FZD4

Summary

FZD4 (frizzled class receptor 4, HGNC:4042) is a protein-coding gene on chromosome 11q14.2, encoding Frizzled-4 (Q9ULV1). Receptor for Wnt proteins. It is haploinsufficient (ClinGen: sufficient evidence).

This gene is a member of the frizzled gene family. Members of this family encode seven-transmembrane domain proteins that are receptors for the Wingless type MMTV integration site family of signaling proteins. Most frizzled receptors are coupled to the beta-catenin canonical signaling pathway. This protein may play a role as a positive regulator of the Wingless type MMTV integration site signaling pathway. A transcript variant retaining intronic sequence and encoding a shorter isoform has been described, however, its expression is not supported by other experimental evidence.

Source: NCBI Gene 8322 — RefSeq curated summary.

At a glance

• Gene–disease (curated): FZD4-related exudative vitreoretinopathy (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 467 total — 58 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 67
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_012193

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4042
Approved symbol	FZD4
Name	frizzled class receptor 4
Location	11q14.2
Locus type	gene with protein product
Status	Approved
Aliases	CD344
Ensembl gene	ENSG00000174804
Ensembl biotype	protein_coding
OMIM	604579
Entrez	8322

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000531380

RefSeq mRNA: 1 — MANE Select: NM_012193 NM_012193

CCDS: CCDS8279

Canonical transcript exons

ENST00000531380 — 2 exons

Exon	Start	End
ENSE00001200454	86954801	86955395
ENSE00002191517	86945679	86952470

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 95.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.8629 / max 963.6610, expressed in 1497 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121753	25.8401	1494
121754	0.6817	255
121751	0.2338	116
121752	0.1073	45

Top tissues by expression

270 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adipose tissue	UBERON:0001013	95.32	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.14	gold quality
right lung	UBERON:0002167	95.00	gold quality
connective tissue	UBERON:0002384	94.60	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.59	gold quality
omental fat pad	UBERON:0010414	94.50	gold quality
peritoneum	UBERON:0002358	94.47	gold quality
parietal pleura	UBERON:0002400	93.37	gold quality
synovial joint	UBERON:0002217	92.71	gold quality
tendon of biceps brachii	UBERON:0008188	91.89	gold quality
pericardium	UBERON:0002407	91.88	gold quality
seminal vesicle	UBERON:0000998	91.70	gold quality
pleura	UBERON:0000977	91.21	gold quality
diaphragm	UBERON:0001103	90.95	silver quality
right coronary artery	UBERON:0001625	90.33	gold quality
mammary duct	UBERON:0001765	90.30	gold quality
thoracic mammary gland	UBERON:0005200	90.26	gold quality
mammary gland	UBERON:0001911	90.24	gold quality
superficial temporal artery	UBERON:0001614	90.09	gold quality
descending thoracic aorta	UBERON:0002345	90.08	gold quality
tendon	UBERON:0000043	90.07	gold quality
calcaneal tendon	UBERON:0003701	89.94	gold quality
apex of heart	UBERON:0002098	89.81	gold quality
upper lobe of left lung	UBERON:0008952	89.69	gold quality
coronary artery	UBERON:0001621	89.61	gold quality
upper lobe of lung	UBERON:0008948	89.61	gold quality
gluteal muscle	UBERON:0002000	89.52	silver quality
left coronary artery	UBERON:0001626	89.50	gold quality
lower lobe of lung	UBERON:0008949	89.39	gold quality
adrenal tissue	UBERON:0018303	89.32	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.51
E-MTAB-6386	no	13.38

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ERG, FLT3, SPI1

miRNA regulators (miRDB)

295 targeting FZD4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4645-5P	99.98	65.81	1284

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Functions in retinal angiogenesis. Mutations disrupts angiogenesis in vitreoretinopathy. (PMID:12172548)
• High-resolution genotyping and haplotype analysis excluded FZD4 as the defective gene in a family previously linked to the EVR1 locus. (PMID:14737064)
• Familial exudative vitreoretinopathy has mutations in a second gene at the EVR1 locus, low-density-lipoprotein receptor-related protein 5 (LRP5), a Wnt coreceptor (PMID:15024691)
• Eight mutations have been identified in the FZD4 gene in a cohort of 40 unrelated patients with FEVR (familial exudative vitreoretinopathy) (PMID:15223780)
• FZD4 mutations are associated with autosomal dominant familial exudative vitreoretinopathy (PMID:15370539)
• A novel missense mutation in the FZD4 gene was identified in Japanese patients with FEVR (familial exudative vitreoretinopathy). (PMID:15488808)
• mutations in the LRP5 and/or FZD4 genes may have roles in familial exudative vitreoretinopathy (PMID:15981244)
• Mutations in FZD4 were observed in 5.6% of studied clinically diagnosed familial exudative vitreoretinopathy in Indian population. Could play vital role in pathogenesis and provide greater insight in to genotype/phenotypic functions of FZD4 gene. (PMID:17093393)
• Fz4 expression may play a critical role in responses to Wnt signaling in the tumor microenvironment. (PMID:17386109)
• sFRP-1 can interact with Wnt receptors Frizzled 4 and 7 on endothelial cells to transduce downstream to cellular machineries requiring Rac-1 activity in cooperation with GSK-3beta (PMID:18156211)
• Homozygous state for the FZD4 gene is possibly involved in the severity of the familial exudative vitreoretinopathy phenotype (PMID:18161623)
• Report activation of Wnt signalling in acute myeloid leukemia by induction of Frizzled-4. (PMID:19020754)
• The clinical features in the three children and their relatives with a documented FZD4 mutation support the previous reports of a high degree of intrafamilial and interfamilial variability in familial exudative vitreoretinopathy (FEVR). (PMID:19172507)
• Mutations occurring in the FZD4 gene affect patients diagnosed with both autosomal-dominant familial exudative vitreoretinopathy (AdFEVR) or retinopathy of prematurity (ROP) (PMID:20008721)
• Mutations in the FZD4 gene in this group of premature infants supports a role for the FZD4 pathway in the development of severe retinopathy of prematurity. (PMID:20141357)
• Studies report 21 novel variants for FZD4, LRP5, and NDP. (PMID:20340138)
• Results provide mechanistic insights to ERG oncogenesis in prostate cancer, involving activation of WNT signaling through FZD4, leading to cancer-promoting phenotypic effects, including EMT and loss of cell adhesion. (PMID:20713528)
• The profile of the mutations obtained in FZD4 further illustrates the complexity of familial exudative vitreoretinopathy (FEVR)and provides a better understanding of the genotype-phenotype correlations. (PMID:20938005)
• FZD4 mutation screening can be a useful tool especially in mild or atypical cases of familial exudative vitreoretinopathy & Germ-line mutations in FZD4 do not appear to be a common cause of Coats disease. (PMID:21097938)
• Frizzled 4 is a member of the Wnt signaling family that governs both stemness and invasiveness of glioma stem cells, and that it may be a major cause of GBM recurrence and poor prognosis. (PMID:21363911)
• miR-493 is a new tumor suppressor miRNA in bladder cancer and inhibits cell motility through downregulation of RhoC and FZD4. (PMID:22057916)
• Genetic analysis revealed that all affected family members of one pedigree carried an exon 2 mutation of COL2A1, and in the second pedigree, all affected members carried an FZD4 mutation. (PMID:22574936)
• Five mutations have been found in the FZD4 gene in six Chinese families with familial exudative vitreoretinopathy. (PMID:23077402)
• Six different nonsynonymous DNA variants are identified in the coding region of either the FZD4 gene (p.H69Y, p.R127H, and p.Y211H) or the LRP5 gene (p.R1219H, p.H1383P, and p.T1540M) in seven patients with advanced retinopathy of prematurity (PMID:23441120)
• Polymorphisms in several genes involved in the Wnt signaling pathway were associated with hepatic fibrosis or inflammation risk in HCV-infected males. (PMID:24386373)
• Defective trafficking resulting in haploinsufficiency is a major cellular mechanism for several missense FEVR-causing FZD4 mutants. (PMID:24744206)
• analysis of allosteric ligands of Frizzled4 (PMID:25751279)
• The relatively high prevalence of the p.[P33S(;)P168S] variant in ROP (retinopathy of prematurity) and intrauterine growth restriction suggests that it also may be a marker for increased risk of developing ROP and preterm birth. (PMID:26119001)
• These structural, biophysical and cellular data, map Fz4 and putative Lrp5/6 binding sites to distinct patches on Norrin, and reveal a GAG binding site spanning Norrin and Fz4 cysteine-rich domain. (PMID:26158506)
• Mutations of FZD4 accounted for the largest proportion, which could be directly applied to the testing strategy to start with screening for FZD4 mutations. (PMID:26244290)
• Letter: FZD4+ and FZD4- melanocytes were significantly lower in hair follicles of patients with rhododenol-induced leukoderma. (PMID:26277630)
• Two were novel mutations: p.E134* and p.T503fs of FZD4 lead to the loss of FZD4 activity. (PMID:26530129)
• Several novel mutations (missense, non-stop and insertion) were detected in the coding regions of FZD4, TSPAN12 and ZNF408 genes among the unrelated familial exudative vitreoretinopathy probands. The mutations in FZD4 and TSPAN12 were involved in autosomal dominant and autosomal recessive families and further validates the involvement of these gene in exudative vitreoretinopathy development. (PMID:27316669)
• human FZD4 assembles-in a DVL-independent manner-with Galpha12/13 but not representatives of other heterotrimeric G protein subfamilies. (PMID:27458145)
• novel role of let-7b/Fzd4 axis through wnt signaling (PMID:27510711)
• Seven novel mutations found in this study have broadened the spectrum of mutations in FZD4 known to cause familial exudative vitreoretinopathy (FEVR), providing a deeper understanding of this disease. The results show that mutations in FZD4 are associated with the phenotypes of retinal folds or ectopic macula in FEVR (PMID:27555740)
• The findings in this family support the concept that some mutated FZD4 alleles can be associated with recessive rather than dominant disease. (PMID:27668459)
• Three affected individuals within a family with FEVR presented with variable disease severity. All three affected family members harboured mutation c.349T>C (p.Cys117Arg) in FZD4. (PMID:28211206)
• FZD4 down-regulation leads to loss of WNT/beta-catenin signal activity and subsequently to reduced alveolar epithelial cell wound repair capacity and impaired expression of elastogenic components. (PMID:28245136)
• Among the detected mutations, LRP5 accounted for the largest proportion with a mean mutation rate of 16.1% (5/31, 16.1%), followed by NDP (3/31, 9.7%), FZD4 (2/31, 6.5%), TSPAN12 (1/31, 3.2%), and KIF11 (1/31, 3.2%). All the novel changes were predicted to be pathogenic by a series of bioinformatics analyses. (PMID:28494495)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
		ENSDARG00000104117
mus_musculus	Fzd4	ENSMUSG00000049791
rattus_norvegicus	Fzd4	ENSRNOG00000063590
drosophila_melanogaster	fz4	FBGN0027342
caenorhabditis_elegans	lin-17	WBGENE00003006

Paralogs (15): FZD3 (ENSG00000104290), SFRP1 (ENSG00000104332), SFRP4 (ENSG00000106483), FZD10 (ENSG00000111432), SFRP5 (ENSG00000120057), SMO (ENSG00000128602), SFRP2 (ENSG00000145423), FZD7 (ENSG00000155760), FZD1 (ENSG00000157240), FRZB (ENSG00000162998), FZD5 (ENSG00000163251), FZD6 (ENSG00000164930), FZD8 (ENSG00000177283), FZD2 (ENSG00000180340), FZD9 (ENSG00000188763)

Protein

Protein identifiers

Frizzled-4 — Q9ULV1 (reviewed: Q9ULV1)

Alternative names: FzE4

All UniProt accessions (1): Q9ULV1

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for Wnt proteins. 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. Plays a critical role in retinal vascularization by acting as a receptor for Wnt proteins and norrin (NDP). 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. 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.

Subunit / interactions. Interacts with MAGI3 and NDP. Component of a complex, at least composed of TSPAN12, FZD4 and norrin (NDP). Interacts (via FZ domain) with TSKU; TSKU competes with WNT2B for binding to FZD4, inhibiting Wnt signaling and repressing peripheral eye development. Interacts with glypican GPC3.

Subcellular location. Cell membrane.

Tissue specificity. Almost ubiquitous. Largely expressed in adult heart, skeletal muscle, ovary, and fetal kidney. Moderate amounts in adult liver, kidney, pancreas, spleen, and fetal lung, and small amounts in placenta, adult lung, prostate, testis, colon, fetal brain and liver.

Post-translational modifications. Ubiquitinated by ZNRF3, leading to its degradation by the proteasome.

Disease relevance. Vitreoretinopathy, exudative 1 (EVR1) [MIM:133780] An autosomal dominant disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina. This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult. New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness. Clinical features can be highly variable, even within the same family. Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery. In many ways the disease resembles retinopathy of prematurity but there is no evidence of prematurity or small birth weight in the patient history. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway. The FZ domain is involved in binding with Wnt ligands.

Similarity. Belongs to the G-protein coupled receptor Fz/Smo family.

RefSeq proteins (1): NP_036325* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000539	Frizzled/Smoothened_7TM	Domain
IPR015526	Frizzled/SFRP	Family
IPR017981	GPCR_2-like_7TM	Domain
IPR020067	Frizzled_dom	Domain
IPR026551	FZD4_7TM	Domain
IPR036790	Frizzled_dom_sf	Homologous_superfamily
IPR041765	FZ4_CRD	Domain

Pfam: PF01392, PF01534

UniProt features (116 total): helix 25, sequence variant 25, mutagenesis site 20, strand 12, topological domain 8, disulfide bond 8, transmembrane region 7, turn 2, short sequence motif 2, glycosylation site 2, sequence conflict 2, signal peptide 1, chain 1, domain 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
5BPB	X-RAY DIFFRACTION	2.2
5BQE	X-RAY DIFFRACTION	2.3
5BPQ	X-RAY DIFFRACTION	2.4
5CM4	X-RAY DIFFRACTION	2.4
6BD4	X-RAY DIFFRACTION	2.4
5UWG	X-RAY DIFFRACTION	2.56
5BQC	X-RAY DIFFRACTION	3
6NE1	X-RAY DIFFRACTION	3.01
8WMA	ELECTRON MICROSCOPY	3.47
8WM9	ELECTRON MICROSCOPY	3.53
5CL1	X-RAY DIFFRACTION	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULV1-F1	84.79	0.57

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (8): 45–106, 53–99, 90–128, 117–158, 121–145, 181–200, 204–282, 302–377

Glycosylation sites (2): 59, 144

Mutagenesis-validated functional residues (20):

Position	Phenotype
233	increased signaling activity in presence of ndp/norrin but not in presence of wnt3a.
233	slightly increased signaling activity in presence of ndp/norrin and reduced signaling in presence of wnt3a.
250	reduced signaling activity in presence of ndp/norrin.
250	reduced signaling activity.
253	reduced signaling activity in presence of ndp/norrin.
265	slight increase in signaling activity.
269	increased signaling activity.
341	reduced signaling activity in presence of ndp/norrin.
371	no effect on signaling activity.
378	increased signaling activity.
381	slight increase in signaling activity.
399	no effect on signaling activity.
418	increased signaling activity.
444	reduced signaling activity.
455	increased signaling activity in presence of wnt3a but not in presence of ndp/norrin.
458	no effect on signaling activity.
477	increased signaling activity in presence of wnt3a but not in presence of ndp/norrin.
480	increased signaling activity.
494	reduced signaling activity.
496	reduced signaling activity.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-373080	Class B/2 (Secretin family receptors)
R-HSA-4086398	Ca2+ pathway
R-HSA-4608870	Asymmetric localization of PCP proteins
R-HSA-4641263	Regulation of FZD by ubiquitination
R-HSA-5099900	WNT5A-dependent internalization of FZD4
R-HSA-5340588	Signaling by RNF43 mutants
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis

MSigDB gene sets: 537 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_DENDRITE_DEVELOPMENT, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_BEHAVIOR, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_NON_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_REGULATION_OF_DENDRITE_MORPHOGENESIS, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_HORMONE_LEVELS

GO Biological Process (36): angiogenesis (GO:0001525), vasculogenesis (GO:0001570), response to hypoxia (GO:0001666), Wnt signaling pathway, calcium modulating pathway (GO:0007223), sensory perception of sound (GO:0007605), cell population proliferation (GO:0008283), negative regulation of cell-substrate adhesion (GO:0010812), Wnt signaling pathway (GO:0016055), neuron differentiation (GO:0030182), positive regulation of cell migration (GO:0030335), regulation of vascular endothelial growth factor receptor signaling pathway (GO:0030947), locomotion involved in locomotory behavior (GO:0031987), substrate adhesion-dependent cell spreading (GO:0034446), extracellular matrix-cell signaling (GO:0035426), non-canonical Wnt signaling pathway (GO:0035567), progesterone secretion (GO:0042701), endothelial cell differentiation (GO:0045446), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of dendrite morphogenesis (GO:0050775), canonical Wnt signaling pathway (GO:0060070), establishment of blood-brain barrier (GO:0060856), retina vasculature morphogenesis in camera-type eye (GO:0061299), cerebellum vasculature morphogenesis (GO:0061301), retinal blood vessel morphogenesis (GO:0061304), cellular response to retinoic acid (GO:0071300), Norrin signaling pathway (GO:0110135), positive regulation of neuron projection arborization (GO:0150012), cellular response to leukemia inhibitory factor (GO:1990830), luteinization (GO:0001553), blood vessel development (GO:0001568), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), cytokine-mediated signaling pathway (GO:0019221), retina vasculature development in camera-type eye (GO:0061298)

GO Molecular Function (14): amyloid-beta binding (GO:0001540), cytokine receptor activity (GO:0004896), G protein-coupled receptor activity (GO:0004930), Wnt-protein binding (GO:0017147), cytokine binding (GO:0019955), PDZ domain binding (GO:0030165), ubiquitin protein ligase binding (GO:0031625), signaling receptor activity (GO:0038023), protein homodimerization activity (GO:0042803), Wnt receptor activity (GO:0042813), protein-containing complex binding (GO:0044877), protein heterodimerization activity (GO:0046982), transmembrane signaling receptor activity (GO:0004888), protein binding (GO:0005515)

GO Cellular Component (10): nucleoplasm (GO:0005654), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), cilium (GO:0005929), cell surface (GO:0009986), dendrite (GO:0030425), clathrin-coated endocytic vesicle membrane (GO:0030669), glutamatergic synapse (GO:0098978), membrane (GO:0016020), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
PCP/CE pathway	2
GPCR ligand binding	1
Beta-catenin independent WNT signaling	1
TCF dependent signaling in response to WNT	1
Signaling by WNT in cancer	1
Clathrin-mediated endocytosis	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transmembrane signaling receptor activity	3
cellular anatomical structure	3
blood vessel morphogenesis	2
cell differentiation	2
cell-substrate adhesion	2
Wnt signaling pathway	2
protein binding	2
protein dimerization activity	2
binding	2
anatomical structure formation involved in morphogenesis	1
response to stress	1
response to decreased oxygen levels	1
non-canonical Wnt signaling pathway	1
sensory perception of mechanical stimulus	1
cellular process	1
negative regulation of cell adhesion	1
regulation of cell-substrate adhesion	1
cell surface receptor signaling pathway	1
generation of neurons	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
regulation of signal transduction	1
vascular endothelial growth factor receptor signaling pathway	1
regulation of cellular response to growth factor stimulus	1
locomotory behavior	1
locomotion	1
cell communication	1
signaling	1
luteinization	1
cellular process involved in reproduction in multicellular organism	1
ovulation cycle process	1
steroid hormone secretion	1
endothelium development	1
epithelial cell differentiation	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1

Protein interactions and networks

STRING

1702 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FZD4	LRP5	O75197	999
FZD4	NDP	Q00604	999
FZD4	WNT5A	P41221	998
FZD4	TSPAN12	O95859	997
FZD4	LRP6	O75581	996
FZD4	WNT7A	O00755	973
FZD4	WNT7B	P56706	958
FZD4	WNT11	O96014	933
FZD4	DVL2	O14641	919
FZD4	WNT5B	Q9H1J7	900
FZD4	MAGI3	Q5TCQ9	890
FZD4	WNT3A	P56704	882
FZD4	WNT4	P56705	873
FZD4	WNT2B	Q93097	851
FZD4	DVL1	O14640	849

IntAct

149 interactions, top by confidence:

