FZD3

Summary

FZD3 (frizzled class receptor 3, HGNC:4041) is a protein-coding gene on chromosome 8p21.1, encoding Frizzled-3 (Q9NPG1). Receptor for Wnt proteins.

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. The function of this protein is unknown, although it may play a role in mammalian hair follicle development. Alternative splicing results in multiple transcript variants. This gene is a susceptibility locus for schizophrenia.

Source: NCBI Gene 7976 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 83 total — 2 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_017412

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4041
Approved symbol	FZD3
Name	frizzled class receptor 3
Location	8p21.1
Locus type	gene with protein product
Status	Approved
Aliases	Fz-3
Ensembl gene	ENSG00000104290
Ensembl biotype	protein_coding
OMIM	606143
Entrez	7976

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000240093, ENST00000517911, ENST00000523546, ENST00000537916, ENST00000878250, ENST00000927846, ENST00000927847, ENST00000927848

RefSeq mRNA: 16 — MANE Select: NM_017412 NM_001412905, NM_001412906, NM_001412909, NM_001412910, NM_001412911, NM_001412912, NM_001412913, NM_001412917, NM_001412919, NM_001412921, NM_001412922, NM_001412924, NM_001412925, NM_001412927, NM_017412, NM_145866

CCDS: CCDS6069

Canonical transcript exons

ENST00000240093 — 8 exons

Exon	Start	End
ENSE00001120188	28520638	28520834
ENSE00001120189	28555738	28555971
ENSE00001120190	28527147	28528164
ENSE00001120191	28551603	28551751
ENSE00001167323	28562798	28574258
ENSE00001196105	28499933	28499978
ENSE00001196111	28494212	28494343
ENSE00001196134	28502670	28503202

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 98.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.3184 / max 327.8028, expressed in 1188 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
88205	12.9478	1181
88206	0.2724	137
88204	0.0982	58

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	98.21	gold quality
secondary oocyte	CL:0000655	97.43	gold quality
corpus epididymis	UBERON:0004359	97.16	gold quality
middle temporal gyrus	UBERON:0002771	96.78	gold quality
endothelial cell	CL:0000115	96.26	gold quality
entorhinal cortex	UBERON:0002728	94.67	gold quality
parietal lobe	UBERON:0001872	94.59	gold quality
postcentral gyrus	UBERON:0002581	94.19	gold quality
cerebellar vermis	UBERON:0004720	94.10	gold quality
buccal mucosa cell	CL:0002336	93.98	gold quality
pons	UBERON:0000988	93.72	gold quality
oocyte	CL:0000023	93.44	gold quality
superior vestibular nucleus	UBERON:0007227	92.65	gold quality
pigmented layer of retina	UBERON:0001782	92.41	gold quality
retina	UBERON:0000966	92.39	gold quality
superior frontal gyrus	UBERON:0002661	92.23	gold quality
seminal vesicle	UBERON:0000998	91.75	gold quality
caput epididymis	UBERON:0004358	91.72	gold quality
embryo	UBERON:0000922	90.88	gold quality
ventral tegmental area	UBERON:0002691	90.51	gold quality
ventricular zone	UBERON:0003053	90.22	gold quality
ganglionic eminence	UBERON:0004023	90.13	gold quality
bronchial epithelial cell	CL:0002328	89.62	gold quality
occipital lobe	UBERON:0002021	89.32	gold quality
nipple	UBERON:0002030	89.30	gold quality
cauda epididymis	UBERON:0004360	89.16	gold quality
saphenous vein	UBERON:0007318	89.12	gold quality
lateral globus pallidus	UBERON:0002476	88.13	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.13	gold quality
primary visual cortex	UBERON:0002436	87.96	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10018	yes	257.21
E-ANND-3	yes	7.65
E-GEOD-124858	no	88.69

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1

miRNA regulators (miRDB)

477 targeting FZD3, 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-3163	100.00	77.23	8605
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-98-3P	100.00	74.08	3907
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681

Literature-anchored findings (GeneRIF, showing 24)

• This study found a significant association between schizophrenia and the FZD3 gene in single nucleotide polymorphisms and haplotype analyses. (PMID:14642436)
• Results suggested that the FZD3 gene might be involved in the predisposition to schizophrenia. (PMID:15274031)
• The FZD3 gene does not play a role in conferring susceptibility to schizophrenia variants in a Japanese sample. (PMID:15657645)
• In German patients, neither single markers nor haplotypes in FZD3 were associated with schizophrenia. Further exploratory analyses using a different diagnostic approach did also not yield significant results. (PMID:17982906)
• Fzd3 is expressed in Ewing sarcoma family tumor cell lines. Fzd3 mediated Wnt-3a-dependent neurite outgrowth. (PMID:18212053)
• Genetic variants of the FZD3 gene may affect susceptibility to schizophrenia in Chinese Han and Va populations. (PMID:22027177)
• clinical significance of frizzled homolog 3 protein in colorectal cancer patients (PMID:24255701)
• Aberrant methylation modification of the FZD3 gene increases the risk of congenital hydrocephalus by altering chromatin structure and disturbing gene expression. (PMID:24796881)
• Wnt3a/Frizzled-3 signaling plays important role in regulating the proliferation and differentiation of neural crest cells and various developmental stages of melanocyte precursors. (PMID:24815018)
• Our analysis showed no significant association between the rs2241802 polymorphism in FZD3 gene and neural tube defects (PMID:24816679)
• FZD3 signaling sensitized peripheral sensory neurons in pain hypersensitivity. (PMID:24991956)
• DNA methylation aberrations rather than polymorphisms of FZD3 gene increase the risk of spina bifida in a high-risk region for neural tube defects. (PMID:25131656)
• seven-transmembrane domain receptors Celsr3 and Fzd3, in particular, control the development of most longitudinal tracts in the central nervous system. [Review] (PMID:25813877)
• marked reduction in the prominence of TUJ1 bundles in number, thickness, and length. Our results showed that deregulation of the planar cell polarity genes CELSR3 and FZD3 might disrupt the enteric innervation pattern (PMID:27619161)
• schizophrenia may be related to some polymorphisms of gene FZD3 that are in stronger linkage disequilibrium to Chinese than to the other populations studied (Meta-Analysis) (PMID:27755292)
• This study identified Circular RNA circ-CBFB as a sponge of miR-607, which targeted FZD3. (PMID:29902450)
• Changes in gene-expression patterns mediated by FZD3 activity occur in the absence of nuclear beta-catenin function, thus representing an important therapeutic target for the melanoma patients whose disease progresses independent of canonical WNT signaling (PMID:30792348)
• In breast cancer cells 5’-tiRNA(Val) functions as a new tumor-suppressor through inhibition of FZD3/Wnt/beta-Catenin signaling pathway. (PMID:31078732)
• Over-expressed LOC101927196 suppressed oxidative stress levels and neuron cell proliferation in a rat model of autism through disrupting the Wnt signaling pathway by targeting FZD3. (PMID:31145996)
• Non-coding variants in MYH11, FZD3, and SORCS3 are associated with dementia in women. (PMID:32966694)
• MiR-340 regulates the growth and metabolism of renal cell carcinoma cells by targeting frizzled class receptor 3. (PMID:33609235)
• Frizzled-3 suppression overcomes multidrug chemoresistance by Wnt/beta-catenin signaling pathway inhibition in hepatocellular carcinoma cells. (PMID:36843499)
• FZD3 regulates the viability, apoptosis, and extracellular matrix degradation of vaginal wall fibroblasts in pelvic organ prolapse via the Wnt signaling pathway. (PMID:38348712)
• WNT5B promotes the malignant phenotype of non-small cell lung cancer via the FZD3-DVL3-RAC1-PCP-JNK pathway. (PMID:39094673)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fzd3a	ENSDARG00000021664
danio_rerio	fzd3b	ENSDARG00000058692
mus_musculus	Fzd3	ENSMUSG00000007989
rattus_norvegicus	Fzd3	ENSRNOG00000047211
drosophila_melanogaster	fz3	FBGN0027343

Paralogs (15): SFRP1 (ENSG00000104332), SFRP4 (ENSG00000106483), FZD10 (ENSG00000111432), SFRP5 (ENSG00000120057), SMO (ENSG00000128602), SFRP2 (ENSG00000145423), FZD7 (ENSG00000155760), FZD1 (ENSG00000157240), FRZB (ENSG00000162998), FZD5 (ENSG00000163251), FZD6 (ENSG00000164930), FZD4 (ENSG00000174804), FZD8 (ENSG00000177283), FZD2 (ENSG00000180340), FZD9 (ENSG00000188763)

Protein

Protein identifiers

Frizzled-3 — Q9NPG1 (reviewed: Q9NPG1)

All UniProt accessions (2): E5RGI9, Q9NPG1

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. 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. Activation by Wnt5A stimulates PKC activity via a G-protein-dependent mechanism. Involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Plays a role in controlling early axon growth and guidance processes necessary for the formation of a subset of central and peripheral major fiber tracts. Required for the development of major fiber tracts in the central nervous system, including: the anterior commissure, the corpus callosum, the thalamocortical, corticothalamic and nigrostriatal tracts, the corticospinal tract, the fasciculus retroflexus, the mammillothalamic tract, the medial lemniscus, and ascending fiber tracts from the spinal cord to the brain. In the peripheral nervous system, controls axon growth in distinct populations of cranial and spinal motor neurons, including the facial branchimotor nerve, the hypoglossal nerve, the phrenic nerve, and motor nerves innervating dorsal limbs. Involved in the migration of cranial neural crest cells. May also be implicated in the transmission of sensory information from the trunk and limbs to the brain. Controls commissural sensory axons guidance after midline crossing along the anterior-posterior axis in the developing spinal cord in a Wnt-dependent signaling pathway. Together with FZD6, is involved in the neural tube closure and plays a role in the regulation of the establishment of planar cell polarity (PCP), particularly in the orientation of asymmetric bundles of stereocilia on the apical faces of a subset of auditory and vestibular sensory cells located in the inner ear. Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle in a beta-catenin-dependent manner.

Subunit / interactions. Interacts with VANGL2.

Subcellular location. Membrane. Cell membrane. Cell surface. Apical cell membrane.

Tissue specificity. Widely expressed. Relatively high expression in the CNS, including regions of the limbic system, in kidney, pancreas, skeletal muscle, uterus and testis.

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

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.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NPG1-1	Long	yes
Q9NPG1-2	Short, FZD3deltaC

RefSeq proteins (16): NP_001399834, NP_001399835, NP_001399838, NP_001399839, NP_001399840, NP_001399841, NP_001399842, NP_001399846, NP_001399848, NP_001399850, NP_001399851, NP_001399853, NP_001399854, NP_001399856, NP_059108, NP_665873 (=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
IPR036790	Frizzled_dom_sf	Homologous_superfamily
IPR041769	FZ3_CRD	Domain

Pfam: PF01392, PF01534

UniProt features (87 total): helix 27, strand 15, topological domain 8, turn 8, transmembrane region 7, disulfide bond 5, compositionally biased region 3, glycosylation site 3, sequence variant 3, sequence conflict 3, signal peptide 1, chain 1, domain 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8Q7O	X-RAY DIFFRACTION	1.76
8QW4	ELECTRON MICROSCOPY	2.9
8JHI	ELECTRON MICROSCOPY	3.2
8JHC	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPG1-F1	75.85	0.46

Antibody-complex structures (SAbDab): 4 — 8JHC, 8JHI, 8Q7O, 8QW4

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 (5): 28–89, 36–82, 73–110, 99–133, 103–127

Glycosylation sites (3): 42, 265, 356

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-373080	Class B/2 (Secretin family receptors)
R-HSA-4086398	Ca2+ pathway
R-HSA-4086400	PCP/CE pathway
R-HSA-4608870	Asymmetric localization of PCP proteins

MSigDB gene sets: 403 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_RESPONSE_TO_ELECTRICAL_STIMULUS, GOBP_NON_CANONICAL_WNT_SIGNALING_PATHWAY, GOCC_CELL_SURFACE, GOBP_NEUROGENESIS, GOBP_NEURAL_TUBE_DEVELOPMENT, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_NEUROBLAST_PROLIFERATION, GOBP_MORPHOGENESIS_OF_EMBRYONIC_EPITHELIUM, GOBP_NEURAL_PRECURSOR_CELL_PROLIFERATION, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_EAR_DEVELOPMENT

GO Biological Process (27): establishment of planar polarity (GO:0001736), neural tube closure (GO:0001843), hair follicle development (GO:0001942), positive regulation of neuroblast proliferation (GO:0002052), response to xenobiotic stimulus (GO:0009410), neuron differentiation (GO:0030182), cell proliferation in midbrain (GO:0033278), non-canonical Wnt signaling pathway (GO:0035567), post-anal tail morphogenesis (GO:0036342), dopaminergic neuron axon guidance (GO:0036514), serotonergic neuron axon guidance (GO:0036515), inner ear morphogenesis (GO:0042472), negative regulation of mitotic cell cycle, embryonic (GO:0045976), response to electrical stimulus (GO:0051602), canonical Wnt signaling pathway (GO:0060070), Wnt signaling pathway, planar cell polarity pathway (GO:0060071), sympathetic ganglion development (GO:0061549), commissural neuron axon guidance (GO:0071679), motor neuron migration (GO:0097475), negative regulation of execution phase of apoptosis (GO:1900118), midbrain morphogenesis (GO:1904693), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), nervous system development (GO:0007399), Wnt signaling pathway (GO:0016055), midbrain development (GO:0030901)

GO Molecular Function (6): G protein-coupled receptor activity (GO:0004930), Wnt-protein binding (GO:0017147), PDZ domain binding (GO:0030165), Wnt receptor activity (GO:0042813), transmembrane signaling receptor activity (GO:0004888), protein binding (GO:0005515)

GO Cellular Component (14): cytoplasm (GO:0005737), plasma membrane (GO:0005886), cell surface (GO:0009986), apical plasma membrane (GO:0016324), lateral plasma membrane (GO:0016328), axon (GO:0030424), dendrite (GO:0030425), filopodium tip (GO:0032433), neuronal cell body (GO:0043025), presynaptic active zone membrane (GO:0048787), glutamatergic synapse (GO:0098978), membrane (GO:0016020), apical part of cell (GO:0045177), presynaptic active zone (GO:0048786)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Beta-catenin independent WNT signaling	2
GPCR ligand binding	1
PCP/CE pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
Wnt signaling pathway	3
axon guidance	3
transmembrane signaling receptor activity	2
neuron projection	2
morphogenesis of a polarized epithelium	1
establishment of tissue polarity	1
primary neural tube formation	1
tube closure	1
hair cycle process	1
anatomical structure development	1
skin epidermis development	1
neuroblast proliferation	1
positive regulation of neurogenesis	1
regulation of neuroblast proliferation	1
positive regulation of neural precursor cell proliferation	1
response to chemical	1
cell differentiation	1
generation of neurons	1
midbrain development	1
neural precursor cell proliferation	1
anatomical structure morphogenesis	1
ear morphogenesis	1
embryonic morphogenesis	1
inner ear development	1
regulation of mitotic cell cycle, embryonic	1
mitotic cell cycle, embryonic	1
negative regulation of mitotic cell cycle	1
response to abiotic stimulus	1
non-canonical Wnt signaling pathway	1
sympathetic nervous system development	1
ganglion development	1
neuron migration	1
negative regulation of apoptotic process	1
execution phase of apoptosis	1
regulation of execution phase of apoptosis	1
G protein-coupled receptor signaling pathway	1
protein binding	1
protein domain specific binding	1
Wnt-protein binding	1

Protein interactions and networks

STRING

1348 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FZD3	WNT5A	P41221	995
FZD3	WNT11	O96014	963
FZD3	CELSR3	Q9NYQ7	909
FZD3	VANGL2	Q9ULK5	892
FZD3	CELSR1	Q9NYQ6	872
FZD3	DVL1	O14640	867
FZD3	WNT4	P56705	855
FZD3	WNT5B	Q9H1J7	834
FZD3	WNT3A	P56704	818
FZD3	WNT7B	P56706	818
FZD3	WNT7A	O00755	812
FZD3	MCAM	P43121	806
FZD3	WNT2B	Q93097	781
FZD3	CTHRC1	Q96CG8	769
FZD3	CTNNB1	P35222	758

IntAct

25 interactions, top by confidence:

A	B	Type	Score
GPR21	TMEM120B	psi-mi:“MI:0914”(association)	0.530
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
XAGE1A	THAP12	psi-mi:“MI:0914”(association)	0.530
FZD3	SDCBP	psi-mi:“MI:0407”(direct interaction)	0.440
UPK1A	TMEM223	psi-mi:“MI:0914”(association)	0.350
SYNE4	GOLIM4	psi-mi:“MI:0914”(association)	0.350
VNN2	ATP2A1	psi-mi:“MI:0914”(association)	0.350
ZBBX	ZZEF1	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
CSTL1	DENND11	psi-mi:“MI:0914”(association)	0.350
ADAMTS13	C2CD4B	psi-mi:“MI:0914”(association)	0.350
C2CD4B	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
TMEM169	GPR89A	psi-mi:“MI:0914”(association)	0.350
HPN	TOR1A	psi-mi:“MI:0914”(association)	0.350
OR10H2	ABCD4	psi-mi:“MI:0914”(association)	0.350
DPM2	WDR46	psi-mi:“MI:0914”(association)	0.350
DCANP1	IDE	psi-mi:“MI:0914”(association)	0.350

BioGRID (40): FZD3 (Affinity Capture-MS), FZD3 (Affinity Capture-Western), FZD3 (Co-localization), FZD3 (Affinity Capture-MS), FZD3 (Affinity Capture-MS), FZD3 (Affinity Capture-MS), FZD3 (Affinity Capture-MS), FZD3 (Affinity Capture-MS), FZD3 (Affinity Capture-MS), FZD3 (Affinity Capture-MS), FZD3 (Proximity Label-MS), FZD3 (Proximity Label-MS), FZD3 (Proximity Label-MS), FZD3 (Proximity Label-MS), FZD3 (Proximity Label-MS)

ESM2 similar proteins: A0A084B9Z2, A0A0A2JY25, A0A0D1E6B3, A0A0R8YXT5, A0A142I738, A0A2I1CSG1, A0A2L0P0K0, A0A348HAY3, A1CIM4, B2KWI0, G1X9E2, G1X9H9, G1XJN1, G5EDW2, I1RLA6, O13780, O13880, O42579, O60353, P0DUT8, P13773, P31302, P31303, P31397, P49190, P70555, P78741, P9WEL3, P9WEU1, P9WEV3, Q05659, Q09460, Q0CRW7, Q0V6Q8, Q12256, Q2KI97, Q4D3E8, Q4G2T3, Q4WR17, Q54ET0

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

34 interactions.

A	Effect	B	Mechanism
FZD3	up-regulates	CXCL1	binding
FZD3	up-regulates	GNA12	binding
FZD3	up-regulates	GNA13	binding
FZD3	up-regulates	GNAQ	binding
WNT1	“up-regulates activity”	FZD3	binding
WNT10A	up-regulates	FZD3	binding
WNT10B	up-regulates	FZD3	binding
WNT11	“up-regulates activity”	FZD3	binding
WNT16	up-regulates	FZD3	binding
WNT2B	up-regulates	FZD3	binding
WNT3	up-regulates	FZD3	binding
WNT5A	“up-regulates activity”	FZD3	binding
WNT5B	up-regulates	FZD3	binding
WNT6	up-regulates	FZD3	binding
WNT7A	“up-regulates activity”	FZD3	binding
WNT7B	up-regulates	FZD3	binding
WNT8A	up-regulates	FZD3	binding
WNT8B	up-regulates	FZD3	binding
WNT9A	up-regulates	FZD3	binding
WNT9B	up-regulates	FZD3	binding
FZD3	“up-regulates activity”	DVL1	binding
FZD3	up-regulates	GNB1	binding
FZD3	up-regulates	GNB3	binding
FZD3	up-regulates	GNGT1	binding
FZD3	up-regulates	NLK	binding
FZD3	“up-regulates activity”	RHOA	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	66
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
815113	GRCh37/hg19 8p21.2-21.1(chr8:24305969-28673405)x1	Pathogenic
998142	NM_017412.4(FZD3):c.888del (p.Phe296fs)	Pathogenic
632606	NM_017412.4(FZD3):c.1616dup (p.Asp539fs)	Likely pathogenic

SpliceAI

1918 predictions. Top by Δscore:

Variant	Effect	Δscore
8:28520632:CCCTA:C	acceptor_loss	1.0000
8:28520633:CCTA:C	acceptor_loss	1.0000
8:28520634:CTAGC:C	acceptor_loss	1.0000
8:28520635:TAGC:T	acceptor_loss	1.0000
8:28520636:A:AG	acceptor_gain	1.0000
8:28520636:A:G	acceptor_loss	1.0000
8:28520637:G:GA	acceptor_gain	1.0000
8:28520637:G:GT	acceptor_loss	1.0000
8:28520637:GCC:G	acceptor_gain	1.0000
8:28520831:G:GG	donor_gain	1.0000
8:28551597:TTCCA:T	acceptor_loss	1.0000
8:28551598:TCCAG:T	acceptor_loss	1.0000
8:28551599:CCAGG:C	acceptor_loss	1.0000
8:28551600:CAGG:C	acceptor_loss	1.0000
8:28551601:A:AG	acceptor_gain	1.0000
8:28551601:AGGTT:A	acceptor_loss	1.0000
8:28551602:G:GG	acceptor_gain	1.0000
8:28551750:GA:G	donor_gain	1.0000
8:28551752:G:GG	donor_gain	1.0000
8:28555737:GGATA:G	acceptor_gain	1.0000
8:28495760:GAGGT:G	donor_gain	0.9900
8:28520637:GC:G	acceptor_gain	0.9900
8:28520637:GCCA:G	acceptor_gain	0.9900
8:28520637:GCCAT:G	acceptor_gain	0.9900
8:28520828:GCA:G	donor_gain	0.9900
8:28527143:TTA:T	acceptor_loss	0.9900
8:28527145:A:AG	acceptor_gain	0.9900
8:28527145:A:T	acceptor_loss	0.9900
8:28527146:G:GC	acceptor_loss	0.9900
8:28527146:G:GG	acceptor_gain	0.9900

AlphaMissense

4412 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:28503119:T:A	C36S	1.000
8:28503119:T:C	C36R	1.000
8:28503120:G:C	C36S	1.000
8:28520811:G:C	W121C	1.000
8:28520811:G:T	W121C	1.000
8:28527430:T:C	F224L	1.000
8:28527432:T:A	F224L	1.000
8:28527432:T:G	F224L	1.000
8:28527451:T:C	F231L	1.000
8:28527452:T:C	F231S	1.000
8:28527453:C:A	F231L	1.000
8:28527453:C:G	F231L	1.000
8:28527680:T:C	L307P	1.000
8:28527691:T:A	W311R	1.000
8:28527691:T:C	W311R	1.000
8:28527766:T:A	W336R	1.000
8:28527766:T:C	W336R	1.000
8:28528033:A:C	S425R	1.000
8:28528035:C:A	S425R	1.000
8:28528035:C:G	S425R	1.000
8:28551717:T:A	W507R	1.000
8:28551717:T:C	W507R	1.000
8:28503096:G:A	C28Y	0.999
8:28503120:G:A	C36Y	0.999
8:28503121:C:G	C36W	0.999
8:28503153:C:A	P47H	0.999
8:28503157:T:A	N48K	0.999
8:28503157:T:G	N48K	0.999
8:28520665:T:A	C73S	0.999
8:28520665:T:C	C73R	0.999

dbSNP variants (sampled 300 via entrez): RS1000025463 (8:28555217 A>G,T), RS1000049128 (8:28520907 CATCT>C), RS1000068874 (8:28512219 A>C), RS1000072951 (8:28506230 T>C), RS1000236437 (8:28557703 C>A), RS1000249895 (8:28527076 A>G), RS1000281345 (8:28532091 T>C), RS1000296495 (8:28568650 T>G), RS1000299472 (8:28564631 C>G), RS1000311082 (8:28531834 G>A), RS1000324068 (8:28550271 C>T), RS1000392681 (8:28568908 T>C), RS1000439538 (8:28507968 T>G), RS1000531794 (8:28550185 A>G), RS1000576650 (8:28543670 C>T)

Disease associations

OMIM: gene MIM:606143 | disease phenotypes: MIM:213000, MIM:217990, MIM:617468, MIM:114500

GenCC curated gene-disease

Mondo (6): hydrocephalus (MONDO:0001150), isolated cerebellar hypoplasia/agenesis (MONDO:0008939), corpus callosum, agenesis of (MONDO:0009022), arthrogryposis multiplex congenita (MONDO:0015168), multicystic dysplastic kidney (MONDO:0015988), colorectal cancer (MONDO:0005575)

Orphanet (6): Arthrogryposis multiplex congenita (Orphanet:1037), Isolated cerebellar agenesis (Orphanet:1398), Multicystic dysplastic kidney (Orphanet:1851), Isolated corpus callosum agenesis (Orphanet:200), Cerebellar hypoplasia-tapetoretinal degeneration syndrome (Orphanet:2246), NON RARE IN EUROPE: Colorectal cancer (Orphanet:466667)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D061085	Agenesis of Corpus Callosum	C10.500.034; C16.131.666.034; C23.300.008
D006849	Hydrocephalus	C10.228.140.602
D021782	Multicystic Dysplastic Kidney	C12.050.351.875.558; C12.050.351.968.419.403.750; C12.200.706.629; C12.200.777.419.403.750; C12.800.629; C12.950.419.403.750; C16.131.939.629
C562568	Cerebellar Hypoplasia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7001034	FZD3, MIR4288		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Class Frizzled GPCRs

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, decreases methylation	7
trichostatin A	affects cotreatment, decreases expression	3
entinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Tretinoin	decreases expression	2
Aflatoxin B1	affects expression, increases methylation	2
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	decreases methylation	1
beta-lapachone	decreases expression, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
nickel sulfate	decreases expression	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
cordycepin	increases expression	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
perfluorobutanesulfonic acid	increases expression	1
bisphenol S	decreases methylation	1
jinfukang	decreases expression	1
imeglimin	increases expression	1
Temozolomide	increases expression	1
Glyphosate	decreases expression	1
Acrolein	increases oxidation, increases abundance, affects cotreatment	1
Adenosine	increases expression	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7Q9	Ubigene A-549 FZD3 KO	Cancer cell line	Male
CVCL_D8LN	Ubigene HCT 116 FZD3 KO	Cancer cell line	Male
CVCL_D9F7	Ubigene HEK293 FZD3 KO	Transformed cell line	Female
CVCL_SP13	HAP1 FZD3 (-) 1	Cancer cell line	Male
CVCL_SP14	HAP1 FZD3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01323764	PHASE4	COMPLETED	ShuntCheck Versus Radionuclide in Evaluating Shunt Function in Symptomatic NPH Patients
NCT01685450	PHASE4	UNKNOWN	NIMIP: Non Invasive Measurement of the Intracranial Pressure
NCT03513757	PHASE4	COMPLETED	Dexmedetomidine and Propofol for Pediatric MRI Sedation
NCT07547826	PHASE4	NOT_YET_RECRUITING	Efficacy and Cost-Effectiveness of Topical Vancomycin Powder in Preventing Pediatric Ventriculoperitoneal Shunt Infections Across Different Etiologies
NCT00114829	PHASE4	UNKNOWN	Preoperative Assessment of Colon Tumor
NCT00114842	PHASE4	COMPLETED	Magnetic Resonance (MR) Colonography With Fecal Tagging
NCT00114946	PHASE4	TERMINATED	A Study to Compare Two Avastin-Based Treatment Regimens for the Treatment of Metastatic Colorectal Cancer
NCT00122720	PHASE4	COMPLETED	The Effect of Darbepoetin Upon Rehabilitation for Colorectal Cancer Surgery
NCT00129870	PHASE4	TERMINATED	CONCEPT: Comparison of Oxaliplatin vs Conventional Methods With Calcium/Magnesium in First-Line Metastatic Colorectal Cancer
NCT00138060	PHASE4	COMPLETED	Toxicity/Benefit Ratio Optimization of Chemotherapy in Colorectal Cancer (CRC) Patients by Determination of Individual Genotypic Determinants
NCT00216424	PHASE4	TERMINATED	Capecitabine (Xeloda) and Radiation for Patients With Rectosigmoid Carcinoma
NCT00327093	PHASE4	TERMINATED	Elaboration of a Model for Predicting Efficacy of Monoclonal Antibodies (Cetuximab and Bevacizumab) in Patients With Colorectal Cancer and Liver Metastases
