FZD1

Summary

FZD1 (frizzled class receptor 1, HGNC:4038) is a protein-coding gene on chromosome 7q21.13, encoding Frizzled-1 (Q9UP38). Receptor for Wnt proteins.

Members of the ‘frizzled’ gene family encode 7-transmembrane domain proteins that are receptors for Wnt signaling proteins. The FZD1 protein contains a signal peptide, a cysteine-rich domain in the N-terminal extracellular region, 7 transmembrane domains, and a C-terminal PDZ domain-binding motif. The FZD1 transcript is expressed in various tissues.

Source: NCBI Gene 8321 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 89 total
• Druggable target: yes
• MANE Select transcript: NM_003505

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4038
Approved symbol	FZD1
Name	frizzled class receptor 1
Location	7q21.13
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp564G072, Hfz1
Ensembl gene	ENSG00000157240
Ensembl biotype	protein_coding
OMIM	603408
Entrez	8321

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000287934

RefSeq mRNA: 1 — MANE Select: NM_003505 NM_003505

CCDS: CCDS5620

Canonical transcript exons

ENST00000287934 — 1 exons

Exon	Start	End
ENSE00001031400	91264433	91271326

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 94.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.1840 / max 115.1482, expressed in 1525 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
79489	3.3073	1215
79488	1.5471	851
79487	1.0563	583
79492	0.5039	270
79490	0.4139	239
79491	0.3556	185

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mammary duct	UBERON:0001765	94.98	gold quality
epithelium of mammary gland	UBERON:0003244	94.26	gold quality
blood vessel layer	UBERON:0004797	93.86	gold quality
visceral pleura	UBERON:0002401	93.11	gold quality
cervix squamous epithelium	UBERON:0006922	92.11	gold quality
cervix epithelium	UBERON:0004801	91.90	gold quality
pleura	UBERON:0000977	91.66	gold quality
cauda epididymis	UBERON:0004360	91.65	gold quality
tendon of biceps brachii	UBERON:0008188	91.18	gold quality
choroid plexus epithelium	UBERON:0003911	91.08	gold quality
parietal pleura	UBERON:0002400	90.99	gold quality
trigeminal ganglion	UBERON:0001675	90.85	gold quality
superficial temporal artery	UBERON:0001614	90.47	gold quality
hair follicle	UBERON:0002073	90.14	gold quality
dorsal root ganglion	UBERON:0000044	90.07	gold quality
germinal epithelium of ovary	UBERON:0001304	90.05	gold quality
seminal vesicle	UBERON:0000998	89.69	gold quality
lower lobe of lung	UBERON:0008949	89.41	gold quality
caput epididymis	UBERON:0004358	89.37	gold quality
popliteal artery	UBERON:0002250	88.85	gold quality
tibial artery	UBERON:0007610	88.80	gold quality
synovial joint	UBERON:0002217	88.67	gold quality
mammary gland	UBERON:0001911	88.63	gold quality
thoracic mammary gland	UBERON:0005200	88.60	gold quality
gingival epithelium	UBERON:0001949	88.52	gold quality
saphenous vein	UBERON:0007318	88.30	gold quality
tongue squamous epithelium	UBERON:0006919	88.19	gold quality
squamous epithelium	UBERON:0006914	87.93	gold quality
urethra	UBERON:0000057	87.88	gold quality
aorta	UBERON:0000947	87.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.46

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, E2F1, NME1, PITX2, STAT3

miRNA regulators (miRDB)

105 targeting FZD1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-LET-7A-2-3P	99.87	70.53	1921

Literature-anchored findings (GeneRIF, showing 32)

