Human Gene HP (uc021tld.1) Description and Page Index
Description: Homo sapiens haptoglobin (HP), transcript variant 1, mRNA. RefSeq Summary (NM_001126102): 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]. Transcript (Including UTRs) Position: hg19 chr16:72,088,508-72,094,955 Size: 6,448 Total Exon Count: 5 Strand: + Coding Region Position: hg19 chr16:72,088,552-72,094,789 Size: 6,238 Coding Exon Count: 5
ID:HPT_HUMAN DESCRIPTION: RecName: Full=Haptoglobin; AltName: Full=Zonulin; Contains: RecName: Full=Haptoglobin alpha chain; Contains: RecName: Full=Haptoglobin beta chain; Flags: Precursor; FUNCTION: Haptoglobin combines with free plasma hemoglobin, preventing loss of iron through the kidneys and protecting the kidneys from damage by hemoglobin, while making the hemoglobin accessible to degradative enzymes. 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. SUBUNIT: Tetramer of two alpha and two beta chains. SUBCELLULAR LOCATION: Secreted. TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma. POLYMORPHISM: In the human populations there are two major allelic forms, alpha-1 with 83 residues and alpha-2 with 142 residues. These alleles determine the 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). DISEASE: Defects in HP are the cause of anhaptoglobinemia (AHP) [MIM:614081]. AHP is 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. SIMILARITY: Belongs to the peptidase S1 family. SIMILARITY: Contains 1 peptidase S1 domain. SIMILARITY: Contains 2 Sushi (CCP/SCR) domains. CAUTION: Although homologous to serine proteases, it has lost all essential catalytic residues and has no enzymatic activity. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/HP"; WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and polymorphism database; URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=HP"; WEB RESOURCE: Name=Wikipedia; Note=Haptoglobin entry; URL="http://en.wikipedia.org/wiki/Haptoglobin";
Genetic Association Studies of Complex Diseases and Disorders
Mikael Ryndel , et al. Clinica chimica acta 2010 Jan, The haptoglobin 2-2 genotype is associated with carotid atherosclerosis in 64-year old women with established diabetes., Clinica chimica acta 2010 Jan.
Apolipoproteins B Sekar Kathiresan et al. BMC medical genetics 2007, A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study., BMC medical genetics.
Using a 100K genome-wide scan, we have generated a set of putative associations for common sequence variants and lipid phenotypes. Validation of selected hypotheses in additional samples did not identify any new loci underlying variability in blood lipids. Lack of replication may be due to inadequate statistical power to detect modest quantitative trait locus effects (i.e., <1% of trait variance explained) or reduced genomic coverage of the 100K array. GWAS in FHS using a denser genome-wide genotyping platform and a better-powered replication strategy may identify novel loci underlying blood lipids.
atherosclerosis, coronary Levy, A. P. et al. 2004, Haptoglobin phenotype and prevalent coronary heart disease in the Framingham offspring cohort., Atherosclerosis. 2004 Feb;172(2):361-5.
These data are consistent with an interaction between Hp type and diabetes in the prevalence of CHD. These findings will need to be confirmed in other cohorts and in longitudinal studies.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P00738
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.