# CD177
**CD177**, also known as human neutrophil antigen 2 (HNA-2), NB1, or polycythemia rubra vera-1 (PRV-1), is a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein of about 58 to 64 kDa that is expressed predominantly on human neutrophils and plays a role in neutrophil activation, migration, and the presentation of the autoantigen proteinase 3.[1](https://www.ncbi.nlm.nih.gov/gene/57126) • [2](https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1653587/pdf) The gene is a member of the leukocyte antigen 6 (Ly-6) superfamily, sits on chromosome 19q13.31, and encodes a protein of 437 amino acids.[2](https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1653587/pdf)
| Key fact | Detail |
|---|---|
| Protein type | GPI-anchored glycoprotein of 58–64 kDa, Ly-6 family, 437 amino acids, no transmembrane domain[2](https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1653587/pdf) • [3](https://onlinelibrary.wiley.com/doi/full/10.1111/voxs.12536) |
| Gene location | Chromosome 19q13.31, 9 exons, with a downstream pseudogene CD177P1[3](https://onlinelibrary.wiley.com/doi/full/10.1111/voxs.12536) |
| Expression pattern | Present on 40–60% of neutrophils in most donors (range 0–100%); completely absent in 3–5% of healthy individuals (CD177-null)[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC6409342/) • [2](https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1653587/pdf) |
| Binding partners | Proteinase 3 (PR3), PECAM-1 (CD31), β2 integrins (CD11b/CD18), and human IgG Fc[2](https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1653587/pdf) • [5](https://pubmed.ncbi.nlm.nih.gov/39131159/) |
| Transfusion relevance | Anti-HNA-2 isoantibodies are implicated in neonatal alloimmune neutropenia, transfusion-related acute lung injury, and graft rejection[3](https://onlinelibrary.wiley.com/doi/full/10.1111/voxs.12536) |
| Clinical biomarker | The CD177/CD10 ratio on neutrophils distinguished infection from non-infectious inflammation with an AUC of 0.92 at a cutoff of 6.07 in a 2025 prospective cohort[6](https://www.sciencedirect.com/science/article/pii/S235239642500550X) |
| Disease association | Overexpressed (as PRV-1) in polycythemia rubra vera; mutations associated with myeloproliferative diseases[1](https://www.ncbi.nlm.nih.gov/gene/57126) |
## Structure and expression
CD177 was first described in 1971 as the neutrophil-specific antigen NB1, in a case of neonatal neutropenia.[3](https://onlinelibrary.wiley.com/doi/full/10.1111/voxs.12536) The protein is tethered to the neutrophil membrane by a GPI anchor rather than a transmembrane domain, so it cannot transmit signals into the cell on its own; signaling occurs through partner molecules such as β2 integrins with which it associates at the neutrophil surface.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC6409342/) The mature glycoprotein carries three potential [N-linked glycosylation](https://www.edgepedia.org/n-linked-glycosylation) sites and is found both on the plasma membrane and in secondary (specific) granules.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC6257083/) • [8](https://pmc.ncbi.nlm.nih.gov/articles/PMC411062/)
Expression is bimodal and stable within an individual. In most donors, CD177 appears on 40 to 60 percent of circulating neutrophils, with individual values ranging from 0 to 100 percent, and the fraction remains constant over time in healthy people.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC6409342/) • [2](https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1653587/pdf) About 3 to 5 percent of the population are CD177-null, with no detectable CD177 on any neutrophils; these individuals are healthy, with normal neutrophil function.[2](https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1653587/pdf) • [3](https://onlinelibrary.wiley.com/doi/full/10.1111/voxs.12536) The proportion of CD177-positive neutrophils is higher in women than in men, rises during pregnancy, and increases to nearly 90 percent after several days of G-CSF administration to healthy subjects.[3](https://onlinelibrary.wiley.com/doi/full/10.1111/voxs.12536) • [8](https://pmc.ncbi.nlm.nih.gov/articles/PMC411062/) CD177 appears during terminal neutrophil differentiation, peaking in band cells, and is also expressed at lower levels on monocytes and lymphocytes.[3](https://onlinelibrary.wiley.com/doi/full/10.1111/voxs.12536) • [2](https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1653587/pdf)
