This gene encodes a member of the homeobox family of transcription factors, many of which are involved in developmental processes. Expression in specific hematopoietic lineages suggests that this protein may play a role in hematopoietic differentiation. [provided by RefSeq, Jul 2008] See more...

Aliases for HHEX Gene

Aliases for HHEX Gene

  • Hematopoietically Expressed Homeobox 2 3 5
  • HEX 2 3 4
  • Hematopoietically-Expressed Homeobox Protein HHEX 3 4
  • Homeobox Protein HEX 3 4
  • Homeobox Protein PRH 3 4
  • HOX11L-PEN 2 3
  • PRHX 3 4
  • PRH 3 4
  • Proline-Rich Homeodomain-Containing Transcription Factor 3
  • Homeobox, Hematopoietically Expressed 3
  • HMPH 3
  • HHEX 5

External Ids for HHEX Gene

Previous HGNC Symbols for HHEX Gene

  • PRHX

Previous GeneCards Identifiers for HHEX Gene

  • GC10P093330
  • GC10P093671
  • GC10P094580
  • GC10P094114
  • GC10P094439
  • GC10P088077

Summaries for HHEX Gene

Entrez Gene Summary for HHEX Gene

  • This gene encodes a member of the homeobox family of transcription factors, many of which are involved in developmental processes. Expression in specific hematopoietic lineages suggests that this protein may play a role in hematopoietic differentiation. [provided by RefSeq, Jul 2008]

GeneCards Summary for HHEX Gene

HHEX (Hematopoietically Expressed Homeobox) is a Protein Coding gene. Diseases associated with HHEX include Acute Myeloid Leukemia With T(8;21)(Q22;Q22) Translocation and Maturity-Onset Diabetes Of The Young. Among its related pathways are Transcriptional misregulation in cancer and Mesodermal Commitment Pathway. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and sequence-specific DNA binding.

UniProtKB/Swiss-Prot Summary for HHEX Gene

  • Recognizes the DNA sequence 5'-ATTAA-3' (By similarity). Transcriptional repressor (By similarity). Activator of WNT-mediated transcription in conjunction with CTNNB1 (PubMed:20028982). Establishes anterior identity at two levels; acts early to enhance canonical WNT-signaling by repressing expression of TLE4, and acts later to inhibit NODAL-signaling by directly targeting NODAL (By similarity). May play a role in hematopoietic differentiation (PubMed:8096636).

Gene Wiki entry for HHEX Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for HHEX Gene

Genomics for HHEX Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for HHEX Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH10J092688 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE dbSUPER 265.8 +3.4 3376 10.7 NCOR1 MYC ZNF600 IKZF1 ZNF592 ZMYM3 KLF9 CEBPA ATF3 ZSCAN16 HHEX BTAF1 RPL17P34 KIF11 PDE6C IDE TNKS2 EIF2S2P3 lnc-IDE-3 HSALNG0079722
GH10J092846 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 11.4 +158.6 158588 3.7 ZNF600 KLF9 POLR2A CEBPA YY1 CTCF CEBPB SMAD5 SIN3A TBP EXOC6 HHEX HSALNG0079727 ENSG00000225118 CYP26C1
GH10J092699 Promoter/Enhancer 1.9 EPDnew FANTOM5 ENCODE CraniofacialAtlas dbSUPER 7 +9.9 9929 1.3 IKZF1 ZNF592 ZNF10 ZIC2 ZBTB10 ETS1 ZNF341 GABPA ZBTB48 MLLT1 HSALNG0079722 EXOC6 EIF2S2P3 HHEX ENSG00000201412
GH10J092601 Enhancer 0.5 Ensembl 22.7 -86.7 -86655 4.6 ZBTB33 ZNF362 ZNF133 ZNF202 ZNF680 MLLT1 HHEX KIF11 BTAF1 RPL17P34 IDE EIF2S2P3 RPL11P4 MN309194
GH10J092644 Enhancer 0.9 Ensembl ENCODE 12 -45.2 -45154 2 ZNF654 REST MNT CTCF MAX MAFF SAP130 RAD21 SMC3 ZNF316 HHEX IDE KIF11 MN309194 lnc-KIF11-2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around HHEX on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for HHEX

Top Transcription factor binding sites by QIAGEN in the HHEX gene promoter:
  • E2F
  • GATA-1
  • PPAR-gamma1
  • PPAR-gamma2
  • SRF
  • SRF (504 AA)
  • STAT3

Genomic Locations for HHEX Gene

Latest Assembly
chr10:92,689,955-92,695,647
(GRCh38/hg38)
Size:
5,693 bases
Orientation:
Plus strand

Previous Assembly
chr10:94,449,712-94,455,404
(GRCh37/hg19 by Entrez Gene)
Size:
5,693 bases
Orientation:
Plus strand

chr10:94,447,945-94,455,403
(GRCh37/hg19 by Ensembl)
Size:
7,459 bases
Orientation:
Plus strand

Genomic View for HHEX Gene

Genes around HHEX on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HHEX Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HHEX Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HHEX Gene

Proteins for HHEX Gene

  • Protein details for HHEX Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q03014-HHEX_HUMAN
    Recommended name:
    Hematopoietically-expressed homeobox protein HHEX
    Protein Accession:
    Q03014
    Secondary Accessions:
    • B1AQ17
    • Q96CE9

    Protein attributes for HHEX Gene

    Size:
    270 amino acids
    Molecular mass:
    30022 Da
    Quaternary structure:
    • Interacts with CD81; the interaction prevents nuclear translocation of HHEX (By similarity). Interacts (via N-terminus) with SOX13; abolishes the SOX13-mediated inhibition of WNT-mediated transcriptional activity via competitive inhibition of the SOX13-TCF7 complex (PubMed:20028982).

