HP haptoglobin [Homo sapiens (human)] - Gene

Summary

Official Symbol: HPprovided by HGNC
Official Full Name: haptoglobinprovided by HGNC
Primary source: HGNC:HGNC:5141
See related: Ensembl:ENSG00000257017 MIM:140100
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. 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]
Expression: Restricted expression toward liver (RPKM 13200.4) See more
Orthologs: mouse all

Genomic context

Location:: 16q22.2

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
109.20191205	current	GRCh38.p13 (GCF_000001405.39)	16	NC_000016.10 (72054505..72061056)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (72088470..72094955)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Haptoglobin phenotype is significantly associated with the presence of coronary endothelial dysfunction and a determinant of HDL-bound hemoglobin content, specifically in diabetes mellitus. Genetic susceptibility for endothelial dysfunction determined by the haptoglobin polymorphism and may provide a mechanistic explanation of the association between impaired HDL function and endothelial dysfunction.
Title: Haptoglobin Phenotype Is Associated With High-Density Lipoprotein-Bound Hemoglobin Content and Coronary Endothelial Dysfunction in Patients With Mild Nonobstructive Coronary Artery Disease.
the angiogenic effects of prohaptoglobin are dependent on PlGF and mediated via a TGF-beta1-ALK1-Smad1/5-PlGF/VEGFR1-VEGF-A/VEGFR2 signaling pathway.
Title: Involvement of placental growth factor upregulated via TGF-β1-ALK1-Smad1/5 signaling in prohaptoglobin-induced angiogenesis.
The Hp1 allele has five exons and is conserved among species. The Hp2 allele is human-specific and has seven exons. The Hp1-Hp1 genotype was showed to be associated to T2DM according to additive and dominant models, but Hp2 allele carriers contributed with higher Hp levels in T2DM as compared to controls.
Title: Haptoglobin levels are influenced by Hp1-Hp2 polymorphism, obesity, inflammation, and hypertension in type 2 diabetes mellitus.
This comprehensive IPLD analysis, carefully controlling for covariates, refutes previous studies showing that HP1-1 associates with better outcome after aneurysmal subarachnoid hemorrhage.
Title: Haptoglobin genotype and aneurysmal subarachnoid hemorrhage: Individual patient data analysis.
identified two proteins, haptoglobin and fibrinogen, as potential biomarker-candidates of fibromyalgia
Title: Insight into the biological pathways underlying fibromyalgia by a proteomic approach.
Increased risk of the Hp 1-1/2-1 phenotypes for developing actinic keratoses (AK) compared with Hp 2-2 patients; patients carrying the Hp 1-1 type developed squamous cell carcinoma (SCC) at an earlier age. Hp 1-1 and to a lesser extent Hp 2-1 seems to increase the risk for AK and SCC in sun-exposed areas as compared with the Hp 2-2 phenotype.
Title: Haptoglobin polymorphism and the risk of actinic keratoses and cutaneous squamous cell carcinoma: A case-control study.
The rs2000999 polymorphism in the haptoglobin-encoding gene Mexican carriers have increased levels of Low Density Cholesterol and total Cholesterol independently of Type 2 Diabetes diagnosis, and also increased concentrations of High-Density Lipoprotein Cholesterol in the Type 2 Diabetes sample.
Title: Association of rs2000999 in the haptoglobin gene with total cholesterol, HDL-C, and LDL-C levels in Mexican type 2 diabetes patients.
data lead to the hypothesis that kidney iron deposition is increased among Hp 2-2 carriers with albuminuria in type 1 diabetes
Title: Is Magnetic Resonance Imaging Detection of Kidney Iron Deposition Increased in Haptoglobin 2-2 Genotype Carriers with Type 1 Diabetes?
Hp 1-1 genotype, which is 2-fold (approximately 30%) more prevalent among African American individuals than among individuals of white race/ethnicity, was associated with poorer cognitive function and greater cognitive decline than the other Hp genotypes.
Title: Association of the Haptoglobin Gene Polymorphism With Cognitive Function and Decline in Elderly African American Adults With Type 2 Diabetes: Findings From the Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND) Study.
Higher CSF ceruloplasmin, haptoglobin, and VEGF are associated with a significantly greater likelihood of HIV-associated neurocognitive disorders.
Title: Cerebrospinal Fluid Ceruloplasmin, Haptoglobin, and Vascular Endothelial Growth Factor Are Associated with Neurocognitive Impairment in Adults with HIV Infection.

