PPP2R5C

Chr 14AD

protein phosphatase 2 regulatory subunit B'gamma

Also known as: B56G, B56gamma, HJS4, PR61G

NCBI Gene: 5527 ENSG00000078304 UniProt: Q13362 OMIM: 601645

The protein encodes the gamma isoform of the B56 regulatory subunit of protein phosphatase 2A, which modulates substrate selectivity and catalytic activity of this major serine/threonine phosphatase involved in controlling cell growth and division. Mutations cause Houge-Janssens syndrome 4, inherited in an autosomal dominant pattern. The high pLI score (0.97) and low LOEUF score (0.32) indicate the gene is highly intolerant to loss-of-function variants, suggesting haploinsufficiency as the likely pathogenic mechanism.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

ADLOEUF 0.321 OMIM phenotype

Clinical Summary— PPP2R5C

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

10 unique Pathogenic / Likely Pathogenic· 74 VUS of 162 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.32LOEUF

pLI 0.971

Z-score 4.51

OE 0.15 (0.08–0.32)

Highly constrained

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

Missense Constraint?

3.08Z-score

OE missense 0.50 (0.44–0.57)

150 obs / 300.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.15 (0.08–0.32)

0≤0.351.4

Missense OE?0.50 (0.44–0.57)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 5 / 33.0Missense obs/exp: 150 / 300.4Syn Z: 0.69

ClinVar Variant Classifications

162 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

Likely Pathogenic4

VUS74

Likely Benign39

Benign14

Conflicting3

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	5	0	6
Likely Pathogenic	0	4	0	0	4
VUS	3	62	9	0	74
Likely Benign	2	3	20	14	39
Benign	0	3	9	2	14
Conflicting	—				3
Total	5	73	43	16	140

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

41 pathogenic / likely-pathogenic (of 45) ClinVar copy-number / structural variants overlap PPP2R5C — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →