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HP Gene(Protein Coding)

Haptoglobin

GCID:
GC16P072089
GIFtS:
63
Genes Participants
UDN Logo

Aliases for HP Gene

Aliases for HP Gene

  • Haptoglobin 2 3 3 5
  • Zonulin 3 4
  • Haptoglobin, Alpha Polypeptide 3
  • Haptoglobin, Beta Polypeptide 3
  • Haptoglobin Alpha(2FS)-Beta 3
  • Haptoglobin Alpha(1S)-Beta 3
  • Binding Peptide 3
  • HP2ALPHA2 3
  • HPA1S 3
  • BP 3

External Ids for HP Gene

Previous GeneCards Identifiers for HP Gene

  • GC16P062982
  • GC16P072811
  • GC16P071824
  • GC16P071864
  • GC16P070646
  • GC16P057856

Summaries for HP Gene

Entrez Gene Summary for HP Gene

  • This gene encodes a preproprotein, which is processed to yield both alpha and beta chains, which subsequently combine as a tetramer to produce haptoglobin. Haptoglobin functions to bind free plasma hemoglobin, which allows degradative enzymes to gain access to the hemoglobin, while at the same time preventing loss of iron through the kidneys and protecting the kidneys from damage by hemoglobin. Mutations in this gene and/or its regulatory regions cause ahaptoglobinemia or hypohaptoglobinemia. This gene has also been linked to diabetic nephropathy, the incidence of coronary artery disease in type 1 diabetes, Crohn's disease, inflammatory disease behavior, primary sclerosing cholangitis, susceptibility to idiopathic Parkinson's disease, and a reduced incidence of Plasmodium falciparum malaria. The protein encoded also exhibits antimicrobial activity against bacteria. A similar duplicated gene is located next to this gene on chromosome 16. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2014]

GeneCards Summary for HP Gene

HP (Haptoglobin) is a Protein Coding gene. Diseases associated with HP include Anhaptoglobinemia and Plasmodium Falciparum Malaria. Among its related pathways are Innate Immune System and amb2 Integrin signaling. GO annotations related to this gene include serine-type endopeptidase activity and hemoglobin binding. An important paralog of this gene is HPR.

UniProtKB/Swiss-Prot for HP Gene

  • As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of heme iron and to prevent kidney damage. Haptoglobin also acts as an Antimicrobial; Antioxidant, has antibacterial activity and plays a role in modulating many aspects of the acute phase response. Hemoglobin/haptoglobin complexes are rapidely cleared by the macrophage CD163 scavenger receptor expressed on the surface of liver Kupfer cells through an endocytic lysosomal degradation pathway.

  • Uncleaved haptoglogin, also known as zonulin, plays a role in intestinal permeability, allowing intercellular tight junction disassembly, and controlling the equilibrium between tolerance and immunity to non-self antigens.

Gene Wiki entry for HP Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HP Gene

Genomics for HP Gene

Products:

  1. Regulatory Element

Regulatory Elements for HP Gene

Enhancers for HP Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH16G072012 1.2 Ensembl ENCODE 17.2 -40.9 -40917 2.2 ATF1 TBL1XR1 NFIB ZFP64 SIN3A YY1 TCF12 GATA2 EGR1 FOS TXNL4B HP HPR DHODH DHX38 PIR31360
GH16G072124 1.1 Ensembl ENCODE 17.5 +70.7 70669 1.5 HDGF RB1 TBL1XR1 MLX DMAP1 ZNF48 RAD21 ZNF143 CREM ZNF654 HP DHX38 TXNL4B HPR DHODH PIR57952 PMFBP1
GH16G072189 1.7 FANTOM5 Ensembl ENCODE dbSUPER 6.7 +135.4 135444 1.5 HDAC1 PKNOX1 FOXA2 ARID4B RARA ELK1 FOS CREM ZNF362 USF2 IST1 HPR PMFBP1 HP AP1G1 DHX38 ATXN1L LOC105371341
GH16G072017 1 ENCODE 11.3 -37.3 -37296 0.2 FOXA2 MLX ARID4B DMAP1 ZNF48 YY1 SP5 ZHX2 MXD4 MIER2 HP GC16M072022 PIR38556 PIR51938
GH16G072171 1.1 Ensembl ENCODE 9.2 +117.8 117848 1.5 PKNOX1 ATF1 WRNIP1 BMI1 ZBTB40 RFX5 ZNF766 CBX5 ZNF143 ZNF207 HP HPR PMFBP1 PIR57952
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around HP on UCSC Golden Path with GeneCards custom track

Transcription factor binding sites by QIAGEN in the HP gene promoter:

