HP haptoglobin [Homo sapiens (human)] - Gene

Summary

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Official Symbol: HPprovided by HGNC
Official Full Name: haptoglobinprovided by HGNC
Primary source: HGNC:5141
See related: Ensembl:ENSG00000257017; HPRD:00772; MIM:140100; Vega:OTTHUMG00000173009
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: BP; HPA1S; HP2ALPHA2
Summary: 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. 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, Jul 2008]

Genomic context

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Location :: 16q22.2

Sequence :: Chromosome: 16; NC_000016.9 (72088508..72094955)

See HP in Epigenomics, MapViewer

Chromosome 16 - NC_000016.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

specific changes in glycan structures of Hpt, such as enhanced glycan branching and fucose content, are associated with psoriasis, and that differences between circulating and skin Hpt do exist.
Title: Differences between the glycosylation patterns of haptoglobin isolated from skin scales and plasma of psoriatic patients.
study of effect of occupational exposure to lead in metallurgy workers in Poland on blood levels of transferrin (TRF), ceruloplasmin (CER) and haptoglobin (HPG): Significant increase in haptoglobin level was observed only in low lead exposure group.
Title: The effect of occupational lead exposure on blood levels of zinc, iron, copper, selenium and related proteins.
Suggest that haptoglobin is part of the surfactant system in the human lung.
Title: Pulmonary haptoglobin (pHp) is part of the surfactant system in the human lung.
study found Hp 2-1 was the predominant phenotype among Saudi type 2 diabetics as well as healthy subjects
Title: Inflammatory markers and haptoglobin polymorphism in Saudi with non-insulin-dependent diabetes mellitus.
Haptoglobin genotype is a significant predictor of coronary heart disease among individuals with elevated HBA1c.
Title: Haptoglobin genotype is a consistent marker of coronary heart disease risk among individuals with elevated glycosylated hemoglobin.
Increased plasma zonulin is associated with sepsis.
Title: Increased plasma zonulin in patients with sepsis.
Subjects with metabolic syndrome have elevated serum haptoglobin levels.
Title: Erythropoietin, ferritin, haptoglobin, hemoglobin and transferrin receptor in metabolic syndrome: a case control study.
High haptoglobin expression is associated with benign neoplasm of pancreas.
Title: Improved diagnostic accuracy of pancreatic diseases with a combination of various novel serum biomarkers--case control study from Manipal Teaching Hospital, Pokhara, Nepal.
Hp type 2-2 carries a high risk of cardiovascular events in diabetic patients. A pharmacogenomic approach towards treatment of diabetic patients with vitamin E may be warranted. [Review Article]
Title: Haptoglobin genotype and cardiovascular outcomes in diabetes mellitus - natural history of the disease and the effect of vitamin E treatment. Meta-analysis of the medical literature.
the relationship between insulin sensitivity and circulating zonulin might be mediated through the obesity-related circulating IL-6 increase.
Title: Circulating zonulin, a marker of intestinal permeability, is increased in association with obesity-associated insulin resistance.

Submit: New GeneRIF Correction See all (158)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

A genome-wide association study identifies rs2000999 as a strong genetic determinant of circulating haptoglobin levels.

Biological, clinical and population relevance of 95 loci for blood lipids.

Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis.

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
P00738	O75173	ADAMTS4	HPRD	PubMed
P00738	Complement C1r like proteinase	C1RL	HPRD	PubMed
P00738	Q86VB7	CD163	HPRD	PubMed
P00738	P20273	CD22	HPRD	PubMed
P00738	P68871	HBB	HPRD	PubMed
P00738	P11215	ITGAM	HPRD	PubMed
P00738	P05107	ITGB2	HPRD	PubMed
BioGRID:109480	BioGRID:106715	ALB	BioGRID	PubMed	Affinity Capture-MS
BioGRID:109480	BioGRID:107022	ATP7B	BioGRID	PubMed	Two-hybrid
BioGRID:109480	BioGRID:108309	ELAVL1	BioGRID	PubMed	Affinity Capture-RNA
BioGRID:109480	BioGRID:116117	GADD45G	BioGRID	PubMed	Two-hybrid
BioGRID:109480	BioGRID:109142	GRB2	BioGRID	PubMed	Two-hybrid
BioGRID:109480	BioGRID:109293	HBB	BioGRID	PubMed	Affinity Capture-Western
BioGRID:109480	BioGRID:115603	LAMC3	BioGRID	PubMed	Two-hybrid
BioGRID:109480	BioGRID:122474	MIS12	BioGRID	PubMed	Affinity Capture-MS
BioGRID:109480	BioGRID:115286	MVP	BioGRID	PubMed	Two-hybrid
BioGRID:109480	BioGRID:111865	RBBP6	BioGRID	PubMed	Two-hybrid
BioGRID:109480	BioGRID:112055	RPL11	BioGRID	PubMed	Two-hybrid
BioGRID:109480	BioGRID:110263	SMAD3	BioGRID	PubMed	Two-hybrid
BioGRID:109480	BioGRID:112770	TBL1X	BioGRID	PubMed	Two-hybrid
BioGRID:109480	BioGRID:112910	TGM2	BioGRID	PubMed	Two-hybrid
BioGRID:109480	BioGRID:114181	TP63	BioGRID	PubMed	Two-hybrid
BioGRID:109480	BioGRID:122472	VKORC1	BioGRID	PubMed	Two-hybrid
BioGRID:109480	BioGRID:114466	WASL	BioGRID	PubMed	Two-hybrid

