FZD9

Chr 7

frizzled class receptor 9

Also known as: CD349, FZD3

NCBI Gene: 8326ENSG00000188763UniProt: O00144OMIM: 601766

FZD9 encodes a 7-transmembrane domain receptor for WNT2 that activates the beta-catenin canonical signaling pathway and regulates neuromuscular junction assembly, neural progenitor cell viability, and bone formation. Heterozygous deletions of FZD9 may contribute to Williams syndrome, which involves intellectual disability, cardiovascular abnormalities, and distinctive facial features typically recognized in early childhood. The gene shows tolerance to loss-of-function variants (pLI 0.002), suggesting that complete loss of function may be required for pathogenicity.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.83
Clinical Summary— FZD9
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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
161 unique Pathogenic / Likely Pathogenic· 85 VUS of 248 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.83LOEUF
pLI 0.002
Z-score 2.05
OE 0.44 (0.25–0.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
2.01Z-score
OE missense 0.71 (0.65–0.79)
275 obs / 386.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.44 (0.25–0.83)
0≤0.351.4
Missense OE0.71 (0.65–0.79)
0≤0.61.4
Synonymous OE0.85
0≤1.21.6
LoF obs/exp: 7 / 15.8Missense obs/exp: 275 / 386.0Syn Z: 1.64
DN
0.7132th %ile
GOF
0.78top 25%
LOF
0.2582th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

248 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic155
Likely Pathogenic6
VUS85
Likely Benign2
155
Pathogenic
6
Likely Pathogenic
85
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
155
0
155
Likely Pathogenic
0
0
6
0
6
VUS
0
78
7
0
85
Likely Benign
0
0
0
2
2
Benign
0
0
0
0
0
Total0781682248

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

FZD9 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Neuropsychological Genotype-Phenotype in Patients with Williams Syndrome with Atypical Deletions: A Systematic Review.
Serrano-Juárez CA et al.·Neuropsychol Rev
2023Review
Shared pathogenic mechanisms of Parkinson's disease and ulcerative colitis: α7 nicotinic acetylcholine receptor as a potential therapeutic target.
Li Y et al.·Int J Biol Macromol
2025Functional
Modeling Williams syndrome from a neurodevelopmental perspective: recent advances, model-based translational insights and future directions.
Chen YY et al.·World J Pediatr
2026Review
Gelatin scaffold combined with bone morphogenetic protein-4 induces odontoblast-like cell differentiation involving integrin profile changes, autophagy-related gene 10, and Wnt5 sequentially in human induced pluripotent stem cells.
Ozeki N et al.·Differentiation
2017
Prostacyclin reverses the cigarette smoke-induced decrease in pulmonary Frizzled 9 expression through miR-31.
Tennis MA et al.·Sci Rep
2016
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
The Wnt signaling receptor Fzd9 is essential for Myc-driven tumorigenesis in pancreatic islets.
Zacarías-Fluck MF et al.·Life Sci Alliance
2021Open Access
An In Silico Analysis Identified FZD9 as a Potential Prognostic Biomarker in Triple-Negative Breast Cancer Patients.
de Bastos DR et al.·Eur J Breast Health
2021Cohort
Involvement of c-Fos in cell proliferation, migration, and invasion in osteosarcoma cells accompanied by altered expression of Wnt2 and Fzd9.
Wang Q et al.·PLoS One
2017Open Access
Upregulation of SOX-2, FZD9, Nestin, OCT-4 and FGF-4 expression in human chorion derived-stem cells after angiogenic induction.
Abdul Rahman H et al.·Med J Malaysia
2008
Characterization and expression pattern of the frizzled gene Fzd9, the mouse homolog of FZD9 which is deleted in Williams-Beuren syndrome.
Wang YK et al.·Genomics
1999Functional
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients