and thus help orchestrate cell-matrix interactions.

External Links
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Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PPFIA1 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Breakpoint mapping by next generation sequencing reveals causative gene disruption in patients carrying apparently balanced chromosome rearrangements with intellectual deficiency and/or congenital malformations Schluth-Bolard C , et al. (2013) No Autistic behavior
2 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
3 Recent Recommendation An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders Chen S , et al. (2018) No -
4 Support - Zhou X et al. (2022) Yes -
5 Support - Wang J et al. (2023) Yes -
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - translocation De novo - Simplex 23315544 Schluth-Bolard C , et al. (2013)
c.2735C>T p.Ser912Leu missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.3346_3348del p.Trp1116del inframe_deletion De novo - - 35982159 Zhou X et al. (2022)
c.1250G>A p.Arg417Gln missense_variant De novo - Simplex 37393044 Wang J et al. (2023)
c.2085G>A p.Pro695%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.988C>T p.Leu330Phe missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo complex chromosomal rearrangement with breakpoints disrupting the intronic sequence of the RAB19, PPFIA1, and SHANK2 genes was identified in a 3.5-year-old male patient with moderate ID, speech delay, autistic behavior, and facial dysmorphism (Schluth-Bolard et al., 2013). A rare de novo missense variant that was predicted to be probably damaging was identified in the PPFIA1 gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014; yeast two-hybrid experiments in Chen et al., 2018 demonstrated that this variant disrupted the interaction of PPFIA1 with several genes, including the ASD candidate gene PPP2R5D.

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 complex chromosomal rearrangement with breakpoints disrupting the intronic sequence of the RAB19, PPFIA1, and SHANK2 genes was identified in a 3.5-year-old male patient with moderate ID, speech delay, autistic behavior, and facial dysmorphism (Schluth-Bolard et al., 2013). A rare de novo missense variant that was predicted to be probably damaging was identified in the PPFIA1 gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014; yeast two-hybrid experiments in Chen et al., 2018 demonstrated that this variant disrupted the interaction of PPFIA1 with several genes, including the ASD candidate gene PPP2R5D.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A de novo complex chromosomal rearrangement with breakpoints disrupting the intronic sequence of the RAB19, PPFIA1, and SHANK2 genes was identified in a 3.5-year-old male patient with moderate ID, speech delay, autistic behavior, and facial dysmorphism (Schluth-Bolard et al., 2013). A rare de novo missense variant that was predicted to be probably damaging was identified in the PPFIA1 gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014; yeast two-hybrid experiments in Chen et al., 2018 demonstrated that this variant disrupted the interaction of PPFIA1 with several genes, including the ASD candidate gene PPP2R5D.

Reports Added
[New Scoring Scheme]
7/1/2018
icon
4

Increased from to 4

Description

A de novo complex chromosomal rearrangement with breakpoints disrupting the intronic sequence of the RAB19, PPFIA1, and SHANK2 genes was identified in a 3.5-year-old male patient with moderate ID, speech delay, autistic behavior, and facial dysmorphism (Schluth-Bolard et al., 2013). A rare de novo missense variant that was predicted to be probably damaging was identified in the PPFIA1 gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014; yeast two-hybrid experiments in Chen et al., 2018 demonstrated that this variant disrupted the interaction of PPFIA1 with several genes, including the ASD candidate gene PPP2R5D.

Reports Added
[An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders.2018]
Krishnan Probability Score

Score 0.49616181348549

Ranking 2666/25841 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 0.99999987433872

Ranking 204/18225 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 0.90593325135194

Ranking 7020/18665 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 0.25771362449728

Ranking 3368/20870 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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