FRZB
protein-codingfrizzled related protein, the group of Secreted frizzled-related proteins
Gene summary
The protein encoded by this gene is a secreted protein that is involved in the regulation of bone development. Defects in this gene are a cause of female-specific osteoarthritis (OA) susceptibility. [provided by RefSeq, Apr 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~33.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to FRZB variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001463.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 4 | 1 | 7 | ||
| missense | 50 | 1 | 51 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 55 | 5 | 1 | 61 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001454.2 | 6 | MANE Select | |
| Ensembl | ENSP00000295113.4 | 6 | MANE Select | |
| Ensembl | ENSP00000558404.1 | 5 | Standard | |
| Ensembl | ENSP00000558404.1 | 5 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| frzb | Danio rerio | Structure: palate Quality: decreased length abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- WNT-Core
- Adipogenesis
- Hepatitis C and Hepatocellular Carcinoma
- Endochondral Ossification
- Wnt Canonical
Biological Process
- skeletal system development
- negative regulation of cell population proliferation
- negative regulation of cell development
- neural crest cell differentiation
- negative regulation of Wnt signaling pathway
Molecular Function
- Wnt-protein binding
Cellular Component
- extracellular space
- cytoplasm
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000295113
- Coding exons
- 6
- Length
- 33889
- Individuals with no LoFs
- 125711
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 37
- Defined
- 125748
- p
- 0.000147
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.949 | 156 | 193 | 0.808 | 0.0000106 | 2111 |
| Missense (PolyPhen) | 63 | 80.232 | 0.78522 | 905 | ||
| Synonymous | -0.462 | 77 | 72.0 | 1.07 | 0.00000376 | 640 |
| Loss of Function | 1.79 | 7 | 14.3 | 0.490 | 6.70e-7 | 164 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00021 | 0.00021 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types. SFRP3/FRZB appears to be involved in limb skeletogenesis. Antagonist of Wnt8 signaling. Regulates chondrocyte maturation and long bone development.;
- Disease
- DISEASE: Osteoarthritis 1 (OS1) [MIM:165720]: A degenerative disease of the joints characterized by degradation of the hyaline articular cartilage and remodeling of the subchondral bone with sclerosis. Clinical symptoms include pain and joint stiffness often leading to significant disability and joint replacement. {ECO:0000269|PubMed:15210948}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.224
Intolerance Scores
- LoFtool
- 0.795
- RVIS EVS
- 0.44
- RVIS percentile EVS
- 77.8
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.876
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |