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PHLPP2 PH domain and leucine rich repeat protein phosphatase 2 [ Homo sapiens (human) ]

Gene ID: 23035, updated on 25-Nov-2025
Official Symbol
PHLPP2provided by HGNC
Official Full Name
PH domain and leucine rich repeat protein phosphatase 2provided by HGNC
Primary source
HGNC:HGNC:29149
See related
Ensembl:ENSG00000040199 MIM:611066; AllianceGenome:HGNC:29149
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
PPM3B; PHLPPL
Summary
Predicted to enable metal ion binding activity and phosphoprotein phosphatase activity. Predicted to be involved in intracellular signal transduction. Located in several cellular components, including cilium; intercellular bridge; and mitotic spindle. [provided by Alliance of Genome Resources, Apr 2025]
Expression
Broad expression in small intestine (RPKM 11.5), colon (RPKM 5.9) and 22 other tissues See more
Orthologs
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See PHLPP2 in Genome Data Viewer
Location:
16q22.2
Exon count:
20
Annotation release Status Assembly Chr Location
RS_2025_08 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (71644924..71724701, complement)
RS_2025_08 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (77462088..77541847, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (71678827..71758604, complement)

Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105371334 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7681 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7682 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr16:71671387-71671938 Neighboring gene uncharacterized LOC124903711 Neighboring gene MARVEL domain containing 3 Neighboring gene Sharpr-MPRA regulatory region 2747 Neighboring gene uncharacterized LOC124903712 Neighboring gene RNA, U6 small nuclear 208, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11076 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:71741784-71742412 Neighboring gene small nucleolar RNA, H/ACA box 70D Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:71756941-71757442 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7684 Neighboring gene adaptor related protein complex 1 subunit gamma 1 Neighboring gene small nucleolar RNA, C/D box 71 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:71808874-71809101 Neighboring gene parathymosin-like

Go to nucleotide: Graphics FASTA GenBank

  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Related articles in PubMed

  1. PHLPP2 Downregulation Contributes to Lung Carcinogenesis Following B[a]P/B[a]PDE Exposure. Huang H, et al. Clin Cancer Res, 2015 Aug 15. PMID 25977341, Free PMC Article
  2. PHLPP2 is regulated by competing endogenous RNA network in pathogenesis of colon cancer. Wu HK, et al. Aging (Albany NY), 2020 Jul 7. PMID 32633726, Free PMC Article
  3. PHLPP2 as a novel metastatic and prognostic biomarker in non-small cell lung cancer patients. Wang H, et al. Thorac Cancer, 2019 Nov. PMID 31571378, Free PMC Article
  4. Integrated Analysis of Ulcerative Colitis Revealed an Association between PHLPP2 and Immune Infiltration. Li T, et al. Dis Markers, 2022. PMID 35308140, Free PMC Article
  5. miR-372 regulates glioma cell proliferation and invasion by directly targeting PHLPP2. Chen X, et al. J Cell Biochem, 2015 Feb. PMID 25160587

See all (88) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. PHLPP2 gene L1016S (rs61733127) and PIK3R1 gene Met326Ile (rs3730089) polymorphisms are associated with the risk of colon and breast cancers.
    Title: PHLPP2 gene L1016S (rs61733127) and PIK3R1 gene Met326Ile (rs3730089) polymorphisms are associated with the risk of colon and breast cancers.
  2. Pleckstrin Homology Domain Leucine-rich Repeat Protein Phosphatase Acts as a Tumor Suppressor in Oral Squamous Cell Carcinoma.
    Title: Pleckstrin Homology Domain Leucine-rich Repeat Protein Phosphatase Acts as a Tumor Suppressor in Oral Squamous Cell Carcinoma.
  3. TRIM22 induces cellular senescence by targeting PHLPP2 in hepatocellular carcinoma.
    Title: TRIM22 induces cellular senescence by targeting PHLPP2 in hepatocellular carcinoma.
  4. PHLPP isoforms differentially regulate Akt isoforms and AS160 affecting neuronal insulin signaling and insulin resistance via Scribble.
    Title: PHLPP isoforms differentially regulate Akt isoforms and AS160 affecting neuronal insulin signaling and insulin resistance via Scribble.
  5. MARCH1 silencing suppresses growth of oral squamous cell carcinoma through regulation of PHLPP2.
    Title: MARCH1 silencing suppresses growth of oral squamous cell carcinoma through regulation of PHLPP2.
  6. Integrated Analysis of Ulcerative Colitis Revealed an Association between PHLPP2 and Immune Infiltration.
    Title: Integrated Analysis of Ulcerative Colitis Revealed an Association between PHLPP2 and Immune Infiltration.
  7. Mutant p53 achieved Gain-of-Function by promoting tumor growth and immune escape through PHLPP2/AKT/PD-L1 pathway.
    Title: Mutant p53 achieved Gain-of-Function by promoting tumor growth and immune escape through PHLPP2/AKT/PD-L1 pathway.
  8. TRIM46 activates AKT/HK2 signaling by modifying PHLPP2 ubiquitylation to promote glycolysis and chemoresistance of lung cancer cells.
    Title: TRIM46 activates AKT/HK2 signaling by modifying PHLPP2 ubiquitylation to promote glycolysis and chemoresistance of lung cancer cells.
  9. MiR-509-3p is oncogenic, targets the tumor suppressor PHLPP2, and functions as a novel tumor adjacent normal tissue based prognostic biomarker in colorectal cancer.
    Title: MiR-509-3p is oncogenic, targets the tumor suppressor PHLPP2, and functions as a novel tumor adjacent normal tissue based prognostic biomarker in colorectal cancer.
  10. Circular RNA circ_0001017 Sensitizes Cisplatin-Resistant Gastric Cancer Cells to Chemotherapy by the miR-543/PHLPP2 Axis.
    Title: Circular RNA circ_0001017 Sensitizes Cisplatin-Resistant Gastric Cancer Cells to Chemotherapy by the miR-543/PHLPP2 Axis.
Submit: New GeneRIF Correction See all GeneRIFs (56)

