Details for: HPR

Gene ID: 3250

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: HPR

Ensembl ID: ENSG00000261701

Description: haptoglobin-related protein

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • midzonal region hepatocyte CL0019028
    CSI 8.2
    rCSI 19.25%
    PRS 97.7
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 7.15
    rCSI 8.66%
    PRS 89.97
  • cardiac muscle cell CL0000746
    CSI 7.06
    rCSI 10.13%
    PRS 96.66
  • regulatory T cell CL0000815
    CSI 6.41
    rCSI 7.43%
    PRS 95.03
  • hepatocyte CL0000182
    CSI 3.17
    rCSI 5.68%
    PRS 97.96
  • periportal region hepatocyte CL0019026
    CSI 3.08
    rCSI 11.96%
    PRS 97.56
  • innate lymphoid cell CL0001065
    CSI 2.8
    rCSI 5.77%
    PRS 95.66
  • helper T cell CL0000912
    CSI 2.59
    rCSI 3.66%
    PRS 95.99
  • centrilobular region hepatocyte CL0019029
    CSI 2.3
    rCSI 6.01%
    PRS 97.26
  • regular ventricular cardiac myocyte CL0002131
    CSI 2.13
    rCSI 13.29%
    PRS 97.01
  • cytotoxic T cell CL0000910
    CSI 1.93
    rCSI 11.04%
    PRS 96.55

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [HPR](/details-gene/3250) (haptoglobin-related protein) is a protein-coding gene located on chromosome 16q22.2. Structurally and functionally related to haptoglobin ([Link](https://doi.org/10.1016/s0021-9258(18)88836-6)), [HPR](/details-gene/3250) is primarily known for its role as a secreted plasma protein with a high affinity for hemoglobin ([Link](https://doi.org/10.1182/blood-2006-05-022327)). Its main function involves scavenging free heme from the plasma to prevent oxidative damage. Expression data indicates that **Overall**, [HPR](/details-gene/3250) shows the highest significance in liver cells, specifically [midzonal region hepatocytes](/details-cell/CL0019028), which is consistent with its role in systemic protein secretion. Notably, it also demonstrates significant expression in various immune subsets, including [CD8-positive, alpha-beta memory T cells](/details-cell/CL0001203), and in [cardiac muscle cells](/details-cell/CL0000746), suggesting more localized or specialized functions beyond its systemic role. A clinical association for this gene is recorded in OMIM ([140210](https://omim.org/entry/140210)). ## Cellular Roles and Expression Landscape The **Overall** expression profile of [HPR](/details-gene/3250) underscores its dual importance in hepatic function and the immune system. The gene exhibits its highest significance in [midzonal region hepatocytes](/details-cell/CL0019028) (CSI: 8.20), with strong signals also observed in general [hepatocytes](/details-cell/CL0000182) and their sub-regions. This hepatic-centric pattern is consistent with the liver's primary role in synthesizing and secreting plasma proteins involved in systemic metabolic and detoxification processes. Beyond the liver, [HPR](/details-gene/3250) is a significant marker across multiple T lymphocyte populations. It is highly ranked in [CD8-positive, alpha-beta memory T cells, CD45RO-positive](/details-cell/CL0001203) (CSI: 7.15), [regulatory T cells](/details-cell/CL0000815) (CSI: 6.41), [helper T cells](/details-cell/CL0000912) (CSI: 2.59), and [cytotoxic T cells](/details-cell/CL0000910) (CSI: 1.93). This broad and high expression within the T cell compartment, supported by observations of its transcriptional activity in leukemic T-cell lines ([Link](https://doi.org/10.1089/dna.1996.15.1001)), suggests a potential cell-intrinsic role in T cell biology, possibly related to local iron handling or signaling. A third prominent site of [HPR](/details-gene/3250) significance is in [cardiac muscle cells](/details-cell/CL0000746) (CSI: 7.06). This suggests a potential localized, protective function within the heart, where managing oxidative stress is critical. ## Pathways and Molecular Function The annotated functions of [HPR](/details-gene/3250) align closely with its identity as a hemoglobin-scavenging protein. Its primary molecular function is defined by [hemoglobin binding](/details-go/GO:0030492), and it is also annotated with [serine-type endopeptidase activity](/details-go/GO:0004252). As a secreted protein, it is found in the [extracellular space](/details-go/GO:0005615) and is a component of [blood microparticles](/details-go/GO:0072562) and [extracellular exosomes](/details-go/GO:0070062), highlighting its role in systemic circulation and intercellular communication. Functionally, [HPR](/details-gene/3250) is a key player in the [Scavenging of heme from plasma](/details-pathway/R-HSA-2168880) pathway. This process is critical for preventing the toxic effects of free heme, which can catalyze the formation of reactive oxygen species and induce inflammation. This role is executed through its participation in the [Binding and uptake of ligands by scavenger receptors](/details-pathway/R-HSA-2173782) pathway, where the HPR-hemoglobin complex is cleared, primarily by hepatocytes and macrophages. Its association with [Vesicle-mediated transport](/details-pathway/R-HSA-5653656) further supports its involvement in the secretion and uptake of extracellular factors. ## Research Directions While the role of [HPR](/details-gene/3250) in systemic heme scavenging is well-established, its high significance in specific non-hepatic cell types like T cells and cardiomyocytes opens new avenues for investigation. The existing data prompts several testable hypotheses. 1. **Hypothesis 1:** [HPR](/details-gene/3250) expression in T cells provides a cell-intrinsic mechanism to mitigate oxidative stress during inflammation or activation, thereby influencing T cell survival, differentiation, and memory formation. 2. **Hypothesis 2:** In [cardiac muscle cells](/details-cell/CL0000746), [HPR](/details-gene/3250) acts as a local defense mechanism to scavenge heme released during myocardial injury or ischemia-reperfusion, thus limiting tissue damage and supporting cardiac function. To test the first hypothesis regarding its function in T cells, a key experiment would be to use a T-cell-specific conditional knockout mouse model (e.g., Lck-Cre or CD4-Cre crossed with Hpr-floxed mice). These mice could be subjected to an immune challenge, such as viral infection (e.g., LCMV). The primary and memory T cell responses could then be characterized in detail by comparing knockout and wild-type animals. Endpoints would include T cell proliferation (e.g., Ki67 staining), effector function (cytokine production), and the size and quality of the memory T cell pool, as assessed by flow cytometry and functional assays. This approach would elucidate whether the T-cell-intrinsic expression of [HPR](/details-gene/3250) is essential for an effective adaptive immune response. Given its function as a protective, secreted protein, [HPR](/details-gene/3250) holds therapeutic potential as a biologic rather than a target for inhibition. An **augmentation** strategy using recombinant [HPR](/details-gene/3250) protein could be explored for diseases characterized by excessive hemolysis, such as sickle cell anemia or severe malaria. In these conditions, the endogenous haptoglobin system is often overwhelmed, leading to heme-mediated kidney injury and vascular dysfunction. Supplementing with recombinant [HPR](/details-gene/3250) could restore heme-scavenging capacity, reduce oxidative stress, and mitigate end-organ damage.

Genular Protein ID: 2363720509

Symbol: HPTR_HUMAN

Name: Haptoglobin-related protein

UniProtKB Accession Codes:

P00739 Q7LE20 Q92658 Q92659 Q9ULB0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CORUM 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 3 EMBL 11 Ensembl 1 ExpressionAtlas 1 GO 7 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MEROPS 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PIRSF 1 PRIDE 1 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 1 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 4018023

Title: Structure and expression of the human haptoglobin locus.

PubMed ID: 4018023

DOI: 10.1002/j.1460-2075.1985.tb02325.x

PubMed ID: 2987228

Title: Nucleotide sequence of the haptoglobin and haptoglobin-related gene pair. The haptoglobin-related gene contains a retrovirus-like element.

PubMed ID: 2987228

DOI: 10.1016/s0021-9258(18)88836-6

PubMed ID: 1478675

Title: Junctions between genes in the haptoglobin gene cluster of primates.

PubMed ID: 1478675

DOI: 10.1016/s0888-7543(05)80116-8

PubMed ID: 15616553

Title: The sequence and analysis of duplication-rich human chromosome 16.

PubMed ID: 15616553

DOI: 10.1038/nature03187

PubMed ID: 8945641

Title: Transcriptionally active haptoglobin-related (Hpr) gene in Hepatoma G2 and leukamia molt-4 cells.

PubMed ID: 8945641

DOI: 10.1089/dna.1996.15.1001

PubMed ID: 10493829

Title: Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q.

PubMed ID: 10493829

DOI: 10.1006/geno.1999.5927

PubMed ID: 16778136

Title: Haptoglobin-related protein is a high-affinity hemoglobin-binding plasma protein.

PubMed ID: 16778136

DOI: 10.1182/blood-2006-05-022327

PubMed ID: 25037218

Title: A retained secretory signal peptide mediates high density lipoprotein (HDL) assembly and function of haptoglobin-related protein.

PubMed ID: 25037218

DOI: 10.1074/jbc.m114.567578

Sequence Information:

  • Length: 348
  • Mass: 39030
  • Checksum: CF9EC3352B8182FA
  • Sequence:
    • MSDLGAVISL LLWGRQLFAL YSGNDVTDIS DDRFPKPPEI ANGYVEHLFR YQCKNYYRLR 
TEGDGVYTLN DKKQWINKAV GDKLPECEAV CGKPKNPANP VQRILGGHLD AKGSFPWQAK 
MVSHHNLTTG ATLINEQWLL TTAKNLFLNH SENATAKDIA PTLTLYVGKK QLVEIEKVVL 
HPNYHQVDIG LIKLKQKVLV NERVMPICLP SKNYAEVGRV GYVSGWGQSD NFKLTDHLKY 
VMLPVADQYD CITHYEGSTC PKWKAPKSPV GVQPILNEHT FCVGMSKYQE DTCYGDAGSA 
FAVHDLEEDT WYAAGILSFD KSCAVAEYGV YVKVTSIQHW VQKTIAEN