Submit: New GeneRIF Correction See all GeneRIFs (275)

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

Associated conditions

Description	Tests
Anhaptoglobinemia MedGen: C3279786 OMIM: 614081 GeneReviews: Not available	Compare labs

NHGRI GWAS Catalog

Description
A genome-wide association study identifies rs2000999 as a strong genetic determinant of circulating haptoglobin levels. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Biological, clinical and population relevance of 95 loci for blood lipids. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

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

Homology

Homologs of the HP gene: The HP gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, and rat.
Orthologs from Annotation Pipeline: 72 organisms have orthologs with human gene HP
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
antioxidant activity	IEA Inferred from Electronic Annotation more info
hemoglobin binding	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
serine-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Process	Evidence Code	Pubs
acute inflammatory response	IBA Inferred from Biological aspect of Ancestor more info	PubMed
acute-phase response	IEA Inferred from Electronic Annotation more info
cellular oxidant detoxification	IEA Inferred from Electronic Annotation 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
neutrophil degranulation	TAS Traceable Author Statement more info
positive regulation of cell death	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of cell death	IDA Inferred from Direct Assay more info	PubMed
proteolysis	IEA Inferred from Electronic Annotation more info
receptor-mediated endocytosis	TAS Traceable Author Statement more info
response to hydrogen peroxide	IDA Inferred from Direct Assay more info	PubMed
response to organic substance	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Component	Evidence Code	Pubs
blood microparticle	HDA more info	PubMed
endocytic vesicle lumen	TAS Traceable Author Statement more info
extracellular exosome	HDA more info	PubMed
extracellular region	NAS Non-traceable Author Statement more info	PubMed
extracellular region	TAS Traceable Author Statement more info
extracellular space	HDA more info	PubMed
extracellular space	IBA Inferred from Biological aspect of Ancestor more info	PubMed
extracellular space	IDA Inferred from Direct Assay more info	PubMed
haptoglobin-hemoglobin complex	IDA Inferred from Direct Assay more info	PubMed
specific granule lumen	TAS Traceable Author Statement more info
tertiary granule lumen	TAS Traceable Author Statement more info

General protein information

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Preferred Names: haptoglobin

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

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

4897..11447

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001126102.2 → NP_001119574.1 haptoglobin isoform 2 preproprotein

See identical proteins and their annotated locations for NP_001119574.1

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, BJ994335

Consensus CDS

CCDS45525.1

UniProtKB/Swiss-Prot

P00738

UniProtKB/TrEMBL

Q6PEJ8

Related

ENSP00000381199.2, ENST00000398131.6

Conserved Domains (3) summary

cd00033
Location:33 → 87

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

smart00020
Location:102 → 340

Tryp_SPc; Trypsin-like serine protease

cd00190
Location:103 → 343

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 ...
NM_001318138.2 → NP_001305067.1 haptoglobin isoform 3 preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks two alternate in-frame exons in the coding region, compared to variant 1. It encodes isoform 3, which is shorter than isoform 1.

Source sequence(s)

AC009087, BC017862, BC121124, BJ994335

Consensus CDS

CCDS82010.1

UniProtKB/Swiss-Prot

P00738

UniProtKB/TrEMBL

A0A0C4DGL8, Q6PEJ8

Related

ENSP00000454966.1, ENST00000565574.5

Conserved Domains (3) summary

cd00033
Location:33 → 87

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

smart00020
Location:102 → 340

Tryp_SPc; Trypsin-like serine protease

cd00190
Location:103 → 343

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 ...
NM_005143.5 → NP_005134.1 haptoglobin isoform 1 preproprotein

See identical proteins and their annotated locations for NP_005134.1

Status: REVIEWED

Description

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

Source sequence(s)

AC009087, AK314700, BC017862, BJ994335

Consensus CDS

CCDS45524.1

UniProtKB/Swiss-Prot

P00738

UniProtKB/TrEMBL

Q6PEJ8

Related

ENSP00000348170.5, ENST00000355906.10

Conserved Domains (3) summary

cd00033
Location:33 → 87

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

smart00020
Location:161 → 399

Tryp_SPc; Trypsin-like serine protease

cd00190
Location:162 → 402

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 ...