This gene encodes a member of the multicopper oxidase protein family. The encoded protein is involved in the transport of dietary iron from epithelial cells of the intestinal lumen into the circulatory system, and may be involved in copper transport and homeostasis. In mouse, defects in this gene can lead to severe microcytic anemia. Alternative splicing results in multiple tra... See more...

Aliases for HEPH Gene

Aliases for HEPH Gene

  • Hephaestin 2 3 4 5
  • KIAA0698 2 4
  • CPL 2 3
  • EC 1.16.3.1 51
  • EC 1.-.-.- 4
  • HEPH 5

External Ids for HEPH Gene

Previous GeneCards Identifiers for HEPH Gene

  • GC0XP061603
  • GC0XP062847
  • GC0XP063615
  • GC0XP064249
  • GC0XP065165
  • GC0XP065299
  • GC0XP059211

Summaries for HEPH Gene

Entrez Gene Summary for HEPH Gene

  • This gene encodes a member of the multicopper oxidase protein family. The encoded protein is involved in the transport of dietary iron from epithelial cells of the intestinal lumen into the circulatory system, and may be involved in copper transport and homeostasis. In mouse, defects in this gene can lead to severe microcytic anemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

GeneCards Summary for HEPH Gene

HEPH (Hephaestin) is a Protein Coding gene. Diseases associated with HEPH include Hemochromatosis, Type 1 and Iron Metabolism Disease. Among its related pathways are Mineral absorption and Insulin receptor recycling. Gene Ontology (GO) annotations related to this gene include oxidoreductase activity and ferrous iron binding. An important paralog of this gene is HEPHL1.

UniProtKB/Swiss-Prot Summary for HEPH Gene

  • May function as a ferroxidase for ferrous (II) to ferric ion (III) conversion and may be involved in copper transport and homeostasis. Implicated in iron homeostasis and may mediate iron efflux associated to ferroportin 1.

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

Genomics for HEPH Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for HEPH 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
GH0XJ066160 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE CraniofacialAtlas 609.9 +1.9 1910 8 ZNF512 LEF1 IKZF1 RFX5 JUND DDX20 MTA2 PKNOX1 MTA1 REST HEPH piR-52680-389 EDA2R
GH0XJ066169 Promoter 0.3 EPDnew 600.4 +7.4 7356 0.1 HEPH piR-52680-389 EDA2R
GH0XJ066006 Promoter/Enhancer 1.7 FANTOM5 Ensembl ENCODE dbSUPER 4.2 -147.4 -147372 16.4 CTCF RFX1 LEF1 IKZF1 ETV6 JUND PRDM1 DDX20 MTA2 PHF21A MIR223HG VSIG4 MSN HEPH MIR223 5MWI_A-192
GH0XJ066632 Promoter/Enhancer 1.7 EPDnew Ensembl ENCODE CraniofacialAtlas 3.6 +473.6 473605 7.5 PRDM10 PRDM1 IKZF2 ZNF341 SCRT2 EED MNT ZBTB20 SP2 JUND EDA2R RNU6-394P HEPH piR-51154-016
GH0XJ065996 Enhancer 1.4 FANTOM5 ENCODE dbSUPER 4.3 -162.5 -162488 8.1 HNRNPL ZNF512 LEF1 IKZF1 JUND DDX20 MTA2 PKNOX1 MTA1 REST 5MWI_A-192 MSN ZC3H12B HEPH piR-38051-325 VSIG4 ENSG00000237311
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

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

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

Top Transcription factor binding sites by QIAGEN in the HEPH gene promoter:
  • AREB6
  • Bach2
  • E47
  • Hand1
  • Lmo2
  • TBP
  • TFIID

Genomic Locations for HEPH Gene

Genomic Locations for HEPH Gene
chrX:66,162,526-66,268,867
(GRCh38/hg38)
Size:
106,342 bases
Orientation:
Plus strand
chrX:65,382,391-65,488,709
(GRCh37/hg19)
Size:
106,319 bases
Orientation:
Plus strand

Genomic View for HEPH Gene

Genes around HEPH on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for HEPH Gene

Proteins for HEPH Gene

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

    Protein Symbol:
    Q9BQS7-HEPH_HUMAN
    Recommended name:
    Hephaestin
    Protein Accession:
    Q9BQS7
    Secondary Accessions:
    • B1AJX8
    • D3DVT7
    • E9PHN8
    • O75180
    • Q6UW45
    • Q9C058

    Protein attributes for HEPH Gene

    Size:
    1158 amino acids
    Molecular mass:
    130449 Da
    Cofactor:
    Name=Cu cation; Xref=ChEBI:CHEBI:23378;
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=AAQ89349.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=EAX05385.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=EAX05388.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

    Alternative splice isoforms for HEPH Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for HEPH Gene

