FZD6 (Frizzled Class Receptor 6)
Wnt Signaling Pathway Receptor and Its Role in Development and Disease
Gene Information Card
| Symbol | FZD6 |
|---|---|
| Full Name | Frizzled Class Receptor 6 |
| Gene Type | Protein coding |
| Chromosomal Location | 8q22.3 |
| NCBI Gene ID | 8323 ncbi.nlm.nih.gov/gene/8323 |
| Ensembl ID | ENSG00000164930 |
| UniProt ID | O60353 |
| OMIM ID | 603409 |
| HGNC ID | 4044 |
| Aliases | Fz-6, Frizzled-6, FZD6_HUMAN |
Description
FZD6 encodes a member of the frizzled family of seven-transmembrane domain receptors that function in the Wnt signaling pathway. FZD6 is involved in planar cell polarity (PCP) signaling, embryonic development, and tissue morphogenesis. Mutations in FZD6 are associated with autosomal recessive nail dysplasia and have been implicated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Nail Dysplasia, Autosomal Recessive (NDNC10) | Loss-of-function mutations in FZD6 disrupt Wnt/PCP signaling, impairing nail development. | ClinVar, OMIM |
| Colorectal Cancer | FZD6 overexpression activates Wnt/β-catenin signaling, promoting tumor growth. | COSMIC, NCBI |
| Breast Cancer | FZD6 upregulation correlates with poor prognosis and metastasis via non-canonical Wnt signaling. | COSMIC, NCBI |
| Gastric Cancer | FZD6 overexpression enhances cell proliferation and invasion through Wnt pathway activation. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.5 | Medium |
| Kidney | 8.3 | Low |
| Lung | 7.1 | Low |
| Brain | 5.6 | Low |
| Liver | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.0 | Embryonic kidney cells; high expression |
| HeLa | 10.2 | Cervical cancer cells; moderate expression |
| MCF7 | 8.5 | Breast cancer cells; moderate expression |
| HCT 116 | 12.8 | Colorectal cancer cells; high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1108C>T (p.Arg370*) | Nonsense | Rare | Loss of function; associated with nail dysplasia |
| c.1237G>A (p.Gly413Arg) | Missense | Rare | Loss of function; associated with nail dysplasia |
| c.1465C>T (p.Arg489Trp) | Missense | Rare | Loss of function; associated with nail dysplasia |
| c.1573C>T (p.Arg525*) | Nonsense | Rare | Loss of function; associated with nail dysplasia |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations in FZD6 (e.g., p.Arg370*, p.Gly413Arg) result in loss of receptor function, impairing Wnt/PCP signaling and leading to nail dysplasia.
Gain of Function (GOF)
Not well documented; overexpression in cancers may mimic gain-of-function effects.
Dominant Negative (DN)
Not reported for FZD6.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Wnt signaling pathway (KEGG: hsa04310)
• Planar cell polarity pathway (Reactome: R-HSA-4086400)
• Non-canonical Wnt signaling (Reactome: R-HSA-4641262)
Protein Summary
FZD6 is a 706-amino acid seven-transmembrane receptor protein with an N-terminal cysteine-rich domain (CRD) for Wnt ligand binding. It localizes to the plasma membrane and transduces signals primarily through the planar cell polarity (PCP) pathway, involving Dishevelled and Rho GTPases. FZD6 also modulates canonical Wnt/β-catenin signaling in a context-dependent manner.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FZD6 Knockout HEK293 Cell Line | EDJ-KQ307 | Human | 8323 | Details Get a Quote |
| FZD6 Knockout A-549 Cell Line | EDJ-KQ18437 | Human | 8323 | Details Get a Quote |
| FZD6 Knockout HCT 116 Cell Line | EDJ-KQ18438 | Human | 8323 | Details Get a Quote |
| FZD6 Knockout HeLa Cell Line | EDJ-KQ18439 | Human | 8323 | Details Get a Quote |
