FZD9

Chr 7

frizzled class receptor 9

Also known as: CD349, FZD3

NCBI Gene: 8326ENSG00000188763UniProt: O00144OMIM: 601766

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]

OMIMResearchGenerating clinical summary…
MultiplemechanismLOEUF 0.83
Clinical Summary— FZD9
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
78 VUS of 80 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 OE?0.44 (0.25–0.83)
0≤0.351.4
Missense OE?0.71 (0.65–0.79)
0≤0.61.4
Synonymous OE?0.85
0≤1.21.6
LoF obs/exp: 7 / 15.8Missense obs/exp: 275 / 386.0Syn Z: 1.64

This gene — mechanism propensity

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

80 submitted variants in ClinVar

ClinVar

Classification Summary

VUS78
Likely Benign2
78
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
78
0
0
78
Likely Benign
0
0
0
2
2
Benign
0
0
0
0
0
Total0780280

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

View in ClinVar →

162 pathogenic / likely-pathogenic (of 169) ClinVar copy-number / structural variants overlap FZD9 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

FZD9 · protein map & ClinVar variants

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

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