Pathways from BioSystems

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Binding and Uptake of Ligands by Scavenger Receptors, organism-specific biosystem (from REACTOME)
Binding and Uptake of Ligands by Scavenger Receptors, organism-specific biosystemScavenger receptors bind free extracellular ligands as the initial step in clearance of the ligands from the body (reviewed in Ascenzi et al. 2005, Areschoug and Gordon 2009, Nielsen et al. 2010). So...
Scavenging of Heme from Plasma, organism-specific biosystem (from REACTOME)
Scavenging of Heme from Plasma, organism-specific biosystemFree heme is damaging to tissues as it intercalates into biologic membranes, perturbing lipid bilayers and promoting the conversion of low-density lipoprotein to cytotoxic oxidized products. Moreover...
amb2 Integrin signaling, organism-specific biosystem (from Pathway Interaction Database)
amb2 Integrin signaling, organism-specific biosystem
amb2 Integrin signaling

General gene information

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Markers

hshp1g5 (e-PCR)
- UniSTS:90142

D8S2279 (e-PCR)
- UniSTS:473907

SHGC-61149 (e-PCR)
- UniSTS:9031

HP_143 (e-PCR)
- UniSTS:277326

RH70305 (e-PCR)
- UniSTS:52609

GDB:181556 (e-PCR)
- UniSTS:155282

NoName (e-PCR)
- UniSTS:483222

GDB:181606 (e-PCR)
- UniSTS:155313

RH79153 (e-PCR)
- UniSTS:72133

GDB:180916 (e-PCR)
- UniSTS:155121

Genotypes

See HP SNP Geneview Report
See HP SNP Genotype Report
See HP SNP Variation Viewer Report

Homology

Homologs of the HP gene: The HP gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, and rat.
Map Viewer (Mouse, Rat)

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
antioxidant activity	IEA Inferred from Electronic Annotation more info
catalytic activity	IEA Inferred from Electronic Annotation more info
hemoglobin binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
acute-phase response	IEA Inferred from Electronic Annotation more info
cellular iron ion homeostasis	NAS Non-traceable Author Statement more info
defense response	TAS Traceable Author Statement more info	PubMed
defense response to bacterium	IEA Inferred from Electronic Annotation more info
negative regulation of hydrogen peroxide catabolic process	IDA Inferred from Direct Assay more info	PubMed
negative regulation of oxidoreductase activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cell death	IDA Inferred from Direct Assay more info	PubMed
response to hydrogen peroxide	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
endocytic vesicle lumen	TAS Traceable Author Statement more info
extracellular region	NAS Non-traceable Author Statement more info	PubMed
extracellular region	TAS Traceable Author Statement more info
extracellular space	IDA Inferred from Direct Assay more info	PubMed
haptoglobin-hemoglobin complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: haptoglobin

Names: haptoglobin; zonulin; binding peptide; haptoglobin alpha(1S)-beta; haptoglobin alpha(2FS)-beta; haptoglobin, beta polypeptide; haptoglobin, alpha polypeptide

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_012651.1 RefSeqGene

Range

5001..11448

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001126102.1 → NP_001119574.1 haptoglobin isoform 2 preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks two alternate in-frame exons in the mid-coding region, compared to variant 1, resulting in a shorter protein (isoform 2), compared to isoform 1.

Source sequence(s)

AK314700, BC017862, BC107587, CB117006

Consensus CDS

CCDS45525.1

UniProtKB/Swiss-Prot

P00738

UniProtKB/TrEMBL

Q6PEJ8

Related

ENSP00000381199, ENST00000398131

Conserved Domains (2) summary

cd00190
Location:103 – 343
Blast Score: 464

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

cd00033
Location:33 – 87
Blast Score: 83

CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
NM_005143.3 → NP_005134.1 haptoglobin isoform 1 preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AK314700, BC017862, CB117006

Consensus CDS

CCDS45524.1

UniProtKB/Swiss-Prot

P00738

UniProtKB/TrEMBL

Q6PEJ8

Related

ENSP00000348170, OTTHUMP00000249890, ENST00000355906, OTTHUMT00000421680

Conserved Domains (2) summary

cd00190
Location:162 – 402
Blast Score: 463

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

cd00033
Location:33 – 87
Blast Score: 83

CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000016.9 Reference GRCh37.p10 Primary Assembly

Range

72088508..72094955

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000148.1 Alternate HuRef

Range

57855340..57861787

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018927.1 Alternate CHM1_1.0

Range

73100192..73106639

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01016797.1 (17433..23880)	None
genomic	AC004682.1	AAC27432.1
genomic	AC009087.4 (56321..62770)	None
genomic	AMYH01007795.1 (107791..114238)	None
genomic	CH471166.2	EAW59194.1
		EAW59195.1
		EAW59196.1
		EAW59197.1
genomic	DQ314870.1	ABC40729.1
genomic	M10935.1	AAA88080.1
genomic	M69197.1	AAA88078.1
genomic	X00606.1	CAA25248.1
genomic	X01793.1	CAA25926.1
mRNA	AK055872.1	BAG51589.1
mRNA	AK314700.1	BAF98793.1
mRNA	BC017862.1	AAH17862.1
mRNA	BC058031.1	AAH58031.1
mRNA	BC070299.1	AAH70299.1
mRNA	BC107587.1	AAI07588.1
mRNA	BC121124.1	AAI21125.1
mRNA	BC121125.1	AAI21126.1
mRNA	CB117006.1	None
mRNA	CB134891.1	None
mRNA	K00422.1	AAA52687.1
mRNA	K01763.1	AAA52684.1
mRNA	L29394.1	AAA52685.1
mRNA	T71743.1	None
mRNA	X00637.1	CAA25267.1