PLAGL1 (Pleomorphic adenoma gene-like 1)

2007-08-01   Abbas Abdollahi  

Sbarro Institute for Cancer Research, Molecular Medicine, College of Science, Technology, BioLife Sciences Building, Suite 446, Temple University, 1900 North 12th Street, Philadelphia, PA 19122, USA

Identity

HGNC
PLAGL1
LOCATION
6q24.2
LOCUSID
5325
ALIAS
LOT1,ZAC,ZAC1
FUSION GENES
Show Gene Fusions

DNA/RNA

Atlas Image
Schematic view of the PLAGL1 gene. A. The six exons, shown in red, are 326; 72; 1443; 75; 475; 2380 bp, respectively. The introns are approximately 39; 2.6; 4.2; 12.5; 5.5 kbp in size, respectively. B. The figure shows three splice variants of PLAGL1; the exons are shown as a box.

Description

The genome is about 64 kbp with six exons and five introns. The major mRNA transcript is about 4.7 kb in size.

Transcription

At least three splicing variants (See Figure, above)

Proteins

Description

The PLAGL1 protein is a seven C2H2-type zinc finger protein. The seven zinc finger domain is located at the amino terminal region, from the amino acid residue 1 to 210. Additional features of note are proline and glutamine rich regions at the carboxyl terminal portion (residues 220 to 444). There are two nuclear localization signals at the amino terminal region.

Expression

Ovary, breast, brain, liver, spleen, thymus, prostate, uterus, testis, intestine, colon, leukocytes.

Localisation

Nuclear

Function

The PLAGL1 protein is a candidate tumor suppressor gene and has been shown to have transactivation and DNA-binding activity and to exhibit antiproliferative activities.

Homology

Homologous to the mouse and Rat plagl1 and to the human PLAG1 and PLAGL2 proteins.

Mutations

Note

Mutation has not been found in the PLAGL1 coding region.

Implicated in

Entity name
Carcinogenicity
Note
Alteration of the gene expression was found to be a potential genetic event silencing the PLAGL1 gene in cancers such as breast primary tumors, ovarian primary tumors and tumor-derived cell lines, basal cell carcinoma, head and neck squamous cell carcinoma (HNSCC), and extraskeletal myxoid chondrosarcoma (EMC). Several mechanisms have been shown to regulate the PLAGL1 gene expression, including growth factor receptor activation, epigenetic factors, maternal imprinting, and loss of heterozygosity (LOH). Allelic deletion of 6q24-q25, the PLAGL1 locus, in the tumor tissues has been shown in the cancers of ovarian, breast, HNSCC, and pheochromocytomas (PCCs).
Disease
Cancer
Entity name
Transient Neonatal Diabetes (TNDM)
Note
Initial reports suggested that transient neonatal diabetes mellitus (TNDM), a rare condition characterized in the patients by intrauterine growth retardation, dehydration, failure to thrive, and hyperglycemia due to a lack of normal insulin secretion, is associated with paternal uniparental disomy (UPD) of chromosome 6 (UPD 6). Later studies showed the involvement of an imprinted gene in this disease within the chromosomal region 6q24.1-q24.3 between markers D6S1699 and D6S1010. Analysis of the CpG islands in the TNDM critical region, using DNA from TNDM patients with paternal UPD 6 and normal controls, suggested PLAGL1/LOT1/ZAC1 as a candidate imprinted gene for this disease.
Disease
Diabetes mellitus

Article Bibliography

Pubmed IDLast YearTitleAuthors

Other Information

Locus ID:

NCBI: 5325
MIM: 603044
HGNC: 9046
Ensembl: ENSG00000118495

Variants:

dbSNP: 5325
ClinVar: 5325
TCGA: ENSG00000118495
COSMIC: PLAGL1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000118495ENST00000354765Q9UM63
ENSG00000118495ENST00000360537Q9UM63
ENSG00000118495ENST00000367571Q9UM63
ENSG00000118495ENST00000367572Q9UM63
ENSG00000118495ENST00000392307Q68DN7
ENSG00000118495ENST00000416623Q9UM63
ENSG00000118495ENST00000417959Q9UM63
ENSG00000118495ENST00000437412Q9UM63
ENSG00000118495ENST00000444202Q9UM63
ENSG00000118495ENST00000625622Q9UM63
ENSG00000118495ENST00000626294A0A0D9SGF7
ENSG00000118495ENST00000626373A1YLA2
ENSG00000118495ENST00000626462A0A0D9SFM8
ENSG00000118495ENST00000627449A0A0D9SEQ4
ENSG00000118495ENST00000628651A0A0D9SFI7
ENSG00000118495ENST00000629195A1YLA1
ENSG00000118495ENST00000647880Q9UM63
ENSG00000118495ENST00000647988A0A3B3IRN7
ENSG00000118495ENST00000649211Q9UM63
ENSG00000118495ENST00000649307Q9UM63
ENSG00000118495ENST00000650125Q9UM63