• Fz1 and LRP1 bind, which disrupts the receptor/coreceptor complex formation and leads to the repression of the canonical Wnt signaling (PMID:14739301)
• subcellular Fz localization, through the association with other membrane proteins, is a critical aspect in regulating the signaling specificity within the Wnt/Fz signaling pathways (PMID:15252441)
• Bone morphogenetic protein-2 modulates Wnt and frizzled expression and enhances the canonical pathway of Wnt signaling in normal keratinocytes (PMID:16442268)
• FZD1 links epithelial/mesenchymal disruption to idiopathic pulmonary fibrosis. (PMID:17496152)
• Data demonstrate that Frizzled receptors can functionally replace mating factor receptors in yeast and offer an experimental system to study modulators of Frizzled receptors. (PMID:17895994)
• a frizzled module in cell surface collagen 18 inhibits Wnt/beta-catenin signaling (PMID:18382662)
• a cis-regulatory polymorphism in the FZD1 promoter region may have a functional role in determining bone structural geometry (PMID:18715140)
• The proportion of frizzled-1 positive ovaries was lower in normal patients than in those with ovarian cancer or bening neoplasia (PMID:19148501)
• RNA samples from 21 neuroblastoma showed a highly significant FZD1 and/or MDR1 overexpression after treatment, underlining a role for FZD1-mediated Wnt/beta-catenin pathway in clinical chemoresistance. (PMID:19421142)
• These results suggest that FZD1 expression is regulated in a haplotype-dependent manner in osteoblasts and that these same haplotypes may be associated with biomechanical indices of bone strength. (PMID:20051274)
• Soluble FZC18 and Wnt3a physically interact in a cell-free system and soluble FZC18 binds the frizzled 1 and 8 receptors. (PMID:22303445)
• FZD1 appears to mediate multidrug resistance by regulating the Wnt/beta-catenin pathway (PMID:22484497)
• Fz1 is a Wnt responsive gene in colon-derived tissues. Fz1 expression exhibited increased expression in normal mucosa only in close proximity to colon cancer (PMID:23442549)
• Experiments demonstrate a role of E2F1 in osteoblast differentiation and mineralization and suggest that FZD1 is required, in part, for E2F1 regulation of osteoblast mineralization. (PMID:23806799)
• ACE2 and FZD1 are prognosis markers in squamous cell/adenosquamous carcinoma and adenocarcinoma of gallbladder. (PMID:23921915)
• Polymorphisms in several genes involved in the Wnt signaling pathway were associated with hepatic fibrosis or inflammation risk in HCV-infected males. (PMID:24386373)
• our data demonstrate that FZD1 regulates PKCdelta, and the PKCdelta/AP-1 signalling transduction pathway plays an important role in drug resistance in MES-SA/Dx5 cells. (PMID:24814288)
• Our study suggests that Sox9 siRNA inhibits the proliferation capability of human osteosarcoma cells by down-regulating the expression of Wnt1 and its receptor Fzd1 (PMID:25197350)
• FZD1 expression was down-regulated by AP2 expression and mediated osteoblast differentiation and mineralization. (PMID:25369469)
• The amplification of miR-135b suppressed non-small cell lung cancer chemoresistance by directly mediating FZD1 down-regulation. (PMID:27643554)
• aken together, our results suggest that Sp1 plays a role in human osteoblast differentiation and mineralization, which is at least partially mediated by Sp1-dependent transactivation of FZD1. (PMID:27695039)
• FZD1 and CAIX might be important biological markers for the carcinogenesis, metastasis, invasion, and prognosis of pancreatic ductal adenocarcinoma (PMID:28921449)
• activated FZD1 observed in leukemic cells likely confers acquired drug resistance, whereas FZD1 silencing may be more effective in reversing multidrug resistance (PMID:29482174)
• FZD1 expression levels were remarkably reduced in the articular cartilage of patients with Kashin-Beck disease. (PMID:30719180)
• study has demonstrated that aberrant CpG island hypermethylation of the FZD1 gene is present in patients with ONFH, resulting in Wnt/beta-catenin signaling inactivation and subsequent cell dysfunction. (PMID:30808872)
• Wnt receptor gene FZD1 was associated with schizophrenia in genome-wide SNP analysis of the Australian Schizophrenia Research Bank cohort. (PMID:31735061)
• Frizzled 1 and Wnt1 as new potential therapeutic targets in the traumatically injured spinal cord. (PMID:31900623)
• Hypoxia-Induced Suppression of Alternative Splicing of MBD2 Promotes Breast Cancer Metastasis via Activation of FZD1. (PMID:33402389)
• LINC00942 Promotes Tumor Proliferation and Metastasis in Lung Adenocarcinoma via FZD1 Upregulation. (PMID:34253104)
• Protein disulfide isomerase family 6 promotes the imatinib-resistance of renal cell carcinoma by regulation of Wnt3a-Frizzled1 axis. (PMID:34781823)
• [RBM38 Mediates the Proliferation of Acute Myeloid Leukemia Cells HL-60 by Regulating FZD1 mRNA Stability]. (PMID:34893109)
• Epigenetic repression of Wnt receptors in AD: a role for Sirtuin2-induced H4K16ac deacetylation of Frizzled1 and Frizzled7 promoters. (PMID:35296808)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fzd1	ENSDARG00000106062
mus_musculus	Fzd1	ENSMUSG00000044674
rattus_norvegicus	Fzd1	ENSRNOG00000062541
drosophila_melanogaster	fz3	FBGN0027343
caenorhabditis_elegans		WBGENE00022242

Paralogs (15): FZD3 (ENSG00000104290), SFRP1 (ENSG00000104332), SFRP4 (ENSG00000106483), FZD10 (ENSG00000111432), SFRP5 (ENSG00000120057), SMO (ENSG00000128602), SFRP2 (ENSG00000145423), FZD7 (ENSG00000155760), FRZB (ENSG00000162998), FZD5 (ENSG00000163251), FZD6 (ENSG00000164930), FZD4 (ENSG00000174804), FZD8 (ENSG00000177283), FZD2 (ENSG00000180340), FZD9 (ENSG00000188763)

Protein

Protein identifiers

Frizzled-1 — Q9UP38 (reviewed: Q9UP38)

Alternative names: FzE1

All UniProt accessions (1): Q9UP38

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for Wnt proteins. Activated by WNT3A, WNT3, WNT1 and to a lesser extent WNT2, but apparently not by WNT4, WNT5A, WNT5B, WNT6, WNT7A or WNT7B. Contradictory results showing activation by WNT7B have been described for mouse. Functions in the canonical Wnt/beta-catenin signaling pathway. The canonical Wnt/beta-catenin signaling pathway 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. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. (Microbial infection) Acts as a receptor for C.difficile toxin TcdB in the colonic epithelium.

Subunit / interactions. Interacts with MYOC. Interacts with WNT7B. (Microbial infection) Interacts with C.difficile toxin TcdB; frizzled receptors constitute the major host receptors for TcdB in the colonic epithelium.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in adult heart, placenta, lung, kidney, pancreas, prostate, and ovary and in fetal lung and kidney.

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.

RefSeq proteins (1): NP_003496* (*=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

Pfam: PF01392, PF01534

UniProt features (61 total): helix 14, strand 10, topological domain 8, transmembrane region 7, turn 7, disulfide bond 5, short sequence motif 2, glycosylation site 2, signal peptide 1, chain 1, domain 1, region of interest 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8J9O	ELECTRON MICROSCOPY	3.4
8J9N	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UP38-F1	79.35	0.53

Antibody-complex structures (SAbDab): 2 — 8J9N, 8J9O

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): 116–177, 124–170, 161–198, 187–227, 191–215

Glycosylation sites (2): 130, 231

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-201681	TCF dependent signaling in response to WNT
R-HSA-373080	Class B/2 (Secretin family receptors)
R-HSA-4086400	PCP/CE pathway
R-HSA-4608870	Asymmetric localization of PCP proteins
R-HSA-4641262	Disassembly of the destruction complex and recruitment of AXIN to the membrane

MSigDB gene sets: 379 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, BENPORATH_ES_WITH_H3K27ME3, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_VENTRICULAR_SEPTUM_MORPHOGENESIS, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, GOBP_SYNAPSE_ASSEMBLY, PEREZ_TP63_TARGETS, GOBP_NON_CANONICAL_WNT_SIGNALING_PATHWAY, BIOCARTA_GSK3_PATHWAY, GOCC_CELL_SURFACE, GOBP_OSTEOBLAST_DIFFERENTIATION

GO Biological Process (29): membranous septum morphogenesis (GO:0003149), muscular septum morphogenesis (GO:0003150), outflow tract morphogenesis (GO:0003151), cell-cell signaling (GO:0007267), response to xenobiotic stimulus (GO:0009410), positive regulation of neuron projection development (GO:0010976), neuron differentiation (GO:0030182), negative regulation of BMP signaling pathway (GO:0030514), autocrine signaling (GO:0035425), non-canonical Wnt signaling pathway (GO:0035567), astrocyte-dopaminergic neuron signaling (GO:0036520), endothelial cell differentiation (GO:0045446), positive regulation of osteoblast differentiation (GO:0045669), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), hard palate development (GO:0060022), canonical Wnt signaling pathway (GO:0060070), negative regulation of canonical Wnt signaling pathway (GO:0090090), presynapse assembly (GO:0099054), negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway (GO:1903377), midbrain dopaminergic neuron differentiation (GO:1904948), regulation of presynapse assembly (GO:1905606), regulation of mesenchymal stem cell differentiation (GO:2000739), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), Wnt signaling pathway (GO:0016055), ventricular septum morphogenesis (GO:0060412)

GO Molecular Function (8): G protein-coupled receptor activity (GO:0004930), signaling receptor binding (GO:0005102), frizzled binding (GO:0005109), 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 (5): plasma membrane (GO:0005886), focal adhesion (GO:0005925), cell surface (GO:0009986), Wnt signalosome (GO:1990909), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Signaling by WNT	1
GPCR ligand binding	1
Beta-catenin independent WNT signaling	1
PCP/CE pathway	1
TCF dependent signaling in response to WNT	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
Wnt signaling pathway	3
anatomical structure morphogenesis	2
ventricular septum morphogenesis	2
DNA-templated transcription	2
regulation of DNA-templated transcription	2
transmembrane signaling receptor activity	2
protein binding	2
cellular anatomical structure	2
muscle tissue morphogenesis	1
heart morphogenesis	1
cell communication	1
signaling	1
response to chemical	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
cell differentiation	1
generation of neurons	1
BMP signaling pathway	1
regulation of BMP signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
negative regulation of cellular response to growth factor stimulus	1
cell-cell signaling	1
glial cell-neuron signaling	1
endothelium development	1
epithelial cell differentiation	1
osteoblast differentiation	1
positive regulation of cell differentiation	1
regulation of osteoblast differentiation	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
anatomical structure development	1
secondary palate development	1
negative regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
synapse assembly	1

Protein interactions and networks

STRING

1408 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FZD1	WNT3A	P56704	994
FZD1	LRP5	O75197	993
FZD1	WNT1	P04628	971
FZD1	WNT5A	P41221	955
FZD1	DVL1	O14640	936
FZD1	LRP6	O75581	879
FZD1	AXIN1	O15169	861
FZD1	DKK1	O94907	839
FZD1	WNT7B	P56706	835
FZD1	WNT10B	O00744	834
FZD1	WNT4	P56705	816
FZD1	CTNNB1	P35222	815
FZD1	WNT2	P09544	779
FZD1	DVL2	O14641	774
FZD1	WNT11	O96014	774

IntAct

114 interactions, top by confidence:

A	B	Type	Score
FZD1	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
FZD1	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
FZD1	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.440
FZD1	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
FZD1	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
FZD1	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
FZD1	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
SNTB1	FZD1	psi-mi:“MI:0407”(direct interaction)	0.440
FZD1	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
FZD1	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
FZD1	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
FZD1	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
FZD1	SNTA1	psi-mi:“MI:0407”(direct interaction)	0.440
FZD1	LIN7C	psi-mi:“MI:0407”(direct interaction)	0.440
FZD1	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
FZD1	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
DLG3	FZD1	psi-mi:“MI:0407”(direct interaction)	0.440
FZD1	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
FZD1	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
FZD1	SNTG1	psi-mi:“MI:0407”(direct interaction)	0.440
FZD1	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.440
FZD1	PICK1	psi-mi:“MI:0407”(direct interaction)	0.440
GIPC2	FZD1	psi-mi:“MI:0407”(direct interaction)	0.440
FZD1	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.440
FZD1	SNTG2	psi-mi:“MI:0407”(direct interaction)	0.440
FZD1	RHPN1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (28): ATP5B (Affinity Capture-MS), GOLGA2 (Affinity Capture-MS), DERL2 (Affinity Capture-MS), RBM26 (Affinity Capture-MS), FZD1 (Affinity Capture-MS), FZD1 (Affinity Capture-MS), FZD1 (Affinity Capture-MS), FZD1 (Affinity Capture-Western), FZD1 (Affinity Capture-Western), FZD1 (Affinity Capture-RNA), FZD1 (Two-hybrid), FZD1 (Affinity Capture-MS), FZD1 (Affinity Capture-RNA), FZD1 (Cross-Linking-MS (XL-MS)), FZD1 (Co-fractionation)

ESM2 similar proteins: A0A0P0UZP7, B0KZ40, B2DBE9, B6UV92, B8B016, O22241, O70421, O88696, P08196, P0C586, P24322, P37271, P37272, P37294, P49085, P49293, P53797, Q01IJ3, Q08463, Q0DDE3, Q1LVN8, Q28CH3, Q2QLV9, Q2R1U4, Q498S8, Q52QW5, Q5QNM6, Q5VP70, Q5Z5B7, Q5ZJT0, Q61091, Q67UU0, Q6EI12, Q6L534, Q6L5F6, Q6Z1Y6, Q6Z2T8, Q74ZW4, Q7X745, Q7XAP4

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

14 interactions.

A	Effect	B	Mechanism
WNT1	“up-regulates activity”	FZD1	binding
WNT7B	up-regulates	FZD1	binding
WNT3A	“up-regulates activity”	FZD1	binding
WNT10B	“up-regulates activity”	FZD1	binding
FZD1	“up-regulates activity”	DVL1	binding
NME1	“down-regulates quantity by repression”	FZD1	“transcriptional regulation”
FZD1	“up-regulates activity”	DVL2	binding
FZD1	“up-regulates activity”	DVL3	binding
FZD1	down-regulates	CEBPA
FZD1	down-regulates	PPARG
WNT10B	up-regulates	FZD1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 86 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	51.0×	2e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	48.5×	2e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	48.5×	2e-06
Long-term potentiation	5	42.5×	4e-06
Assembly and cell surface presentation of NMDA receptors	9	40.8×	2e-10
Neurexins and neuroligins	9	31.6×	9e-10
Protein-protein interactions at synapses	5	23.7×	7e-05
RHOA GTPase cycle	5	6.7×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	9	67.0×	3e-12
receptor clustering	7	56.0×	9e-09
protein localization to synapse	5	49.1×	5e-06
regulation of postsynaptic membrane neurotransmitter receptor levels	5	31.8×	4e-05
cell-cell adhesion	10	13.0×	9e-07
regulation of small GTPase mediated signal transduction	5	9.2×	7e-03
chemical synaptic transmission	8	7.9×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	87
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

96 predictions. Top by Δscore:

Variant	Effect	Δscore
7:91266773:G:GT	donor_gain	0.9800
7:91266809:G:T	donor_gain	0.9100
7:91267062:ACC:A	donor_gain	0.8800
7:91267067:G:GT	donor_gain	0.8800
7:91267054:ACTCT:A	donor_gain	0.7400
7:91267027:G:T	donor_gain	0.7300
7:91267091:A:G	donor_gain	0.7100
7:91267058:T:A	donor_gain	0.6800
7:91267026:G:GT	donor_gain	0.6600
7:91267068:A:T	donor_gain	0.6400
7:91267063:CCAG:C	donor_gain	0.6300
7:91267106:TTTTT:T	donor_gain	0.6200
7:91264629:G:GT	donor_gain	0.6000
7:91266809:G:GT	donor_gain	0.5900
7:91267111:G:GG	donor_gain	0.5900
7:91267104:G:GT	donor_gain	0.5400
7:91267061:TACC:T	donor_gain	0.5300
7:91264462:G:GT	donor_gain	0.5000
7:91266692:GAT:G	donor_gain	0.5000
7:91267110:T:G	donor_gain	0.4800
7:91264492:C:A	donor_gain	0.4700
7:91267030:G:GT	donor_gain	0.4700
7:91264896:GCGCC:G	donor_gain	0.4600
7:91264513:G:GT	donor_gain	0.4400
7:91265330:GCACC:G	donor_gain	0.4300
7:91266694:T:TG	donor_gain	0.4300
7:91264555:A:T	donor_gain	0.4200
7:91267064:C:G	donor_gain	0.4100
7:91264458:A:T	donor_gain	0.4000
7:91266773:G:T	donor_gain	0.4000

AlphaMissense

4196 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:91265226:T:A	C116S	1.000
7:91265226:T:C	C116R	1.000
7:91265227:G:A	C116Y	1.000
7:91265227:G:C	C116S	1.000
7:91265227:G:T	C116F	1.000
7:91265228:C:G	C116W	1.000
7:91265236:T:A	I119N	1.000
7:91265250:T:A	C124S	1.000
7:91265250:T:C	C124R	1.000
7:91265251:G:A	C124Y	1.000
7:91265251:G:C	C124S	1.000
7:91265251:G:T	C124F	1.000
7:91265252:C:G	C124W	1.000
7:91265265:T:A	Y129N	1.000
7:91265265:T:C	Y129H	1.000
7:91265265:T:G	Y129D	1.000
7:91265266:A:G	Y129C	1.000
7:91265275:C:T	T132I	1.000
7:91265283:C:T	P135S	1.000
7:91265284:C:A	P135H	1.000
7:91265288:C:A	N136K	1.000
7:91265288:C:G	N136K	1.000
7:91265309:G:C	Q143H	1.000
7:91265309:G:T	Q143H	1.000
7:91265316:G:C	A146P	1.000
7:91265331:C:G	H151D	1.000
7:91265337:T:C	F153L	1.000
7:91265338:T:C	F153S	1.000
7:91265338:T:G	F153C	1.000
7:91265339:C:A	F153L	1.000

dbSNP variants (sampled 300 via entrez): RS1000469409 (7:91265816 G>A), RS1000764756 (7:91270842 C>T), RS1001681044 (7:91268532 G>A), RS1002028473 (7:91266531 G>A), RS1002096196 (7:91264951 G>A,C,T), RS1003015745 (7:91264478 T>C,G), RS1003356679 (7:91270059 T>A,C), RS1003450548 (7:91269698 C>T), RS1003534593 (7:91262447 T>C), RS1003629028 (7:91262834 T>C), RS1003755198 (7:91268349 A>G), RS1004107814 (7:91268025 G>A), RS1004314143 (7:91264416 C>A,T), RS1004612392 (7:91270463 G>GT), RS1004645902 (7:91265127 C>T)

Disease associations

OMIM: gene MIM:603408 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001786_29	Dental caries	7.000000e-06
GCST001786_9	Dental caries	4.000000e-06
GCST006988_10	Blond vs. brown/black hair color	6.000000e-30
GCST007096_222	Pulse pressure	2.000000e-09
GCST007099_184	Systolic blood pressure	4.000000e-06
GCST009603_1	Schizophrenia	2.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0003924	hair color
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2346493 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Class Frizzled GPCRs

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
vantictumab	Antagonist	9.15	pIC50

ChEMBL bioactivities

7 potent at pChembl≥5 of 7 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.47	Kd	0.34	nM	CHEMBL4557583
9.00	IC50	1	nM	CHEMBL4849630
8.95	Kd	1.12	nM	CHEMBL4445160
8.62	Kd	2.42	nM	CHEMBL4554351
8.00	EC50	10	nM	CHEMBL4847020

PubChem BioAssay actives

3 with measured affinity, of 37 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-acetamido-3-hydroxybutanoyl]amino]-3-carboxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-(3-chlorophenyl)propanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2R)-3-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-acetamido-3-hydroxybutanoyl]amino]-3-carboxypropanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoyl]amino]-4-carboxybutanoyl]amino]-3-(3-chlorophenyl)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-oxopropyl]disulfanyl]-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid	1577920: Binding affinity to recombinant human Frizzled-1 (Gln73 to His253 residues)/human IgG1 chimeric protein expressed in mouse NS0 cells by SPR assay	kd	0.0003	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2R)-3-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoyl]amino]-4-carboxybutanoyl]amino]-3-phenylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-oxopropyl]disulfanyl]-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-oxopentanoic acid	1577920: Binding affinity to recombinant human Frizzled-1 (Gln73 to His253 residues)/human IgG1 chimeric protein expressed in mouse NS0 cells by SPR assay	kd	0.0011	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-acetamido-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2R)-3-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-acetamido-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoyl]amino]-4-carboxybutanoyl]amino]-3-phenylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-oxopropyl]disulfanyl]-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-oxopentanoic acid	1577920: Binding affinity to recombinant human Frizzled-1 (Gln73 to His253 residues)/human IgG1 chimeric protein expressed in mouse NS0 cells by SPR assay	kd	0.0024	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	4
sodium arsenite	affects expression, increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Cisplatin	decreases expression, increases expression	2
Tretinoin	decreases expression, increases expression	2
bisphenol F	increases expression, affects cotreatment	1
methylmercuric chloride	decreases expression	1
bisphenol A	increases expression, affects cotreatment	1
arsenite	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
epigallocatechin gallate	affects cotreatment, increases expression	1
pentabromodiphenyl ether	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
pyrimidifen	decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
PKF115-584	increases expression	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	increases expression	1
Adenine	decreases expression	1
Antimycin A	decreases expression	1
Cadmium	decreases expression	1

ChEMBL screening assays

20 unique, capped per target: 17 functional, 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2354178	Binding	Induction of internalization of Frizzled1-GFP (unknown origin) expressed in human U2OS cells at 12.5 uM after 6 hrs by confocal microscopy	Small molecule modulators of Wnt/β-catenin signaling. — Bioorg Med Chem Lett
CHEMBL4276087	Functional	Induction of GFP-tagged Fzd1 (unknown origin) internalization expressed in human U2OS cells at 12.5 after 6 hrs by confocal microscopic method	Identification of DK419, a potent inhibitor of Wnt/β-catenin signaling and colorectal cancer growth. — Bioorg Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1SG	Abcam HeLa FZD1 KO	Cancer cell line	Female
CVCL_D7Q7	Ubigene A-549 FZD1 KO	Cancer cell line	Male
CVCL_SP10	HAP1 FZD1 (-) 1	Cancer cell line	Male
CVCL_SP11	HAP1 FZD1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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