NCT00332943	PHASE4	COMPLETED	MR Colonography With Fecal Tagging. Barium vs. BariumFerumoxsil
NCT00441311	PHASE4	COMPLETED	Dissemination of Colorectal Cancer Screening to Primary Care Physicians
NCT00460837	PHASE4	WITHDRAWN	Comparison of Bowel Preparation in Virtual Colonoscopy (VC) - Patient Experience
NCT00473980	PHASE4	COMPLETED	Preoperative Non-steroidal Anti-inflammatory Drugs(NSAID) to Colorectal Cancer Patients
NCT00488904	PHASE4	COMPLETED	Omega-3 Fatty Acids and Postoperative Complications After Colorectal Surgery
NCT00496678	PHASE4	COMPLETED	Trial of Patient Navigation-Activation
NCT00502671	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) as Adjuvant Monotherapy in Patients With Colon Cancer.
NCT00559676	PHASE4	COMPLETED	Study of Biomarkers in Patients Undergoing Chemotherapy for Metastatic Colorectal Cancer
NCT00577031	PHASE4	COMPLETED	OBELIX Study: A Study of Avastin (Bevacizumab) in Combination With XELOX in Patients With Metastatic Cancer of the Colon or Rectum.
NCT00626054	PHASE4	COMPLETED	Comparison of Two Methods of Administration of a PEG Solution
NCT00812864	PHASE4	COMPLETED	Pharmacokinetic Study of Capecitabine in Elderly Cancer Patient (≥ 75 Years)
NCT00868569	PHASE4	UNKNOWN	Transhepatic Arterial Chemotherapy (TAC) Versus Transcatheter Arterial Chemoembolization (TACE) Plus Folfox4 as the Treatment of Unresectable Liver Metastasis of Colorectal Cancer
NCT00868816	PHASE4	COMPLETED	Oxaliplatine Based Adjuvant Chemotherapy for Stage II/III Colorectal Cancer: 8 Cycles Versus 12 Cycles
NCT00874406	PHASE4	UNKNOWN	Preoperative Transhepatic Arterial Chemotherapy (TAC) in the Treatment of Liver Metastasis of Resectable Colorectal Cancer
NCT00928928	PHASE4	COMPLETED	Oxidative Stress Markers in Open and Laparoscopic Colectomy for Cancer
NCT00942461	PHASE4	COMPLETED	Inflammatory Response in Laparoscopic and Open Colectomy
NCT01023633	PHASE4	UNKNOWN	OPTIMOX1 in Chinese mCRC Patients
NCT01271582	PHASE4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01315990	PHASE4	UNKNOWN	FOLFIRI in Combination With Cetuximab in the First-line Treatment of Metastatic Colorectal Cancer Including a Regular Dermal Prophylaxis to Prevent Acneiforme Follicular Exanthema
NCT01493713	PHASE4	COMPLETED	Correlation Between RECIST, Morphologic Response by CT- Histopathologic Response in Hepatic Metastasis Secondary to Colorectal Cancer
NCT01609660	PHASE4	COMPLETED	Impact of Probiotics on the Intestinal Microbiota
NCT01641458	PHASE4	COMPLETED	Pharmacology-driven Dosing of Fluoropyrimidines in Cancer Patients
NCT01689792	PHASE4	COMPLETED	A Multi-centre Study Comparing the Polyp Detection Rate of Two Different Types of Bowel Preparation: a 2-litre Solution (MOVIPREP®) Versus a Hyperosmotic and Stimulant Combined Low Volume Bowel Preparation (Sodium Picosulfate and Magnesium Citrate)
NCT01695772	PHASE4	COMPLETED	A Study of Bevacizumab Plus 5-Flurouracil (5-FU) Based Doublet Chemotherapy as Neoadjuvant Therapy for Participants With Previously Untreated Unresectable Liver-Only Metastases From Colorectal Cancer
NCT01695863	PHASE4	COMPLETED	Efficacy and Patient Satisfaction of Miralax and Gatorade Versus Movi Prep
NCT01706822	PHASE4	TERMINATED	Radial Reload Laparoscopic LAR Case Series
NCT01740947	PHASE4	TERMINATED	Does Administration of Antibiotics in Patients Undergoing Surgery for Colorectal Cancer Result in Less Complications and Better Prognosis?
NCT01831310	PHASE4	COMPLETED	Nutrition for Colorectal Cancer Patients and Neutrophil Functions