OLFM4 (olfactomedin 4)

2010-01-01 Wenli Liu , Griffin P Rodgers Affiliation

Molecular, 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

OLFM4

LOCATION

13q14.3

IMAGE

LOCUSID

10562

ALIAS

GC1,GW112,OLM4,OlfD,UNQ362,bA209J19.1,hGC-1,hOLfD

FUSION GENES

Show Gene Fusions

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.

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.

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)

100

200

300

400

500

600

700

800

900

1000

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

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)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
19450592	2009	OLFM4 is a robust marker for stem cells in human intestine and marks a subset of colorectal cancer cells.	160
22484627	2012	A genome-wide association meta-analysis identifies new childhood obesity loci.	137
21415212	2011	Genomic loss of miR-486 regulates tumor progression and the OLFM4 antiapoptotic factor in gastric cancer.	95
22187488	2012	Olfactomedin 4 defines a subset of human neutrophils.	47
16566923	2006	The glycoprotein hGC-1 binds to cadherin and lectins.	35
19670418	2009	Serum olfactomedin 4 (GW112, hGC-1) in combination with Reg IV is a highly sensitive biomarker for gastric cancer patients.	34
21986994	2011	A quantitative proteomic approach of the different stages of colorectal cancer establishes OLFM4 as a new nonmetastatic tumor marker.	34
22844115	2012	Olfactomedin 4 inhibits cathepsin C-mediated protease activities, thereby modulating neutrophil killing of Staphylococcus aureus and Escherichia coli in mice.	30
18281536	2008	Reduced hGC-1 protein expression is associated with malignant progression of colon carcinoma.	28
20724538	2010	Olfactomedin 4 is a novel target gene of retinoic acids and 5-aza-2'-deoxycytidine involved in human myeloid leukemia cell growth, differentiation, and apoptosis.	26

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