GPNMB (Glycoprotein Nmb): A Transmembrane Glycoprotein with Dual Roles in Cancer and Inflammation
Explore the GPNMB gene, its protein product, tissue expression, associated diseases, and mutation landscape. A comprehensive resource for researchers and clinicians.
Gene Information Card
| Symbol | GPNMB |
|---|---|
| Full Name | Glycoprotein Nmb |
| Gene Type | Protein coding |
| Chromosomal Location | 7p15.3 |
| NCBI Gene ID | 10457 ncbi.nlm.nih.gov/gene/10457 |
| Ensembl ID | ENSG00000136235 |
| UniProt ID | Q14956 |
| OMIM ID | 604368 |
| HGNC ID | 4462 |
| Aliases | DC-HIL, HGFIN, NMB, PLDC |
Description
The GPNMB gene encodes glycoprotein Nmb, a type I transmembrane glycoprotein belonging to the melanotransferrin family. It is characterized by a large extracellular domain containing a polycystic kidney disease (PKD) domain and an integrin-binding motif (RGD). GPNMB is expressed in various tissues, including the bone, skin, and immune cells, and plays a role in cell adhesion, migration, and proliferation. It has been implicated in multiple physiological and pathological processes, including osteoblast differentiation, melanosome formation, and immune regulation. Notably, GPNMB is overexpressed in several cancers, where it can promote tumor progression and metastasis, and is also linked to inflammatory conditions and fibrosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (Multiple Types) | Overexpression of GPNMB promotes tumor cell proliferation, migration, and invasion. It can also mediate immunosuppression within the tumor microenvironment by inhibiting T-cell activation. | High expression is observed in breast, melanoma, lung, and liver cancers. Studies show GPNMB expression correlates with poor prognosis and metastasis. (Source: NCBI Gene, COSMIC) |
| Gaucher Disease | GPNMB is a biomarker for alternatively activated macrophages (M2), which accumulate in Gaucher disease. Its expression is elevated in the plasma of patients and may reflect the disease burden. | Elevated soluble GPNMB levels are found in Gaucher disease patients and correlate with disease severity. (Source: NCBI Gene, UniProt) |
| Amyotrophic Lateral Sclerosis (ALS) | GPNMB is expressed in activated microglia and reactive astrocytes in the central nervous system. It may play a role in neuroinflammation and disease progression. | Increased GPNMB expression is found in the spinal cord of ALS patients and in mouse models of the disease. (Source: NCBI Gene) |
| Pigmentary Glaucoma | GPNMB is involved in melanosome formation and is expressed in the trabecular meshwork. Variants in the GPNMB gene have been associated with an increased risk of pigmentary glaucoma. | Genome-wide association studies have linked GPNMB variants to pigmentary glaucoma. (Source: NCBI Gene, OMIM) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 18.2 | High |
| Bone Marrow | 15.1 | High |
| Lung | 12.8 | Medium |
| Spleen | 11.5 | Medium |
| Liver | 8.9 | Medium |
| Brain | 6.3 | Low |
| Heart | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (Lung Carcinoma) | 25.3 | High expression; associated with invasive phenotype. |
| MCF7 (Breast Carcinoma) | 18.7 | Moderate expression; linked to tumor progression. |
| HepG2 (Hepatocellular Carcinoma) | 15.2 | Moderate expression; may contribute to metastasis. |
| K562 (Chronic Myelogenous Leukemia) | 8.4 | Low expression; role in leukemia less defined. |
| SH-SY5Y (Neuroblastoma) | 5.1 | Low expression; potential role in neuronal differentiation. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1493C>T (p.Pro498Leu) | Missense | Rare (<0.1%) | Located in the cytoplasmic tail; may affect intracellular signaling and protein trafficking. |
| c.1126G>A (p.Asp376Asn) | Missense | Rare (<0.1%) | Located in the PKD domain; may alter protein-protein interactions. |
| c.782A>G (p.Asn261Ser) | Missense | Rare (<0.1%) | Located in the extracellular domain; potential effect on ligand binding. |
| c.1540C>T (p.Arg514*) | Nonsense | Very Rare | Introduces a premature stop codon, likely leading to a truncated, non-functional protein. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in GPNMB are rare and not well characterized. A nonsense mutation (p.Arg514*) is predicted to result in a truncated protein lacking the transmembrane and cytoplasmic domains, which would likely impair its function in cell adhesion and signaling.
Gain of Function (GOF)
Gain-of-function mutations are not commonly reported. However, gene amplification and overexpression, rather than specific activating mutations, are the primary mechanisms by which GPNMB contributes to oncogenesis.
Dominant Negative (DN)
No dominant-negative mutations have been described for GPNMB. Its function as a homodimer or heterodimer could theoretically be affected by such mutations, but this has not been experimentally demonstrated.
View complete mutation data：
Gene Ontology (GO)
| • protein binding | • integrin binding |
| • cell adhesion | • cell migration |
| • cell proliferation | • signal transduction |
| • immune response | • melanosome organization |
| • osteoblast differentiation | • negative regulation of T cell activation |
Pathways
• Integrin Signaling Pathway
• PI3K-Akt Signaling Pathway
• MAPK Signaling Pathway
• Regulation of Actin Cytoskeleton
• Antigen Processing and Presentation
Protein Summary
Glycoprotein Nmb (GPNMB) is a type I transmembrane protein with a large extracellular domain, a single transmembrane helix, and a short cytoplasmic tail. The extracellular domain contains a polycystic kidney disease (PKD) domain and an integrin-binding RGD motif. GPNMB is synthesized as a precursor protein that is cleaved to form a mature protein. It can be shed from the cell surface to produce a soluble form. GPNMB functions as a cell adhesion molecule and is involved in cell migration and proliferation. It is highly expressed in various cancers, where it promotes tumor progression and metastasis. It also plays a role in the immune system, particularly in the regulation of macrophage and T-cell function. Its expression is a marker for M2 macrophages and is associated with tissue repair and fibrosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GPNMB Knockout HEK293 Cell Line | EDJ-KQ2335 | Human | 10457 | Details Get a Quote |
| GPNMB Knockout HeLa Cell Line | EDJ-KQ21417 | Human | 10457 | Details Get a Quote |
| GPNMB Knockout A-549 Cell Line | EDJ-KQ22738 | Human | 10457 | Details Get a Quote |
| GPNMB Knockout HCT 116 Cell Line | EDJ-KQ22739 | Human | 10457 | Details Get a Quote |
| GPNMB Knockout THP-1 Cell Line | EDJ-KZ268 | Human | 10457 | Details Get a Quote |
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