Seroatlas · Human Serome Atlas

HRG

Histidine-rich glycoprotein

Also known as: HPRG, HRG_HUMAN, HRGP

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P04196
Gene
HRG
Ensembl
ENSG00000113905
Chromosome
3
Canonical length
525 aa
Protein class
Disease related genes, Human disease related genes, Plasma proteins, Predicted secreted proteins
Secretome location
Secreted to blood

OverviewNCBI Gene

This histidine-rich glycoprotein contains two cystatin-like domains and is located in plasma and platelets. The physiological function has not been determined but it is known that the protein binds heme, dyes and divalent metal ions. The encoded protein also has a peptide that displays antimicrobial activity against C. albicans, E. coli, S. aureus, P. aeruginosa, and E. faecalis. It can inhibit rosette formation and interacts with heparin, thrombospondin and plasminogen. Two of the protein's effects, the inhibition of fibrinolysis and the reduction of inhibition of coagulation, indicate a potential prothrombotic effect. Mutations in this gene lead to thrombophilia due to abnormal histidine-rich glycoprotein levels. [provided by RefSeq, Nov 2014]

Canonical amino-acid sequenceUniProt

525 residues, UniProt reviewed canonical sequence.

>P04196|HRG
     1  MKALIAALLL ITLQYSCAVS PTDCSAVEPE AEKALDLINK RRRDGYLFQL LRIADAHLDR
    61  VENTTVYYLV LDVQESDCSV LSRKYWNDCE PPDSRRPSEI VIGQCKVIAT RHSHESQDLR
   121  VIDFNCTTSS VSSALANTKD SPVLIDFFED TERYRKQANK ALEKYKEEND DFASFRVDRI
   181  ERVARVRGGE GTGYFVDFSV RNCPRHHFPR HPNVFGFCRA DLFYDVEALD LESPKNLVIN
   241  CEVFDPQEHE NINGVPPHLG HPFHWGGHER SSTTKPPFKP HGSRDHHHPH KPHEHGPPPP
   301  PDERDHSHGP PLPQGPPPLL PMSCSSCQHA TFGTNGAQRH SHNNNSSDLH PHKHHSHEQH
   361  PHGHHPHAHH PHEHDTHRQH PHGHHPHGHH PHGHHPHGHH PHGHHPHCHD FQDYGPCDPP
   421  PHNQGHCCHG HGPPPGHLRR RGPGKGPRPF HCRQIGSVYR LPPLRKGEVL PLPEANFPSF
   481  PLPHHKHPLK PDNQPFPQSV SESCPGKFKS GFPQVSMFFT HTFPK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HRG can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Secreted
Secreted
Yes
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.46
Highest tissue expression
5,081 nTPM

Expression across tissuesHPA

Tissue

  • liver: 5,081 nTPM
  • kidney: 29 nTPM
  • spleen: 0.2 nTPM
  • adipose tissue: 0.1 nTPM
  • heart muscle: 0.1 nTPM
  • pancreas: 0.1 nTPM

Single-cell type

  • hepatocytes: 513 nCPM
  • kupffer cells: 9.2 nCPM
  • distal convoluted tubule cells: 6.7 nCPM
  • loop of henle epithelial cells: 4 nCPM
  • cholangiocytes: 3.9 nCPM
  • renal connecting tubule cells: 2.1 nCPM

Immune cell

  • basophil: 0 nTPM
  • classical monocyte: 0 nTPM
  • eosinophil: 0 nTPM
  • gdT-cell: 0 nTPM
  • intermediate monocyte: 0 nTPM
  • MAIT T-cell: 0 nTPM

Brain region

  • amygdala: 0 nTPM
  • basal ganglia: 0 nTPM
  • cerebellum: 0 nTPM
  • cerebral cortex: 0 nTPM
  • choroid plexus: 0 nTPM
  • hippocampal formation: 0 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HRG.

Disease | AllUniProt

Conditions HRG is implicated in, by any mechanism.

  • Thrombophilia due to histidine-rich glycoprotein deficiency (THPH11) MIM:613116

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 160 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

  • Hereditary thrombophilia due to congenital histidine-rich (poly-L) glycoprotein deficiency
  • Familial early-onset deep venous thrombosis

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
1.5
gnomAD pLI
0
gnomAD missense Z
-0.37
DepMap mean gene effect
-0.03
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of HRG in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads HRG as an antibody target. Whether an autoantibody or antibody against HRG could matter depends on whether native HRG is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

HRG is annotated as secreted, so native HRG circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.

Annotation status

The present source text does not explicitly label HRG as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/HRG. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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