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PRDM1 (PR domain containing 1, with ZNF domain)

Written2011-09Wayne Tam
Department of Pathology, Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_namesBLIMP1
PR domain containing 1, with ZNF domain
PR domain 1
Alias_symbol (synonym)PRDI-BF1
Other aliasBLIMP-1
HGNC (Hugo) PRDM1
LocusID (NCBI) 639
Atlas_Id 41831
Location 6q21  [Link to chromosome band 6q21]
Location_base_pair Starts at 106086320 and ends at 106109939 bp from pter ( according to hg19-Feb_2009)  [Mapping PRDM1.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
LOC100507412 (-) / PRDM1 (6q21)PRDM1 (6q21) / SLC22A16 (6q21)RNF217 (6q22.31) / PRDM1 (6q21)

DNA/RNA

 
  Figure 1.
Description The gene encompasses 23,6 kb DNA in humans, from 106534195 to 106557814 (hg19-Feb, 2009) in the long arm of chromosome 6. It encodes 7 exons. The open reading frame spans all 7 exons.
Transcription The mRNAs encoded by PRDM1 have two transcript isoforms, PRDM1alpha and PRDM1beta, which are 5164 and 4675 bp long, respectively. The shorter isoform is generated by usage of the alternative promoter located in intron 3 and contains a different 5' untranslated region. It lacks the 5' inframe portion of the coding region present in PRDM1alpha. A deletion exon 6 (exon 7 in mice) variant has also been described (Schmidt et al., 2008).
Pseudogene None.

Protein

Description PRDM1alpha is the larger isoform and contains 825 amino acids, with a predicted molecular weight of 92 kD. It has a PR domain at the N-terminal portion (86-207 aa) of the protein, which is related to the SET domain (SM00317, SMART) found in many histone methyltransferases. In contrast to bona fide SET-domain proteins, the PR domain in PRDM1 does not possess intrinsic histone methyltransferase activity. Five C2H2-type zinc fingers (SM00355, SMART), which represent the DNA binding domain, are present at the C-terminal portion of the protein (575-707 aa). The middle part of PRDM1 (about 300-400 aa) is rich in proline and serine. PRDM1beta lacks the N-terminal 101 amino acids of the PRDM1alpha, and has a truncated PR domain. PRDM1beta has been shown to be functionally impaired in its transcriptional repression activity (Gyory et al., 2003). The proximal 3 zinc fingers in PRDM1/Blimp-1 delta exon 6 variant are disrupted (Schmidt et al., 2008). This protein variant has auto-regulatory potential through negative regulation of PRDM1/Blimp-1 expression and functions.
 