Selected DME Specific Peptides for HEPH Gene

Q9BQS7:
  • HCHVTDH
  • HLGILGP
  • IYHSHVDAP
  • YYSAVDP

Post-translational modifications for HEPH Gene

  • Glycosylation at Asn164, Asn236, Asn588, Asn714, Asn758, Asn829, Asn873, Asn931, Ser1070, Thr1073, Thr1076, and Thr1079
  • Modification sites at PhosphoSitePlus

Domains & Families for HEPH Gene

Gene Families for HEPH Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for HEPH Gene

InterPro:
Blocks:
  • Multicopper oxidase, type 2
ProtoNet:

Suggested Antigen Peptide Sequences for HEPH Gene

GenScript: Design optimal peptide antigens:
  • Hephaestin (HEPH_HUMAN)
  • Hephaestin (Q1HE23_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9BQS7

UniProtKB/Swiss-Prot:

HEPH_HUMAN :
  • Belongs to the multicopper oxidase family.
Family:
  • Belongs to the multicopper oxidase family.
genes like me logo Genes that share domains with HEPH: view

Function for HEPH Gene

Molecular function for HEPH Gene

UniProtKB/Swiss-Prot Function:
May function as a ferroxidase for ferrous (II) to ferric ion (III) conversion and may be involved in copper transport and homeostasis. Implicated in iron homeostasis and may mediate iron efflux associated to ferroportin 1.

Enzyme Numbers (IUBMB) for HEPH Gene

Phenotypes From GWAS Catalog for HEPH Gene

Gene Ontology (GO) - Molecular Function for HEPH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004322 ferroxidase activity IBA,IMP 22961397
GO:0005507 copper ion binding IEA,IMP 22961397
GO:0008198 ferrous iron binding IMP 22961397
GO:0016491 oxidoreductase activity IEA,IBA 21873635
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with HEPH: view
genes like me logo Genes that share phenotypes with HEPH: view

Animal Models for HEPH Gene

MGI Knock Outs for HEPH:
  • Heph Heph<tm1.2Jdun>

Animal Model Products

CRISPR Products

Inhibitory RNA Products

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

Clone Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for HEPH Gene

Localization for HEPH Gene

Subcellular locations from UniProtKB/Swiss-Prot for HEPH Gene

Membrane. Single-pass type I membrane protein.

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 HEPH gene
Compartment Confidence
plasma membrane 5
extracellular 2
mitochondrion 2
nucleus 2
endoplasmic reticulum 2
endosome 2
cytosol 2
lysosome 2
cytoskeleton 1
peroxisome 1
golgi apparatus 1

Subcellular locations from the

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

Gene Ontology (GO) - Cellular Components for HEPH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005623 cell IEA --
GO:0005886 plasma membrane IEA,TAS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
GO:0016323 basolateral plasma membrane IDA 20019163
genes like me logo Genes that share ontologies with HEPH: view

Pathways & Interactions for HEPH Gene

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

Interacting Proteins for HEPH Gene

Gene Ontology (GO) - Biological Process for HEPH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006811 ion transport IEA --
GO:0006825 copper ion transport IEA --
GO:0006826 iron ion transport IEA,IMP 22961397
GO:0006879 cellular iron ion homeostasis IEA,TAS --
GO:0055072 iron ion homeostasis IEA,IBA 21873635
genes like me logo Genes that share ontologies with HEPH: view

No data available for SIGNOR curated interactions for HEPH Gene

Drugs & Compounds for HEPH Gene

(3) Drugs for HEPH Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Copper Approved, Investigational Pharma Carrier, binder 249
Iron Approved, Experimental Pharma 1560
Ferrous sulfate anhydrous Approved Pharma Enzyme, substrate 0
genes like me logo Genes that share compounds with HEPH: view

Transcripts for HEPH Gene

mRNA/cDNA for HEPH Gene

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

CRISPR Products

Inhibitory RNA Products

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

Clone Products

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

ExUns: 1 ^ 2a · 2b ^ 3a · 3b ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22
SP1: - - -
SP2: -
SP3:
SP4: - -

Relevant External Links for HEPH Gene

GeneLoc Exon Structure for
HEPH

Expression for HEPH Gene

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

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

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

This gene is overexpressed in Colon - Transverse (x5.2) and Colon - Sigmoid (x4.4).

Protein differential expression in normal tissues from HIPED for HEPH Gene

This gene is overexpressed in Heart (23.6), Fetal gut (14.9), and Colon (6.3).

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



Protein tissue co-expression partners for HEPH Gene

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

SOURCE GeneReport for Unigene cluster for HEPH Gene:

Hs.31720

mRNA Expression by UniProt/SwissProt for HEPH Gene:

Q9BQS7-HEPH_HUMAN
Tissue specificity: Detected in breast, colon, bone trabecular cells and fibroblasts.

