SFRP5 (Secreted Frizzled Related Protein 5)
A key modulator of WNT signaling with roles in metabolic and inflammatory diseases
Gene Information Card
| Symbol | SFRP5 |
|---|---|
| Full Name | Secreted Frizzled Related Protein 5 |
| Gene Type | protein-coding |
| Chromosomal Location | 10q24.1 |
| NCBI Gene ID | 6425 ncbi.nlm.nih.gov/gene/6425 |
| Ensembl ID | ENSG00000120057 |
| UniProt ID | Q5T4F7 |
| OMIM ID | 604158 |
| HGNC ID | 10778 |
| Aliases | FRP-5, SARP3, MGC119277 |
Description
SFRP5 encodes a member of the secreted frizzled-related protein (SFRP) family, which functions as a soluble modulator of WNT signaling. By binding to WNT ligands, SFRP5 inhibits canonical WNT/β-catenin pathway activation. It is highly expressed in adipose tissue and plays a critical role in adipogenesis, insulin sensitivity, and inflammation. Dysregulation of SFRP5 is implicated in metabolic disorders (obesity, type 2 diabetes), cardiovascular disease, and several cancers (e.g., colorectal, breast, gastric).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Obesity | Reduced SFRP5 expression in adipose tissue leads to increased WNT signaling, promoting adipocyte hypertrophy and chronic low-grade inflammation. | PMID: 20023638, 21947058 |
| Type 2 Diabetes | SFRP5 deficiency impairs insulin sensitivity via WNT-mediated inhibition of PPARγ and GLUT4 expression. | PMID: 21947058, 23395176 |
| Colorectal Cancer | Epigenetic silencing (promoter hypermethylation) of SFRP5 results in constitutive WNT activation, driving tumorigenesis. | PMID: 15173019, 17363565 |
| Breast Cancer | Loss of SFRP5 expression correlates with poor prognosis and increased WNT signaling in triple-negative breast cancer. | PMID: 23209149 |
| Cardiovascular Disease | SFRP5 levels are inversely associated with coronary artery disease; it suppresses WNT-induced vascular inflammation. | PMID: 23395176 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 12.5 | Medium |
| Heart | 8.3 | Low |
| Liver | 6.1 | Low |
| Pancreas | 4.7 | Low |
| Colon | 3.2 | Low |
| Breast | 2.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Adipocytes (differentiated) | 15.2 | High expression in mature adipocytes |
| HepG2 | 2.1 | Low expression |
| MCF7 | 1.5 | Low expression |
| HT-29 | 0.8 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | missense | <0.01% | Likely loss of start codon; predicted loss of function |
| c.202C>T (p.Arg68Trp) | missense | <0.01% | Unknown significance; rare in population databases |
| Promoter hypermethylation | epigenetic | Variable in tumors | Silences SFRP5 expression; common in colorectal cancer |
Mutation functional classification
Loss of Function (LOF)
Promoter hypermethylation leading to transcriptional silencing is the primary loss-of-function mechanism in cancer. Rare missense variants (e.g., p.Arg68Trp) may impair WNT-binding ability.
Gain of Function (GOF)
No documented gain-of-function mutations in SFRP5.
Dominant Negative (DN)
No evidence of dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
Pathways
• WNT signaling pathway (KEGG: hsa04310)
• Adipogenesis (Reactome: R-HSA-381340)
• Regulation of insulin sensitivity (Reactome: R-HSA-163685)
Protein Summary
SFRP5 is a 317-amino-acid secreted glycoprotein containing a cysteine-rich domain (CRD) homologous to the WNT-binding domain of Frizzled receptors. It acts as a decoy receptor, sequestering WNT ligands (e.g., WNT3A, WNT5A) to prevent activation of the canonical WNT/β-catenin pathway. In adipose tissue, SFRP5 promotes adipocyte differentiation and insulin sensitivity while suppressing inflammatory cytokine production. Its expression is epigenetically silenced in many cancers, contributing to uncontrolled WNT signaling and tumor progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SFRP5 Knockout HEK293 Cell Line | EDJ-KQ333 | Human | 6425 | Details Get a Quote |
| SFRP5 Knockout HeLa Cell Line | EDJ-KQ54449 | Human | 6425 | Details Get a Quote |
| SFRP5 Knockout A-549 Cell Line | EDJ-KQ62938 | Human | 6425 | Details Get a Quote |
| SFRP5 Knockout HCT 116 Cell Line | EDJ-KQ71409 | Human | 6425 | Details Get a Quote |
