SFRP4 (Secreted Frizzled Related Protein 4)
A key modulator of Wnt signaling with roles in development, metabolism, and cancer
Gene Information Card
| Symbol | SFRP4 |
|---|---|
| Full Name | Secreted Frizzled Related Protein 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 7p14.1 |
| NCBI Gene ID | 6424 ncbi.nlm.nih.gov/gene/6424 |
| Ensembl ID | ENSG00000106483 |
| UniProt ID | Q6FHJ7 |
| OMIM ID | 606570 |
| HGNC ID | 10778 |
| Aliases | FRP-4, FRPHE, sFRP-4, SFRP4_HUMAN |
Description
SFRP4 encodes a member of the secreted frizzled-related protein (SFRP) family, which functions as modulators of Wnt signaling. The protein contains a cysteine-rich domain homologous to the Wnt-binding site of frizzled receptors, allowing it to bind Wnt ligands and inhibit canonical and non-canonical Wnt pathways. SFRP4 is involved in developmental processes, regulation of bone mass, insulin secretion, and is frequently epigenetically silenced in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Endometrial cancer | Epigenetic silencing of SFRP4 leads to aberrant Wnt activation, promoting tumor growth | PMID: 19029981; COSMIC |
| Colorectal cancer | Promoter hypermethylation reduces SFRP4 expression, contributing to Wnt pathway dysregulation | PMID: 15122354; COSMIC |
| Type 2 diabetes | Reduced SFRP4 expression in pancreatic islets impairs insulin secretion | PMID: 23395171; ClinVar |
| Osteoporosis | SFRP4 variants associated with low bone mineral density | PMID: 26973436; ClinVar |
| Phelan-McDermid syndrome | Deletion of 7p14.1 including SFRP4 may contribute to phenotype | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 12.5 | Medium |
| Bone marrow | 8.3 | Low |
| Colon | 15.2 | Medium |
| Endometrium | 20.1 | High |
| Pancreas | 18.7 | High |
| Prostate | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 5.2 | Low expression |
| HCT116 (colorectal cancer) | 2.1 | Very low (hypermethylated) |
| HeLa (cervical cancer) | 8.9 | Medium |
| K562 (leukemia) | 1.5 | Very low |
| HepG2 (liver cancer) | 11.3 | Medium |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | missense | <0.1% | Likely loss of start codon; ClinVar |
| c.202C>T (p.Arg68Trp) | missense | <0.1% | Uncertain significance; ClinVar |
| c.563G>A (p.Arg188Gln) | missense | <0.1% | Uncertain significance; ClinVar |
| Promoter hypermethylation | epigenetic | Common in cancers | Transcriptional silencing; COSMIC |
Mutation functional classification
Loss of Function (LOF)
Promoter hypermethylation leading to transcriptional silencing is the primary loss-of-function mechanism in cancers. Rare missense variants may also reduce protein function.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in SFRP4.
Dominant Negative (DN)
No evidence of dominant-negative effects for SFRP4 mutations.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Wnt signaling pathway (KEGG: hsa04310)
• Regulation of Wnt-mediated beta-catenin signaling (Reactome: R-HSA-4641263)
Protein Summary
SFRP4 is a secreted protein of approximately 346 amino acids (UniProt Q6FHJ7) that contains a signal peptide and a frizzled-like cysteine-rich domain (CRD). It binds directly to Wnt ligands, preventing their interaction with frizzled receptors and thereby inhibiting both canonical (β-catenin-dependent) and non-canonical Wnt signaling. The protein is implicated in bone homeostasis, adipogenesis, and pancreatic β-cell function. Altered expression or epigenetic silencing of SFRP4 is associated with several cancers and metabolic disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SFRP4 Knockout HEK293 Cell Line | EDJ-KQ4986 | Human | 6424 | Details Get a Quote |
| SFRP4 Knockout A-549 Cell Line | EDJ-KQ29131 | Human | 6424 | Details Get a Quote |
| SFRP4 Knockout HeLa Cell Line | EDJ-KQ54448 | Human | 6424 | Details Get a Quote |
| SFRP4 Knockout HCT 116 Cell Line | EDJ-KQ71408 | Human | 6424 | Details Get a Quote |
