FZD6
frizzled class receptor 6, the group of G protein-coupled receptors, Class F frizzled
Basic information
Region (hg38): 8:103298433-103332866
Links
Phenotypes
GenCC
Source:
- autosomal recessive nail dysplasia (Definitive), mode of inheritance: AR
- autosomal recessive nail dysplasia (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Nail disorder, nonsyndromic noncongenital 10 | AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Dermatologic | 21665003 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (1 variants)
- Nonsyndromic congenital nail disorder 1 (1 variants)
- Nephroblastoma (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the FZD6 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | |||||
| missense | 32 | 36 | ||||
| nonsense | 2 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 1 | |||||
| Total | 2 | 0 | 32 | 6 | 3 |
Highest pathogenic variant AF is 0.0000461
Variants in FZD6
This is a list of pathogenic ClinVar variants found in the FZD6 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 8-103300150-C-A | Inborn genetic diseases | Uncertain significance (Apr 25, 2023) | ||
| 8-103300153-C-G | FZD6-related disorder | Likely benign (Jan 13, 2020) | ||
| 8-103300204-A-G | Nonsyndromic congenital nail disorder 1 | Benign (Aug 10, 2021) | ||
| 8-103300265-T-G | Inborn genetic diseases | Uncertain significance (Mar 15, 2024) | ||
| 8-103318590-C-T | Inborn genetic diseases | Uncertain significance (Feb 28, 2024) | ||
| 8-103318630-T-C | Inborn genetic diseases | Uncertain significance (Mar 29, 2022) | ||
| 8-103318675-A-C | Inborn genetic diseases | Uncertain significance (Apr 17, 2023) | ||
| 8-103318698-C-T | Nonsyndromic congenital nail disorder 1 | Uncertain significance (Jan 04, 2017) | ||
| 8-103318756-T-G | Inborn genetic diseases | Uncertain significance (Feb 07, 2023) | ||
| 8-103318758-C-T | Nephroblastoma | Pathogenic (Nov 24, 2017) | ||
| 8-103318794-A-G | FZD6-related disorder | Benign (Jan 27, 2020) | ||
| 8-103324494-G-A | Inborn genetic diseases | Uncertain significance (Jun 07, 2023) | ||
| 8-103324496-T-A | Inborn genetic diseases | Uncertain significance (May 01, 2022) | ||
| 8-103324543-C-T | Inborn genetic diseases | Uncertain significance (Mar 05, 2024) | ||
| 8-103324572-G-C | Inborn genetic diseases | Uncertain significance (Mar 20, 2023) | ||
| 8-103324579-G-T | Inborn genetic diseases | Uncertain significance (Dec 08, 2023) | ||
| 8-103324597-A-G | Inborn genetic diseases | Uncertain significance (Nov 17, 2022) | ||
| 8-103324611-G-A | Inborn genetic diseases | Uncertain significance (May 13, 2024) | ||
| 8-103324666-A-G | Inborn genetic diseases | Uncertain significance (Dec 15, 2022) | ||
| 8-103324731-T-G | Inborn genetic diseases | Uncertain significance (Feb 07, 2023) | ||
| 8-103324741-C-A | Inborn genetic diseases | Uncertain significance (Sep 15, 2021) | ||
| 8-103324763-T-C | FZD6-related disorder | Likely benign (Apr 27, 2024) | ||
| 8-103324846-T-C | Inborn genetic diseases | Uncertain significance (Aug 01, 2022) | ||
| 8-103324888-A-G | Inborn genetic diseases | Uncertain significance (May 23, 2023) | ||
| 8-103324893-G-A | Inborn genetic diseases | Uncertain significance (Apr 22, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| FZD6 | protein_coding | protein_coding | ENST00000358755 | 6 | 34434 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 2.00e-12 | 0.381 | 125697 | 0 | 51 | 125748 | 0.000203 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.40 | 297 | 373 | 0.796 | 0.0000191 | 4632 |
| Missense in Polyphen | 109 | 163.59 | 0.6663 | 2115 | ||
| Synonymous | 0.610 | 125 | 134 | 0.933 | 0.00000737 | 1376 |
| Loss of Function | 1.22 | 22 | 29.1 | 0.756 | 0.00000170 | 340 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000392 | 0.000391 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000163 | 0.000163 |
| Finnish | 0.000139 | 0.000139 |
| European (Non-Finnish) | 0.000238 | 0.000237 |