## Function in neutrophils
**Proteinase 3 presentation.** CD177 is required for the surface presentation of proteinase 3 (PR3), a serine protease normally stored in primary granules; among activated neutrophils, the CD177-positive and PR3-positive subsets are identical.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC6409342/) PR3 docks on the neutrophil surface largely through CD177, mediated by a hydrophobic patch on the C-terminus of PR3, and this interaction aids neutrophil transmigration through the endothelium.[3](https://onlinelibrary.wiley.com/doi/full/10.1111/voxs.12536) • [7](https://pmc.ncbi.nlm.nih.gov/articles/PMC6257083/) Because PR3 is the target of antineutrophil cytoplasmic antibodies (ANCA), the CD177/PR3 complex, together with CD11b/CD18 in lipid rafts, transduces the activation signals triggered by anti-PR3 antibodies, driving neutrophil activation and degranulation.[3](https://onlinelibrary.wiley.com/doi/full/10.1111/voxs.12536)
**Migration and adhesion.** CD177 binds PECAM-1 (CD31), an adhesion molecule at endothelial cell junctions, an interaction essential for neutrophil transendothelial migration in vitro and dependent on calcium.[2](https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1653587/pdf) Ligation of CD177 with the antibody MEM166 selectively impairs migration of CD177-positive neutrophils in a PECAM-1-independent transwell system: the cells become activated through cooperation between CD177 and β2 integrins, increase surface β2 integrin expression and affinity, reduce internalization of integrin adhesions, and show ERK-mediated impairment of chemokine signaling, so they immobilize and spread rather than migrate.[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC5680608/) [In vivo](https://www.edgepedia.org/in-vivo), however, CD177-positive and CD177-negative neutrophils migrate equally to inflamed joints, the peritoneum, and the oral cavity, leaving the physiological significance of the in vitro findings uncertain.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC6409342/) • [9](https://pmc.ncbi.nlm.nih.gov/articles/PMC5680608/)
**Inflammatory effector functions.** Under pathological conditions, high CD177 expression facilitates neutrophil activation, adhesion, migration, and release of inflammatory cytokines, and CD177-positive neutrophils modulate the formation of neutrophil extracellular traps (NETs).[2](https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1653587/pdf) Exogenous CD177 protein inhibits NETosis and neutrophil-mediated cytotoxicity, an effect that depends on heterophilic binding of CD177 to CD31 and SHP-1 phosphorylation.[2](https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1653587/pdf) A 2024 study identified human IgG as a ligand for CD177, establishing CD177 as a novel IgG Fc receptor whose genetic variants affect IgG-mediated functions such as antibody-dependent cell-mediated cytotoxicity.[5](https://pubmed.ncbi.nlm.nih.gov/39131159/)
## Genetics of CD177 expression
The molecular basis of the bimodal expression pattern is complex. The CD177-null phenotype is associated with the missense mutation c.787A>T in exon 7, which introduces a premature stop codon (Lysine 263 Stop); this variant arises from gene conversion of exon 7 of the adjacent pseudogene CD177P1 into the CD177 gene.[3](https://onlinelibrary.wiley.com/doi/full/10.1111/voxs.12536) Because some CD177-null individuals carry the c.787A>T variant only in the heterozygous state, additional mechanisms must contribute: the c.1291G>A polymorphism (Gly431Arg) in exon 9, located in the hydrophobic GPI-signal region, destabilizes the protein at the neutrophil surface, and epigenetic mechanisms such as [DNA methylation](https://www.edgepedia.org/dna-methylation) of the CD177 promoter have also been implicated.[3](https://onlinelibrary.wiley.com/doi/full/10.1111/voxs.12536) The percentage of CD177-positive neutrophils and the presence of two expression subsets are associated with five single-nucleotide polymorphisms.[10](https://pubmed.ncbi.nlm.nih.gov/21912255/)
## Clinical roles
**Transfusion medicine.** Antibodies against HNA-2 arise when CD177-null individuals are exposed to CD177-positive cells during pregnancy, transfusion, or transplantation.[3](https://onlinelibrary.wiley.com/doi/full/10.1111/voxs.12536) These isoantibodies are involved in [neonatal alloimmune neutropenia](https://www.edgepedia.org/neonatal-alloimmune-neutropenia), transfusion-related acute lung injury (TRALI), and graft rejection, and passive transfer from the mother through the placenta can destroy fetal neutrophils.[3](https://onlinelibrary.wiley.com/doi/full/10.1111/voxs.12536) In an ex vivo rat lung model, anti-CD77 isoantibodies induced neutrophil activation and reactive oxygen species production dependent on surface antigen density.[3](https://onlinelibrary.wiley.com/doi/full/10.1111/voxs.12536)
**Critical care biomarker.** A 2025 prospective cohort study of 219 healthy volunteers and 145 patients evaluated the ratio of CD177 to CD10 expression on polymorphonuclear neutrophils as a marker of infection in critically ill patients.