FZD6

frizzled class receptor 6, the group of G protein-coupled receptors, Class F frizzled

Basic information

Region (hg38): 8:103298432-103332866

Links

ENSG00000164930 ∙ NCBI:8323 ∙ OMIM:603409 ∙ HGNC:4044 ∙ Uniprot:O60353 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nail dysplasia (Definitive), mode of inheritance: AR
• autosomal recessive nail dysplasia (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the FZD6 gene.

• Inborn genetic diseases (23 variants)
• Nonsyndromic congenital nail disorder 1 (5 variants)
• not provided (2 variants)
• Non-immune hydrops fetalis (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						0
missense			23	1	2	26
nonsense	2					2
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	2	0	23	1	2

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)
8-103318590-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)
8-103324666-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)
8-103324846-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)
8-103324967-G-A		Inborn genetic diseases	Uncertain significance (Dec 13, 2022)
8-103324975-A-G		Non-immune hydrops fetalis • Nonsyndromic congenital nail disorder 1	Conflicting classifications of pathogenicity (Mar 17, 2024)
8-103325066-C-T		FZD6-related disorder	Likely benign (Dec 20, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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