FZD4

Chr 11q14.2

frizzled class receptor 4

Aliases:: CD344
MANE:: ENST00000531380.2

OMIM: 604579 ↗NCBI: 8322 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

FZD4 · Q9ULV1

v62025-08-01

Predicted Aligned Error matrix for FZD4 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

84.3/ 100

Confident

537 residues

Confidence breakdown

Very high(≥ 90)57%
Confident(70–90)26%
Low(50–70)7%
Very low(< 50)10%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Retinal disorders
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Structural eye disease
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Bilateral congenital or childhood onset cataracts
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Glaucoma (developmental)

Disease associations (Open Targets)

Familial exudative vitreoretinopathy
0.82
Retinal dystrophy
0.51
exudative vitreoretinopathy
0.47
Coats disease
0.43
eye disorder
0.42
retinopathy of prematurity
0.39
persistent hyperplastic primary vitreous
0.38
FZD4-related exudative vitreoretinopathy
0.37
Norrie disease
0.36
retinal disorder
0.27

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Frizzled-4

Receptor for Wnt proteins (PubMed:30135577). Most frizzled receptors are coupled to the beta-catenin (CTNNB1) canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin (CTNNB1) and activation of Wnt target genes (PubMed:30135577). Plays a critical role in retinal vascularization by acting as a receptor for Wnt proteins and norrin (NDP) (By similarity). In retina, it can be activated by Wnt protein-binding and also by Wnt-independent signaling via binding of norrin (NDP), promoting in both cases beta-catenin (CTNNB1) accumulation and stimulation of LEF/TCF-mediated transcriptional programs (By similarity). A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues