FZD6

Chr 8AR

frizzled class receptor 6

Also known as: FZ-6, FZ6, HFZ6, NDNC1, NDNC10

This gene encodes a 7-transmembrane receptor for Wnt signaling proteins that regulates canonical Wnt/beta-catenin signaling and planar cell polarity, particularly in inner ear sensory cells and during neural tube closure. Autosomal recessive mutations cause nonsyndromic congenital nail disorder, with the gene showing low constraint to loss-of-function variation. The phenotype appears to be congenital and primarily affects nail development without other syndromic features.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Nail disorder, nonsyndromic congenital, 1MIM #161050
AR
0
Active trials
17
Pubs (1 yr)
51
P/LP submissions
4%
P/LP missense
1.08
LOEUF
LOF
Mechanism· G2P
Clinical SummaryFZD6
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
46 unique Pathogenic / Likely Pathogenic· 88 VUS of 155 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.08LOEUF
pLI 0.000
Z-score 1.22
OE 0.76 (0.541.08)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.40Z-score
OE missense 0.80 (0.720.88)
297 obs / 373.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.76 (0.541.08)
00.351.4
Missense OE0.80 (0.720.88)
00.61.4
Synonymous OE0.93
01.21.6
LoF obs/exp: 22 / 29.1Missense obs/exp: 297 / 373.0Syn Z: 0.61
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveFZD6-related nail disorder non-syndromic congenitalLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6937th %ile
GOF
0.75top 25%
LOF
0.3259th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

155 submitted variants in ClinVar

Classification Summary

Pathogenic45
Likely Pathogenic1
VUS88
Likely Benign9
Benign3
Conflicting1
45
Pathogenic
1
Likely Pathogenic
88
VUS
9
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
2
42
0
45
Likely Pathogenic
1
0
0
0
1
VUS
0
81
7
0
88
Likely Benign
0
4
1
4
9
Benign
0
1
1
1
3
Conflicting
1
Total288515147

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

View in ClinVar →

Protein Context — Lollipop Plot

FZD6 · protein map & ClinVar variants

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

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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