FZD8

Chr 10

frizzled class receptor 8

Also known as: FZ-8, hFZ8

NCBI Gene: 8325 ENSG00000177283 UniProt: Q9H461 OMIM: 606146

The FZD8 protein is a seven-transmembrane receptor for Wnt signaling proteins that activates the beta-catenin canonical pathway, which is essential for tissue morphogenesis and cellular polarity during development. Mutations cause autosomal dominant microcephaly, seizures, and developmental delay, with onset in infancy or early childhood. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

This intronless gene is a member of the frizzled gene family. Members of this family encode seven-transmembrane domain proteins that are receptors for the Wingless type MMTV integration site family of signaling proteins. Most frizzled receptors are coupled to the beta-catenin canonical signaling pathway. This gene is highly expressed in two human cancer cell lines, indicating that it may play a role in several types of cancer. The crystal structure of the extracellular cysteine-rich domain of a similar mouse protein has been determined. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

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Mechanism

Some data sources returned errors (1)

gnomad: Error: Service overloaded

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in FZD8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 97

866 rare PASS variants

Rare truncating (LoF)

1 in 2,900

86 rare PASS variants

Rare synonymous (reference)

1 in 74

627 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FZD8. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 1,900
South Asian	~43k	1 in 76	1 in 1,000
Remaining (unassigned)	~30k	1 in 78	1 in 5,800
European (Finnish)	~27k	1 in 410	1 in 1,600
Admixed American	~22k	1 in 62	1 in 360
African / African American	~21k	1 in 86	1 in 1,700
East Asian	~20k	1 in 90	≈ 1 in 6,500
Ashkenazi Jewish	~13k	1 in 360	none seen
Middle Eastern	~2,884	1 in 140	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 0 of 1 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 1.? see exons ↓