PPP2R5D
  • 1
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
PPP2R5D (HGNC:9312) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
protein phosphatase 2 regulatory subunit B'delta
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
B56D, B56delta
%HI
19.74(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.23(Read more about gnomAD LOEUF score)
Cytoband
6p21.1
Genomic Coordinates
GRCh37/hg19: chr6:42952308-42980080 NCBI Ensembl UCSC
GRCh38/hg38: chr6:42984570-43012342 NCBI Ensembl UCSC
MANE Select Transcript
NM_006245.4 ENST00000485511.6 (Read more about MANE Select)
Function
The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-31413
ClinGen Curation ID:
CCID:007706
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Little Evidence for Haploinsufficiency (1)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
05/26/2021

Haploinsufficiency (HI) Score Details

HI Score:
1
HI Evidence Strength:
Little Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • intellectual disability-macrocephaly-hypotonia-behavioral abnormalities syndrome Monarch
HI Evidence:
  • PUBMED: 32595695
    Hu, et al (2020) identified a de novo nonsense variant (c.1492C>T, p.Arg498Ter) in PPP2R5D via whole exome sequencing in a 6 year old male with a diagnosis of "mental retardation, autosomal dominant 35."
  • PUBMED: 25363768
    Iossifov, et al (2014) observed a de novo frameshift variant (c.663delT, p.Glu222Serfs) in PPP2R5D in a female proband with intellectual disability. This same proband is also reported on SFARI as part of the Simons Simplex Collection and is also referenced in several other more recent papers (PMID: 28191890, 31981491).
HI Evidence Comments:
The PPP2R5D gene encodes one of the 15 regulatory B-type subunits of protein phosphatase 2A (PP2A), a major serine/threonine phosphatase in humans that is critical for cell signaling and physiology. De novo pathogenic missense variants in the PPP2R5D gene appear to act in a dominant-negative manner to cause PPP2R5D-related neurodevelopmental disorder. This disorder is characterized by mild to severe neurodevelopmental delay, but several other features have also been reported including hypotonia, ataxia, and speech impairment. At the time of this curation at least 13 missense variants have been observed in more than 100 individuals with PPP2R5D-related neurodevelopmental disorder (reviewed in PMID: 32074998). Functional analysis of PPP2R5D missense variants in human cell lines demonstrated improper formation of the PP2A enzyme and altered phosphorylation patterns (PMID: 26168268). At this time, isolated deletions of the PPP2R5D gene have not been reported and the only predicted loss of function variants reported in the literature are the two with limited information described above. While there are many cases of missense variation in this gene in individuals with neurodevelopmental disorders, it is unclear at this time whether or not haploinsufficiency is a disease mechanism.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000006.11) (NC_000006.12)