FZD5

Chr 2AD

frizzled class receptor 5

Also known as: C2orf31, HFZ5, MCOPCB11

FZD5 encodes a 7-transmembrane domain receptor for Wnt signaling proteins that functions in the canonical Wnt/beta-catenin pathway and plays roles in synaptic formation, tissue morphogenesis, and ocular development. Mutations cause autosomal dominant coloboma with or without other eye abnormalities. The gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to have significant clinical consequences.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismADLOEUF 0.281 OMIM phenotype
Clinical SummaryFZD5
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.28LOEUF
pLI 0.983
Z-score 3.56
OE 0.06 (0.020.28)
Highly constrained

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

Missense Constraint
3.00Z-score
OE missense 0.57 (0.510.64)
222 obs / 388.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.06 (0.020.28)
00.351.4
Missense OE0.57 (0.510.64)
00.61.4
Synonymous OE0.84
01.21.6
LoF obs/exp: 1 / 16.7Missense obs/exp: 222 / 388.1Syn Z: 1.78
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongFZD5-related colobomaDNAD
DN
0.5181th %ile
GOF
0.6833th %ile
LOF
0.50top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFLOEUF 0.28
GOFprediction 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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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