PLAGL1 (Pleomorphic adenoma gene-like 1)

2007-08-01 Abbas Abdollahi Affiliation

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

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 ID	Last Year	Title	Authors
17063461	2007	LOT1 (ZAC1/PLAGL1) and its family members: mechanisms and functions.	Abdollahi A et al
12473647	2003	LOT1 (PLAGL1/ZAC1), the candidate tumor suppressor gene at chromosome 6q24-25, is epigenetically regulated in cancer.	Abdollahi A et al
10936046	2000	A novel imprinted gene, HYMAI, is located within an imprinted domain on human chromosome 6 containing ZAC.	Arima T et al
15888726	2005	ZAC, LIT1 (KCNQ1OT1) and p57KIP2 (CDKN1C) are in an imprinted gene network that may play a role in Beckwith-Wiedemann syndrome.	Arima T et al
16575187	2006	Establishment of the primary imprint of the HYMAI/PLAGL1 imprint control region during oogenesis.	Arima T et al
16928428	2006	The human HYMAI/PLAGL1 differentially methylated region acts as an imprint control region in mice.	Arima T et al
17178896	2006	Peroxisome proliferator-activated receptor gamma is a Zac target gene mediating Zac antiproliferation.	Barz T et al
16179495	2005	The candidate tumor suppressor gene ZAC is involved in keratinocyte differentiation and its expression is lost in basal cell carcinomas.	Basyuk E et al
11313869	2001	Alternative splicing of the imprinted candidate tumor suppressor gene ZAC regulates its antiproliferative and DNA binding activities.	Bilanges B et al
12711370	2003	Developmental expression of the cell cycle and apoptosis controlling gene, Lot1, in the rat cerebellum and in cultures of cerebellar granule cells.	Ciani E et al
16061485	2005	Cyclic AMP-mediated regulation of transcription factor Lot1 expression in cerebellar granule cells.	Contestabile A et al
15581945	2004	Altered expression and loss of heterozygosity of the LOT1 gene in ovarian cancer.	Cvetkovic D et al
9795221	1998	Delayed up-regulation of Zac1 and PACAP type I receptor after transient focal cerebral ischemia in mice.	Gillardon F et al
11888928	2002	The tumorigenic diversity of the three PLAG family members is associated with different DNA binding capacities.	Hensen K et al
16809786	2006	Multitasking C2H2 zinc fingers link Zac DNA binding to coordinated regulation of p300-histone acetyltransferase activity.	Hoffmann A et al
11360197	2001	Enhancement of p53-dependent gene activation by the transcriptional coactivator Zac1.	Huang SM et al
10669760	2000	Mouse Zac1, a transcriptional coactivator and repressor for nuclear receptors.	Huang SM et al
15751035	2005	Epigenetic silencing of the imprinted gene ZAC by DNA methylation is an early event in the progression of human ovarian cancer.	Kamikihara T et al
10655556	2000	The cell cycle control gene ZAC/PLAGL1 is imprinted--a strong candidate gene for transient neonatal diabetes.	Kamiya M et al
9722527	1998	Transcriptional activation capacity of the novel PLAG family of zinc finger proteins.	Kas K et al
15054737	2004	Loss of expression of ZAC/LOT1 in squamous cell carcinomas of head and neck.	Koy S et al
11935319	2002	Relaxation of imprinted expression of ZAC and HYMAI in a patient with transient neonatal diabetes mellitus.	Mackay DJ et al
11156367	2000	The expression of the antiproliferative gene ZAC is lost or highly reduced in nonfunctioning pituitary adenomas.	Pagotto U et al
10757814	2000	Zac1 (Lot1), a potential tumor suppressor gene, and the gene for epsilon-sarcoglycan are maternally imprinted genes: identification by a subtractive screen of novel uniparental fibroblast lines.	Piras G et al
16112421	2005	The PLAGL1 gene is down-regulated in human extraskeletal myxoid chondrosarcoma tumors.	Poulin H et al
12119104	2002	The mouse Zac1 locus: basis for imprinting and comparison with human ZAC.	Smith RJ et al
9184226	1997	Regulation of apoptosis and cell cycle arrest by Zac1, a novel zinc finger protein expressed in the pituitary gland and the brain.	Spengler D et al
11578877	2001	Expression pattern of Zac1 mouse gene, a new zinc-finger protein that regulates apoptosis and cellular cycle arrest, in both adult brain and along development.	Valente T et al
15350644	2004	Zac1 is up-regulated in neural cells of the limbic system of mouse brain following seizures that provoke strong cell activation.	Valente T et al
15844099	2005	Zac1 is expressed in progenitor/stem cells of the neuroectoderm and mesoderm during embryogenesis: differential phenotype of the Zac1-expressing cells during development.	Valente T et al
17341487	2007	Tissue-specific imprinting of the ZAC/PLAGL1 tumour suppressor gene results from variable utilization of monoallelic and biallelic promoters.	Valleley EM et al
17084362	2006	Zac1 regulates an imprinted gene network critically involved in the control of embryonic growth.	Varrault A et al
17697379	2007	DFsn collaborates with Highwire to down-regulate the Wallenda/DLK kinase and restrain synaptic terminal growth.	Wu C et al
17376404	2007	Physical and functional interactions of human papillomavirus E2 protein with nuclear receptor coactivators.	Wu MH et al

