OLFM4 (olfactomedin 4)
2010-01-01 Wenli Liu  , Griffin P Rodgers   AffiliationMolecular, Clinical Hematology Branch, National Institute of Diabetes, Digestive, Kidney Diseases, National Institutes of Health, Building 10, Room 9N115, 10 Center Drive, Bethesda, MD 20892, USA
Identity
HGNC
LOCATION
13q14.3
IMAGE

LOCUSID
ALIAS
GC1,GW112,OLM4,OlfD,UNQ362,bA209J19.1,hGC-1,hOLfD
FUSION GENES
DNA/RNA

Description
OLFM4 gene locus was mapped to chromosome 13q14.3 with five exons spanning 23220 bp.
Transcription
OLFM4 is transcribed to 2861 bp mRNA with an open reading frame of 1530 nucleotides. There is no alternative mRNA splicing.
mRNA expression: highly in bone marrow and small intestine; lowly expressed in stomach, colon, pancreas and prostate; no expression is detected in other tissues determined by Northern blot. OLFM4 transcription is regulated by transcription factors, PU1 and NF-kB.
mRNA expression: highly in bone marrow and small intestine; lowly expressed in stomach, colon, pancreas and prostate; no expression is detected in other tissues determined by Northern blot. OLFM4 transcription is regulated by transcription factors, PU1 and NF-kB.
Proteins
Description
OLFM4 encodes a 510 amino acid protein with a molecular weight of 55 kD. OLFM4 has a signal peptide and six N-linked glycosylation motifs and forms disulfide-bonded multimers. It has a N-terminal coil-coil domain and C-terminal olfactomedin domain.
Expression
OLFM4 protein is endogenously expressed in mature neutrophils and gastric and intestinal epithelial cells. Its expression in bone marrow neutrophils is significantly higher than peripheral blood neutrophils. OLFM4 is more abundantly expressed in intestinal crypts than in surface epithelial cells.
Localisation
OLFM4 is localized in multiple subcellular compartments including cytoplasm, mitochondria and membrane. It is also secreted extracellularly.
Function
OLFM4 binds to cadherins and lectins and mediates cell adhesion. OLFM4 is a robust marker for stem cells in human intestine.
Homology
Human OLFM4 is highly homologous to its mouse homologue (pDP4) with 93% amino acid identity. OLFM4 C-terminal olfactomedin domain has significant homology with other olfactomedin-related proteins including olfactomedin, TIGR, Noelin-1, Noeline-2 and latrophilin-1, etc.
Mutations
Note
No known genetic mutation in normal or cancer tissues.
Implicated in
Entity name
Stomach cancer
Note
OLFM4 mRNA expression is upregulated in gastric cancer patients. OLFM4 protein staining by immunohistochemistry was observed more frequently in well-differentiated cancer tissues and more frequently in stage I/II cases than in stage III/IV cases. Serum OLFM4 is a useful marker for gastric cancer patients.
Entity name
Colon cancer
Note
OLFM4 mRNA is upregulated in colon cancer patients. OLFM4 protein expression is correlated with prognosis for colon cancer patients. Lower or lost OLFM4 protein expression is correlated with more malignancy and poor survival.
Entity name
Prostate cancer
Note
OLFM4 mRNA expression is upregulated in prostate cancer patients. OLFM4 interacts with GRIM-19, a mitochondria pro-apoptosis protein and has an anti-apoptotic function in prostate cancer cells when it is overexpressed.
Entity name
Pancreatic cancer
Note
OLFM4 mRNA is upregulated in pancreatic cancer patients. OLFM4 promotes S-phase transition in proliferation of pancreatic cancer cells.
Entity name
Breast cancer
Note
OLFM4 mRNA is upregulated in breast cancer patients.
Entity name
Chronic bowel disease (Crohns disease and ulcerative colitis)
Note
OLFM4 mRNA expression is upregulated in the intestines of chronic bowel disease patients including Crohns disease and ulcerative colitis.
Entity name
H. pylori gastritis
Note
OLFM4 mRNA expression is upregulated in the gastric mucosa of H. pylori infected patients than normal individuals.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 16331256 | 2006 | Systematic search for gastric cancer-specific genes based on SAGE data: melanoma inhibitory activity and matrix metalloproteinase-10 are novel prognostic factors in patients with gastric cancer. | Aung PP et al |
| 18764868 | 2008 | The regulation of OLFM4 expression in myeloid precursor cells relies on NF-kappaB transcription factor. | Chin KL et al |
| 18798264 | 2008 | Identification of new accessible tumor antigens in human colon cancer by ex vivo protein biotinylation and comparative mass spectrometry analysis. | Conrotto P et al |
| 17270022 | 2007 | Olfactomedin 4 promotes S-phase transition in proliferation of pancreatic cancer cells. | Kobayashi D et al |
| 17270020 | 2007 | Specific overexpression of OLFM4(GW112/HGC-1) mRNA in colon, breast and lung cancer tissues detected using quantitative analysis. | Koshida S et al |
| 16566923 | 2006 | The glycoprotein hGC-1 binds to cadherin and lectins. | Liu W et al |
| 18281536 | 2008 | Reduced hGC-1 protein expression is associated with malignant progression of colon carcinoma. | Liu W et al |
| 17650212 | 2007 | Expression of hGC-1 is correlated with differentiation of gastric carcinoma. | Liu W et al |
| 16210872 | 2005 | Genes involved in invasion and metastasis of gastric cancer identified by array-based hybridization and serial analysis of gene expression. | Oue N et al |
| 19670418 | 2009 | Serum olfactomedin 4 (GW112, hGC-1) in combination with Reg IV is a highly sensitive biomarker for gastric cancer patients. | Oue N et al |
| 14962908 | 2004 | pDP4, a novel glycoprotein secreted by mature granulocytes, is regulated by transcription factor PU.1. | Rosenbauer F et al |
| 11302958 | 2001 | Upregulation of Reg 1alpha and GW112 in the epithelium of inflamed colonic mucosa. | Shinozaki S et al |
| 15864715 | 2005 | Molecular-pathological prognostic factors of gastric cancer: a review. | Yasui W et al |
| 11867215 | 2002 | Identification and characterization of a novel member of olfactomedin-related protein family, hGC-1, expressed during myeloid lineage development. | Zhang J et al |
| 15059901 | 2004 | GW112, a novel antiapoptotic protein that promotes tumor growth. | Zhang X et al |
| 19450592 | 2009 | OLFM4 is a robust marker for stem cells in human intestine and marks a subset of colorectal cancer cells. | van der Flier LG et al |
Other Information
Locus ID:
NCBI: 10562
MIM: 614061
HGNC: 17190
Ensembl: ENSG00000102837
Variants:
dbSNP: 10562
ClinVar: 10562
TCGA: ENSG00000102837
COSMIC: OLFM4
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000102837 | ENST00000219022 | Q6UX06 |
| ENSG00000102837 | ENST00000219022 | A0A024QZ95 |
Expression (GTEx)
Pathways
| Pathway | Source | External ID |
|---|---|---|
| Immune System | REACTOME | R-HSA-168256 |
| Innate Immune System | REACTOME | R-HSA-168249 |
| Neutrophil degranulation | REACTOME | R-HSA-6798695 |
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38613883 | 2024 | Blocking OLFM4/galectin-3 axis in placental polymorphonuclear myeloid-derived suppressor cells triggers intestinal inflammation in newborns. | 0 |
| 38613883 | 2024 | Blocking OLFM4/galectin-3 axis in placental polymorphonuclear myeloid-derived suppressor cells triggers intestinal inflammation in newborns. | 0 |
| 36349502 | 2023 | Olfactomedin 4 associates with expression of differentiation markers but not with properties of cancer stemness, EMT nor metastatic spread in colorectal cancer. | 0 |
| 36549285 | 2023 | Olfactomedin-4-Positive Neutrophils in Neonates: Link to Systemic Inflammation and Bronchopulmonary Dysplasia. | 1 |
| 36577836 | 2023 | Olfactomedin 4 produces dysplasia but suppresses metastasis of colon cancer. | 0 |
| 37280213 | 2023 | LRFN5 and OLFM4 as novel potential biomarkers for major depressive disorder: a pilot study. | 3 |
| 36349502 | 2023 | Olfactomedin 4 associates with expression of differentiation markers but not with properties of cancer stemness, EMT nor metastatic spread in colorectal cancer. | 0 |
| 36549285 | 2023 | Olfactomedin-4-Positive Neutrophils in Neonates: Link to Systemic Inflammation and Bronchopulmonary Dysplasia. | 1 |
| 36577836 | 2023 | Olfactomedin 4 produces dysplasia but suppresses metastasis of colon cancer. | 0 |
| 37280213 | 2023 | LRFN5 and OLFM4 as novel potential biomarkers for major depressive disorder: a pilot study. | 3 |
| 34906535 | 2022 | Olfactomedin 4 Is Not a Precise Marker for Human Intestinal Stem Cells, But Is Involved in Intestinal Carcinogenesis. | 4 |
| 35337817 | 2022 | Olfactomedin 4 regulates migration and proliferation of immortalized non-transformed keratinocytes through modulation of the cell cycle machinery and actin cytoskeleton remodelling. | 5 |
| 35410162 | 2022 | Increased expression of OLFM4 and lysozyme during necrotizing enterocolitis in neonates: an observational research study. | 1 |
| 35487976 | 2022 | OLFM4 deficiency delays the progression of colitis to colorectal cancer by abrogating PMN-MDSCs recruitment. | 6 |
| 35806447 | 2022 | New Insights of OLFM2 and OLFM4 in Gut-Liver Axis and Their Potential Involvement in Nonalcoholic Fatty Liver Disease. | 2 |
Citation
Wenli Liu ; Griffin P Rodgers
OLFM4 (olfactomedin 4)
Atlas Genet Cytogenet Oncol Haematol. 2010-01-01
Online version: http://atlasgeneticsoncology.org/gene/49730/olfm4