[6](https://www.sciencedirect.com/science/article/pii/S235239642500550X) At a cutoff of 6.07, the ratio differentiated non-septic infection from sepsis with an area under the curve of 0.92, exceeding CRP and PCT (0.85 each), and it also separated non-infectious inflammation from non-septic infection.[6](https://www.sciencedirect.com/science/article/pii/S235239642500550X) A dynamic subtyping system based on whether the ratio rose, fell, or stayed stable stratified prognosis: patients with a rising ratio had a 7-day mortality rate of 62.5 percent, while those with decreasing and stable patterns had survival rates of 85 and 92.59 percent, respectively.[6](https://www.sciencedirect.com/science/article/pii/S235239642500550X) The authors noted that the thresholds require validation in a multi-center trial.[6](https://www.sciencedirect.com/science/article/pii/S235239642500550X)
**Inflammatory and malignant disease.** CD177-positive neutrophils have been identified as regulators of the BMP signaling pathway in inflammatory bowel disease, sepsis, and intestinal tumors, with shared key genes including [BMP2](https://www.edgepedia.org/bmp2), BMP4, BMP6, BMP8A, and CD177.[11](https://www.sciencedirect.com/science/article/pii/S1936523325000671) In Behçet's disease, CD177-positive neutrophils promote endothelial senescence through extracellular traps.[12](https://www.sciencedirect.com/science/article/pii/S0003496725016577) In cancer, CD177 expression shows a dual pattern: high expression on neutrophils in colorectal and gastric tumors correlates positively with overall and disease-free survival, whereas CD177-positive tumor-infiltrating regulatory T cells, about 22.4 percent of tumor-infiltrating Tregs in breast cancer and 16.8 percent in [clear cell renal carcinoma](https://www.edgepedia.org/clear-cell-renal-carcinoma), show enhanced immunosuppressive capability and correlate with poor prognosis.[2](https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1653587/pdf) In myelodysplastic syndrome, the proportion of CD177-positive neutrophils is decreased, and CD177 serves as a flow cytometry marker for the condition.[2](https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1653587/pdf) Overexpression of the gene, historically named PRV-1, has been found in patients with polycythemia rubra vera, and mutations in the gene are associated with myeloproliferative diseases.[1](https://www.ncbi.nlm.nih.gov/gene/57126) • [8](https://pmc.ncbi.nlm.nih.gov/articles/PMC411062/)
## References
1. [CD177 CD177 molecule [Homo sapiens (human)], NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/57126)
2. [Yang D and Hu X (2025). Unveiling CD177: a key player in tumors, autoimmune diseases, and inflammatory disorders. Frontiers in Immunology](https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1653587/pdf)
3. [Bayat B (2020). Molecular basis of human neutrophil antigen 2 (HNA-2) expression. ISBT Science Series](https://onlinelibrary.wiley.com/doi/full/10.1111/voxs.12536)
4. [Neutrophil Heterogeneity as Therapeutic Opportunity in Immune-Mediated Disease, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC6409342/)
5. [CD177 is a novel IgG Fc receptor and CD177 genetic variants affect IgG-mediated function, PubMed](https://pubmed.ncbi.nlm.nih.gov/39131159/)
6. [Dynamic CD177/CD10 ratio for infection diagnosis and mortality risk stratification in critically ill patients, ScienceDirect](https://www.sciencedirect.com/science/article/pii/S235239642500550X)
7. [Molecular Genetics of the Human Neutrophil Antigens, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC6257083/)
8. [CD177: A member of the Ly-6 gene superfamily involved with neutrophil proliferation and polycythemia vera, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC411062/)
9. [CD177 modulates human neutrophil migration through activation-mediated integrin and chemoreceptor regulation, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC5680608/)
10. [Developments in the definition and clinical impact of human neutrophil antigens, PubMed](https://pubmed.ncbi.nlm.nih.gov/21912255/)
11. [Regulatory role of CD177+ neutrophils in BMP signaling pathway and its implications for inflammatory bowel disease, sepsis, and intestinal tumors, ScienceDirect](https://www.sciencedirect.com/science/article/pii/S1936523325000671)
12. [POS0237 CD177+ neutrophils promote endothelial senescence through extracellular traps in Behçet's disease, Annals of the Rheumatic Diseases](https://www.sciencedirect.com/science/article/pii/S0003496725016577)
---
*Topic: Encyclopedia › Life and health › Biological foundations › Genetics and genomic reference › Human gene and locus records › Receptors and membrane protein genes › Toll-like and immune cell receptors*
*Initially written Oct 21, 2026*
*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*
License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license