Evidence on tissue expression from TISSUES for HEPH Gene

  • Intestine(4.8)
  • Nervous system(4.6)
  • Heart(2.6)
  • Muscle(2.5)
  • Liver(2.5)
  • Blood(2.2)
  • Kidney(2.2)
  • Eye(2.2)
  • Spleen(2.1)
genes like me logo Genes that share expression patterns with HEPH: view

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

Orthologs for HEPH Gene

This gene was present in the common ancestor of chordates.

Orthologs for HEPH Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia HEPH 30
  • 96.04 (n)
Dog
(Canis familiaris)
Mammalia HEPH 30 31
  • 88.84 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia HEPH 30 31
  • 88.4 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Heph 30 17 31
  • 85.35 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Heph 30
  • 85.31 (n)
Oppossum
(Monodelphis domestica)
Mammalia HEPH 31
  • 68 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia HEPH 31
  • 56 (a)
OneToOne
Chicken
(Gallus gallus)
Aves HEPH 30 31
  • 66.03 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia HEPH 31
  • 59 (a)
OneToOne
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 39 (a)
OneToMany
Species where no ortholog for HEPH was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • Fruit Fly (Drosophila melanogaster)
  • 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)
  • Rainbow Trout (Oncorhynchus mykiss)
  • 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)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)
  • Zebrafish (Danio rerio)

Evolution for HEPH Gene

ENSEMBL:
Gene Tree for HEPH (if available)
TreeFam:
Gene Tree for HEPH (if available)
Aminode:
Evolutionary constrained regions (ECRs) for HEPH: view image

Paralogs for HEPH Gene

(7) SIMAP similar genes for HEPH Gene using alignment to 6 proteins:

  • HEPH_HUMAN
  • E7ES21_HUMAN
  • F8WBZ8_HUMAN
  • Q1HE23_HUMAN
  • Q5JZ07_HUMAN
  • Q5JZ08_HUMAN
genes like me logo Genes that share paralogs with HEPH: view

Variants for HEPH Gene

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

SNP ID Clinical significance and condition Chr 0X pos Variation AA Info Type
709010 Likely Benign: not provided 66,203,394(+) G/A MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT
773380 Benign: not provided 66,197,877(+) G/A MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT,INTRON_VARIANT
rs17216603 - p.Ala595Thr

Additional dbSNP identifiers (rs#s) for HEPH Gene

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

Variant ID Type Subtype PubMed ID
esv1584074 OTHER inversion 17803354
esv3574014 CNV loss 25503493
esv3576919 CNV gain 25503493
nsv1078114 CNV duplication 25765185
nsv1110609 CNV duplication 24896259
nsv1141685 CNV duplication 24896259
nsv1154108 CNV duplication 26484159

Variation tolerance for HEPH Gene

Residual Variation Intolerance Score: 18% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.86; 48.29% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HEPH Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
HEPH

SNP Genotyping and Copy Number Assay Products

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

Disorders for HEPH Gene

MalaCards: The human disease database

(18) MalaCards diseases for HEPH Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
hemochromatosis, type 1
  • hfe1
iron metabolism disease
  • disorder of iron metabolism
iron deficiency anemia
  • iron-deficiency anemia
microcytic anemia
  • iron-refractory iron deficiency anemia
hemosiderosis
  • haemosiderosis
- elite association - COSMIC cancer census association via MalaCards
Search HEPH in MalaCards View complete list of genes associated with diseases

Additional Disease Information for HEPH

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

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

Publications for HEPH Gene

  1. Analysis of the human hephaestin gene and protein: comparative modelling of the N-terminus ecto-domain based upon ceruloplasmin. (PMID: 11932491) Syed BA … Srai SK (Protein engineering 2002) 3 4 23
  2. Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. (PMID: 9734811) Ishikawa K … Ohara O (DNA research : an international journal for rapid publication of reports on genes and genomes 1998) 2 3 4
  3. Human hephaestin expression is not limited to enterocytes of the gastrointestinal tract but is also found in the antrum, the enteric nervous system, and pancreatic {beta}-cells. (PMID: 20019163) Hudson DM … MacGillivray RT (American journal of physiology. Gastrointestinal and liver physiology 2010) 3 23
  4. Examination of genetic polymorphisms in newborns for signatures of sex-specific prenatal selection. (PMID: 20587610) Ucisik-Akkaya E … Dorak MT (Molecular human reproduction 2010) 3 41
  5. Genome-wide association study to identify single nucleotide polymorphisms (SNPs) associated with the development of erectile dysfunction in African-American men after radiotherapy for prostate cancer. (PMID: 20932654) Kerns SL … Rosenstein BS (International journal of radiation oncology, biology, physics 2010) 3 41

Products for HEPH Gene

  • Signalway ELISA kits for HEPH
  • Signalway Proteins for HEPH

Sources for HEPH Gene