HRG
Chr 3ADhistidine rich glycoprotein
Also known as: HPRG, HRGP, THPH11
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]
Moderate evidence — consider for supplementary testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene — mechanism propensity
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
References
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
HRG · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Patritumab Deruxtecan in Patients With Solid Tumor Harboring an NRG1 Fusion
RECRUITINGStudy of an Anti-HER3 Antibody, HMBD-001, With or Without Chemotherapy in Patients With Solid Tumors Harboring an NRG1 Fusion or HER3 Mutation
ACTIVE NOT RECRUITINGEfficacy of Olaparib in Advanced Cancers Occurring in Patients With Germline Mutations or Somatic Tumor Mutations in Homologous Recombination Genes
ACTIVE NOT RECRUITINGA Study of a Selective ERBB2 Inhibitor (CGT4255), in Patients With Advanced Solid Tumors
RECRUITINGA Phase I/IIa Trial of HMBD-001 in Advanced HER3 Positive Solid Tumours
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools