FZD4 Gene: Frizzled Class Receptor 4
Key regulator of Wnt signaling, associated with familial exudative vitreoretinopathy and bone density disorders
Gene Information Card
| Symbol | FZD4 |
|---|---|
| Full Name | Frizzled Class Receptor 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q14.2 |
| NCBI Gene ID | 8322 ncbi.nlm.nih.gov/gene/8322 |
| Ensembl ID | ENSG00000174804 |
| UniProt ID | Q9ULV1 |
| OMIM ID | 604579 |
| HGNC ID | 4042 |
| Aliases | Fz-4, Frizzled-4, CD344, EVR1, FEVR, Fz4, hFz4 |
Description
The FZD4 gene encodes a member of the frizzled family of seven-transmembrane domain receptors that function as receptors for Wnt signaling proteins. FZD4 plays a critical role in the canonical Wnt/β-catenin signaling pathway, which regulates cell proliferation, differentiation, and angiogenesis. Mutations in FZD4 are primarily associated with familial exudative vitreoretinopathy (FEVR), a disorder of retinal vascular development, and have also been linked to osteoporosis and bone density variation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Familial exudative vitreoretinopathy (FEVR) | Loss-of-function mutations impair Wnt signaling, disrupting retinal angiogenesis | ClinVar, OMIM |
| Osteoporosis | Variants in FZD4 affect Wnt/β-catenin signaling, altering bone mineral density | NCBI Gene, OMIM |
| Retinopathy of prematurity | FZD4 mutations may contribute to abnormal retinal vascularization | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Retina | 15.3 | High |
| Lung | 8.2 | Low |
| Kidney | 6.7 | Low |
| Bone | 9.1 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 18.4 | High expression in embryonic kidney cells |
| HUVEC | 14.2 | Endothelial cells, relevant to angiogenesis |
| MCF7 | 7.8 | Breast cancer cell line, moderate expression |
| SH-SY5Y | 11.5 | Neuroblastoma cell line, medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.313G>A (p.Gly105Arg) | Missense | Rare | Loss of function, associated with FEVR |
| c.205C>T (p.Arg69Cys) | Missense | Rare | Impaired Wnt signaling, FEVR |
| c.1120C>T (p.Arg374Ter) | Nonsense | Rare | Truncated protein, loss of function, FEVR |
| c.1465G>A (p.Gly489Arg) | Missense | Rare | Dominant negative effect, FEVR |
Mutation functional classification
Loss of Function (LOF)
Most FEVR-associated mutations (e.g., p.Gly105Arg, p.Arg374Ter) reduce or abolish FZD4 receptor activity, impairing Wnt/β-catenin signaling.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in FZD4.
Dominant Negative (DN)
Some missense mutations (e.g., p.Gly489Arg) act in a dominant-negative manner, interfering with wild-type FZD4 function.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • Wnt-protein binding |
| • Wnt signaling pathway | • canonical Wnt signaling pathway |
| • cell surface receptor signaling pathway | • angiogenesis |
| • retinal blood vessel morphogenesis | • plasma membrane |
Pathways
• Wnt/β-catenin signaling pathway
• Wnt signaling in bone metabolism
• Retinal angiogenesis
Protein Summary
FZD4 is a 537-amino acid seven-transmembrane receptor with an N-terminal cysteine-rich domain (CRD) that binds Wnt ligands. It forms a complex with LRP5/6 coreceptors to transduce Wnt signals, stabilizing β-catenin and activating transcription of target genes. The protein is essential for retinal vascular development and bone homeostasis. Mutations in FZD4 disrupt these processes, leading to FEVR and osteoporosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FZD4 Knockout HEK293 Cell Line | EDJ-KQ305 | Human | 8322 | Details Get a Quote |
| FZD4 Knockout A-549 Cell Line | EDJ-KQ18431 | Human | 8322 | Details Get a Quote |
| FZD4 Knockout HCT 116 Cell Line | EDJ-KQ18432 | Human | 8322 | Details Get a Quote |
| FZD4 Knockout HeLa Cell Line | EDJ-KQ18433 | Human | 8322 | Details Get a Quote |
