Gene Symbol: PHLDA3
Description: pleckstrin homology like domain family A member 3
Alias: TIH1, pleckstrin homology-like domain family A member 3, TDAG51/Ipl homolog 1, pleckstrin homology-like domain, family A, member 2
Species: human
Products:     PHLDA3

Top Publications

  1. Kojima M, Chen Y, Ikeda K, Tsukada Y, Takahashi D, Kawano S, et al. Recommendation of long-term and systemic management according to the risk factors in rectal NETs patients. Sci Rep. 2019;9:2404 pubmed publisher
    ..Recently, we reported that in pancreatic NET patients, a loss of heterozygosity (LOH) in PHLDA3 was associated with poorer prognosis, and that LOH of both PHLDA3 and MEN1 was frequently observed...
  2. Furihata C, Suzuki T. Evaluation of 12 mouse marker genes in rat toxicogenomics public data, Open TG-GATEs: Discrimination of genotoxic from non-genotoxic hepatocarcinogens. Mutat Res. 2019;838:9-15 pubmed publisher
    Previously, we proposed 12 marker genes (Aen, Bax, Btg2, Ccnf, Ccng1, Cdkn1a, Gdf15, Lrp1, Mbd1, Phlda3, Plk2 and Tubb4b) to discriminate mouse genotoxic hepatocarcinogens (GTHC) from non-genotoxic hepatocarcinogens (NGTHC)...
  3. Quanz M, Bender E, Kopitz C, Grünewald S, Schlicker A, Schwede W, et al. Preclinical Efficacy of the Novel Monocarboxylate Transporter 1 Inhibitor BAY-8002 and Associated Markers of Resistance. Mol Cancer Ther. 2018;17:2285-2296 pubmed publisher
    ..i>Mol Cancer Ther; 17(11); 2285-96. ©2018 AACR. ..
  4. Furihata C, Toyoda T, Ogawa K, Suzuki T. Using RNA-Seq with 11 marker genes to evaluate 1,4-dioxane compared with typical genotoxic and non-genotoxic rat hepatocarcinogens. Mutat Res. 2018;834:51-55 pubmed publisher
    ..Previously, we selected 11 marker genes (Aen, Bax, Btg2, Ccnf, Ccng1, Cdkn1a, Lrp1, Mbd1, Phlda3, Plk2, and Tubb4b) to discriminate GTHCs and NGTHCs...
  5. Nelissen E, Dumoulin J, Busato F, Ponger L, Eijssen L, Evers J, et al. Altered gene expression in human placentas after IVF/ICSI. Hum Reprod. 2014;29:2821-31 pubmed publisher
    ..No conflict of interests to declare. Dutch Trial Registry (NTR) number 1298. ..
  6. Lee C, Kang Y, Kim H, Moon A, Kim S. Phlda3, a urine-detectable protein, causes p53 accumulation in renal tubular cells injured by cisplatin. Cell Biol Toxicol. 2015;31:121-30 pubmed publisher
    ..In our previous study, pleckstrin homology-like domain, family A, member 3 (Phlda3) was a most greatly up-regulated molecule downstream from p53, culminating with kidney tubular injury...
  7. Leszczynska K, Foskolou I, Abraham A, Anbalagan S, Tellier C, Haider S, et al. Hypoxia-induced p53 modulates both apoptosis and radiosensitivity via AKT. J Clin Invest. 2015;125:2385-98 pubmed publisher
    ..targets of p53, including inositol polyphosphate-5-phosphatase (INPP5D), pleckstrin domain-containing A3 (PHLDA3), sulfatase 2 (SULF2), B cell translocation gene 2 (BTG2), cytoplasmic FMR1-interacting protein 2 (CYFIP2), and KN ..
  8. Minchenko O, Tsymbal D, Minchenko D, Prylutska S, Hnatiuk O, Prylutskyy Y, et al. Single-walled carbon nanotubes affect the expression of genes associated with immune response in normal human astrocytes. Toxicol In Vitro. 2018;52:122-130 pubmed publisher
    ..Deregulation of lamin B1 expression indicates the possibility of alterations in genome stability following treatment of astrocytes with SWCNTs. Thus, more caution is needed in biomedical application of SWCNTs. ..
  9. Moore G, Ishida M, Demetriou C, Al Olabi L, Leon L, Thomas A, et al. The role and interaction of imprinted genes in human fetal growth. Philos Trans R Soc Lond B Biol Sci. 2015;370:20140074 pubmed publisher
    ..In conclusion, we have found that the expression of key imprinted genes show a strong correlation with fetal growth and that for both genetic and genomics data analyses, it is important not to overlook parent-of-origin effects. ..

More Information


  1. Koso H, Tsuhako A, Lai C, Baba Y, Otsu M, Ueno K, et al. Conditional rod photoreceptor ablation reveals Sall1 as a microglial marker and regulator of microglial morphology in the retina. Glia. 2016;64:2005-24 pubmed publisher
    ..microglia and infiltrating macrophages, we identified microglia-specific genes, including Ak1, Ctsf, Sall1, Phlda3, and Spns2...
  2. Pappas K, Xu J, Zairis S, Resnick Silverman L, Abate F, Steinbach N, et al. p53 Maintains Baseline Expression of Multiple Tumor Suppressor Genes. Mol Cancer Res. 2017;15:1051-1062 pubmed publisher
    ..binds and activates numerous tumor suppressor genes, including PTEN, STK11(LKB1), miR-34a, KDM6A(UTX), FOXO1, PHLDA3, and TNFRSF10B through consensus binding sites in enhancers and promoters...
  3. Arnold D, Gaspar R, da Rocha C, Sangalli J, De Bem T, Corrêa C, et al. Nuclear transfer alters placental gene expression and associated histone modifications of the placental-specific imprinted gene pleckstrin homology-like domain, family A, member 2 (PHLDA2) in cattle. Reprod Fertil Dev. 2017;29:458-467 pubmed publisher
    ..These results suggest that the altered expression of imprinted genes associated with NT are also caused by changes in histone modifications. ..
  4. Mukhopadhyay A, Ravikumar G, Dwarkanath P, Meraaj H, Thomas A, Crasta J, et al. Placental expression of the insulin receptor binding protein GRB10: Relation to human fetoplacental growth and fetal gender. Placenta. 2015;36:1225-30 pubmed publisher
    ..Hence, we speculate that placental GRB10 plays a role in regulating fetoplacental growth and thereby in the pathophysiology of fetal growth restriction in the context of fetal gender. ..
  5. Tunster S, McNamara G, Creeth H, John R. Increased dosage of the imprinted Ascl2 gene restrains two key endocrine lineages of the mouse Placenta. Dev Biol. 2016;418:55-65 pubmed publisher
    ..This "belts and braces" approach demonstrates the importance of genomic imprinting in regulating the size of the placental endocrine compartment for optimal placental development and fetal growth. ..
  6. Tunster S, Creeth H, John R. The imprinted Phlda2 gene modulates a major endocrine compartment of the placenta to regulate placental demands for maternal resources. Dev Biol. 2016;409:251-260 pubmed publisher
    ..Furthermore, this work suggests that Phlda2 manipulates the placenta's demands for maternal resources, a process that must be tightly regulated by epigenetic marks to ensure optimal foetal growth. ..
  7. Qiao M, Wu M, Shi R, Hu W. PHLDA3 impedes somatic cell reprogramming by activating Akt-GSK3β pathway. Sci Rep. 2017;7:2832 pubmed publisher
    ..In this study, we report that PHLDA3, a p53 target gene, functions as a blockage of iPSCs generation by activating the Akt-GSK3β pathway...
  8. Jin F, Qiao C, Luan N, Shang T. The expression of the imprinted gene pleckstrin homology-like domain family A member 2 in placental tissues of preeclampsia and its effects on the proliferation, migration and invasion of trophoblast cells JEG-3. Clin Exp Pharmacol Physiol. 2015;42:1142-51 pubmed publisher
    ..These findings illustrate that PHLDA2 may participate in PE pathogenesis and indicate its potential application in the early diagnosis of PE. ..
  9. Sakata N, Yamaguchi Y, Chen Y, Shimoda M, Yoshimatsu G, Unno M, et al. Pleckstrin homology-like domain family A, member 3 (PHLDA3) deficiency improves islets engraftment through the suppression of hypoxic damage. PLoS ONE. 2017;12:e0187927 pubmed publisher
    ..Pleckstrin homology-like domain family A, member 3 (PHLDA3) is a known suppressor of neuroendocrine tumorigenicity, yet deficiency of this gene increases islet proliferation,..
  10. Yoo N, Kim Y, Lee S. Expressional and mutational analysis of PHLDA3 gene in common human cancers. Pathology. 2011;43:510-1 pubmed publisher
  11. Frank D, Mendelsohn C, Ciccone E, Svensson K, Ohlsson R, Tycko B. A novel pleckstrin homology-related gene family defined by Ipl/Tssc3, TDAG51, and Tih1: tissue-specific expression, chromosomal location, and parental imprinting. Mamm Genome. 1999;10:1150-9 pubmed
    ..Ipl is similar to TDAG51, a gene that is involved in FAS/CD95 expression. Here we describe another gene, Tih1 (TDAG/Ipl homologue 1), with equivalent sequence similarity to Ipl...
  12. Mattes K, Berger G, Geugien M, Vellenga E, Schepers H. CITED2 affects leukemic cell survival by interfering with p53 activation. Cell Death Dis. 2017;8:e3132 pubmed publisher
    ..which was indicated by decreased levels of phosphorylated AKT and altered expression of the AKT-pathway regulators PHLDA3 and SOX4...
  13. Muroi H, Nakajima M, Satomura H, Takahashi M, Yamaguchi S, Sasaki K, et al. Low PHLDA3 expression in oesophageal squamous cell carcinomas is associated with poor prognosis. Anticancer Res. 2015;35:949-54 pubmed
    ..Pleckstrin homology-like domain, family A, member 3 (PHLDA3) has been identified as a direct target gene of p53 and as a potent inhibitor of Akt activation...
  14. Ohki R, Saito K, Chen Y, Kawase T, Hiraoka N, Saigawa R, et al. PHLDA3 is a novel tumor suppressor of pancreatic neuroendocrine tumors. Proc Natl Acad Sci U S A. 2014;111:E2404-13 pubmed publisher
    ..We report here that the genomic region of the PHLDA3 gene undergoes loss of heterozygosity (LOH) at a remarkably high frequency in human PanNETs, and this genetic ..
  15. Kawase T, Ohki R, Shibata T, Tsutsumi S, Kamimura N, Inazawa J, et al. PH domain-only protein PHLDA3 is a p53-regulated repressor of Akt. Cell. 2009;136:535-50 pubmed publisher
    ..We now identify PHLDA3 as a p53 target gene that encodes a PH domain-only protein...