  Figure 2.
Expression PRDM1/Blimp-1 is expressed in several tissues and organs, including hematopoietic tissues, skin, central nervous system, testis and gut. Within the hematopoitic system, PRDM1/Blimp-1 is expressed in plasma cells, B cells, T cells, natural killer cells, monocytes, granulocytes and dendritic cells. In the B cell population, PRDM1/Blimp-1 starts to be expressed when they are committed to undergo terminal differentiation (Cattoretti et al., 2005). Consistent with its expression in normal lymphoid cells, PRDM1 is also expressed in 100% of multiple myeloma, and in various frequency in B and T lymphomas (Garcia et al., 2006; D'Costa et al., 2009). PRDM1/Blimp-1 expression is regulated by a number of transcription activators and repressors (Martins and Calame, 2008). MicroRNAs have also been implicated in the down-regulation of PRDM1 in both normal germinal center B cells (Malumbres et al., 2009; Zhang et al., 2009; Gururajan et al., 2010) and in neoplastic lymphoid cells (Nie et al., 2008; Nie et al., 2010). Among PRDM1 isoforms, PRDM1alpha is the most abundantly expressed, although relative abundance between PRDM1alpha and PRDM1beta may vary between cell types (Garcia et al., 2006). PRDM1/Blimp-1 delta 6 isoform is preferentially expressed in resting B cells (Schmidt et al., 2008).
Localisation Nuclear.
Function Mechanisms of action
PRDM1/Blimp-1 is a transcription repressor that binds to specific DNA sequences through its zinc fingers, and functions as a scaffold for recruiting co-repressors that catalyze histone modifications. It has no known intrinsic histone methyltransferase activity. PRDM1/blimp-1 has been shown to mediate transcriptional silencing via interactions with H3 lysine methyltransferase G9a (Gyory et al., 2004), histone deacetylases HDAC1 and HDAC2 (Yu et al., 2000), and H3 lysine demethylase LSD1 (Su et al., 2009). PRDM1 can also tether Groucho family of transcription factors to mediate repression of gene transcription (Ren et al., 1999). Interaction of PRDM1/Blimp-1 with these co-repressors is mediated through the proline/serine rich domain and/or the zinc fingers. PRDM1 exerts its biological functions by repressing expressions of various target genes, which can be cell-type specific. For example, PRDM1/Blimp-1 mediates cell-cycle arrest in B cells by repressing c-myc, and in CD4 positive helper T cells by inhibiting expressions of IL-2 and Fos, an IL-2 activator (Martins and Calame, 2008).
Biologic functions
PRDM1 was originally identified as a novel repressor of human beta-interferon gene expression called PRDI-BF1 (positive regulatory domain I binding factor 1) (Keller and Maniatis, 1991). Later Blimp-1 (B lymphocyte-induced maturation protein), which represents the murine homolog of PRDI-BF1(Huang, 1994), was discovered as a protein the enforced expression of which was sufficient to drive plasma cell differentiation of a mouse lymphoma cell line with an activated B cell phenotype (Turner et al., 1994). Studies since then have revealed a role of PRDM1/Blimp-1 in multiple cell types.
PRDM1/Blimp-1 is the master regulator of plasma cell differentiation, critical for the generation of immunoglobulin-secreting plasma cells and maintenance of long-lived plasma cells (Shapiro-Shelef et al., 2003; Shapiro-Shelef et al., 2005; Martins and Calame, 2008). It mediates terminal B cell differentiation by extinguishing gene programs related to B cell signaling and proliferation (Shaffer et al., 2002), and allowing induction of XBP1 which coordinates phenotypic changes, including expansion of endoplasmic reticulum and increased protein synthesis, that define the plasma cell phenotype (Shaffer et al., 2004).
PRDM1/Blimp-1 is also required for T cell homeostasis (Kallies et al., 2006; Martins et al., 2006; Calame, 2010). It attenuates proliferation and survival of CD4 positive helper T cells by repressing IL-2-dependent activation; inhibits Th1 differentiation by down-regulating IFNgamma, Tbx21 and BCL6; and antagonizes BCL6-dependent follicular T cell differentiation. PRDM1/Blimp-1 also plays critical role in the differentiation of CD8-positive T cells.
Besides its critical functions in B and T cells, PRDM1/Blimp-1 promotes differentiation of macrophages (Chang et al., 2000). It is also important for homeostatic development of dendritic cells as well as dendritic cell maturation (Chan et al., 2009). PRDM1/Blimp-1 negatively regulates NK cell activation by suppressing effector cytokine production (Smith et al., 2010).
In the non-hematopoietic cell types, PRDM1/Blimp-1 plays an important role in the terminal differentiation of keratinocytes (Magnusdottir et al., 2007) and sebaceous cells (Sellheyer and Krahl, 2010). It also regulates postnatal reprogramming of intestinal enterocytes (Harper et al., 2011).
Furthermore, PRDM1/Blimp-1 is required in embryonic developmental cell fate specification and organ morphogenesis, as demonstrated by mouse and zebrafish model systems (Bikoff et al., 2009). Blimp-1 specifies cell fate of primordial germ cells (Vincent et al., 2005), neural crests and neuron progenitors (Roy and Ng, 2004), and also muscle fiber identity (Baxendale et al., 2004; Hofsten et al., 2008). Blimp-1 is also critical for the normal development of the cardiovascular system, forelimbs and vibrissae (Robertson et al., 2007).
Homology PRDM1 is conserved in chimpanzee, dog, cow, mouse, rat, chicken and zebrafish.

Mutations

Somatic Somatic mutations have been identified in diffuse large B cell lymphomas (DLBCL) at a frequency of about 8 to 23% (Tam et al., 2006; Pasqualucci et al., 2006; Mandelbaum et al., 2010). One group did not detect mutations in 82 cases of DLBCLs in the Chinese population, suggesting geographic differences in PRDM1 mutations in DLBCL (Liu et al., 2007). PRDM1 mutations are exclusively detected in about 24 to 35% of the activated B cell(ABC)/non-germinal center B cell (non-GCB) subtype of DLBCL, and have not been identified in GCB-like DLBCL. In addition, about 20% of primary DLBCL of the central nervous system, a subtype of DLBCL, harbor PRDM1 mutations (Courts et al., 2008). PRDM1 mutation was also found in one case of primary effusion lymphoma out of 2 cases analyzed (Tate et al., 2007). The types of somatic mutations seen in PRDM1 include splice site mutations, frameshift insertion/deletion and less frequently, nonsense and missense mutations. The vast majority of these mutations result in inactivating truncations lacking one or more of the critical domains including PR, proline rich region, and the zinc fingers. Missense mutations have been demonstrated to affect PRDM1 functions (Mandelbaum et al., 2010). Most of the somatic mutations (about 90%) are associated with inactivation of the other allele by deletion, consistent with biallelic inactivation characteristic of a tumor suppressor gene. Mutations in acute leukemias and solid tumors have been not identified (Hangaishi and Kurokawa, 2010).

