GPNMB
Transmembrane glycoprotein NMB
Also known as: GPNMB_HUMAN, HGFIN, NMB
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q14956
- Gene
- GPNMB
- Ensembl
- ENSG00000136235
- Chromosome
- 7
- Canonical length
- 572 aa
- Protein class
- Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins
- Secretome location
- Intracellular and membrane
OverviewNCBI Gene
The protein encoded by this gene is a type I transmembrane glycoprotein which shows homology to the pMEL17 precursor, a melanocyte-specific protein. GPNMB shows expression in the lowly metastatic human melanoma cell lines and xenografts but does not show expression in the highly metastatic cell lines. GPNMB may be involved in growth delay and reduction of metastatic potential. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
572 residues, UniProt reviewed canonical sequence.
>Q14956|GPNMB
1 MECLYYFLGF LLLAARLPLD AAKRFHDVLG NERPSAYMRE HNQLNGWSSD ENDWNEKLYP
61 VWKRGDMRWK NSWKGGRVQA VLTSDSPALV GSNITFAVNL IFPRCQKEDA NGNIVYEKNC
121 RNEAGLSADP YVYNWTAWSE DSDGENGTGQ SHHNVFPDGK PFPHHPGWRR WNFIYVFHTL
181 GQYFQKLGRC SVRVSVNTAN VTLGPQLMEV TVYRRHGRAY VPIAQVKDVY VVTDQIPVFV
241 TMFQKNDRNS SDETFLKDLP IMFDVLIHDP SHFLNYSTIN YKWSFGDNTG LFVSTNHTVN
301 HTYVLNGTFS LNLTVKAAAP GPCPPPPPPP RPSKPTPSLA TTLKSYDSNT PGPAGDNPLE
361 LSRIPDENCQ INRYGHFQAT ITIVEGILEV NIIQMTDVLM PVPWPESSLI DFVVTCQGSI
421 PTEVCTIISD PTCEITQNTV CSPVDVDEMC LLTVRRTFNG SGTYCVNLTL GDDTSLALTS
481 TLISVPDRDP ASPLRMANSA LISVGCLAIF VTVISLLVYK KHKEYNPIEN SPGNVVRSKG
541 LSVFLNRAKA VFFPGNQEKD PLLKNQEFKG VSLocalizationUniProt · AlphaFold · HPA
Whether an antibody against GPNMB 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
- Cell surface
- Secreted
- No
- Transmembrane segments
- 1
- Mean surface accessibility (rSASA)
- 0.4
- Highest tissue expression
- 548 nTPM
Expression across tissuesHPA
Tissue
- skin: 548 nTPM
- heart muscle: 302 nTPM
- cervix: 286 nTPM
- gallbladder: 254 nTPM
- lung: 203 nTPM
- blood vessel: 182 nTPM
Single-cell type
- melanocytes: 1,124 nCPM
- hofbauer cells: 548 nCPM
- kupffer cells: 374 nCPM
- macrophages: 361 nCPM
- basal keratinocytes: 316 nCPM
- fibroblasts: 287 nCPM
Immune cell
- intermediate monocyte: 3.9 nTPM
- classical monocyte: 2.1 nTPM
- basophil: 0.6 nTPM
- neutrophil: 0.5 nTPM
- total PBMC: 0.5 nTPM
- myeloid DC: 0.4 nTPM
Brain region
- choroid plexus: 134 nTPM
- white matter: 110 nTPM
- thalamus: 44 nTPM
- medulla oblongata: 38 nTPM
- pons: 36 nTPM
- spinal cord: 29 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about GPNMB.
Disease | AllUniProt
Conditions GPNMB is implicated in, by any mechanism.
- Amyloidosis, primary localized cutaneous, 3 (PLCA3) MIM:617920
Disease | GeneticClinVar
16 pathogenic / likely-pathogenic of 139 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Amyloidosis, primary localized cutaneous, 3
- GPNMB-related disorder
- Familial cancer of breast
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)
- 1.68
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.12
- DepMap mean gene effect
- -0.01
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- cell adhesion
- cell-cell signaling
- negative regulation of cell population proliferation
- negative regulation of cytokine production
- negative regulation of G1/S transition of mitotic cell cycle
- negative regulation of T cell activation
- negative regulation of T cell proliferation
- negative regulation of tumor necrosis factor production
- positive chemotaxis
- positive regulation of cell migration
- positive regulation of ERK1 and ERK2 cascade
- regulation of angiogenesis
- regulation of tissue remodeling
- signal transduction
Molecular functions
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads GPNMB as an antibody target. Whether an autoantibody or antibody against GPNMB could matter depends on whether native GPNMB is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
GPNMB is annotated at the cell surface, where native GPNMB is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label GPNMB as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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