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer.
EBI GWAS Catalog

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • KIAA0931

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables hydrolase activity IEA
Inferred from Electronic Annotation
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables phosphoprotein phosphatase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein serine/threonine phosphatase activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in hippocampus development IEA
Inferred from Electronic Annotation
more info
  
involved_in intracellular signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
located_in cilium IDA
Inferred from Direct Assay
more info
  
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytoplasm IDA
Inferred from Direct Assay
more info
  
located_in cytoplasm IEA
Inferred from Electronic Annotation
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in intercellular bridge IDA
Inferred from Direct Assay
more info
  
located_in membrane IEA
Inferred from Electronic Annotation
more info
  
located_in mitotic spindle IDA
Inferred from Direct Assay
more info
  
located_in nucleus IEA
Inferred from Electronic Annotation
more info
  
located_in photoreceptor inner segment IEA
Inferred from Electronic Annotation
more info
  
located_in photoreceptor outer segment membrane IEA
Inferred from Electronic Annotation
more info
  
Preferred Names
PH domain leucine-rich repeat-containing protein phosphatase 2
Names
protein phosphatase, Mg2+/Mn2+ dependent 3B
NP_001275932.1
NP_055835.2

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001289003.1 → NP_001275932.1  PH domain leucine-rich repeat-containing protein phosphatase 2 isoform 2

    See identical proteins and their annotated locations for NP_001275932.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR and lacks an in-frame exon in the central coding region, compared to variant 1. The encoded isoform (2) is shorter, compared to isoform 1.
    Source sequence(s)
    AB023148, AC009097, BC129927
    Consensus CDS
    CCDS73910.1
    UniProtKB/TrEMBL
    H3BMS5
    Related
    ENSP00000377159.2, ENST00000393524.6
    Conserved Domains (5) summary
    cd00116
    Location:444 → 660
    LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...
    cd00143
    Location:717 → 966
    PP2Cc; Serine/threonine phosphatases, family 2C, catalytic domain; The protein architecture and deduced catalytic mechanism of PP2C phosphatases are similar to the PP1, PP2A, PP2B family of protein Ser/Thr phosphatases, with which PP2C shares no sequence ...
    cd13322
    Location:149 → 243
    PH_PHLPP-like; PH domain leucine-rich repeat protein phosphatase family Pleckstrin homology-like domain
    sd00033
    Location:442 → 461
    LRR_RI; leucine-rich repeat [structural motif]
    pfam13855
    Location:572 → 636
    LRR_8; Leucine rich repeat

  2. NM_015020.3 → NP_055835.2  PH domain leucine-rich repeat-containing protein phosphatase 2 isoform 1

    See identical proteins and their annotated locations for NP_055835.2

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AC009097, BC129927, BX647823
    Consensus CDS
    CCDS32479.1
    UniProtKB/Swiss-Prot
    A1L374, Q6ZVD8, Q9NV17, Q9Y2E3
    UniProtKB/TrEMBL
    H3BMS5
    Related
    ENSP00000457991.1, ENST00000568954.5
    Conserved Domains (6) summary
    cd00116
    Location:313 → 606
    LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...
    cd00143
    Location:784 → 1033
    PP2Cc; Serine/threonine phosphatases, family 2C, catalytic domain; The protein architecture and deduced catalytic mechanism of PP2C phosphatases are similar to the PP1, PP2A, PP2B family of protein Ser/Thr phosphatases, with which PP2C shares no sequence ...
    cd13322
    Location:149 → 243
    PH_PHLPP-like; PH domain leucine-rich repeat protein phosphatase family Pleckstrin homology-like domain
    sd00033
    Location:482 → 503
    LRR_RI; leucine-rich repeat [structural motif]
    pfam12799
    Location:645 → 685
    LRR_4; Leucine Rich repeats (2 copies)
    pfam13855
    Location:645 → 703
    LRR_8; Leucine rich repeat

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2025_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000016.10 Reference GRCh38.p14 Primary Assembly

    Range
    71644924..71724701 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060940.1 Alternate T2T-CHM13v2.0

    Range
    77462088..77541847 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q6ZVD8.3 GenPept UniProtKB/Swiss-Prot:Q6ZVD8

Gene LinkOut

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