Implicated in

Note
  
Entity Diffuse large B cell lymphomas
Prognosis Diffuse large B cell lymphoma (DLBCL) with partial plasmablastic differentiation, as indicated by PRDM1 expression, has a worse overall and failure free survival compared to conventional DLBLC without PRDM1 expression, suggesting that PRDM1 may be useful as a prognostic marker in DLBCL (Montes-Moreno et al., 2010).
Expression of PRDM1beta has been implicated as a poor prognostic marker in DBLCL treated with CHOP (but not R-CHOP) and in T cell lymphomas. Resistance to chemotherapeutic agents mediated by PRDM1beta has been proposed as a potential mechanism (Liu et al., 2007; Zhao et al., 2008).
Oncogenesis Inactivation or down-regulation of PRDM1 appears to be an important event in the pathogenesis of DLBCLs of the ABC/non-GCB subtype. In about 50% of DLBCLs of this subtype, PRDM1 is inactivated by truncating or missense mutations, biallele gene deletions or transcription repression by a constitutively active, translocated BCL6 (Mandelbaum et al., 2010). In non-GCB/ABC-like DLBCL without these genetic lesions, asynchronous PRDM1 mRNA and protein expressions have been observed, suggesting a post-transcriptional down-regulation (Mandelbaum et al., 2010; Nie et al., 2010). MicroRNAs have been postulated as a potential mechanism of down-regulation (Nie et al., 2010). All these findings are consistent with a tumor suppressor role of PRDM1 in DLBCL. In addition, PRDM1/Blimp-1 has been directly demonstrated in mouse models to function as a tumor suppressor gene (Calado et al., 2010; Mandelbaum et al., 2010). Mice lacking PRDM1/Blimp-1 are predisposed to develop lymphoproliferative disorders resembling human ABC-like DLBCL. One of these mouse models also demonstrated a cooperative pathogenic effect between PRDM1 inactivation and constitutive NF-kB activation. These findings suggest that PRDM1 inactivation contributes to the pathogenesis of ABC-like DLBCL by inhibiting terminal B cell differentiation induced by constitutive canonical NF-kB activation characteristically present in this lymphoma type.
  
  
Entity Natural killer cell neoplasms
Oncogenesis PRDM1 is frequently (about 40%) deleted as part of a minimal deleted region in aggressive natural killer (NK) cell neoplasms such as extranodal NK/T cell lymphomas, nasal type, and aggressive NK cell leukemias (Iqbal et al., 2009; Karube et al., 2011). This deletion is generally associated with a down-regulation of PRDM1 expression, associated with focal hypermethylation of the 5' region of the other PRDM1 allele. Enforced expression of PRDM1 in NK lymphoma cell lines results in cell cycle arrest and apoptosis (Karube et al., 2011). Inactivating nonsense mutations have also been found in two NK cell lines and one clinical NK neoplasm (Iqbal et al., 2009; Karube et al., 2011). These findings indicate a tumor suppressor role of PRDM1 in NK cell neoplasms.
  
  
Entity Radiation-therapy induced second malignant neoplasms
Prognosis Pediatric Hodgkin lymphoma patients treated by radiation are at risk of developing second malignancies later in life. Two SNP variants were identified at 6q21 (intergenic between ATG5 and PRDM1) in a genome wide association study that are associated with increased risk of second neoplasms for pediatric patients with Hodgkin lymphoma who received radiation therapy. These variants correlate with decreased basal PRDM1 expression and reduced PRDM1 induction after radiation therapy, implicating PRDM1 in the etiology of radiation-therapy induced second malignancies (Best et al., 2011).
  
  
Entity Plasma cell myeloma
Oncogenesis PRDM1 is consistently expressed in plasma cell myeloma. A plasmacytoma transgenic mouse model demonstrates that PRDM1/Blimp-1 is not a tumor suppressor gene in myeloma. Instead, it appears to be a limiting factor in plasma cell transformation (D'Costa et al., 2009). Reducing PRDM1/Blimp-1 dosage decreases incidence of plasmacytoma in mice but does not cause reduction of normal plasma cells in nontransgenic mice. Loss of PRDM1/Blimp-1 eliminates plasmacytoma development.
  

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Citation

This paper should be referenced as such :
Tam, W
PRDM1 (PR domain containing 1, with ZNF domain)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(2):135-140.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/PRDM1ID41831ch6q21.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 6 ]
  Aggressive natural killer leukemia (ANKL)
del(6q)
Double Hit Lymphoma (DHL)::Triple Hit Lymphoma (THL)
i(6)(p10)
Plasmablastic lymphoma (PBL)
t(2;6)(p12;p25) IRF4/IGK::t(6;14)(p25;q32) IRF4/IGH::t(6;22)(p25;q11) IRF4/IGL


External links

Nomenclature
HGNC (Hugo)PRDM1   9346
Cards
AtlasPRDM1ID41831ch6q21
Entrez_Gene (NCBI)PRDM1  639  PR/SET domain 1
AliasesBLIMP1; PRDI-BF1
GeneCards (Weizmann)PRDM1
Ensembl hg19 (Hinxton)ENSG00000057657 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000057657 [Gene_View]  chr6:106086320-106109939 [Contig_View]  PRDM1 [Vega]
ICGC DataPortalENSG00000057657
TCGA cBioPortalPRDM1
AceView (NCBI)PRDM1
Genatlas (Paris)PRDM1
WikiGenes639
SOURCE (Princeton)PRDM1
Genetics Home Reference (NIH)PRDM1
Genomic and cartography
GoldenPath hg38 (UCSC)PRDM1  -     chr6:106086320-106109939 +  6q21   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PRDM1  -     6q21   [Description]    (hg19-Feb_2009)
EnsemblPRDM1 - 6q21 [CytoView hg19]  PRDM1 - 6q21 [CytoView hg38]
Mapping of homologs : NCBIPRDM1 [Mapview hg19]  PRDM1 [Mapview hg38]
OMIM603423   
Gene and transcription
Genbank (Entrez)AF084199 AK129768 AK289556 AK301341 AL832963
RefSeq transcript (Entrez)NM_001198 NM_182907
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)PRDM1
Cluster EST : UnigeneHs.436023 [ NCBI ]
CGAP (NCI)Hs.436023
Alternative Splicing GalleryENSG00000057657
Gene ExpressionPRDM1 [ NCBI-GEO ]   PRDM1 [ EBI - ARRAY_EXPRESS ]   PRDM1 [ SEEK ]   PRDM1 [ MEM ]
Gene Expression Viewer (FireBrowse)PRDM1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)639
GTEX Portal (Tissue expression)PRDM1
Human Protein AtlasENSG00000057657-PRDM1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO75626   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO75626  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO75626
Splice isoforms : SwissVarO75626
Catalytic activity : Enzyme2.1.1.- [ Enzyme-Expasy ]   2.1.1.-2.1.1.- [ IntEnz-EBI ]   2.1.1.- [ BRENDA ]   2.1.1.- [ KEGG ]   
PhosPhoSitePlusO75626
Domaine pattern : Prosite (Expaxy)SET (PS50280)    ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
Domains : Interpro (EBI)PRDM1    SET_dom    Znf_C2H2    Znf_C2H2-like    Znf_C2H2/integrase_DNA-bd   
Domain families : Pfam (Sanger)SET (PF00856)    zf-C2H2_6 (PF13912)   
Domain families : Pfam (NCBI)pfam00856    pfam13912   
Domain families : Smart (EMBL)SET (SM00317)  ZnF_C2H2 (SM00355)  
Conserved Domain (NCBI)PRDM1
DMDM Disease mutations639
Blocks (Seattle)PRDM1
PDB (SRS)3DAL   
PDB (PDBSum)3DAL   
PDB (IMB)3DAL   
PDB (RSDB)3DAL   
Structural Biology KnowledgeBase3DAL   
SCOP (Structural Classification of Proteins)3DAL   
CATH (Classification of proteins structures)3DAL   
SuperfamilyO75626
Human Protein Atlas [tissue]ENSG00000057657-PRDM1 [tissue]
Peptide AtlasO75626
HPRD04572
IPIIPI00747253   IPI00915310   IPI00385453   IPI00917506   IPI00896484   
Protein Interaction databases
DIP (DOE-UCLA)O75626
IntAct (EBI)O75626
FunCoupENSG00000057657
BioGRIDPRDM1
STRING (EMBL)PRDM1
ZODIACPRDM1
Ontologies - Pathways
QuickGOO75626
Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  RNA polymerase II core promoter proximal region sequence-specific DNA binding  transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding  morphogenesis of a branching structure  maternal placenta development  adaptive immune response  heart valve development  ventricular septum development  transcription factor activity, sequence-specific DNA binding  protein binding  nucleoplasm  cytoplasm  transcription, DNA-templated  germ cell development  methyltransferase activity  post-embryonic development  positive regulation of gene expression  negative regulation of B cell proliferation  negative regulation of lipopolysaccharide-mediated signaling pathway  methylation  regulation of natural killer cell differentiation  regulation of extrathymic T cell differentiation  aorta development  eye photoreceptor cell development  histone deacetylase binding  innate immune response  cell fate commitment  positive regulation of B cell differentiation  metal ion binding  artery morphogenesis  regulation of NK T cell differentiation  intestinal epithelial cell development  trophoblast giant cell differentiation  coronary vasculature development  sebum secreting cell proliferation  promoter-specific chromatin binding  
Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  RNA polymerase II core promoter proximal region sequence-specific DNA binding  transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding  morphogenesis of a branching structure  maternal placenta development  adaptive immune response  heart valve development  ventricular septum development  transcription factor activity, sequence-specific DNA binding  protein binding  nucleoplasm  cytoplasm  transcription, DNA-templated  germ cell development  methyltransferase activity  post-embryonic development  positive regulation of gene expression  negative regulation of B cell proliferation  negative regulation of lipopolysaccharide-mediated signaling pathway  methylation  regulation of natural killer cell differentiation  regulation of extrathymic T cell differentiation  aorta development  eye photoreceptor cell development  histone deacetylase binding  innate immune response  cell fate commitment  positive regulation of B cell differentiation  metal ion binding  artery morphogenesis  regulation of NK T cell differentiation  intestinal epithelial cell development  trophoblast giant cell differentiation  coronary vasculature development  sebum secreting cell proliferation  promoter-specific chromatin binding  
REACTOMEO75626 [protein]
REACTOME PathwaysR-HSA-6804754 [pathway]   
NDEx NetworkPRDM1
Atlas of Cancer Signalling NetworkPRDM1
Wikipedia pathwaysPRDM1
Orthology - Evolution
OrthoDB639
GeneTree (enSembl)ENSG00000057657
Phylogenetic Trees/Animal Genes : TreeFamPRDM1
HOVERGENO75626
HOGENOMO75626
Homologs : HomoloGenePRDM1
Homology/Alignments : Family Browser (UCSC)PRDM1
Gene fusions - Rearrangements
Fusion : MitelmanRNF217/PRDM1 [6q22.31/6q21]  [t(6;6)(q21;q22)]  
Fusion: TCGAPRDM1 6q21 SLC22A16 6q21 BRCA
Fusion: TCGARNF217 6q22.31 PRDM1 6q21 BRCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPRDM1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PRDM1
dbVarPRDM1
ClinVarPRDM1
1000_GenomesPRDM1 
Exome Variant ServerPRDM1
ExAC (Exome Aggregation Consortium)ENSG00000057657
GNOMAD BrowserENSG00000057657
Genetic variants : HAPMAP639
Genomic Variants (DGV)PRDM1 [DGVbeta]
DECIPHERPRDM1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPRDM1 
Mutations
ICGC Data PortalPRDM1 
TCGA Data PortalPRDM1 
Broad Tumor PortalPRDM1
OASIS PortalPRDM1 [ Somatic mutations - Copy number]
Cancer Gene: CensusPRDM1 
Somatic Mutations in Cancer : COSMICPRDM1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDPRDM1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch PRDM1
DgiDB (Drug Gene Interaction Database)PRDM1
DoCM (Curated mutations)PRDM1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PRDM1 (select a term)
intoGenPRDM1
NCG5 (London)PRDM1
Cancer3DPRDM1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM603423   
Orphanet
MedgenPRDM1
Genetic Testing Registry PRDM1
NextProtO75626 [Medical]
TSGene639
GENETestsPRDM1
Target ValidationPRDM1
Huge Navigator PRDM1 [HugePedia]
snp3D : Map Gene to Disease639
BioCentury BCIQPRDM1
ClinGenPRDM1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD639
Chemical/Pharm GKB GenePA33707
Clinical trialPRDM1
Miscellaneous
canSAR (ICR)PRDM1 (select the gene name)
Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=PRDM1
Probes
Litterature
PubMed131 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePRDM1
EVEXPRDM1
GoPubMedPRDM1
iHOPPRDM1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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