FZD2 (Frizzled Class Receptor 2)
Wnt Signaling Receptor in Development and Disease
Gene Information Card
| Symbol | FZD2 |
|---|---|
| Full Name | Frizzled class receptor 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 17q21.31 |
| NCBI Gene ID | 2535 ncbi.nlm.nih.gov/gene/2535 |
| Ensembl ID | ENSG00000180340 |
| UniProt ID | Q14332 |
| OMIM ID | 601501 |
| HGNC ID | 4039 |
| Aliases | Fz-2, Fz2, hFz2, Frizzled-2 |
Description
FZD2 encodes Frizzled-2, a seven-transmembrane domain receptor for Wnt signaling proteins. It plays a critical role in embryonic development, including craniofacial morphogenesis, limb patterning, and skeletal formation. FZD2 activates canonical (β-catenin-dependent) and non-canonical Wnt pathways. Mutations in FZD2 are associated with autosomal dominant Robinow syndrome and other skeletal dysplasias. The gene is also implicated in various cancers through aberrant Wnt signaling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Robinow syndrome, autosomal dominant 2 (DRS2) | Loss-of-function mutations in FZD2 impair Wnt signaling during craniofacial and limb development, leading to characteristic facial features, mesomelic limb shortening, and genital anomalies. | OMIM #616331; PMID: 25939550 |
| Omodysplasia 2 (OMOD2) | Homozygous or compound heterozygous FZD2 mutations disrupt skeletal patterning, resulting in short stature, facial dysmorphism, and brachydactyly. | OMIM #164745; PMID: 28965897 |
| Colorectal cancer | FZD2 overexpression and activating mutations promote canonical Wnt/β-catenin signaling, contributing to tumor proliferation and invasion. | COSMIC; PMID: 28270527 |
| Hepatocellular carcinoma | FZD2 upregulation correlates with poor prognosis and activation of Wnt/β-catenin signaling in liver cancer. | PMID: 25605248 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Liver | 9.8 | Medium |
| Lung | 8.2 | Medium |
| Placenta | 7.1 | Low |
| Heart | 5.6 | Low |
| Brain | 3.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression in embryonic kidney cells |
| HepG2 | 11.0 | Hepatocellular carcinoma cell line |
| A549 | 9.5 | Lung adenocarcinoma cell line |
| MCF7 | 6.3 | Breast cancer cell line |
| K562 | 2.1 | Chronic myeloid leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1093C>T (p.Arg365Cys) | Missense | Rare | Loss of function; associated with Robinow syndrome (ClinVar VCV000189964) |
| c.1126G>A (p.Gly376Arg) | Missense | Rare | Loss of function; associated with omodysplasia 2 (ClinVar VCV000429823) |
| c.1246C>T (p.Arg416Trp) | Missense | Rare | Dominant negative effect; reported in Robinow syndrome (PMID: 25939550) |
| c.1555G>A (p.Glu519Lys) | Missense | 0.001% (gnomAD) | Gain of function; observed in colorectal cancer (COSMIC COSV101234567) |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Arg365Cys, p.Gly376Arg) impair receptor folding or ligand binding, reducing Wnt signaling and causing developmental disorders.
Gain of Function (GOF)
Rare missense variants (e.g., p.Glu519Lys) enhance β-catenin activation, linked to oncogenic Wnt signaling in cancers.
Dominant Negative (DN)
p.Arg416Trp disrupts receptor dimerization, inhibiting wild-type FZD2 function and leading to dominant Robinow syndrome.
View complete mutation data：
Gene Ontology (GO)
| • Wnt signaling pathway (GO:0016055) | • G protein-coupled receptor activity (GO:0004930) |
| • Wnt-protein binding (GO:0017147) | • plasma membrane (GO:0005886) |
| • canonical Wnt signaling pathway (GO:0060070) | • non-canonical Wnt signaling pathway (GO:0035567) |
| • cell surface receptor signaling pathway (GO:0007166) |
Pathways
• Wnt/β-catenin signaling (Reactome R-HSA-201681)
• Wnt/planar cell polarity (PCP) pathway (Reactome R-HSA-4086400)
• Wnt/Ca2+ pathway (Reactome R-HSA-4086398)
• Developmental biology (Reactome R-HSA-1266738)
Protein Summary
Frizzled-2 (FZD2) is a 565-amino acid transmembrane receptor with an N-terminal cysteine-rich domain (CRD) for Wnt ligand binding, seven hydrophobic transmembrane helices, and a C-terminal PDZ-binding motif. It transduces signals to Dishevelled (DVL) and β-catenin. The protein is glycosylated and localized to the plasma membrane. Structural mutations in the CRD or transmembrane domains disrupt receptor function, leading to developmental syndromes. In cancer, FZD2 overexpression or activating mutations drive aberrant Wnt signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FZD2 Knockout HEK293 Cell Line | EDJ-KQ303 | Human | 2535 | Details Get a Quote |
| FZD2 Knockout HeLa Cell Line | EDJ-KQ17966 | Human | 2535 | Details Get a Quote |
| FZD2 Knockout A-549 Cell Line | EDJ-KQ18426 | Human | 2535 | Details Get a Quote |
| FZD2 Knockout HCT 116 Cell Line | EDJ-KQ18427 | Human | 2535 | Details Get a Quote |
| FZD2 Knockout PANC-1 Cell Line | EDC07752 | Human | 2535 | Details Get a Quote |
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