FZD5

Chr 2AD

frizzled class receptor 5

Also known as: C2orf31, HFZ5, MCOPCB11

NCBI Gene: 7855ENSG00000163251UniProt: Q13467

Members of the 'frizzled' gene family encode 7-transmembrane domain proteins that are receptors for Wnt signaling proteins. The FZD5 protein is believed to be the receptor for the Wnt5A ligand. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Microphthalmia/coloboma 11MIM #620731
AD
161
ClinVar variants
34
Pathogenic / LP
0.98
pLI score· haploinsufficient
0
Active trials
Clinical Summary— FZD5
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
34 Pathogenic / Likely Pathogenic· 99 VUS of 161 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.28LOEUF
pLI 0.983
Z-score 3.56
OE 0.06 (0.02–0.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
3.00Z-score
OE missense 0.57 (0.51–0.64)
222 obs / 388.1 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.0.06 (0.02–0.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.57 (0.51–0.64)
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.0.84
0≤1.21.6
LoF obs/exp: 1 / 16.7Missense obs/exp: 222 / 388.1Syn Z: 1.78

ClinVar Variant Classifications

161 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic3
VUS99
Likely Benign13
Benign13
Conflicting2
31
Pathogenic
3
Likely Pathogenic
99
VUS
13
Likely Benign
13
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
1
26
0
31
Likely Pathogenic
1
0
2
0
3
VUS
8
83
8
0
99
Likely Benign
0
4
0
9
13
Benign
0
3
0
10
13
Conflicting
—2
Total13913619161

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

View in ClinVar →

Protein Context — Lollipop Plot

FZD5 · protein map & ClinVar variants

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

Gene2Phenotype Curations

FZD5-related coloboma

strong
ADDominant NegativeAltered Gene Product Structure
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Microphthalmia/coloboma 11

MIM #620731

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — FZD5
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
FOSL2 promotes VEGF-independent angiogenesis by transcriptionnally activating Wnt5a in breast cancer-associated fibroblasts.
Wan X et al.·Theranostics
2021
Genome-wide CRISPR screens reveal a Wnt-FZD5 signaling circuit as a druggable vulnerability of RNF43-mutant pancreatic tumors.
Steinhart Z et al.·Nat Med
2017
FZD5 prevents epithelial-mesenchymal transition in gastric cancer.
Dong D et al.·Cell Commun Signal
2021
Epigenetics in chronic rhinosinusitis.
Kumar N et al.·Curr Opin Otolaryngol Head Neck Surg
2026Review
Confirming and expanding the phenotypes of FZD5 variants: Coloboma, inferior chorioretinal hypoplasia, and high myopia.
Jiang Y et al.·Mol Vis
2021
ZNF831-YTHDF1-DNMT1/3a feedback loop regulates lung carcinogenesis and progression through WNT7B-FZD5-β-catenin signalling axis.
Chen D et al.·Free Radic Biol Med
2025
FZD5 contributes to TNBC proliferation, DNA damage repair and stemness.
Sun Y et al.·Cell Death Dis
2020
Individuals with heterozygous variants in the Wnt-signalling pathway gene FZD5 delineate a phenotype characterized by isolated coloboma and variable expressivity.
Holt R et al.·Ophthalmic Genet
2022
Chromosomal microarray analysis of consecutive individuals with autism spectrum disorders or learning disability presenting for genetic services.
Roberts JL et al.·Gene
2014
Upregulation of FZD5 in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps by Epigenetic Modification.
Kim JY et al.·Mol Cells
2019
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