Genomic Location for HP Gene

Chromosome:
16
Start:
72,054,592 bp from pter
End:
72,061,056 bp from pter
Size:
6,465 bases
Orientation:
Plus strand

Genomic View for HP Gene

Genes around HP on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for HP Gene

Proteins for HP Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

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

    Protein Symbol:
    P00738-HPT_HUMAN
    Recommended name:
    Haptoglobin
    Protein Accession:
    P00738
    Secondary Accessions:
    • B0AZL5
    • P00737
    • Q0VAC4
    • Q0VAC5
    • Q2PP15
    • Q3B7J0
    • Q6LBY9
    • Q9UC67

    Protein attributes for HP Gene

    Size:
    406 amino acids
    Molecular mass:
    45205 Da
    Quaternary structure:
    • Tetramer of two alpha and two beta chains; disufide-linked. The Hemoglobin/haptoglobin complex is composed of a haptoglobin dimer bound to two hemoglobin alpha-beta dimers. Interacts with CD163.

    Three dimensional structures from OCA and Proteopedia for HP Gene

    Alternative splice isoforms for HP Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for HP Gene

Protein Expression for HP Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for HP Gene

  • Glycosylation at posLast=184184, isoforms=2207, posLast=211211, and isoforms=2241
  • Modification sites at PhosphoSitePlus

Other Protein References for HP Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

No data available for DME Specific Peptides for HP Gene

Domains & Families for HP Gene

Gene Families for HP Gene

HGNC:

Protein Domains for HP Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for HP Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P00738

UniProtKB/Swiss-Prot:

HPT_HUMAN :
  • Belongs to the peptidase S1 family.
Family:
  • Belongs to the peptidase S1 family.
genes like me logo Genes that share domains with HP: view

Function for HP Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line
  7. Flow Cytometry

Molecular function for HP Gene

GENATLAS Biochemistry:
haptoglobin,expressed in liver
UniProtKB/Swiss-Prot Function:
As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of heme iron and to prevent kidney damage. Haptoglobin also acts as an Antimicrobial; Antioxidant, has antibacterial activity and plays a role in modulating many aspects of the acute phase response. Hemoglobin/haptoglobin complexes are rapidely cleared by the macrophage CD163 scavenger receptor expressed on the surface of liver Kupfer cells through an endocytic lysosomal degradation pathway.
UniProtKB/Swiss-Prot Function:
Uncleaved haptoglogin, also known as zonulin, plays a role in intestinal permeability, allowing intercellular tight junction disassembly, and controlling the equilibrium between tolerance and immunity to non-self antigens.

Gene Ontology (GO) - Molecular Function for HP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004252 serine-type endopeptidase activity IEA --
GO:0005515 protein binding IPI 19758344
GO:0016209 antioxidant activity IEA --
GO:0030492 hemoglobin binding IDA,IEA 19740759
genes like me logo Genes that share ontologies with HP: view
genes like me logo Genes that share phenotypes with HP: view

Animal Models for HP Gene

MGI Knock Outs for HP:
  • Hp tm1Skl

Inhibitory RNA Products

Flow Cytometry Products

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

Localization for HP Gene

Subcellular locations from UniProtKB/Swiss-Prot for HP Gene

Secreted.

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 HP gene
Compartment Confidence
extracellular 5
cytosol 3
lysosome 2
plasma membrane 1
cytoskeleton 1
nucleus 1
endoplasmic reticulum 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for HP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS,IEA --
GO:0005615 extracellular space IDA 16502470
GO:0031838 haptoglobin-hemoglobin complex IDA 19740759
GO:0035580 specific granule lumen TAS --
GO:0070062 extracellular exosome IDA 19056867
genes like me logo Genes that share ontologies with HP: view

Pathways & Interactions for HP Gene

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

Gene Ontology (GO) - Biological Process for HP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IEA --
GO:0006898 receptor-mediated endocytosis TAS --
GO:0006952 defense response TAS 7036344
GO:0006953 acute-phase response IEA --
GO:0010942 positive regulation of cell death IDA 19740759
genes like me logo Genes that share ontologies with HP: view

No data available for SIGNOR curated interactions for HP Gene

Drugs & Compounds for HP Gene

Products:

  1. Drug

(67) Drugs for HP Gene - From: ClinicalTrials and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Esomeprazole Approved, Investigational Pharma Proton pump inhibitor 333
Lansoprazole Approved, Investigational Pharma H+,K+-ATPase inhibitor 218
Omeprazole Approved, Investigational, Vet_approved Pharma Activator H+,K+-ATPase inhibitor 348
Pantoprazole Approved Pharma H+/K+-ATPase inhibitor 175
Citrate Nutra 1160

