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HMHB1 Gene

protein-coding   GIFtS: 37
GCID: GC05P143172

Histocompatibility (Minor) HB-1

  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Histocompatibility (Minor) HB-11 2
HLA-HB12 5
HB-12
Minor Histocompatibility Antigen HB-12
Minor Histocompatibility Protein HB-12

External Ids:    HGNC: 296771   Entrez Gene: 578242   Ensembl: ENSG000001584977   OMIM: 6099615   UniProtKB: O979803   

Export aliases for HMHB1 gene to outside databases

Previous GC identifer: GC05P138338


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for HMHB1 Gene:
This gene encodes one of the minor histocompatibility antigens, which play an important role in the induction of
cytotoxic T lymphocyte (CTL) reactivity against leukemia after human histocompatibility leukocyte antigen
(HLA)-identical allogeneic bone marrow transplantation (BMT). This gene is only expressed in B cell acute
lymphoblastic leukemia cells and Epstein-Barr virus-transformed B cells. The translation of this mRNA initiates
at a non-AUG (CUG) codon. (provided by RefSeq, Jul 2008)

GeneCards Summary for HMHB1 Gene:
HMHB1 (histocompatibility (minor) HB-1) is a protein-coding gene. Diseases associated with HMHB1 include lymphoblastic leukemia, and hematopoietic stem cell transplantation.

UniProtKB/Swiss-Prot: HMHB1_HUMAN, O97980
Function: Precursor of the histocomplatibility antigen HB-1. More generally, minor histocomplatibility antigens
(mHags) refer to immunogenic peptide which, when complexed with MHC, can generate an immune response after
recognition by specific T-cells. The peptides are derived from polymorphic intracellular proteins, which are
cleaved by normal pathways of antigen processing. The binding of these peptides to MHC class I or class II
molecules and its expression on the cell surface can stimulate T-cell responses and thereby trigger graft
rejection or graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation from HLA-identical
sibling donor. GVHD is a frequent complication after bone marrow transplantation (BMT), due to mismatch of minor
histocomplatibility antigen in HLA-matched sibling marrow transplants. HB-1 is presented on the cell surface by
MHC class I HLA-B44. This complex specifically elicits donor-cytotoxic T lymphocyte (CTL) reactivity in B-cell
acute lymphoblastic leukemia (B-ALL) after treatment by HLA-identical allogenic bone marrow transplantation
(BMT). It induces cell recognition and lysis by CTL. However, HB-1 restricted expression in B-ALL cells and not
in normal tissues may allow a specific CTL reactivity against B-ALL without the risk of evoking graft-versus-host
disease




(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000005.10  NC_018916.2  NT_029289.12  
Regulatory elements:
   Regulatory transcription factor binding sites in the HMHB1 gene promoter:
         STAT1   HOXA3   STAT4   STAT1beta   RelA   NF-kappaB   STAT1alpha   STAT2   STAT3   NF-kappaB1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidHMHB1 promoter sequence
   Search Chromatin IP Primers for HMHB1

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat HMHB1


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 5q31.3   Ensembl cytogenetic band:  5q31.3   HGNC cytogenetic band: 5q32

HMHB1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
HMHB1 gene location

GeneLoc information about chromosome 5         GeneLoc Exon Structure

GeneLoc location for GC05P143172:  view genomic region     (about GC identifiers)

Start:
143,191,726 bp from pter      End:
143,200,284 bp from pter
Size:
8,559 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: HMHB1_HUMAN, O97980 (See protein sequence)
Recommended Name: Minor histocompatibility protein HB-1  
Size: 41 amino acids; 4965 Da
Subunit: HB-1 forms a complex with MHC class I HLA-B44
Caution: This sequence containing mHag HB-1 may not represent the full-length protein (PubMed:15102363), because
functional domains are absent in this short gene product
Caution: PubMed:9892612 postulated that the initiator methionine is coded by a non-canonical CTG leucine codon
Secondary accessions: Q9MY25

Explore the universe of human proteins at neXtProt for HMHB1: NX_O97980

REFSEQ proteins: NP_067005.1  
ENSEMBL proteins: 
 ENSP00000289448  

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(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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ProtoNet protein and cluster: O97980


