GeneBe

PHLPP1

PH domain and leucine rich repeat protein phosphatase 1, the group of Pleckstrin homology domain containing|Protein phosphatases, Mg2+/Mn2+ dependent

Basic information

Region (hg38): 18:62715541-62980433

Previous symbols: [ "PLEKHE1", "PHLPP" ]

Links

ENSG00000081913 ∙ NCBI:23239 ∙ OMIM:609396 ∙ HGNC:20610 ∙ Uniprot:O60346 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PHLPP1 gene.

  • not_specified (254 variants)
  • not_provided (20 variants)
  • Focal_impaired_awareness_seizure (1 variants)
  • Seizure (1 variants)
  • Attention_deficit_hyperactivity_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PHLPP1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000194449.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
11
clinvar
2
clinvar
 13
missense
250
clinvar
7
clinvar
 257
nonsense
0
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
0
Total 0 0 251 18 2
Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
PHLPP1protein_codingprotein_codingENST00000262719 17264995
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.9990.0007301246690141246830.0000561
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.756918330.8290.000046911022
Missense in Polyphen260358.410.725424223
Synonymous-0.2563693631.020.00002303642
Loss of Function5.95856.10.1430.00000304690

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00005820.0000582
Ashkenazi Jewish0.000.00
East Asian0.0001690.000167
Finnish0.000.00
European (Non-Finnish)0.00004630.0000442
Middle Eastern0.0001690.000167
South Asian0.0001000.0000980
Other0.0001650.000165

dbNSFP

Source: dbNSFP

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 AKT2 and AKT3, 'Ser-660' of PRKCB and 'Ser-657' of PRKCA (PubMed:15808505, PubMed:17386267, PubMed:18162466). Isoform 2 seems to have a major role in regulating Akt signaling in hippocampal neurons (By similarity). 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 suppression of tumor growth. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation (PubMed:18162466). 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 (PubMed:19079341). Dephosphorylates RAF1 inhibiting its kinase activity (PubMed:24530606). May act as a negative regulator of K-Ras signaling in membrane rafts (By similarity). Involved in the hippocampus-dependent long-term memory formation (By similarity). Involved in circadian control by regulating the consolidation of circadian periodicity after resetting (By similarity). Involved in development and function of regulatory T-cells (By similarity). {ECO:0000250|UniProtKB:Q8CHE4, ECO:0000250|UniProtKB:Q9WTR8, ECO:0000269|PubMed:15808505, ECO:0000269|PubMed:17386267, ECO:0000269|PubMed:18162466, ECO:0000269|PubMed:19079341, ECO:0000269|PubMed:21986499, ECO:0000269|PubMed:24530606}.;
Pathway
PI3K-Akt signaling pathway - Homo sapiens (human);Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Signal Transduction;EGFR1;PIP3 activates AKT signaling;Negative regulation of the PI3K/AKT network;Intracellular signaling by second messengers (Consensus)

Recessive Scores

pRec
0.142

Haploinsufficiency Scores

pHI
0.542
hipred
Y
hipred_score
0.639
ghis
0.529

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.715

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Phlpp1
Phenotype
growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; digestive/alimentary phenotype;

Gene ontology

Biological process
regulation of T cell anergy;protein dephosphorylation;apoptotic process;entrainment of circadian clock;regulation of apoptotic process;regulation of MAPK cascade;regulation of JNK cascade;negative regulation of protein kinase B signaling;regulation of p38MAPK cascade
Cellular component
photoreceptor inner segment;cytoplasm;cytosol;nuclear membrane;photoreceptor outer segment membrane
Molecular function
protein serine/threonine phosphatase activity;protein binding;metal ion binding