(48) Additional Compounds for HP Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Fe2+
  • Armco iron
  • Carbonyl iron
  • FE
  • Ferrovac e
  • Hematite
 15438-31-0
genes like me logo Genes that share compounds with HP: view

Transcripts for HP Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone
  5. Flow Cytometry

mRNA/cDNA for HP Gene

(3) REFSEQ mRNAs :
(11) Additional mRNA sequences :
(1046) Selected AceView cDNA sequences:
(18) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for HP Gene

Haptoglobin:
Representative Sequences:

Inhibitory RNA Products

Flow Cytometry Products

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

No ASD Table

Relevant External Links for HP Gene

GeneLoc Exon Structure for
HP
ECgene alternative splicing isoforms for
HP

Expression for HP Gene

Products:

  1. Primer

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

mRNA expression in normal human tissues for HP Gene
mRNA expression by BioGPS for HP GenemRNA expression by GTEx for HP Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

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

This gene is overexpressed in Liver (x51.3).

Protein differential expression in normal tissues from HIPED for HP Gene

This gene is overexpressed in Plasma (9.2) and Synovial fluid (6.6).

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



Protein tissue co-expression partners for HP Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of HP Gene:

HP

SOURCE GeneReport for Unigene cluster for HP Gene:

Hs.513711

mRNA Expression by UniProt/SwissProt for HP Gene:

P00738-HPT_HUMAN
Tissue specificity: Expressed by the liver and secreted in plasma.

Evidence on tissue expression from TISSUES for HP Gene

  • Liver(5)
  • Nervous system(4.7)
  • Bone marrow(4.5)
  • Saliva(4.4)
  • Blood(4)
  • Eye(4)
  • Lung(3.8)
  • Heart(3.7)
  • Spleen(3.6)
  • Muscle(3.5)
  • Intestine(3.4)
  • Kidney(3.4)
  • Skin(2.4)
  • Stomach(2.3)
  • Pancreas(2.1)
  • Urine(2.1)
genes like me logo Genes that share expression patterns with HP: view

Primer Products

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

Orthologs for HP Gene

This gene was present in the common ancestor of chordates.

Orthologs for HP Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia HP 34
  • 98.85 (n)
HPR 35
  • 91 (a)
 ManyToMany
dog
(Canis familiaris)
 Mammalia LOC479668 34
  • 84.73 (n)
HP 35
  • 81 (a)
 OneToMany
cow
(Bos Taurus)
 Mammalia HP 34 35
  • 81.17 (n)
mouse
(Mus musculus)
 Mammalia Hp 34 16 35
  • 79.35 (n)
rat
(Rattus norvegicus)
 Mammalia Hp 34
  • 78.39 (n)
oppossum
(Monodelphis domestica)
 Mammalia -- 35
  • 70 (a)
 OneToMany
platypus
(Ornithorhynchus anatinus)
 Mammalia -- 35
  • 4 (a)
 ManyToMany
zebrafish
(Danio rerio)
 Actinopterygii hp 35
  • 29 (a)
 OneToMany
sea squirt
(Ciona savignyi)
 Ascidiacea -- 35
  • 16 (a)
 ManyToMany
CSA.10613 35
  • 15 (a)
 ManyToMany
-- 35
  • 11 (a)
 ManyToMany
-- 35
  • 10 (a)
 ManyToMany
-- 35
  • 1 (a)
 ManyToMany
Species where no ortholog for HP was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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)
  • chicken (Gallus gallus)
  • 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)
  • lizard (Anolis carolinensis)
  • 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 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)

Evolution for HP Gene

ENSEMBL:
Gene Tree for HP (if available)
TreeFam:
Gene Tree for HP (if available)

Paralogs for HP Gene

Variants for HP Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for HP Gene

HPT_HUMAN-P00738
In the human populations there are two major allelic forms, alpha-1 (1-1) with 83 residues and alpha-2 (2-2) with 142 residues. These alleles determine 3 possible genotypes, homozygous (1-1 or 2-2) and heterozygous (2-1), and 3 major phenotypes HP*1F/HP*1S and HP*2FS. The two main alleles of HP*1 are called HP*1F (fast) and HP*1S (slow). The alleles exhibit different oligomerization properties. In healthy males, but not in females, the Hp 2-2 phenotype is associated with higher serum iron, decreased Antimicrobial; Antioxidant capability, and less efficient clearance from the circulation, than Hp 1-1 and 2-1.

Sequence variations from dbSNP and Humsavar for HP Gene

SNP ID Clin Chr 16 pos Sequence Context AA Info Type
rs104894517 other, Anhaptoglobinemia (AHP) [MIM:614081] 72,060,409(+) AGATA(C/T)TGGGC intron-variant, reference, missense
rs137853233 Benign 72,057,415(+) ATAAG(A/G)AGCAG intron-variant, reference, missense
rs1000244518 -- 72,054,489(+) GGTAT(C/T)GTTTG intron-variant, upstream-variant-2KB
rs1000427142 -- 72,060,967(+) GGACA(A/G)GAGTG intron-variant, utr-variant-3-prime
rs1000636449 -- 72,055,702(+) AGAAG(C/T)AGAGG intron-variant

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

Variant ID Type Subtype PubMed ID
dgv1636e59 CNV duplication 20981092
dgv3017n100 CNV gain 25217958
dgv504e199 CNV deletion 23128226
dgv5186n54 CNV loss 21841781
dgv530e214 CNV gain 21293372
dgv531e214 CNV gain 21293372
esv2215660 CNV deletion 18987734
esv23639 CNV gain+loss 19812545
esv2422047 CNV duplication 20811451
esv2478287 CNV deletion 19546169
esv2714683 CNV deletion 23290073
esv2714685 CNV deletion 23290073
esv2758654 CNV gain 17122850
esv3638989 CNV loss 21293372
esv3638992 CNV loss 21293372
esv3892884 CNV loss 25118596
nsv428329 CNV gain 18775914
nsv514812 CNV gain 21397061
nsv514813 CNV gain 21397061
nsv572951 CNV gain 21841781
nsv572955 CNV loss 21841781
nsv7285 OTHER inversion 18451855
nsv817737 CNV loss 17921354
nsv827729 CNV loss 20364138
nsv833273 CNV loss 17160897
nsv9456 CNV gain+loss 18304495
nsv978167 CNV duplication 23825009

Variation tolerance for HP Gene

Residual Variation Intolerance Score: 73% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.17; 61.72% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for HP Gene

Human Gene Mutation Database (HGMD)
HP
SNPedia medical, phenotypic, and genealogical associations of SNPs for
HP

Disorders for HP Gene

MalaCards: The human disease database

(63) MalaCards diseases for HP Gene - From: ClinVar, GeneTests, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
anhaptoglobinemia
  • hypohaptoglobinemia
plasmodium falciparum malaria
  • falciparum malaria
bronchopneumonia
  • bronchial pneumonia
favism
hemoglobinemia
  • haemoglobinemia
- elite association - COSMIC cancer census association via MalaCards
Search HP in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

HPT_HUMAN
  • Anhaptoglobinemia (AHP) [MIM:614081]: A condition characterized by the absence of the serum glycoprotein haptoglobin. Serum levels of haptoglobin vary among normal persons: levels are low in the neonatal period and in the elderly, differ by population, and can be influenced by environmental factors, such as infection. Secondary hypohaptoglobinemia can occur as a consequence of hemolysis, during which haptoglobin binds to free hemoglobin. Congenital haptoglobin deficiency is a risk factor for anaphylactic non-hemolytic transfusion reactions. {ECO:0000269 PubMed:14999562}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Genatlas disease for HP Gene

haptoglobinemia,Hp0 phenotype (HP deletion)

Relevant External Links for HP

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

Publications for HP Gene

  1. Role of haptoglobin in polycystic ovary syndrome (PCOS), obesity and disorders of glucose tolerance in premenopausal women. (PMID: 19440331) Alvarez-Blasco F. … Escobar-Morreale H.F. (PLoS ONE 2009) 3 22 46 64
  2. Polymorphism of haptoglobin in patients with premature rupture of membrane. (PMID: 19259359) Cho J.K. … Kim I.S. (Yonsei Med. J. 2009) 3 22 46 64
  3. Sex steroid hormones influence the risk for cervical cancer: modulation by haptoglobin genetic polymorphism. (PMID: 19446743) Bicho M.C. … Bicho M.D. (Cancer Genet. Cytogenet. 2009) 3 22 46 64
  4. Mortality in HIV infection is independently predicted by host iron status and SLC11A1 and HP genotypes, with new evidence of a gene-nutrient interaction. (PMID: 19474129) McDermid J.M. … Prentice A.M. (Am. J. Clin. Nutr. 2009) 3 22 46 64
  5. Haptoglobin polymorphism in Mongolian population: comparison of the two genotyping methods. (PMID: 19682981) Nakamura H. … Koda Y. (Clin. Chim. Acta 2009) 3 22 46 64

Products for HP Gene

Sources for HP Gene

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