(According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

     UniProtKB/Swiss-Prot Summary: HMHB1_HUMAN, O97980
Function: Precursor of the histocomplatibility antigen HB-1. More generally, minor histocomplatibility antigens
(mHags) refer to immunogenic peptide which, when complexed with MHC, can generate an immune response after
recognition by specific T-cells. The peptides are derived from polymorphic intracellular proteins, which are
cleaved by normal pathways of antigen processing. The binding of these peptides to MHC class I or class II
molecules and its expression on the cell surface can stimulate T-cell responses and thereby trigger graft
rejection or graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation from HLA-identical
sibling donor. GVHD is a frequent complication after bone marrow transplantation (BMT), due to mismatch of minor
histocomplatibility antigen in HLA-matched sibling marrow transplants. HB-1 is presented on the cell surface by
MHC class I HLA-B44. This complex specifically elicits donor-cytotoxic T lymphocyte (CTL) reactivity in B-cell
acute lymphoblastic leukemia (B-ALL) after treatment by HLA-identical allogenic bone marrow transplantation
(BMT). It induces cell recognition and lysis by CTL. However, HB-1 restricted expression in B-ALL cells and not
in normal tissues may allow a specific CTL reactivity against B-ALL without the risk of evoking graft-versus-host
disease

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(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from COMPARTMENTS: 

CompartmentConfidence
cytosol2
extracellular2
nucleus2

(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for HMHB1
Interactions:

    Search GeneGlobe Interaction Network for HMHB1

Gene Ontology (GO): 1 biological process term:    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0002376immune system process IEA--

HMHB1 for ontologies           About GeneDecksing



(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore
   Browse drugs & compounds from Enzo Life Sciences
  Browse compounds at ApexBio 

Browse Tocris compounds for HMHB1



(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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REFSEQ mRNAs for HMHB1 gene: 
NM_021182.1  

Unigene Cluster for HMHB1:

Histocompatibility (minor) HB-1
Hs.158320
Unigene Representative Sequence: AF103884
1 Ensembl transcript including schematic representation, and UCSC links where relevant:
ENST00000289448(uc003lnj.3)
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Additional mRNA sequence: 

AF103884.1 BC096711.1 BC098145.1 BC098244.1 BC104412.1 BC104413.1 BC113894.1 BC113971.1 

1 DOTS entry:

DT.92011863 

3 AceView cDNA sequences:

AF103884 NM_021182 BG221245 

GeneLoc Exon Structure


(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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HMHB1 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>2/3
CGAP TAG: AAGAAGAGTA
HMHB1 Expression
About this image

HMHB1 Protein expression data from MOPED1, PaxDb2 and MaxQB3 --

SOURCE GeneReport for Unigene cluster: Hs.158320

UniProtKB/Swiss-Prot: HMHB1_HUMAN, O97980
Tissue specificity: Expressed in acute lymphoblastic leukemia B-cells and Epstein-Barr virus-transformed B-cells

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In Situ
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(Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of human and chimp.

Orthologs for HMHB1 gene from 1 species (see representative species )    About this table
Organism Taxonomic
classification
Gene Description Human
Similarity
Orthology
Type
Details
chimpanzee
(Pan troglodytes)
Mammalia HMHB16
histocompatibility (minor) HB-1
100(a)
1 ↔ 1
5(144575552-144583931)


ENSEMBL Gene Tree for HMHB1 (if available)
TreeFam Gene Tree for HMHB1 (if available)

(Paralogs according to 1HomoloGene,
2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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(SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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Selected SNPs for HMHB1 (see all 252)    About this table    
Genomic DataTranscription Related DataAllele Frequencies
SNP IDValidClinical
significance
Chr 5 posSequence#AA
Chg
TypeMore#Allele
freq
PopTotal
sample
More
----------
rs1615691,2
C,F,H--143189770(+) cacagA/Gaagtt 1 -- us2k15Minor allele frequency- G:0.02NS EA WA 498
rs1440387801,2
C--143189806(+) TCTAAC/TTTCAG 1 -- us2k10--------
rs1820719851,2
C--143189956(+) GAAAAA/TTCCAT 1 -- us2k10--------
rs774528801,2
F--143189974(+) GAAGAT/GGGTTT 1 -- us2k11Minor allele frequency- G:0.06WA 118
rs1870575431,2
--143190025(+) GGGGTA/GCATTA 1 -- us2k10--------
rs106441001,2
C--143190140(+) ggctaATTT    
   TTT
/-
atttt
1 -- us2k11Minor allele frequency- -:0.50CSA 2
rs353860441,2
C--143190141(+) GCTAA-/AT    
   TTTTT
TTTTT
1 -- us2k10--------
rs607980681,2
C--143190144(+) TATTTTTTA    
   TTT
/-
ATTAT
1 -- us2k11Minor allele frequency- -:0.00NA 2
rs68796821,2
C,F--143190159(+) tatttT/Attatt 1 -- us2k1 tfbs32Minor allele frequency- A:0.50WA NA 4
rs131683191,2
C--143190170(+) tttttT/Gtgtgt 1 -- us2k13Minor allele frequency- G:0.08NA EA 242

HapMap Linkage Disequilibrium report for HMHB1 (143191726 - 143200284 bp)

Structural Variations
      Database of Genomic Variants (DGV) variations for HMHB1: --
Site Specific Mutation Identification with PCR Assays
SeqTarget long-range PCR primers for resequencing HMHB1
DNA2.0 Custom Variant and Variant Library Synthesis for HMHB1

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 609961    OMIM disorders: --

5 diseases for HMHB1:    About MalaCards
lymphoblastic leukemia    hematopoietic stem cell transplantation    leukemia    graft versus host disease
t-cell leukemia


HMHB1 for disorders           About GeneDecksing

Genetic Association Database (GAD): HMHB1
Human Genome Epidemiology (HuGE) Navigator: HMHB1 (3 documents)

Export disorders for HMHB1 gene to outside databases

(in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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PubMed articles for HMHB1 gene, integrated from 10 sources (see all 13):
(articles sorted by number of sources associating them with HMHB1)
    Utopia: connect your pdf to the dynamic
world of online information

  1. A human minor histocompatibility antigen specific for B cell acute lymphoblastic leukemia. (PubMed id 9892612)1, 2, 3, 9 Dolstra H.... van de Wiel-van Kemenade E. (J. Exp. Med. 1999)
  2. Role of minor histocompatibility antigens in renal transplantation. (PubMed id 18093280)1, 4, 9 Heinold A....Tran T.H. (Am. J. Transplant. 2008)
  3. Degree of predicted minor histocompatibility antigen mismatch correlates with poorer clinical outcomes in nonmyeloablative allogeneic hematopoietic cell transplantation. (PubMed id 20353833)1, 4 Larsen M.E....Vindelov L. (Biol. Blood Marrow Transplant. 2010)
  4. Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling. (PubMed id 19240061)1, 4 Trynka G....Wijmenga C. (Gut 2009)
  5. Improved genotyping of the human minor histocompatibility antigen HB-1 by polymerase chain reaction with sequence-specific primers using a complementary oligonucleotide. (PubMed id 20718936)1 Park M.J....Kim T.G. (Tissue Antigens 2010)
  6. A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study. (PubMed id 17903299)4 Kathiresan S....Cupples L.A. (BMC Med. Genet. 2007)
  7. Minor histocompatibility antigens -- big in tumour therapy. (PubMed id 15102363)2 Spierings E.... Goulmy E. (Trends Immunol. 2004)
  8. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)2 Gerhard D.S.... Malek J. (Genome Res. 2004)
  9. Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. (PubMed id 12477932)1 Strausberg R.L....Marra M.A. (Proc. Natl. Acad. Sci. U.S.A. 2002)
  10. Bi-directional allelic recognition of the human minor histocompatibility antigen HB-1 by cytotoxic T lymphocytes. (PubMed id 12355426)2 Dolstra H....van de Wiel-van Kemenade E. (Eur. J. Immunol. 2002)

(in PubMed, OMIM, and NCBI Bookshelf)
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 ANDOR
Aliases
Free Text  

  Query String
PubMed
OMIM
NCBI Bookshelf
  (Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 57824 HGNC: 29677 AceView: HB-1 Ensembl:ENSG00000158497 euGenes: HUgn57824
ECgene: HMHB1 H-InvDB: HMHB1

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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NameDescription
PharmGKB entry for HMHB1 Pharmacogenomics, SNPs, Pathways

(Patent information from GeneIP,
Licensable technologies from WIS Yeda, Salk, Tufts,
IP news from LifeMap Sciences, Inc.)
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Patent Information for HMHB1 gene:
Search GeneIP for patents involving HMHB1

GeneCards and IP:
Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript, and ESI BIO, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
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GeneCards Homepage - Last full update: 7 May 2014 - Incrementals: 9 May 2014 , 2 Jun 2014 , 26 Jun 2014 , 30 Jun 2014

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