    Three dimensional structures from OCA and Proteopedia for HHEX Gene

neXtProt entry for HHEX Gene

Post-translational modifications for HHEX Gene

  • Ubiquitination at Lys122
  • Modification sites at PhosphoSitePlus

Other Protein References for HHEX Gene

No data available for DME Specific Peptides for HHEX Gene

Domains & Families for HHEX Gene

Gene Families for HHEX Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for HHEX Gene

InterPro:
Blocks:
  • Lambda and other repressor helix-turn-helix signature

Suggested Antigen Peptide Sequences for HHEX Gene

GenScript: Design optimal peptide antigens:
  • cDNA, FLJ95793, Homo sapiens hematopoietically expressed homeobox (HHEX), mRNA (B1AQ17_HUMAN)
  • Homeobox protein PRH (HHEX_HUMAN)
  • HEX (Q9C057_HUMAN)
genes like me logo Genes that share domains with HHEX: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for HHEX Gene

Function for HHEX Gene

Molecular function for HHEX Gene

UniProtKB/Swiss-Prot Function:
Recognizes the DNA sequence 5'-ATTAA-3' (By similarity). Transcriptional repressor (By similarity). Activator of WNT-mediated transcription in conjunction with CTNNB1 (PubMed:20028982). Establishes anterior identity at two levels; acts early to enhance canonical WNT-signaling by repressing expression of TLE4, and acts later to inhibit NODAL-signaling by directly targeting NODAL (By similarity). May play a role in hematopoietic differentiation (PubMed:8096636).
GENATLAS Biochemistry:
hematopoietically expressed homeo box

Phenotypes From GWAS Catalog for HHEX Gene

Gene Ontology (GO) - Molecular Function for HHEX Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000976 transcription regulatory region sequence-specific DNA binding TAS 19324893
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IDA 15016828
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ISA --
GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific IDA 15016828
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific IMP 20028982
genes like me logo Genes that share ontologies with HHEX: view
genes like me logo Genes that share phenotypes with HHEX: view

Animal Models for HHEX Gene

MGI Knock Outs for HHEX:

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HHEX

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for HHEX Gene

Localization for HHEX Gene

Subcellular locations from UniProtKB/Swiss-Prot for HHEX Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HHEX gene
Compartment Confidence
nucleus 5
plasma membrane 2
extracellular 2
cytoskeleton 2
cytosol 2
lysosome 2
mitochondrion 1
peroxisome 1
endoplasmic reticulum 1
endosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Mitochondria (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for HHEX Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000785 chromatin ISA --
GO:0005634 nucleus IEA,IDA 12554669
GO:0005737 cytoplasm IDA 12554669
GO:0032993 protein-DNA complex IDA 18755198
genes like me logo Genes that share ontologies with HHEX: view

Pathways & Interactions for HHEX Gene

genes like me logo Genes that share pathways with HHEX: view

Pathways by source for HHEX Gene

1 BioSystems pathway for HHEX Gene

SIGNOR curated interactions for HHEX Gene

Is activated by:

Gene Ontology (GO) - Biological Process for HHEX Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IDA 10871399
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006357 regulation of transcription by RNA polymerase II IBA 21873635
GO:0006406 mRNA export from nucleus IDA 12554669
GO:0007275 multicellular organism development IEA --
genes like me logo Genes that share ontologies with HHEX: view

Drugs & Compounds for HHEX Gene

(1) Drugs for HHEX Gene - From: DrugBank

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
N-Acetyl-glucosamine thiazoline Experimental Pharma Target 0
genes like me logo Genes that share compounds with HHEX: view

Transcripts for HHEX Gene

mRNA/cDNA for HHEX Gene

1 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
4 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HHEX

Alternative Splicing Database (ASD) splice patterns (SP) for HHEX Gene

No ASD Table

Relevant External Links for HHEX Gene

GeneLoc Exon Structure for
HHEX

Expression for HHEX Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for HHEX Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for HHEX Gene

This gene is overexpressed in Thyroid (x8.5), Liver (x7.8), and Whole Blood (x5.7).

Protein differential expression in normal tissues from HIPED for HHEX Gene

This gene is overexpressed in Pancreatic juice (50.1) and Blymphocyte (18.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for HHEX Gene



Protein tissue co-expression partners for HHEX Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for HHEX

SOURCE GeneReport for Unigene cluster for HHEX Gene:

Hs.118651

mRNA Expression by UniProt/SwissProt for HHEX Gene:

Q03014-HHEX_HUMAN
Tissue specificity: Liver and promyelocytic leukemia cell line HL-60.

Evidence on tissue expression from TISSUES for HHEX Gene

  • Blood(4.5)
  • Bone marrow(4.5)
  • Liver(3)
  • Thyroid gland(2.9)
  • Pancreas(2.8)
  • Intestine(2.3)
  • Gall bladder(2.3)
  • Spleen(2.3)
  • Heart(2.1)
  • Muscle(2.1)
  • Lymph node(2)
genes like me logo Genes that share expression patterns with HHEX: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for HHEX Gene

Orthologs for HHEX Gene

This gene was present in the common ancestor of animals.

Orthologs for HHEX Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia HHEX 29 30
  • 100 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia HHEX 30
  • 97 (a)
OneToOne
Dog
(Canis familiaris)
Mammalia HHEX 29 30
  • 94.92 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia HHEX 29 30
  • 93.8 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Hhex 29
  • 89.51 (n)
Mouse
(Mus musculus)
Mammalia Hhex 29 16 30
  • 88.89 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia HHEX 30
  • 87 (a)
OneToOne
Chicken
(Gallus gallus)
Aves HHEX 29 30
  • 75 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia HHEX 30
  • 72 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia hhex 29
  • 72.68 (n)
Hex 29
African clawed frog
(Xenopus laevis)
Amphibia MGC69042 29
Zebrafish
(Danio rerio)
Actinopterygii hhex 29
  • 71.34 (n)
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.9768 29
Fruit Fly
(Drosophila melanogaster)
Insecta CG7056 30
  • 24 (a)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea pha-2 30
  • 39 (a)
OneToOne
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.4376 30
  • 21 (a)
OneToOne
Species where no ortholog for HHEX was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for HHEX Gene

ENSEMBL:
Gene Tree for HHEX (if available)
TreeFam:
Gene Tree for HHEX (if available)
Aminode:
Evolutionary constrained regions (ECRs) for HHEX: view image
Alliance of Genome Resources:
Additional Orthologs for HHEX

Paralogs for HHEX Gene

(10) SIMAP similar genes for HHEX Gene using alignment to 2 proteins:

  • HHEX_HUMAN
  • F8VU08_HUMAN
genes like me logo Genes that share paralogs with HHEX: view

No data available for Paralogs for HHEX Gene

Variants for HHEX Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for HHEX Gene

SNP ID Clinical significance and condition Chr 10 pos Variation AA Info Type
rs184882393 Benign: not provided 92,694,656(+) C/G
NM_002729.5(HHEX):c.701C>G (p.Ser234Cys)
MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for HHEX Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for HHEX Gene

Variant ID Type Subtype PubMed ID
dgv1350n54 CNV gain 21841781
dgv1351n54 CNV gain 21841781
dgv1352n54 CNV gain+loss 21841781
dgv168n67 CNV gain 20364138
esv29580 CNV loss 19812545
nsv1046258 CNV gain 25217958
nsv551929 CNV gain+loss 21841781
nsv551938 CNV loss 21841781
nsv551939 CNV gain+loss 21841781

Variation tolerance for HHEX Gene

Residual Variation Intolerance Score: 53.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.51; 10.98% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HHEX Gene

Human Gene Mutation Database (HGMD)
HHEX
SNPedia medical, phenotypic, and genealogical associations of SNPs for
HHEX
Leiden Open Variation Database (LOVD)
HHEX

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HHEX Gene

Disorders for HHEX Gene

MalaCards: The human disease database

(12) MalaCards diseases for HHEX Gene - From: COP and GCD

- elite association - COSMIC cancer census association via MalaCards
Search HHEX in MalaCards View complete list of genes associated with diseases

Additional Disease Information for HHEX

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with HHEX: view

No data available for UniProtKB/Swiss-Prot and Genatlas for HHEX Gene

Publications for HHEX Gene

  1. PCR cloning of an orphan homeobox gene (PRH) preferentially expressed in myeloid and liver cells. (PMID: 8103988) Hromas R … Collins S (Biochemical and biophysical research communications 1993) 2 3 4 22
  2. The influence of genetic variations in HHEX gene on insulin metabolism in the German MESYBEPO cohort. (PMID: 19117022) Pivovarova O … Rudovich N (Diabetes/metabolism research and reviews 2009) 3 22 40
  3. Contribution of type 2 diabetes associated loci in the Arabic population from Tunisia: a case-control study. (PMID: 19368707) Ezzidi I … Vaxillaire M (BMC medical genetics 2009) 3 22 40
  4. Impact of nine common type 2 diabetes risk polymorphisms in Asian Indian Sikhs: PPARG2 (Pro12Ala), IGF2BP2, TCF7L2 and FTO variants confer a significant risk. (PMID: 18598350) Sanghera DK … Kamboh MI (BMC medical genetics 2008) 3 22 40
  5. HEX: a novel homeobox gene expressed during haematopoiesis and conserved between mouse and human. (PMID: 8096636) Bedford FK … Wiedemann LM (Nucleic acids research 1993) 2 3 4

Products for HHEX Gene

Sources for HHEX Gene