FZD2

frizzled class receptor 2, the group of G protein-coupled receptors, Class F frizzled

Basic information

Region (hg38): 17:44557484-44561262

Links

ENSG00000180340 ∙ NCBI:2535 ∙ OMIM:600667 ∙ HGNC:4040 ∙ Uniprot:Q14332 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant omodysplasia (Limited), mode of inheritance: AD
• autosomal dominant Robinow syndrome (Supportive), mode of inheritance: AD
• autosomal dominant omodysplasia (Supportive), mode of inheritance: AD
• autosomal dominant omodysplasia (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Omodysplasia 2	AD	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	Craniofacial; Genitourinary; Musculoskeletal	25759469

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FZD2 gene.

• Autosomal dominant Robinow syndrome 2 (1 variants)
• Autosomal dominant Robinow syndrome 1 (1 variants)
• not provided (1 variants)
• Autosomal dominant omodysplasia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FZD2 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			5	42	8	55
missense		4	82	6	4	96
nonsense	1	1				2
start loss			1			1
frameshift			2			2
inframe indel			3		1	4
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	1	5	93	48	14

Variants in FZD2

This is a list of pathogenic ClinVar variants found in the FZD2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-44557689-A-G			Uncertain significance (Feb 02, 2023)
17-44557692-C-A			Uncertain significance (Nov 24, 2023)
17-44557703-C-G			Uncertain significance (Nov 15, 2022)
17-44557707-C-T		FZD2-related disorder	Benign (Oct 17, 2023)
17-44557714-G-A		not specified	Uncertain significance (Aug 28, 2024)
17-44557720-T-TGATGCC			Benign (Oct 01, 2024)
17-44557726-C-T		FZD2-related disorder	Likely benign (Jan 30, 2024)
17-44557727-G-A			Likely benign (Aug 19, 2022)
17-44557726-C-CGCT			Uncertain significance (Sep 27, 2023)
17-44557731-C-G			Uncertain significance (Nov 15, 2021)
17-44557742-C-T			Likely benign (Nov 08, 2022)
17-44557745-C-G			Likely benign (Jul 30, 2022)
17-44557749-G-A			Uncertain significance (May 17, 2021)
17-44557749-G-C			Benign (Dec 13, 2023)
17-44557754-G-C			Likely benign (Jun 28, 2018)
17-44557764-C-G		not specified	Uncertain significance (May 26, 2023)
17-44557767-G-C		not specified	Uncertain significance (Sep 24, 2024)
17-44557778-C-T			Likely benign (Jul 04, 2018)
17-44557787-C-G			Uncertain significance (Feb 24, 2022)
17-44557811-C-T			Likely benign (Feb 20, 2023)
17-44557815-T-G			Uncertain significance (May 16, 2023)
17-44557838-C-A			Likely benign (Jan 13, 2021)
17-44557856-C-T		FZD2-related disorder	Benign (Jul 11, 2022)
17-44557923-C-T			Likely benign (Sep 12, 2022)
17-44557936-A-C			Uncertain significance (Sep 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FZD2	protein_coding	protein_coding	ENST00000315323	1	1983

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.653	0.347	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.67	165	361	0.457	0.0000203	3638
Missense in Polyphen		30	137.11	0.2188		1396
Synonymous	1.81	137	167	0.822	0.0000101	1201
Loss of Function	3.08	3	16.5	0.182	7.11e-7	162

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
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.
• 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);MicroRNAs in cardiomyocyte hypertrophy;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;Disassembly of the destruction complex and recruitment of AXIN to the membrane;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;Asymmetric localization of PCP proteins;WNT5A-dependent internalization of FZD2, FZD5 and ROR2;PCP/CE pathway;Ca2+ pathway;Beta-catenin independent WNT signaling;Noncanonical Wnt signaling pathway;GPCR signaling-G alpha i;Wnt Canonical;Wnt signaling network;TCF dependent signaling in response to WNT;Wnt Mammals (Consensus)

Recessive Scores

• pRec: 0.221

Intolerance Scores

• loftool: 0.0748
• rvis_EVS: 0.48
• rvis_percentile_EVS: 79.25

Haploinsufficiency Scores

• pHI: 0.817
• ghis: 0.412

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.855

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Fzd2
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); hearing/vestibular/ear phenotype; digestive/alimentary phenotype; skeleton phenotype; homeostasis/metabolism phenotype; taste/olfaction phenotype; growth/size/body region phenotype; craniofacial phenotype

Zebrafish Information Network

• Gene name: fzd2
• Affected structure: dorsal fin
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: membranous septum morphogenesis;muscular septum morphogenesis;outflow tract morphogenesis;G protein-coupled receptor signaling pathway;Wnt signaling pathway, calcium modulating pathway;sensory perception of smell;neuron differentiation;epithelial cell differentiation;non-canonical Wnt signaling pathway;positive regulation of G protein-coupled receptor signaling pathway;positive regulation of transcription, DNA-templated;positive regulation of DNA-binding transcription factor activity;hard palate development;canonical Wnt signaling pathway;Wnt signaling pathway, planar cell polarity pathway;inner ear receptor cell development;cochlea morphogenesis;planar cell polarity pathway involved in neural tube closure;beta-catenin destruction complex disassembly
• Cellular component: cytoplasm;plasma membrane;focal adhesion;integral component of membrane;clathrin-coated endocytic vesicle membrane
• Molecular function: G protein-coupled receptor activity;protein binding;Wnt-protein binding;PDZ domain binding;Wnt-activated receptor activity