PPP2R5Cprotein phosphatase 2 regulatory subunit B'gamma
Autism Reports / Total Reports
3 / 5Rare Variants / Common Variants
25 / 1Aliases
-Associated Syndromes
-Chromosome Band
14q32.31Associated Disorders
-Relevance to Autism
Verbinnen et al., 2025 described a cohort of 26 individuals with predominantly de novo missense variants in the PPP2R5C gene who presented with a neurodevelopmental disorder within the Houge-Janssens syndrome spectrum characterized by neurodevelopmental delay and hypotonia with a high risk of epilepsy, behavioral problems, macrocephaly, and mildly dysmorphic facial features; 5 individuals in this cohort were reported to have been diagnosed with autism spectrum disorder. Additional biochemical assessment of PPP2R5C variants reported in Verbinnen et al., 2025 demonstrated defects in subunit binding, substrate binding, and/or phosphatase catalytic activity. Muir et al., 2024 had previously reported a recurrent missense variant in PPP2R5C (NM_001161725.2:c.457G>A;p.Glu153Lys) in five unrelated individuals with overlapping clinical features of macrocephaly, intellectual disability, and seizures; detailed clinical summaries of two of the five individuals with this recurrent missense variant reported one individual with autism spectrum disorder. De novo missense variants in PPP2R5C that were predicted to be damaging (CADD > 25) were also reported in an ASD proband from the SAGE cohort (Guo et al., 2019) and in a male ASD proband from the SPARK cohort (Feliciano et al., 2019). Association analysis of ASD families from the Autism Genome Project (AGP) Consortium in Anney et al., 2010 identified an intronic SNP in the PPP2R5C gene (rs7142002) as fulfilling the threshold for association with ASD (P < 5.0E-06).
Molecular Function
The product of this gene belongs to the phosphatase 2A regulatory subunit B family. Protein phosphatase 2A is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The B regulatory subunit might modulate substrate selectivity and catalytic activity. This gene encodes a gamma isoform of the regulatory subunit B56 subfamily.
External Links
SFARI Genomic Platforms
Reports related to PPP2R5C (5 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Positive association | A genome-wide scan for common alleles affecting risk for autism | Anney R , et al. (2010) | Yes | - |
2 | Support | Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes | Guo H , et al. (2018) | Yes | - |
3 | Support | Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes | Feliciano P et al. (2019) | Yes | - |
4 | Support | - | Alison M Muir et al. () | No | ASD, DD |
5 | Primary | - | Iris Verbinnen et al. (2025) | No | ASD, ADHD, epilepsy/seizures |
Rare Variants (25)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
c.457G>A | p.Glu153Lys | missense_variant | Unknown | - | - | 39696819 | Alison M Muir et al. () | |
c.848C>T | p.Leu283Ser | missense_variant | De novo | - | Simplex | 30504930 | Guo H , et al. (2018) | |
c.310T>C | p.Cys104Arg | missense_variant | De novo | - | - | 39978342 | Iris Verbinnen et al. (2025) | |
c.330T>A | p.Phe110Leu | missense_variant | De novo | - | - | 39978342 | Iris Verbinnen et al. (2025) | |
c.524C>G | p.Pro175Arg | missense_variant | De novo | - | - | 39978342 | Iris Verbinnen et al. (2025) | |
c.529G>A | p.Glu177Lys | missense_variant | De novo | - | - | 39978342 | Iris Verbinnen et al. (2025) | |
c.535G>A | p.Glu179Lys | missense_variant | De novo | - | - | 39978342 | Iris Verbinnen et al. (2025) | |
c.556T>C | p.Trp186Arg | missense_variant | De novo | - | - | 39978342 | Iris Verbinnen et al. (2025) | |
c.556T>C | p.Trp186Arg | missense_variant | Unknown | - | - | 39978342 | Iris Verbinnen et al. (2025) | |
c.563A>C | p.His188Pro | missense_variant | De novo | - | - | 39978342 | Iris Verbinnen et al. (2025) | |
c.563A>G | p.His188Arg | missense_variant | De novo | - | - | 39978342 | Iris Verbinnen et al. (2025) | |
c.563A>T | p.His188Leu | missense_variant | De novo | - | - | 39978342 | Iris Verbinnen et al. (2025) | |
c.566T>C | p.Leu189Pro | missense_variant | De novo | - | - | 39978342 | Iris Verbinnen et al. (2025) | |
c.685G>A | p.Glu229Lys | missense_variant | De novo | - | - | 39978342 | Iris Verbinnen et al. (2025) | |
c.689A>T | p.Asp230Val | missense_variant | De novo | - | - | 39978342 | Iris Verbinnen et al. (2025) | |
c.694C>T | p.Arg232Trp | missense_variant | De novo | - | - | 39978342 | Iris Verbinnen et al. (2025) | |
c.695G>T | p.Arg232Leu | missense_variant | Unknown | - | - | 39978342 | Iris Verbinnen et al. (2025) | |
c.895A>G | p.Lys299Glu | missense_variant | De novo | - | - | 39978342 | Iris Verbinnen et al. (2025) | |
c.1080A>C | p.Leu360Phe | missense_variant | Unknown | - | - | 39978342 | Iris Verbinnen et al. (2025) | |
c.1195G>A | p.Glu399Lys | missense_variant | De novo | - | - | 39978342 | Iris Verbinnen et al. (2025) | |
c.457G>A | p.Glu153Lys | missense_variant | De novo | - | Simplex | 39696819 | Alison M Muir et al. () | |
c.416G>A | p.Arg139Gln | missense_variant | De novo | - | Simplex | 31452935 | Feliciano P et al. (2019) | |
c.540_542del | p.Thr181del | inframe_deletion | De novo | - | - | 39978342 | Iris Verbinnen et al. (2025) | |
c.552_554del | p.Ala185del | inframe_deletion | De novo | - | - | 39978342 | Iris Verbinnen et al. (2025) | |
c.326_331del | p.Asp109_Phe110del | inframe_deletion | De novo | - | - | 39978342 | Iris Verbinnen et al. (2025) |
Common Variants (1)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Paternal Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
c.964-99T>C | - | intron_variant | - | - | - | 20663923 | Anney R , et al. (2010) |
SFARI Gene score
Suggestive Evidence, Syndromic


criteria met
See SFARI Gene'scoring criteriaThe 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.
The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."
4/1/2025
Initial score established: 3S
Krishnan Probability Score
Score 0.57391421751029
Ranking 681/25841 scored genes
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ExAC Score
Score 0.99767266348225
Ranking 1298/18225 scored genes
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Sanders TADA Score
Score 0.93268362923132
Ranking 12050/18665 scored genes
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Zhang D Score
Score -0.68749817954354
Ranking 20306/20870 scored genes
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