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Fetal anomalies

Gene: FUZ

Green List (high evidence)
FUZ (fuzzy planar cell polarity protein)
EnsemblGeneIds (GRCh38): ENSG00000010361
EnsemblGeneIds (GRCh37): ENSG00000010361
OMIM: 610622, Gene2Phenotype
FUZ is in 6 panels

2 reviews

Chirag Patel (Genetic Health Queensland)

Green List (high evidence)

FUZ is crucial for the transport of components to the primary cilium and potentially promotes protein complex assembly necessary for downstream cilium formation and function. Previous studies have shown complete knockout of Fuz in a mouse model leads to prenatal lethality, coronal craniosynostosis, micrognathia, facial malformations, eye, and heart defects. Suggested as a skeletal ciliopathy disorder gene.

PMID: 38702430
1 individual (from family with 2 affecteds) with orofaciodigital syndrome like phenotype (dysmorphism, bilateral foot preaxial polysyndactyly, right foot postaxial polysyndactyly, broad thumbs, bilateral 5th finger clinodactyly narrow chest, partial AVSD). They found a homozygous missense variant in FUZ [p.(Glu201Lys)]. Parents were heterozygous carriers. A sibling died at 18mths and had complete AVSD, bilateral cleft lip and palate, right 5th finger clinodactyly, and medially deviated/broad great toes.

1 fetus with orofaciodigital syndrome like phenotype (right cleft lip, 4 limb polydactyly, bilateral duplicated hallux, and AVSD). They found compound heterozygous variants in FUZ [p.(Val209_Leu212del) and p.(Glu201Lys)].

PMID: 29068549
1 fetus with lethal short-rib polydactyly syndrome II-like phenotype and a homozygous variant (c.98_111+9del) in FUZ.
1 individual with asphyxiating thoracic dystrophy (ATD) with polydactyly and a (unclear if homozygous) missense variant [p.(Arg284Leu)] in FUZ.

PMID: 34719684
Monozygotic twins with craniosynostosis (1 x metopic, 1 x metopic/coronal) and a homozygous missense variant in FUZ [p.(Arg284Pro)]. They cultured primary osteoblasts and mouse embryonic fibroblasts from Fuz mutant mice. Loss of Fuz resulted in increased osteoblastic mineralisation, suggesting that the FUZ protein normally acts as a negative regulator of osteogenesis.
Created: 4 Jun 2024, 10:53 p.m. | Last Modified: 4 Jun 2024, 10:53 p.m.
Panel Version: 1.245

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ciliopathy_MONDO_0005308; skeletal ciliopathy

Publications

Variants in this GENE are reported as part of current diagnostic practice

Created: 4 Jun 2024, 10:53 p.m.
Last Modified: 4 Jun 2024, 10:53 p.m.
Panel version: 1.245

Ain Roesley (Victorian Clinical Genetics Services)

Red List (low evidence)

Spina bifida cohort. Negative for VANGL1 and VANGL2, only FUZ was sequenced.
Variants identified in 5 individuals.
Arg404Gln (39 hets in gnomAD) and Asp354Tyr (6 hets in gnomAD). These variants are listed as risk factor in ClinVar
Pro39Ser (absent in gnomAD) was de novo by parental sanger and showed reduced cell mobility on scratch assays.
2 other variants Gly140Glu and Ser142Thr were deemed non-causative due to poor in silicos and conservation
Finally, hom KO mouse models were done to prove neural tube defect
Created: 14 Feb 2022, 3:58 a.m. | Last Modified: 14 Feb 2022, 3:58 a.m.
Panel Version: 0.3400

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
{Neural tube defects, susceptibility to} MIM#182940

Publications

Variants in this GENE are reported as part of current diagnostic practice

Created: 14 Feb 2022, 3:58 a.m.
Last Modified: 14 Feb 2022, 3:58 a.m.
Panel version: 0.3400

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Neural tube defects 182940
  • Ciliopathy_MONDO_0005308, FUZ-related
  • skeletal ciliopathy
OMIM
610622
Clinvar variants
Variants in FUZ
Penetrance
None
Publications
Panels with this gene

History Filter Activity

19 Jun 2024, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: FUZ was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal

7 Jun 2024, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: FUZ were changed from Neural tube defects 182940 to Neural tube defects 182940; Ciliopathy_MONDO_0005308, FUZ-related; skeletal ciliopathy

7 Jun 2024, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: FUZ were set to 21840926

7 Jun 2024, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: FUZ was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

4 Jun 2024, Gel status: 3

Entity classified by Genomics England curator

Chirag Patel (Genetic Health Queensland)

Gene: fuz has been classified as Green List (High Evidence).

15 Feb 2022, Gel status: 1

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: fuz has been classified as Red List (Low Evidence).

15 Feb 2022, Gel status: 1

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: FUZ were set to

15 Feb 2022, Gel status: 1

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: FUZ was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

24 Oct 2021, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: FUZ was added gene: FUZ was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: FUZ was set to Unknown Phenotypes for gene: FUZ were set to Neural tube defects 182940