FZD5

frizzled class receptor 5, the group of G protein-coupled receptors, Class F frizzled

Basic information

Region (hg38): 2:207762597-207769906

Previous symbols: [ "C2orf31" ]

Links

ENSG00000163251 ∙ NCBI:7855 ∙ OMIM:601723 ∙ HGNC:4043 ∙ Uniprot:Q13467 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microphthalmia/coloboma 11	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	Ophthalmologic	26908622; 32737437; 33633439; 36695497

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FZD5 gene.

• Congenital ocular coloboma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FZD5 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				7	8	15
missense			32	4	2	38
nonsense			4			4
start loss						0
frameshift	1		5			6
inframe indel		2				2
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	1	2	41	11	10

Variants in FZD5

This is a list of pathogenic ClinVar variants found in the FZD5 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-207767002-C-T		Inborn genetic diseases	Uncertain significance (Jun 24, 2022)
2-207767024-G-A			Benign (Jan 19, 2024)
2-207767034-G-A		Inborn genetic diseases	Uncertain significance (Sep 13, 2023)
2-207767059-C-A			Uncertain significance (May 21, 2023)
2-207767060-G-A		FZD5-related disorder	Benign (Oct 04, 2023)
2-207767089-T-C		Inborn genetic diseases	Uncertain significance (Mar 14, 2024)
2-207767107-G-A			Benign (Oct 04, 2023)
2-207767153-C-A			Likely benign (Jul 26, 2018)
2-207767177-G-C		Inborn genetic diseases	Uncertain significance (Feb 27, 2023)
2-207767188-C-T		Inborn genetic diseases	Uncertain significance (Dec 08, 2023)
2-207767199-C-T			Uncertain significance (Jul 17, 2023)
2-207767209-G-A		FZD5-related disorder	Benign (Aug 05, 2023)
2-207767222-C-T			Likely benign (Nov 27, 2023)
2-207767227-G-C		Inborn genetic diseases	Uncertain significance (Mar 28, 2024)
2-207767250-T-G			Likely benign (Feb 04, 2022)
2-207767265-C-G		Inborn genetic diseases	Uncertain significance (Jun 17, 2024)
2-207767267-G-A		FZD5-related disorder	Benign/Likely benign (Aug 24, 2023)
2-207767296-G-A		Inborn genetic diseases	Uncertain significance (Jun 02, 2024)
2-207767311-TC-T		Microphthalmia/coloboma 11	Pathogenic (Feb 22, 2024)
2-207767330-G-T			Uncertain significance (Dec 27, 2023)
2-207767333-C-CAGGT		Microphthalmia/coloboma 11	Pathogenic (Feb 22, 2024)
2-207767350-C-T			Uncertain significance (Nov 27, 2021)
2-207767352-A-G		Inborn genetic diseases	Uncertain significance (Jun 10, 2024)
2-207767369-G-A		FZD5-related disorder	Benign (Jan 22, 2024)
2-207767372-G-A		FZD5-related disorder	Benign (Jan 19, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FZD5	protein_coding	protein_coding	ENST00000295417	1	6978

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.983	0.0174	125500	0	5	125505	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.00	222	388	0.572	0.0000240	3684
Missense in Polyphen		55	177.84	0.30927		1720
Synonymous	1.78	161	192	0.837	0.0000137	1255
Loss of Function	3.56	1	16.7	0.0597	7.23e-7	167

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)	0.0000359	0.0000353
Middle Eastern	0.00	0.00
South Asian	0.0000333	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for Wnt proteins (PubMed:9054360, PubMed:10097073, PubMed:20530549). Can activate WNT2, WNT10B, WNT5A, but not WNT2B or WNT4 (in vitro); the in vivo situation may be different since not all of these are known to be coexpressed (By similarity). In neurons, activation of WNT7A promotes formation of synapses (PubMed:20530549). Functions in the canonical Wnt/beta-catenin signaling pathway. The canonical Wnt/beta-catenin signaling pathway leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes (By similarity). 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 (Probable). Plays a role in yolk sac angiogenesis and in placental vascularization (By similarity). {ECO:0000250|UniProtKB:Q9EQD0, ECO:0000269|PubMed:10097073, ECO:0000269|PubMed:20530549, ECO:0000269|PubMed:9054360, ECO:0000305}.
• 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);WNT-Core;Mesodermal Commitment Pathway;Ectoderm Differentiation;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;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;Wnt Canonical;Wnt signaling network;Degradation of beta catenin;TCF dependent signaling in response to WNT;Canonical Wnt signaling pathway;Wnt Mammals (Consensus)

Recessive Scores

• pRec: 0.201

Intolerance Scores

• loftool: 0.0694
• rvis_EVS: -0.21
• rvis_percentile_EVS: 38.58

Haploinsufficiency Scores

• pHI: 0.714
• hipred: Y
• hipred_score: 0.833
• ghis: 0.407

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.994

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fzd5
• Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; vision/eye 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); embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms 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); digestive/alimentary phenotype

Zebrafish Information Network

• Gene name: fzd5
• Affected structure: optic fissure
• Phenotype tag: abnormal
• Phenotype quality: closure incomplete

Gene ontology

• Biological process: embryonic axis specification;angiogenesis;positive regulation of T cell cytokine production;G protein-coupled receptor signaling pathway;Wnt signaling pathway, calcium modulating pathway;synapse assembly;negative regulation of cell population proliferation;anterior/posterior axis specification, embryo;neuron differentiation;post-embryonic camera-type eye development;positive regulation of interferon-gamma production;T cell differentiation in thymus;non-canonical Wnt signaling pathway;positive regulation of JUN kinase activity;positive regulation of transcription by RNA polymerase II;cell maturation;embryonic camera-type eye morphogenesis;positive regulation of interleukin-1 beta secretion;Spemann organizer formation;canonical Wnt signaling pathway;Wnt signaling pathway, planar cell polarity pathway;apoptotic process involved in morphogenesis;branching involved in labyrinthine layer morphogenesis;syncytiotrophoblast cell differentiation involved in labyrinthine layer development;labyrinthine layer blood vessel development;chorionic trophoblast cell differentiation;cellular response to molecule of bacterial origin;regulation of chorionic trophoblast cell proliferation;regulation of autophagy of mitochondrion;positive regulation of protein targeting to mitochondrion;positive regulation of tumor necrosis factor secretion;beta-catenin destruction complex disassembly;regulation of bicellular tight junction assembly
• Cellular component: Golgi membrane;plasma membrane;integral component of plasma membrane;bicellular tight junction;cell surface;axon;dendrite;clathrin-coated endocytic vesicle membrane;early endosome membrane;perikaryon;synapse;perinuclear region of cytoplasm
• Molecular function: amyloid-beta binding;G protein-coupled receptor activity;protein binding;lipid binding;Wnt-protein binding;protein kinase binding;ubiquitin protein ligase binding;Wnt-activated receptor activity;protein-containing complex binding