FZD3

protein-coding

frizzled class receptor 3, the group of G protein-coupled receptors, Class F frizzled

Gene summary

This gene is a member of the frizzled gene family. Members of this family encode seven-transmembrane domain proteins that are receptors for the wingless type MMTV integration site family of signaling proteins. Most frizzled receptors are coupled to the beta-catenin canonical signaling pathway. The function of this protein is unknown, although it may play a role in mammalian hair follicle development. Alternative splicing results in multiple transcript variants. This gene is a susceptibility locus for schizophrenia. [provided by RefSeq, Dec 2010]

MANE transcript

NM_017412.4

Inheritance

—

ClinVar variants

P:2U:67B:4

Top phenotype

Hydrocephalus

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr8:28,494,205-28,574,267

External References & Databases

Transcript & Mutation Effects

hg38 • Region Span ~80.1 kb
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GenCC 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 FZD3 variants in ClinVar

8 Conditions Cataloged
not specifiedTotal: 67
not providedTotal: 3
HydrocephalusTotal: 1
Isolated cerebellar hypoplasia/agenesisTotal: 1
Multicystic kidney dysplasiaTotal: 1
Corpus callosum, agenesis ofTotal: 1
Arthrogryposis multiplex congenitaTotal: 1
Colorectal cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017412.4. 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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
3
missense
66
clinvar
1
clinvar
67
nonsense
1
clinvar
1
start loss
0
frameshift
1
clinvar
1
clinvar
2
splice donor/acceptor (+/-2bp)
0
Total11671373
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_017412.4RefSeqNP_059108.16MANE Select
ENST00000240093.8EnsemblENSP00000240093.36MANE Select
NM_001412905.1RefSeqNP_001399834.17Standard
NM_001412906.1RefSeqNP_001399835.15Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
fzd3aDanio rerio

Structure: CoPA

Quality: decreased process quality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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)

Biological Process

  • establishment of planar polarity
  • neuron migration
  • neural tube closure
  • hair follicle development
  • positive regulation of neuroblast proliferation

Molecular Function

  • G protein-coupled receptor activity
  • protein binding
  • Wnt-protein binding
  • PDZ domain binding
  • Wnt-activated receptor activity

Cellular Component

  • cytoplasm
  • plasma membrane
  • cell surface
  • integral component of membrane
  • apical plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000240093
Coding exons
6
Length
80047
Individuals with no LoFs
125722
Homozygous LoFs
0
Heterozygous LoFs
24
Defined
125746
p
0.0000954
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.642403860.6220.00002094404
Missense (PolyPhen)59147.380.400331763
Synonymous0.2921221260.9670.000006411287
Loss of Function3.141129.40.3750.00000181316

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish00.0absent
East Asian0.000170.00016rare
Finnish0.0000480.000046rare
European (Non-Finnish)0.000120.00011rare
South Asian0.000200.00020rare
Other00.0absent

dbNSFP Gene Annotations

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. Activation by Wnt5A stimulates PKC activity via a G-protein-dependent mechanism. Involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Plays a role in controlling early axon growth and guidance processes necessary for the formation of a subset of central and peripheral major fiber tracts. Required for the development of major fiber tracts in the central nervous system, including: the anterior commissure, the corpus callosum, the thalamocortical, corticothalamic and nigrostriatal tracts, the corticospinal tract, the fasciculus retroflexus, the mammillothalamic tract, the medial lemniscus, and ascending fiber tracts from the spinal cord to the brain. In the peripheral nervous system, controls axon growth in distinct populations of cranial and spinal motor neurons, including the facial branchimotor nerve, the hypoglossal nerve, the phrenic nerve, and motor nerves innervating dorsal limbs. Involved in the migration of cranial neural crest cells. May also be implicated in the transmission of sensory information from the trunk and limbs to the brain. Controls commissural sensory axons guidance after midline crossing along the anterior-posterior axis in the developing spinal cord in a Wnt-dependent signaling pathway. Together with FZD6, 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. Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle in a beta-catenin-dependent manner (By similarity). {ECO:0000250|UniProtKB:Q61086}.;

Recessive Scores

pRec
0.142

Intolerance Scores

LoFtool
0.373
RVIS EVS
-0.89
RVIS percentile EVS
10.3

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.945

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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