PHLPP2
protein-codingPH domain and leucine rich repeat protein phosphatase 2, the group of Protein phosphatases, Mg2+/Mn2+ dependent|Pleckstrin homology domain containing|Small nucleolar RNA protein coding host genes
Gene summary
Predicted to enable metal ion binding activity and protein serine/threonine phosphatase activity. Predicted to be involved in intracellular signal transduction. Located in cytosol and intercellular bridge. [provided by Alliance of Genome Resources, Jun 2026]
- PHLPPL
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~86.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PHLPP2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015020.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 1 | 3 | |||
| missense | 183 | 6 | 189 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 185 | 8 | 1 | 194 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055835.2 | 18 | MANE Select | |
| Ensembl | ENSP00000457991.1 | 18 | MANE Select | |
| RefSeq | NP_001275932.1 | 17 | Standard | |
| Ensembl | ENSP00000377159.2 | 17 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- PI3K-Akt signaling pathway - Homo sapiens (human)
- Focal Adhesion-PI3K-Akt-mTOR-signaling pathway
- PI3K-Akt Signaling Pathway
- Signal Transduction
- PIP3 activates AKT signaling
Biological Process
- protein dephosphorylation
- hippocampus development
Molecular Function
- protein serine/threonine phosphatase activity
- protein binding
- metal ion binding
Cellular Component
- photoreceptor inner segment
- nucleus
- cytoplasm
- cytosol
- photoreceptor outer segment membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000568954
- Coding exons
- 18
- Length
- 86867
- Individuals with no LoFs
- 125689
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 59
- Defined
- 125748
- p
- 0.000235
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.631 | 765 | 717 | 1.07 | 0.0000386 | 8641 |
| Missense (PolyPhen) | 270 | 286.29 | 0.9431 | 3515 | ||
| Synonymous | -1.65 | 324 | 288 | 1.12 | 0.0000156 | 2688 |
| Loss of Function | 4.48 | 21 | 57.7 | 0.364 | 0.00000353 | 654 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00018 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00049 | 0.00049 | rare |
| Finnish | 0.00042 | 0.00042 | rare |
| European (Non-Finnish) | 0.00024 | 0.00024 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Protein phosphatase involved in regulation of Akt and PKC signaling. Mediates dephosphorylation in the C-terminal domain hydrophobic motif of members of the AGC Ser/Thr protein kinase family; specifically acts on 'Ser-473' of AKT1, 'Ser-660' of PRKCB isoform beta-II and 'Ser-657' of PRKCA. Akt regulates the balance between cell survival and apoptosis through a cascade that primarily alters the function of transcription factors that regulate pro- and antiapoptotic genes. Dephosphorylation of 'Ser- 473' of Akt triggers apoptosis and decreases cell proliferation. Also controls the phosphorylation of AKT3. Dephosphorylates STK4 on 'Thr-387' leading to STK4 activation and apoptosis (PubMed:20513427). Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation (PubMed:21986499). Inhibits cancer cell proliferation and may act as a tumor suppressor. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation. Dephosphorylates RAF1 inhibiting its kinase activity (PubMed:24530606). {ECO:0000269|PubMed:17386267, ECO:0000269|PubMed:18162466, ECO:0000269|PubMed:19079341, ECO:0000269|PubMed:20513427, ECO:0000269|PubMed:21986499, ECO:0000269|PubMed:24530606}.;
Recessive Scores
- pRec
- 0.112
Intolerance Scores
- LoFtool
- 0.658
- RVIS EVS
- -1.23
- RVIS percentile EVS
- 5.56
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.433
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |