FZD9

Chr 7

frizzled class receptor 9

Also known as: CD349, FZD3

NCBI Gene: 8326ENSG00000188763UniProt: O00144

Members of the 'frizzled' gene family encode 7-transmembrane domain proteins that are receptors for Wnt signaling proteins. The FZD9 gene is located within the Williams syndrome common deletion region of chromosome 7, and heterozygous deletion of the FZD9 gene may contribute to the Williams syndrome phenotype. FZD9 is expressed predominantly in brain, testis, eye, skeletal muscle, and kidney. [provided by RefSeq, Jul 2008]

245
ClinVar variants
159
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— FZD9
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
159 Pathogenic / Likely Pathogenic· 84 VUS of 245 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.83LOEUF
pLI 0.002
Z-score 2.05
OE 0.44 (0.25–0.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.44 (0.25–0.83)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.65–0.79)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.85
0≤1.21.6
LoF obs/exp: 7 / 15.8Missense obs/exp: 275 / 386.0Syn Z: 1.64

ClinVar Variant Classifications

245 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic153
Likely Pathogenic6
VUS84
Likely Benign2
153
Pathogenic
6
Likely Pathogenic
84
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
153
0
153
Likely Pathogenic
0
0
6
0
6
VUS
0
77
7
0
84
Likely Benign
0
0
0
2
2
Benign
0
0
0
0
0
Total0771662245

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.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
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
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
Prostacyclin reverses the cigarette smoke-induced decrease in pulmonary Frizzled 9 expression through miR-31.
Tennis MA et al.·Sci Rep
2016
Control of bone formation by the serpentine receptor Frizzled-9.
Albers J et al.·J Cell Biol
2011
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
A human neurodevelopmental model for Williams syndrome.
Chailangkarn T et al.·Nature
2016Functional
Smaller and larger deletions of the Williams Beuren syndrome region implicate genes involved in mild facial phenotype, epilepsy and autistic traits.
Fusco C et al.·Eur J Hum Genet
2014
Atypical deletion of Williams-Beuren syndrome reveals the mechanism of neurodevelopmental disorders.
Zhou J et al.·BMC Med Genomics
2022Functional
Dysregulation of the Wnt signaling pathway in South African patients with diffuse systemic sclerosis.
Frost J et al.·Clin Rheumatol
2019Cohort
Development of a Low Cost Semiquantitative Polymerase Chain Reaction Assay for Molecular Diagnosis of Williams Syndrome.
Ranaweera DM et al.·Clin Lab
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools