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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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FUZ
fuzzy planar cell polarity protein
Chromosome 19 · 19q13.33
NCBI Gene: 80199Ensembl: ENSG00000010361.14HGNC: HGNC:26219UniProt: E9PK12
26PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingneural tube closurenegative regulation of cell migrationpositive regulation of cilium assemblyciliopathycaudal regression sequenceneural tube defectneurodegenerative disease
✦AI Summary

FUZ (fuzzy planar cell polarity protein) is a core component of the CPLANE complex that plays essential roles in ciliogenesis and planar cell polarity signaling 1. As part of the CPLANE complex, FUZ works alongside INTU, WDPCP, JBTS17, and RSG1 to regulate cilium assembly and maintenance 1. The protein functions as a probable GEF (guanine nucleotide exchange factor) for Rab GTPases through its homologous Longin domains, facilitating vesicular trafficking during ciliogenesis 2. FUZ regulates Sonic Hedgehog signaling by controlling ciliary localization of GPR161, a negative regulator of the pathway, demonstrating genetic epistasis between these proteins 3. Clinically, FUZ mutations cause skeletal ciliopathies including short-rib polydactyly syndrome type IV, characterized by skeletal malformations and polydactyly 4. During embryonic development, FUZ is critical for proper neural tube formation, with knockout mice exhibiting exencephaly, spina bifida, and hypoplastic hindbrain development with abnormal rhombomere morphology 5. Additionally, FUZ dysregulation is implicated in neurodegeneration and cancer, where it can trigger apoptosis through dishevelled/Rac1/JNK signaling and shows reduced expression in certain cancers associated with poor prognosis 67.

Sources cited
1
FUZ is a core component of the CPLANE complex involved in ciliogenesis and planar cell polarity
PMID: 35740972
2
FUZ functions as a probable GEF for Rab GTPases through homologous Longin domains
PMID: 31562761
3
FUZ regulates Sonic Hedgehog signaling by controlling GPR161 ciliary localization
PMID: 39369306
4
FUZ mutations cause skeletal ciliopathies including short-rib polydactyly syndrome type IV
PMID: 29068549
5
FUZ knockout mice exhibit neural tube defects including exencephaly and hypoplastic hindbrain development
PMID: 38501709
6
FUZ dysregulation triggers neuronal apoptosis through dishevelled/Rac1/JNK signaling
PMID: 30026307
7
Reduced FUZ expression is associated with poor prognosis in certain cancers
PMID: 33658400
Disease Associationsⓘ20
ciliopathyOpen Targets
0.37Weak
caudal regression sequenceOpen Targets
0.37Weak
neural tube defectOpen Targets
0.34Weak
neurodegenerative diseaseOpen Targets
0.34Weak
Alzheimer diseaseOpen Targets
0.34Weak
lysosomal storage diseaseOpen Targets
0.34Weak
multiple sclerosisOpen Targets
0.34Weak
Parkinson diseaseOpen Targets
0.34Weak
short-rib thoracic dysplasia 6 with or without polydactylyOpen Targets
0.33Weak
Abnormality of the skeletal systemOpen Targets
0.08Suggestive
non-small cell lung carcinomaOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.07Suggestive
cancerOpen Targets
0.07Suggestive
HeterotaxiaOpen Targets
0.06Suggestive
Lung agenesis - heart defect - thumb anomaliesOpen Targets
0.05Suggestive
lung agenesis-heart defect-thumb anomalies syndromeOpen Targets
0.05Suggestive
Congenitally uncorrected transposition of the great arteriesOpen Targets
0.05Suggestive
Patent ductus arteriosus - bicuspid aortic valve - hand anomaliesOpen Targets
0.05Suggestive
patent ductus arteriosus-bicuspid aortic valve-hand anomalies syndromeOpen Targets
0.05Suggestive
Holt-Oram syndromeOpen Targets
0.05Suggestive
Pathogenic Variants1
NM_025129.5(FUZ):c.98_111+9delPathogenic
Short-rib thoracic dysplasia 6 with or without polydactyly
☆☆☆☆2017
View on ClinVar ↗
Related Genes
CPLANE2Protein interaction99%INTUProtein interaction64%WDPCPProtein interaction60%IFT88Shared pathway25%IFT122Shared pathway19%DYNC2I1Shared pathway18%
Tissue Expression6 tissues
Ovary
100%
Brain
93%
Bone Marrow
48%
Lung
45%
Heart
39%
Liver
38%
Gene Interaction Network
Click a node to explore
FUZCPLANE2INTUWDPCPIFT88IFT122DYNC2I1
PROTEIN STRUCTURE
Preparing viewer…
PDB7Q3D · 3.35 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.15LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.86 [0.65–1.15]
RankingsWhere FUZ stands among ~20K protein-coding genes
  • #12,793of 20,598
    Most Researched26
  • #5,298of 5,498
    Most Pathogenic Variants1
  • #11,919of 17,882
    Most Constrained (LOEUF)1.15
Genes detectedFUZ
Sources retrieved10 papers
Response time—
📄 Sources
10â–¼
1
Expanding the genetic architecture and phenotypic spectrum in the skeletal ciliopathies.
PMID: 29068549
Hum Mutat · 2018
1.00
2
CPLANE Complex and Ciliopathies.
PMID: 35740972
Biomolecules · 2022
0.90
3
Hexa-Longin domain scaffolds for inter-Rab signalling.
PMID: 31562761
Bioinformatics · 2020
0.80
4
Planar cell polarity gene
PMID: 30026307
EMBO Rep · 2018
0.70
5
Disruption of Fuz in mouse embryos generates hypoplastic hindbrain development and reduced cranial nerve ganglia.
PMID: 38501709
Dev Dyn · 2024
0.60