PPP2R1A

Chr 19AD

protein phosphatase 2 scaffold subunit Aalpha

Also known as: HJS2, MRD36, PP2A-Aalpha, PP2AA, PP2AAALPHA, PR65A

NCBI Gene: 5518ENSG00000105568UniProt: P30153OMIM: 605983

This gene encodes a constant regulatory subunit of protein phosphatase 2. Protein phosphatase 2 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 constant regulatory subunit A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. This gene encodes an alpha isoform of the constant regulatory subunit A. Alternatively spliced transcript variants have been described. [provided by RefSeq, Apr 2010]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Houge-Janssens syndrome 2MIM #616362
AD

Clinical highlights

Gene-disease validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
A dominant-negative effect is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.
2
Active trials
52
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.30
LOEUF· LoF intol.
DN*
Mechanism· G2P
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GeneReview available — PPP2R1A
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.30LOEUF
pLI 0.984
Z-score 4.42
OE 0.13 (0.06–0.30)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
4.46Z-score
OE missense 0.34 (0.29–0.40)
123 obs / 361.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.13 (0.06–0.30)
0≤0.351.4
Missense OE?0.34 (0.29–0.40)
0≤0.61.4
Synonymous OE?0.94
0≤1.21.6
LoF obs/exp: 4 / 30.2Missense obs/exp: 123 / 361.4Syn Z: 0.55

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

PPP2R1A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients