Atlas of Genetics and Cytogenetics in Oncology and Haematology

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HLF (hepatic leukemia factor)

Written1999-09Franck Viguié
Laboratoire de Cytogenetique - Service d'Hematologie Biologique, Hopital Hotel-Dieu - 75181 Paris Cedex 04, France

(Note : for Links provided by Atlas : click)


Alias_nameshepatic leukemia factor
PAR bZIP transcription factor
Alias_symbol (synonym)MGC33822
Other alias
LocusID (NCBI) 3131
Atlas_Id 47
Location 17q22  [Link to chromosome band 17q22]
Location_base_pair Starts at 53342321 and ends at 53402426 bp from pter ( according to hg19-Feb_2009)  [Mapping HLF.png]
Fusion genes
(updated 2016)
HLF (17q22) / TCF3 (19p13.3)TCF3 (19p13.3) / HLF (17q22)


  DNA diagram
Transcription 3.9 kb


  Protein diagram
Description 295 amino acids, MW 43 kDa
Expression HLF is normally expressed in hepatocytes and liver-derived cell lines, and, to a lesser extent, in lung, kidney and neurons of the central nervous system; it is not expressed in hematopoietic tissues or cell lines
Localisation nuclear
Function the normal function of HLF is largely unknown; HLF is a member of the PAR (proline and acidic amino acid-rich region) subfamily of b/ZIP (basic region leucine zipper) transcription factors; PAR and b/ZIP proteins bind to the DNA as dimers; HLF acts as a transcriptionnal transactivator; there are evidences that HLF protein transactivates factor VIII and factor IX genes, by binding as a homodimer (HLF/HLF) or a heterodimer with one albumin D-element binding protein sub unit (HLF/DBP), to multiple sites in the promoter of these genes; in the mouse central nervous system ontogeny, HLF expression increases markedly with synaptogenesis, suggesting that HLF plays a role in the function of adult differentiated neurons
Homology other members of the b/ZIP PAR subfamily; in mammals: albumin D-element binding protein (DBP) and thyrotroph embryonic factor / vitellogenin gene binding protein (TEF/VBP); like HLF, they are transcription activators; the three proteins have an ability to form heterodimers with one another through the leucine-zipper domain; in other species : vitellogenin binding protein (VBP) in the chicken and Ces-2 gene in the nematode Caenorhabditis elegans

Implicated in

Entity t(17;19)(q22;p13) in acute lymphoblastic leukemia --> E2A - HLF fusion gene
Disease childhood pro-B cell acute lymphoblastic leukemia
Prognosis poor prognosis is likely
Abnormal Protein fusion encodes a protein which contains the AD1 and AD2 transactivation domains of E2A, linked to the bZIP DNA binding / protein dimerization region of HLF
Oncogenesis E2A-HLF alters the apoptotic pathway of pro-B lymphocytic cells, leading to the survival of defective cells that would normally be eliminated; it is to be noted that, in normal tissues, there is no evidence in favour of a role of native HLF in apoptosis regulation


Enhanced binding of HLF/DBP heterodimers represents one mechanism of PAR protein transactivation of the factor VIII and factor IX genes.
Begbie M, Mueller C, Lillicrap D
DNA and cell biology. 1999 ; 18 (2) : 165-173.
PMID 10073576
Expression patterns of the hepatic leukemia factor gene in the nervous system of developing and adult mice.
Hitzler JK, Soares HD, Drolet DW, Inaba T, O'Connel S, MG Rosenfeld, Morgan JI, Look AT
Brain research. 1999 ; 820 (1-2) : 1-11.
PMID 10023025
Chromosomal translocations involving the E2A gene in acute lymphoblastic leukemia: clinical features and molecular pathogenesis.
Hunger SP
Blood. 1996 ; 87 (4) : 1211-1224.
PMID 8608207
The proto-oncogene HLF and the related basic leucine zipper protein TEF display highly similar DNA-binding and transcriptional regulatory properties.
Hunger SP, Li S, Fall MZ, Naumovski L, Cleary ML
Blood. 1996 ; 87 (11) : 4607-4617.
PMID 8639829
Fusion of the leucine zipper gene HLF to the E2A gene in human acute B-lineage leukemia.
Inaba T, Roberts WM, Shapiro LH, Jolly KW, Raimondi SC, Smith SD, Look AT
Science (New York, N.Y.). 1992 ; 257 (5069) : 531-534.
PMID 1386162
Cell transformation mediated by homodimeric E2A-HLF transcription factors.
Inukai T, Inaba T, Yoshihara T, Look AT
Molecular and cellular biology. 1997 ; 17 (3) : 1417-1424.
PMID 9032268
Regulation of the DBP promoter by PAR proteins and in leukemic cells bearing an E2A/HLF translocation.
Newcombe K, Glassco T, Mueller C
Biochemical and biophysical research communications. 1998 ; 245 (2) : 633-639.
PMID 9571207


This paper should be referenced as such :
Viguié, F
HLF (hepatic leukemia factor)
Atlas Genet Cytogenet Oncol Haematol. 1999;3(3):135-136.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ]
  t(1;19)(q23;p13) TCF3/PBX1
t(17;19)(q22;p13) TCF3/HLF

External links

HGNC (Hugo)HLF   4977
Entrez_Gene (NCBI)HLF  3131  hepatic leukemia factor
GeneCards (Weizmann)HLF
Ensembl hg19 (Hinxton)ENSG00000108924 [Gene_View]  chr17:53342321-53402426 [Contig_View]  HLF [Vega]
Ensembl hg38 (Hinxton)ENSG00000108924 [Gene_View]  chr17:53342321-53402426 [Contig_View]  HLF [Vega]
ICGC DataPortalENSG00000108924
TCGA cBioPortalHLF
Genatlas (Paris)HLF
SOURCE (Princeton)HLF
Genetics Home Reference (NIH)HLF
Genomic and cartography
GoldenPath hg19 (UCSC)HLF  -     chr17:53342321-53402426 +  17q22   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)HLF  -     17q22   [Description]    (hg38-Dec_2013)
EnsemblHLF - 17q22 [CytoView hg19]  HLF - 17q22 [CytoView hg38]
Mapping of homologs : NCBIHLF [Mapview hg19]  HLF [Mapview hg38]
Gene and transcription
Genbank (Entrez)AA021027 AF035305 AK074289 AK290043 AK295726
RefSeq transcript (Entrez)NM_002126
RefSeq genomic (Entrez)NC_000017 NC_018928 NT_010783 NW_004929407
Consensus coding sequences : CCDS (NCBI)HLF
Cluster EST : UnigeneHs.196952 [ NCBI ]
CGAP (NCI)Hs.196952
Alternative Splicing GalleryENSG00000108924
Gene ExpressionHLF [ NCBI-GEO ]   HLF [ EBI - ARRAY_EXPRESS ]   HLF [ SEEK ]   HLF [ MEM ]
Gene Expression Viewer (FireBrowse)HLF [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)3131
GTEX Portal (Tissue expression)HLF
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ16534   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ16534  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ16534
Splice isoforms : SwissVarQ16534
Domaine pattern : Prosite (Expaxy)BZIP (PS50217)   
Domains : Interpro (EBI)bZIP    HLF   
Domain families : Pfam (Sanger)bZIP_2 (PF07716)   
Domain families : Pfam (NCBI)pfam07716   
Domain families : Smart (EMBL)BRLZ (SM00338)  
Conserved Domain (NCBI)HLF
DMDM Disease mutations3131
Blocks (Seattle)HLF
Human Protein AtlasENSG00000108924
Peptide AtlasQ16534
IPIIPI00002850   IPI01011539   IPI00910584   
Protein Interaction databases
IntAct (EBI)Q16534
Ontologies - Pathways
Ontology : AmiGODNA binding  double-stranded DNA binding  transcription factor activity, sequence-specific DNA binding  nucleus  regulation of transcription, DNA-templated  transcription from RNA polymerase II promoter  multicellular organism development  skeletal muscle cell differentiation  sequence-specific DNA binding  rhythmic process  
Ontology : EGO-EBIDNA binding  double-stranded DNA binding  transcription factor activity, sequence-specific DNA binding  nucleus  regulation of transcription, DNA-templated  transcription from RNA polymerase II promoter  multicellular organism development  skeletal muscle cell differentiation  sequence-specific DNA binding  rhythmic process  
NDEx NetworkHLF
Atlas of Cancer Signalling NetworkHLF
Wikipedia pathwaysHLF
Orthology - Evolution
GeneTree (enSembl)ENSG00000108924
Phylogenetic Trees/Animal Genes : TreeFamHLF
Homologs : HomoloGeneHLF
Homology/Alignments : Family Browser (UCSC)HLF
Gene fusions - Rearrangements
Fusion : MitelmanTCF3/HLF [19p13.3/17q22]  [t(17;19)(q22;p13)]  
Fusion : TICdbTCF3 [19p13.3]  -  HLF [17q22]
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerHLF [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)HLF
Exome Variant ServerHLF
ExAC (Exome Aggregation Consortium)HLF (select the gene name)
Genetic variants : HAPMAP3131
Genomic Variants (DGV)HLF [DGVbeta]
DECIPHER (Syndromes)17:53342321-53402426  ENSG00000108924
CONAN: Copy Number AnalysisHLF 
ICGC Data PortalHLF 
TCGA Data PortalHLF 
Broad Tumor PortalHLF
OASIS PortalHLF [ Somatic mutations - Copy number]
Cancer Gene: CensusHLF 
Somatic Mutations in Cancer : COSMICHLF  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDHLF
intOGen PortalHLF
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch HLF
DgiDB (Drug Gene Interaction Database)HLF
DoCM (Curated mutations)HLF (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)HLF (select a term)
NCG5 (London)HLF
Cancer3DHLF(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry HLF
NextProtQ16534 [Medical]
Huge Navigator HLF [HugePedia]
snp3D : Map Gene to Disease3131
BioCentury BCIQHLF
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD3131
Chemical/Pharm GKB GenePA29311
Clinical trialHLF
canSAR (ICR)HLF (select the gene name)
PubMed33 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Thu Mar 30 13:09:41 CEST 2017

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