Other Information

Locus ID:

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

Variants:

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

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000118495	ENST00000354765	Q9UM63
ENSG00000118495	ENST00000360537	Q9UM63
ENSG00000118495	ENST00000367571	Q9UM63
ENSG00000118495	ENST00000367572	Q9UM63
ENSG00000118495	ENST00000392307	Q68DN7
ENSG00000118495	ENST00000416623	Q9UM63
ENSG00000118495	ENST00000417959	Q9UM63
ENSG00000118495	ENST00000437412	Q9UM63
ENSG00000118495	ENST00000444202	Q9UM63
ENSG00000118495	ENST00000625622	Q9UM63
ENSG00000118495	ENST00000626294	A0A0D9SGF7
ENSG00000118495	ENST00000626373	A1YLA2
ENSG00000118495	ENST00000626462	A0A0D9SFM8
ENSG00000118495	ENST00000627449	A0A0D9SEQ4
ENSG00000118495	ENST00000628651	A0A0D9SFI7
ENSG00000118495	ENST00000629195	A1YLA1
ENSG00000118495	ENST00000647880	Q9UM63
ENSG00000118495	ENST00000647988	A0A3B3IRN7
ENSG00000118495	ENST00000649211	Q9UM63
ENSG00000118495	ENST00000649307	Q9UM63
ENSG00000118495	ENST00000650125	Q9UM63

Expression (GTEx)

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

Pathway	Source	External ID
Gene Expression	REACTOME	R-HSA-74160
Generic Transcription Pathway	REACTOME	R-HSA-212436
Transcriptional Regulation by TP53	REACTOME	R-HSA-3700989
TP53 Regulates Transcription of Cell Cycle Genes	REACTOME	R-HSA-6791312
TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain	REACTOME	R-HSA-6804115

References

Pubmed ID	Year	Title	Citations
38581034	2024	CNS tumors with PLAGL1-fusion: beyond ZFTA and YAP1 in the genetic spectrum of supratentorial ependymomas.	0
38639853	2024	Central nervous system embryonal tumors with EWSR1-PLAGL1 rearrangements reclassified as INI-1 deficient tumors at relapse.	0
38581034	2024	CNS tumors with PLAGL1-fusion: beyond ZFTA and YAP1 in the genetic spectrum of supratentorial ependymomas.	0
38639853	2024	Central nervous system embryonal tumors with EWSR1-PLAGL1 rearrangements reclassified as INI-1 deficient tumors at relapse.	0
36437415	2023	Amplification of the PLAG-family genes-PLAGL1 and PLAGL2-is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification.	8
36600208	2023	PLAGL1 is associated with prognosis and cell proliferation in pancreatic adenocarcinoma.	1
36437415	2023	Amplification of the PLAG-family genes-PLAGL1 and PLAGL2-is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification.	8
36600208	2023	PLAGL1 is associated with prognosis and cell proliferation in pancreatic adenocarcinoma.	1
34355256	2021	Recurrent fusions in PLAGL1 define a distinct subset of pediatric-type supratentorial neuroepithelial tumors.	24
34355256	2021	Recurrent fusions in PLAGL1 define a distinct subset of pediatric-type supratentorial neuroepithelial tumors.	24
32678267	2020	Gene expression profiling identifies the role of Zac1 in cervical cancer metastasis.	11
32693431	2020	Imprinting aberrations of SNRPN, ZAC1 and INPP5F genes involved in the pathogenesis of congenital heart disease with extracardiac malformations.	7
33171905	2020	Transcription Factor PLAGL1 Is Associated with Angiogenic Gene Expression in the Placenta.	6
32678267	2020	Gene expression profiling identifies the role of Zac1 in cervical cancer metastasis.	11
32693431	2020	Imprinting 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/css/gene-fusions/teaching-explorer/