A	B	Type	Score
FZD4	A2M	psi-mi:“MI:0915”(physical association)	0.560
DMWD	FZD4	psi-mi:“MI:0915”(physical association)	0.560
FZD4	DNM2	psi-mi:“MI:0915”(physical association)	0.560
FZD4	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
HTT	FZD4	psi-mi:“MI:0915”(physical association)	0.560
NDP	FZD4	psi-mi:“MI:0915”(physical association)	0.530
FZD4	tcdB	psi-mi:“MI:0407”(direct interaction)	0.440
NHERF1	FZD4	psi-mi:“MI:0407”(direct interaction)	0.440
FZD4	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.440
FZD4	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
FZD4	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
FZD4	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
FZD4	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
MAST2	FZD4	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (18): Dvl3 (Affinity Capture-Western), PDZRN3 (Affinity Capture-Western), RAB5A (Affinity Capture-Western), PDZRN3 (Co-localization), PDZRN3 (Co-fractionation), Dvl3 (Co-fractionation), FZD4 (Two-hybrid), TSPAN15 (Affinity Capture-MS), C4orf32 (Affinity Capture-MS), CD47 (Affinity Capture-MS), CERS6 (Affinity Capture-MS), MPZL1 (Affinity Capture-MS), BAG6 (Two-hybrid), ZNRF3 (Affinity Capture-Western), FZD4 (Affinity Capture-Western)

ESM2 similar proteins: A2YFN7, B8AJT9, C7EXK4, D3K5L7, E1C6Q1, E2R222, O70133, O70496, O94973, O95544, P51798, P51799, P70704, P97834, P98200, Q0VCK5, Q10D38, Q13098, Q15645, Q304A0, Q3UA06, Q4PKH3, Q5JQD7, Q5XHZ9, Q5XIJ5, Q5ZJL4, Q61187, Q67UQ7, Q6DD70, Q6EPN6, Q6GL10, Q6IRE4, Q6NRT5, Q8L5Y9, Q99JW1, Q99K70, Q99LD4, Q9FLG2, Q9HB90, Q9HCX4

Diamond homologs: A0A0K3AWM6, B3DIG4, G5ECQ2, O00144, O19116, O42579, O57328, O57329, O60353, O70421, O75084, O93274, P18537, P58421, P97299, P97401, Q08463, Q08464, Q13467, Q14332, Q24760, Q498S8, Q5BL72, Q5RCN4, Q5RF67, Q5T4F7, Q61086, Q61088, Q61089, Q61090, Q61091, Q6FHJ7, Q7YRN1, Q80YN4, Q863H1, Q8AVJ9, Q8BKG4, Q8C4U3, Q8CHL0, Q8K4C8

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
FZD4	“up-regulates activity”	DVL2	binding
WNT5A	“up-regulates activity”	FZD4	binding
FZD4	“up-regulates activity”	DVL1	binding
FZD4	“up-regulates activity”	DVL3	binding
FZD4	“up-regulates activity”	LRP6	binding
FZD4	“up-regulates activity”	LRP5	binding
ZNRF3	“down-regulates quantity”	FZD4	ubiquitination
RSPO2	“down-regulates quantity”	FZD4	ubiquitination
hsa-miR-493-5p	“down-regulates quantity by repression”	FZD4	“post transcriptional regulation”
FLT3	“up-regulates quantity by expression”	FZD4	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	52.9×	2e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	50.4×	2e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	50.4×	2e-06
Assembly and cell surface presentation of NMDA receptors	10	47.0×	8e-13
Dopamine Neurotransmitter Release Cycle	5	46.0×	2e-06
Long-term potentiation	5	44.1×	2e-06
Neurexins and neuroligins	11	40.1×	4e-13
Protein-protein interactions at synapses	7	34.4×	8e-08

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	70.9×	5e-14
protein localization to synapse	6	56.0×	1e-07
receptor clustering	7	53.3×	1e-08
synaptic vesicle transport	5	51.4×	3e-06
regulation of postsynaptic membrane neurotransmitter receptor levels	7	42.3×	5e-08
negative regulation of ERK1 and ERK2 cascade	5	13.2×	1e-03
protein-containing complex assembly	9	12.5×	3e-06
cell-cell adhesion	10	12.4×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

467 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	58
Likely pathogenic	12
Uncertain significance	250
Likely benign	94
Benign	25

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012989	NM_012193.4(FZD4):c.1322C>G (p.Ser441Ter)	Pathogenic
1068101	NM_012193.4(FZD4):c.757C>T (p.Arg253Cys)	Pathogenic
1071058	NM_012193.4(FZD4):c.118G>T (p.Glu40Ter)	Pathogenic
1396559	NM_012193.4(FZD4):c.1205del (p.Gly402fs)	Pathogenic
1407085	NM_012193.4(FZD4):c.1362T>A (p.Cys454Ter)	Pathogenic
1412236	NM_012193.4(FZD4):c.1380dup (p.Asn461fs)	Pathogenic
1455388	NM_012193.4(FZD4):c.1340del (p.Pro447fs)	Pathogenic
1457991	NM_012193.4(FZD4):c.633del (p.Leu210_Tyr211insTer)	Pathogenic
1506463	NM_012193.4(FZD4):c.341T>C (p.Ile114Thr)	Pathogenic
1706535	NM_012193.4(FZD4):c.1273del (p.Thr425fs)	Pathogenic
1805086	NM_012193.4(FZD4):c.244_245delinsG (p.Phe82fs)	Pathogenic
1806078	NM_012193.4(FZD4):c.173A>G (p.Tyr58Cys)	Pathogenic
1997471	NM_012193.4(FZD4):c.852dup (p.Glu285Ter)	Pathogenic
2005482	NM_012193.4(FZD4):c.607A>T (p.Lys203Ter)	Pathogenic
2015412	NM_012193.4(FZD4):c.827del (p.Gly276fs)	Pathogenic
2018964	NM_012193.4(FZD4):c.1502_1503del (p.Leu501fs)	Pathogenic
2030454	NM_012193.4(FZD4):c.362_366del (p.Cys121fs)	Pathogenic
2032979	NM_012193.4(FZD4):c.42_51dup (p.Gly18fs)	Pathogenic
2133760	NM_012193.4(FZD4):c.8G>A (p.Trp3Ter)	Pathogenic
2137212	NM_012193.4(FZD4):c.957del (p.Trp319fs)	Pathogenic
2159501	NM_012193.4(FZD4):c.182C>T (p.Thr61Ile)	Pathogenic
2169558	NM_012193.4(FZD4):c.1188_1192del (p.Phe396fs)	Pathogenic
224624	NM_012193.4(FZD4):c.313A>G (p.Met105Val)	Pathogenic
2425773	NC_000011.9:g.(?86662184)(86666127_?)del	Pathogenic
268072	GRCh37/hg19 11q14.2(chr11:86561752-86786833)x1	Pathogenic
2721711	NM_012193.4(FZD4):c.25_35del (p.Ser9fs)	Pathogenic
2730480	NM_012193.4(FZD4):c.1511G>A (p.Trp504Ter)	Pathogenic
2735715	NM_012193.4(FZD4):c.1286_1290del (p.Lys429fs)	Pathogenic
2760685	NM_012193.4(FZD4):c.1497_1498del (p.Lys499fs)	Pathogenic
2762482	NM_012193.4(FZD4):c.360del (p.Met120fs)	Pathogenic

SpliceAI

326 predictions. Top by Δscore:

Variant	Effect	Δscore
11:86954824:A:AC	donor_gain	1.0000
11:86954825:C:CC	donor_gain	1.0000
11:86952450:A:C	acceptor_gain	0.9900
11:86954797:CCAC:C	donor_loss	0.9900
11:86954798:CACCT:C	donor_loss	0.9900
11:86954800:C:CA	donor_loss	0.9900
11:86952449:C:CT	acceptor_gain	0.9800
11:86952471:C:CC	acceptor_gain	0.9700
11:86952468:GAA:G	acceptor_gain	0.9300
11:86952443:T:TC	acceptor_gain	0.9200
11:86952262:TCATC:T	donor_gain	0.9100
11:86952467:AGAA:A	acceptor_gain	0.9100
11:86952441:C:CT	acceptor_gain	0.9000
11:86952447:C:CT	acceptor_gain	0.9000
11:86952450:A:AC	acceptor_gain	0.9000
11:86954801:C:G	donor_loss	0.8900
11:86954818:AGC:A	donor_gain	0.8800
11:86952264:A:AC	donor_gain	0.8700
11:86952436:G:C	acceptor_gain	0.8700
11:86952469:AAC:A	acceptor_loss	0.8700
11:86952471:CTGG:C	acceptor_loss	0.8700
11:86954826:T:C	donor_gain	0.8700
11:86954627:CA:C	donor_gain	0.8600
11:86954803:G:A	donor_gain	0.8600
11:86952442:A:C	acceptor_gain	0.8500
11:86952466:AAGAA:A	acceptor_gain	0.8500
11:86952469:AA:A	acceptor_gain	0.8500
11:86952483:CAAAA:C	acceptor_loss	0.8500
11:86954626:A:AC	donor_gain	0.8500
11:86954627:C:CC	donor_gain	0.8500

AlphaMissense

3529 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:86951276:A:G	W494R	1.000
11:86951276:A:T	W494R	1.000
11:86951293:C:T	G488D	1.000
11:86951294:C:G	G488R	1.000
11:86951416:G:C	P447R	1.000
11:86951416:G:T	P447H	1.000
11:86951436:G:C	F440L	1.000
11:86951436:G:T	F440L	1.000
11:86951438:A:G	F440L	1.000
11:86951443:C:T	G438E	1.000
11:86951444:C:G	G438R	1.000
11:86951444:C:T	G438R	1.000
11:86951458:A:G	L433P	1.000
11:86951530:C:T	G409D	1.000
11:86951531:C:G	G409R	1.000
11:86951551:C:A	G402V	1.000
11:86951551:C:T	G402E	1.000
11:86951552:C:G	G402R	1.000
11:86951552:C:T	G402R	1.000
11:86951575:G:C	P394R	1.000
11:86951575:G:T	P394H	1.000
11:86951617:C:T	G380E	1.000
11:86951625:G:C	C377W	1.000
11:86951626:C:A	C377F	1.000
11:86951626:C:G	C377S	1.000
11:86951626:C:T	C377Y	1.000
11:86951627:A:G	C377R	1.000
11:86951627:A:T	C377S	1.000
11:86951689:G:T	A356E	1.000
11:86951692:G:C	P355R	1.000

dbSNP variants (sampled 300 via entrez): RS1000198849 (11:86955890 A>T), RS1000634447 (11:86955633 C>A,T), RS1000934771 (11:86951972 A>G), RS1001164289 (11:86945500 T>A), RS1001931529 (11:86948465 C>G), RS1001952438 (11:86946145 T>C), RS1001964240 (11:86948134 T>C), RS1002137019 (11:86955343 G>A,C), RS1002140094 (11:86957105 A>G), RS1002686280 (11:86953877 A>C,G), RS1002702364 (11:86949626 C>T), RS1003216961 (11:86953703 G>A,C), RS1003228169 (11:86949943 TC>T), RS1003766881 (11:86952062 T>A,C,G), RS1004006747 (11:86956150 A>G)

Disease associations

OMIM: gene MIM:604579 | disease phenotypes: MIM:133780, MIM:300216, MIM:310600

GenCC curated gene-disease

Disease	Classification	Inheritance
exudative vitreoretinopathy 1	Definitive	Semidominant
exudative vitreoretinopathy	Supportive	Autosomal dominant
persistent hyperplastic primary vitreous	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
FZD4-related exudative vitreoretinopathy	Definitive	AD

Mondo (9): inherited retinal dystrophy (MONDO:0019118), exudative vitreoretinopathy 1 (MONDO:0007589), exudative vitreoretinopathy (MONDO:0019516), Coats disease (MONDO:0010269), Norrie disease (MONDO:0010691), optic atrophy (MONDO:0003608), retinal disorder (MONDO:0005283), retinopathy of prematurity (MONDO:0006952), persistent hyperplastic primary vitreous (MONDO:0019631)

Orphanet (5): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Familial exudative vitreoretinopathy (Orphanet:891), Retinopathy of prematurity (Orphanet:90050), Coats disease (Orphanet:190), Norrie disease (Orphanet:649)

HPO phenotypes

67 total (30 of 67 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000252	Microcephaly
HP:0000365	Hearing impairment
HP:0000482	Microcornea
HP:0000486	Strabismus
HP:0000501	Glaucoma
HP:0000518	Cataract
HP:0000519	Developmental cataract
HP:0000523	Subcapsular cataract
HP:0000533	Chorioretinal atrophy
HP:0000541	Retinal detachment
HP:0000545	Myopia
HP:0000555	Leukocoria
HP:0000557	Buphthalmos
HP:0000565	Esotropia
HP:0000568	Microphthalmia
HP:0000594	Shallow anterior chamber
HP:0000618	Blindness
HP:0000646	Amblyopia
HP:0000667	Phthisis bulbi
HP:0001004	Lymphedema
HP:0001103	Abnormal macular morphology
HP:0001104	Macular hypoplasia
HP:0001136	Retinal arteriolar tortuosity
HP:0001141	Severely reduced visual acuity
HP:0001147	Retinal exudate
HP:0001256	Mild intellectual disability
HP:0001270	Motor delay
HP:0001489	Posterior vitreous detachment
HP:0001493	Falciform retinal fold

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003189_2	Hepatocellular carcinoma in hepatitis B infection	6.000000e-06

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D054514	Persistent Hyperplastic Primary Vitreous	C11.250.616; C16.131.384.725
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
D058456	Retinal Telangiectasis	C11.768.748; C14.907.823.502
D012178	Retinopathy of Prematurity	C11.768.836; C16.614.521.731
C536382	Exudative vitreoretinopathy 1 (supp.)
C537849	Norrie disease (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523491 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs10898563	FZD4, PRSS23		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Class Frizzled GPCRs

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
norrin	Full agonist	8.4	pKd
FzM1.8	Negative	7.8	pIC50
FzM1	Negative	6.2	pIC50

CTD chemical–gene interactions

49 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression	3
Nickel	affects expression, decreases expression, decreases reaction	3
Valproic Acid	decreases methylation, increases expression	3
Cyclosporine	decreases expression	3
bisphenol A	affects expression, increases expression	2
trichostatin A	affects expression, decreases reaction, increases expression	2
Acetaminophen	decreases expression	2
Carbamazepine	affects expression	2
Dexamethasone	increases expression, affects cotreatment	2
Paraquat	decreases expression, decreases reaction	2
Tobacco Smoke Pollution	decreases expression	2
Tretinoin	decreases expression, increases expression	2
8-Bromo Cyclic Adenosine Monophosphate	increases expression	2
Aflatoxin B1	decreases expression	2
Lithium Chloride	increases expression, decreases expression, decreases reaction, increases reaction	2
Particulate Matter	decreases expression, increases abundance	2
quercitrin	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression, increases abundance	1
cobaltous chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	increases expression	1
K 7174	decreases expression	1
abrine	decreases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 6 functional, 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4376176	Binding	Binding affinity to recombinant human Frizzled-4 (Phe37 to Glu180 residues)/human IgG1 chimeric protein expressed in mouse NS0 cells by SPR assay	Lead Optimization Yields High Affinity Frizzled 7-Targeting Peptides That Modulate Clostridium difficile Toxin B Pathogenicity in Epithelial Cells. — J Med Chem
CHEMBL4807088	Functional	Agonist activity at frizzled-4 (unknown origin) expressed in human HEK293superTOP flash cells by luciferase reporter gene assay	Antagonistic peptides for frizzled-1 and frizzled-2

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D7QA	Ubigene A-549 FZD4 KO	Cancer cell line	Male
CVCL_SP15	HAP1 FZD4 (-) 1	Cancer cell line	Male
CVCL_SP16	HAP1 FZD4 (-) 2	Cancer cell line	Male
CVCL_SP17	HAP1 FZD4 (-) 3	Cancer cell line	Male
CVCL_YT19	EHTJUi002-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

231 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT06520410	PHASE4	RECRUITING	Safety and Efficacy of 18 mm Short Vitrectomy Probe for Pediatric Vitreoretinal Surgeries
NCT01955135	PHASE4	COMPLETED	Anesthesia for Retinopathy of Prematurity
NCT00417404	PHASE4	COMPLETED	Vitamin A and Very Low Birthweight Babies (VitAL)
NCT00500396	PHASE4	TERMINATED	Vascular Endothelial Growth Factor in Stage V ROP
NCT00563121	PHASE4	WITHDRAWN	VEGF Levels in Aqueous, Vitreous and Subretinal Fluid in ROP Stage IV and V
NCT00634972	PHASE4	TERMINATED	Efficient Study of ACULAR in Inhibiting Proliferative Retinopathy in Prematurity
NCT00921544	PHASE4	COMPLETED	Sucrose Analgesia for the Reduction of Pain During Retinopathy of Prematurity Screening
NCT04050488	PHASE4	UNKNOWN	Zinc Supplementation on Very Low Birth Weight Infant
NCT04623684	PHASE4	COMPLETED	Efficacy and Safety of Mydriatic Microdrops Compared With Standard Drops for Retinopathy of Prematurity (ROP) Screening: a Pilot Randomized Clinical Trial
NCT04838665	PHASE4	COMPLETED	Changes in Vital Signs and Pupil Diameter Related to Pharmacologic Mydriasis in Premature Infants: A Randomized Double Blind Clinical Study
NCT04902859	PHASE4	UNKNOWN	Clonidine as Pain Relief During ROP Eye Examinations
NCT05043077	PHASE4	COMPLETED	Efficacy and Safety of Mydriatic Microdrops for Retinopathy Of Prematurity Screening
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03940690	PHASE3	TERMINATED	Interest of Intravitreal Injections of Anti-VEGF as Initial and Adjuvant Treatment in Coats Disease
NCT00000156	PHASE3	COMPLETED	The Effects of Light Reduction on Retinopathy of Prematurity (Light-ROP)
NCT00233324	PHASE3	COMPLETED	Surfactant Positive Airway Pressure and Pulse Oximetry Trial
NCT00623220	PHASE3	COMPLETED	Inhaled Nitrous Oxide for Pain Relief During Eye Exam in the Pre-term Infant
NCT01954082	PHASE3	TERMINATED	Inositol to Reduce Retinopathy of Prematurity
NCT02375971	PHASE3	COMPLETED	RAINBOW Study: RAnibizumab Compared With Laser Therapy for the Treatment of INfants BOrn Prematurely With Retinopathy of Prematurity
NCT02640664	PHASE3	COMPLETED	Rainbow Extension Study
NCT02760472	PHASE3	COMPLETED	A Fatty Acids Study in Preventing Retinopathy of Prematurity
NCT04004208	PHASE3	COMPLETED	Aflibercept for Retinopathy of Prematurity - Intravitreal Injection Versus Laser Therapy
NCT04015180	PHASE3	COMPLETED	Extension Study to Evaluate the Long-term Outcomes of Subjects in Study 20090
NCT04101721	PHASE3	COMPLETED	Study to Assess the Efficacy, Safety, and Tolerability of Intravitreal Aflibercept Compared to Laser Photocoagulation in Patients With Retinopathy of Prematurity
NCT04634604	PHASE3	TERMINATED	A Randomized Trial of Low-Dose Bevacizumab vs Laser for Type 1 ROP
NCT05701124	PHASE3	COMPLETED	Intravitreal Ranibizumab Injection for Aggressive Versus Type 1 Prethreshold Retinopathy of Prematurity
NCT05712642	PHASE3	COMPLETED	A Dosing Study of Intravitreal Bevacizumab for Retinopathy of Prematurity
NCT06067958	PHASE3	RECRUITING	Intranasal Dexmedetomidine for Pain Management During Screening for Retinopathy of Prematurity
NCT06461975	PHASE3	COMPLETED	Effect of Benoxinate Hydrochloride Eye Drops on The Premature Infant Pain Profile Score During Retinopathy of Prematurity Screening
NCT05107921	PHASE2	UNKNOWN	Bromfenac Sodium Hydrate Eye Drops in Familial Exudative Vitreoretinopathy
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT01373476	PHASE2	COMPLETED	Multicentre, Randomized, Controlled Trial of Qideng Mingmu Capsule in The Treatment of Diabetic Retinopathy
NCT01793090	PHASE2	COMPLETED	EPI-743 in Cobalamin C Defect: Effects on Visual and Neurological Impairment
NCT00349726	PHASE2	COMPLETED	Single-Dose Intravenous Inositol Pharmacokinetics in Preterm Infants
NCT00622726	PHASE2	UNKNOWN	Bevacizumab Eliminates the Angiogenic Threat for Retinopathy of Prematurity
NCT01030575	PHASE2	COMPLETED	Multi-dose Pharmacokinetics and Dose Ranging of Inositol in Premature Infants (INS-2)
NCT01096784	PHASE2	COMPLETED	IGF-1/IGFBP3 Prevention of Retinopathy of Prematurity