| Middle Eastern | 0.000163 | 0.000163 |
| South Asian | 0.000327 | 0.000294 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK- 3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Together with FZD3, is involved in the neural tube closure and plays a role in the regulation of the establishment of planar cell polarity (PCP), particularly in the orientation of asymmetric bundles of stereocilia on the apical faces of a subset of auditory and vestibular sensory cells located in the inner ear (By similarity). {ECO:0000250|UniProtKB:Q61089}.;
- Disease
- DISEASE: Nail disorder, non-syndromic congenital, 10 (NDNC10) [MIM:614157]: A nail disorder characterized by a variable degree of onychauxis (thick nails), hyponychia, and onycholysis of all nails, with claw-shaped fingernails in some individuals. No other anomalies of ectodermal tissues, including hair, teeth, sweat glands, or skin, are noted, and individuals with dysplastic nails have normal hearing and normal psychomotor development. {ECO:0000269|PubMed:21665003}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Rare non-synonymous variants in FZD6 may contribute to neural tube defects, congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy.;
- Pathway
- Gastric cancer - Homo sapiens (human);mTOR signaling pathway - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Breast cancer - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Basal cell carcinoma - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Melanogenesis - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Association Between Physico-Chemical Features and Toxicity Associated Pathways;ESC Pluripotency Pathways;Wnt Signaling Pathway and Pluripotency;Wnt Signaling in Kidney Disease;EMT transition in Colorectal Cancer;Wnt Signaling Pathway;Signaling by GPCR;Signaling by WNT;Signal Transduction;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Regulation of FZD by ubiquitination;Class B/2 (Secretin family receptors);GPCR ligand binding;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;PCP/CE pathway;Ca2+ pathway;Beta-catenin independent WNT signaling;Noncanonical Wnt signaling pathway;GPCR signaling-G alpha i;Wnt;Wnt Canonical;Wnt signaling network;TCF dependent signaling in response to WNT;Wnt Mammals
(Consensus)
Recessive Scores
- pRec
- 0.191
Intolerance Scores
- loftool
- 0.287
- rvis_EVS
- 1
- rvis_percentile_EVS
- 90.72
Haploinsufficiency Scores
- pHI
- 0.349
- hipred
- N
- hipred_score
- 0.443
- ghis
- 0.448
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.289
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |
Mouse Genome Informatics
- Gene name
- Fzd6
- Phenotype
- integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); reproductive system phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; embryo phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);
Zebrafish Information Network
- Gene name
- fzd6
- Affected structure
- ethmoid cartilage
- Phenotype tag
- abnormal
- Phenotype quality
- decreased size
Gene ontology
- Biological process
- neural tube closure;hair follicle development;G protein-coupled receptor signaling pathway;Wnt signaling pathway, calcium modulating pathway;platelet activation;cell proliferation in midbrain;non-canonical Wnt signaling pathway;embryonic nail plate morphogenesis;inner ear morphogenesis;negative regulation of DNA-binding transcription factor activity;establishment of body hair planar orientation;canonical Wnt signaling pathway;Wnt signaling pathway, planar cell polarity pathway;negative regulation of canonical Wnt signaling pathway;midbrain morphogenesis
- Cellular component
- plasma membrane;integral component of plasma membrane;cell surface;apical plasma membrane;apicolateral plasma membrane;cytoplasmic vesicle membrane
- Molecular function
- amyloid-beta binding;G protein-coupled receptor activity;protein binding;Wnt-protein binding;ubiquitin protein ligase binding;Wnt-activated receptor activity