Expression (GTEx)

0
10
20
30
40
50
60
70
Adipose - Subcutaneous
Adipose - Visceral
Adrenal Gland
Artery - Aorta
Artery - Tibial
Bladder
Brain - Amygdala
Brain - Anterior cingulate cortex
Brain - Caudate
Brain - Cerebellar Hemisphere
Brain - Cerebellum
Brain - Cortex
Brain - Frontal Cortex
Brain - Hippocampus
Brain - Hypothalamus
Brain - Nucleus accumbens
Brain - Putamen
Brain - Spinal cord
Brain - Substantia nigra
Breast - Mammary Tissue
Cells - Cultured fibroblasts
Cells - EBV - transformed lymphocytes
Cervix - Ectocervix
Cervix - Endocervix
Colon - Sigmoid
Colon - Transverse
Esophagus - Gastroesophageal Junction
Esophagus - Mucosa
Esophagus - Muscularis
Fallopian Tube
Heart - Atrial Appendage
Heart - Left Ventricle
Kidney - Cortex
Kidney - Medulla
Liver
Lung
Minor Salivary Gland
Muscle - Skeletal
Nerve - Tibial
Ovary
Pancreas
Pituitary
Prostate
Skin - Not Sun Exposed
Skin - Sun Exposed
Small Intestine - Terminal Ileum
Spleen
Stomach
Testis
Thyroid
Uterus
Vagina
Whole Blood

Pathways

PathwaySourceExternal ID
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Transcriptional Regulation by TP53REACTOMER-HSA-3700989
TP53 Regulates Transcription of Cell Cycle GenesREACTOMER-HSA-6791312
TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertainREACTOMER-HSA-6804115

References

Pubmed IDYearTitleCitations
385810342024CNS tumors with PLAGL1-fusion: beyond ZFTA and YAP1 in the genetic spectrum of supratentorial ependymomas.0
386398532024Central nervous system embryonal tumors with EWSR1-PLAGL1 rearrangements reclassified as INI-1 deficient tumors at relapse.0
385810342024CNS tumors with PLAGL1-fusion: beyond ZFTA and YAP1 in the genetic spectrum of supratentorial ependymomas.0
386398532024Central nervous system embryonal tumors with EWSR1-PLAGL1 rearrangements reclassified as INI-1 deficient tumors at relapse.0
364374152023Amplification of the PLAG-family genes-PLAGL1 and PLAGL2-is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification.8
366002082023PLAGL1 is associated with prognosis and cell proliferation in pancreatic adenocarcinoma.1
364374152023Amplification of the PLAG-family genes-PLAGL1 and PLAGL2-is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification.8
366002082023PLAGL1 is associated with prognosis and cell proliferation in pancreatic adenocarcinoma.1
343552562021Recurrent fusions in PLAGL1 define a distinct subset of pediatric-type supratentorial neuroepithelial tumors.24
343552562021Recurrent fusions in PLAGL1 define a distinct subset of pediatric-type supratentorial neuroepithelial tumors.24
326782672020Gene expression profiling identifies the role of Zac1 in cervical cancer metastasis.11
326934312020Imprinting aberrations of SNRPN, ZAC1 and INPP5F genes involved in the pathogenesis of congenital heart disease with extracardiac malformations.7
331719052020Transcription Factor PLAGL1 Is Associated with Angiogenic Gene Expression in the Placenta.6
326782672020Gene expression profiling identifies the role of Zac1 in cervical cancer metastasis.11
326934312020Imprinting aberrations of SNRPN, ZAC1 and INPP5F genes involved in the pathogenesis of congenital heart disease with extracardiac malformations.7

Citation

Abbas Abdollahi

PLAGL1 (Pleomorphic adenoma gene-like 1)

Atlas Genet Cytogenet Oncol Haematol. 2007-08-01

Online version: http://atlasgeneticsoncology.org/gene/41737/meetings/js/lib/hgnc