FZD7

Chr 2

frizzled class receptor 7

Also known as: FzE3

NCBI Gene: 8324ENSG00000155760UniProt: O75084

Members of the 'frizzled' gene family encode 7-transmembrane domain proteins that are receptors for Wnt signaling proteins. The FZD7 protein contains an N-terminal signal sequence, 10 cysteine residues typical of the cysteine-rich extracellular domain of Fz family members, 7 putative transmembrane domains, and an intracellular C-terminal tail with a PDZ domain-binding motif. FZD7 gene expression may downregulate APC function and enhance beta-catenin-mediated signals in poorly differentiated human esophageal carcinomas. [provided by RefSeq, Jul 2008]

97
ClinVar variants
31
Pathogenic / LP
0.09
pLI score
0
Active trials
Clinical Summary— FZD7
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
31 Pathogenic / Likely Pathogenic· 63 VUS of 97 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.
0.61LOEUF
pLI 0.088
Z-score 2.75
OE 0.29 (0.15–0.61)
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.
2.03Z-score
OE missense 0.70 (0.63–0.78)
257 obs / 366.5 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.0.29 (0.15–0.61)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.63–0.78)
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.1.21
0≤1.21.6
LoF obs/exp: 5 / 17.4Missense obs/exp: 257 / 366.5Syn Z: -2.14

ClinVar Variant Classifications

97 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic1
VUS63
Likely Benign1
Benign2
30
Pathogenic
1
Likely Pathogenic
63
VUS
1
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
30
0
30
Likely Pathogenic
0
0
1
0
1
VUS
0
60
3
0
63
Likely Benign
0
0
0
1
1
Benign
0
1
0
1
2
Total06134297

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

View in ClinVar →

Protein Context — Lollipop Plot

FZD7 · 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
Circular RNA ACTN4 promotes intrahepatic cholangiocarcinoma progression by recruiting YBX1 to initiate FZD7 transcription.
Chen Q et al.·J Hepatol
2022
Integrin-linked kinase-frizzled 7 interaction maintains cancer stem cells to drive platinum resistance in ovarian cancer.
Atwani R et al.·J Exp Clin Cancer Res
2024
Non-canonical Fzd7 signaling contributes to breast cancer mesenchymal-like stemness involving Col6a1.
Yin P et al.·Cell Commun Signal
2020
The Significance of the Wnt/β-Catenin Pathway and Related Proteins in Gastrointestinal Malignancies.
Romanowicz A et al.·Int J Mol Sci
2025Review
FZD7 accelerates hepatic metastases in pancreatic cancer by strengthening EMT and stemness associated with TGF-β/SMAD3 signaling.
Zhang Z et al.·Mol Med
2022
A FZD7-specific Antibody-Drug Conjugate Induces Ovarian Tumor Regression in Preclinical Models.
Do M et al.·Mol Cancer Ther
2022Functional
The FZD7-TWIST1 axis is responsible for anoikis resistance and tumorigenesis in ovarian carcinoma.
Tan M et al.·Mol Oncol
2019
SIRT7 stabilizes β-catenin and promotes canonical Wnt activation via upregulating FZD7.
Gu Y et al.·Life Sci
2024
Expression of LGR5, FZD7, TROY, and MIST1 in Perioperatively Treated Gastric Carcinomas and Correlation with Therapy Response.
Freiin Grote A et al.·Dis Markers
2019
Frizzled-7 Identifies Platinum-Tolerant Ovarian Cancer Cells Susceptible to Ferroptosis.
Wang Y et al.·Cancer Res
2021
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