GPNMB (glycoprotein (transmembrane) nmb)

2009-10-01   Shyam A Patel , Philip K Lim , Pranela Rameshwar 

University of Medicine, Dentistry of New Jersey - New Jersey Medical School,Newark, New Jersey, USA





The GPNMB gene maps (Homo sapiens) on the plus strand of chromosome 7p15 between 23,252,841 and 23,281,254 bp from the promoter and spans 28,414 bp.


2 transcript variants:

Variant 1:
- 2775bp, accession #: NM_001005340.1
- the longer transcript
- encodes the longer isoform (isoform a)
- open reading frame from bp 162 to 1880
- 11 exons

Variant 2:
- accession #: NM_002510.2
- undergoes alternative splicing and uses an in-frame splice site
- conserved N- and C-terminals compared to isoform a, but decreased in length



The GPNMB gene, which is the human homolog of murine osteoactivin, encodes a type I transmembrane glycoprotein. It has homology to the melanocyte specific protein precursor pMEL17. GPNMB expression is inversely correlated with aggressiveness of melanoma cell lines. GPNMB is thought to be inversely correlated with metastatic potential, although limited data is available.


Two protein isoforms exist: isoform a: 572 a.a. ; isoform b: 560 a.a. .


GPNMB is expressed in osteoclasts, dendritic cells, macrophages, and breast epithelia. Its expression is nearly undetectable in monocytes but increases upon conversion of monocytes to macrophages.


GPNMB localizes to the plasma membrane, as it is a type I transmembrane glycoprotein. It is also found in melanosomes and membrane-bound vesicles in the cytoplasm.


GPNMB is involved in binding to heparin sulfate and integrins. It functions in mineralization of bone and differentiation of osteoblasts. It also functions in cellular adhesion. It is thought to reduce inflammation involving macrophages.


Homo sapiens GPNMB shares sequence homology with mouse and rat sequences. GPNMB shares structural homology with neurokinin 1 (NK1) and can interact with the NK ligand substance P.

Implicated in

Entity name
Breast cancer
It is unclear to date whether GPNMB plays a tumor suppressive role or oncogenic role in breast cancer.
In a murine model, osteoactivin (OA) has been associated with enhanced invasiveness of breast cancer cells in vivo, and forced overexpression of OA in weakly bone metastatic cells lines resulted in increased migratory and invasive characteristics in vitro (Rose et al., 2007). Furthermore, analysis of 51 breast cancer cell lines revealed higher osteoactivin expression than normal breast MCF-12A cells and in estrogen receptor negative breast tumors (Rose and Siegel, 2007). However, other studies with non-tumorigenic human breast cancer cells have shown that there was increased migration and evidence of transformation and loss of contact dependency in the absence of GPNMB/HGFIN (Metz et al., 2007).
Entity name
Glioblastoma multiforme (GBM)
In immunocompromised mice, glioma cells expressing osteoactivin and osteonectin (two strucurally bone-related genes) developed a highly invasive phenotype and invaded the brain along blood vessels when implanted intracranially (Rich et al., 2003).
Evaluation of 50 GBM patient tumor samples revealed that 35 out of 50 samples (70%) were positive for GPNMB wild-type and splice variant transcripts while the remaining 30% were positive for wild-type only (Kuan et al., 2006). This is in contrast to normal brain samples that expressed little or no GPNMB mRNA (Kuan et al., 2006).
Detection of GPNMB mRNA and surface membrane protein in glioma cells may potentially be used as a tumor-associated antigen for targeting by therapeutic treatment (Kuan et al., 2006).
Entity name
Analysis of a cDNA library between lowly and highly metastatic human melanoma showed the preferential expresion of GPNMB in low-metastatic cell lines (Weterman et al., 1995). Additionally, transfection of partial GPNMB cDNA into highly-metastatic melanoma cell line resulted in slower subcutaneous tumor growth in nude mice (Weterman et al., 1995).
A potential therapeutic agent in the treatment of malignant melanomas is an antibody-drug conjugate tartgeting GPNMB (Pollack et al., 2007). Intravenous administration of the immunoconjugate in athymic mice with human melanoma xenografts showed inhibition of tumor growth and complete regression of the tumor (Pollack et al., 2007).
Entity name
End-stage kidney disease
Macrophages involved in uremia have elevated levels of GPNMB expression. Its role in end-stage kidney disease may relate to its role in soft tissue calcification and arteriosclerosis (Pahl et al., 2009).
Entity name
Acute liver injury
In normal rat livers, OA was found to be expressed in high levels in Kupffer cells and peritoneal macrophages (Haralanova-Ilieva et al., 2005). Upon induction of acute liver injury after carbon tetrachloride administration, OA expression was upregulated after 2 days and returned to normal levels after 7 days (Haralanova-Ilieva et al., 2005). In normal human liver, OA RNA was not detected while fulminant hepatitis B and C infections, paracetamol intoxication, and liver cirrhosis all resulted in positive OA RNA levels (Haralanova-Ilieva et al., 2005).
Entity name
OA cDNA was found to be overexpressed 3- to 4-fold in rats with osteopetrotic bones when compared to normal rat long bones (Safadi et al., 2001). Furthermore, OA mRNA was primarily localized in cuboidal osteoblasts lining bone surfaces (Safadi et al., 2001).
Osteopetrosis, also known as marble bone disease, is a rare hereditary disease which results in thickening and hardening of bones due to deficient osteoclast activity (Kumar et al., 2003). OA is expressed at highest levels in primary osteoblasts and thus, may account for the imbalance in activity of osteoblasts and osteoclasts in osteopetrosis (Sadafai et al., 2001).


Pubmed IDLast YearTitleAuthors
157633432005Expression of osteoactivin in rat and human liver and isolated rat liver cells.Haralanova-Ilieva B et al
166090062006Glycoprotein nonmetastatic melanoma protein B, a potential molecular therapeutic target in patients with glioblastoma multiforme.Kuan CT et al
178457212007Role of human HGFIN/nmb in breast cancer.Metz RL et al
198339062010Upregulation of monocyte/macrophage HGFIN (Gpnmb/Osteoactivin) expression in end-stage renal disease.Pahl MV et al
175415932007Treatment parameters modulating regression of human melanoma xenografts by an antibody-drug conjugate (CR011-vcMMAE) targeting GPNMB.Pollack VA et al
125901372003Bone-related genes expressed in advanced malignancies induce invasion and metastasis in a genetically defined human cancer model.Rich JN et al
179514012007Osteoactivin promotes breast cancer metastasis to bone.Rose AA et al
180863242007Osteoactivin/HGFIN: is it a tumor suppressor or mediator of metastasis in breast cancer?Rose AA et al
117465122001Cloning and characterization of osteoactivin, a novel cDNA expressed in osteoblasts.Safadi FF et al
78141551995nmb, a novel gene, is expressed in low-metastatic human melanoma cell lines and xenografts.Weterman MA et al

Other Information

Locus ID:

NCBI: 10457
MIM: 604368
HGNC: 4462
Ensembl: ENSG00000136235


dbSNP: 10457
ClinVar: 10457
TCGA: ENSG00000136235


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Signal TransductionREACTOMER-HSA-162582
Signaling by PTK6REACTOMER-HSA-8848021
PTK6 promotes HIF1A stabilizationREACTOMER-HSA-8857538


Pubmed IDYearTitleCitations
256586392015Glioma-associated microglia/macrophages display an expression profile different from M1 and M2 polarization and highly express Gpnmb and Spp1.99
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
166090062006Glycoprotein nonmetastatic melanoma protein B, a potential molecular therapeutic target in patients with glioblastoma multiforme.57
179514012007Osteoactivin promotes breast cancer metastasis to bone.56
207114742010ADAM10 releases a soluble form of the GPNMB/Osteoactivin extracellular domain with angiogenic properties.55
202155302010Glycoprotein nonmetastatic B is an independent prognostic indicator of recurrence and a novel therapeutic target in breast cancer.49
228911582012The potential of GPNMB as novel neuroprotective factor in amyotrophic lateral sclerosis.41
200567112010Glycoprotein nonmetastatic melanoma protein b, a melanocytic cell marker, is a melanosome-specific and proteolytically released protein.32
193207362009Gpnmb is a melanosome-associated glycoprotein that contributes to melanocyte/keratinocyte adhesion in a RGD-dependent fashion.28
193505792009The DC-HIL/syndecan-4 pathway inhibits human allogeneic T-cell responses.27


Shyam A Patel ; Philip K Lim ; Pranela Rameshwar

GPNMB (glycoprotein (transmembrane) nmb)

Atlas Genet Cytogenet Oncol Haematol. 2009-10-01

Online version: