FUZ

protein-coding

fuzzy planar cell polarity protein, the group of Ciliogenesis and planar polarity effector complex subunits

Gene summary

This gene encodes a planar cell polarity protein that is involved in ciliogenesis and directional cell movement. Knockout studies in mice exhibit neural tube defects and defective cilia, and mutations in this gene are associated with neural tube defects in humans. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2012]

MANE transcript

NM_025129.5

Inheritance

AR, AD

ClinVar variants

P:2U:63B:25

Top phenotype

Neural tube defects, susceptibility to

gnomAD constraint

pLI —, LoF o/e 0.55

Max pathogenic AF

—

Genomic locus

chr19:49,806,866-49,817,376

External References & Databases

Ensembl (ENSG00000010361)

Transcript & Mutation Effects

hg38 • Region Span ~10.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

orofaciodigital syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0015375

Submitter: G2P

neural tube defects, susceptibility toLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0020705

Submitter: Labcorp Genetics (formerly Invitae)

neural tube defects, susceptibility toLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0020705

Submitter: PanelApp Australia

ciliopathySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0005308

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Neural tube defects, susceptibility toAD

Manifestation: Musculoskeletal

Intervention: General

Rationale: 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

Refs: 21840926

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FUZ variants in ClinVar

8 Conditions Cataloged

not specifiedTotal: 57

not providedTotal: 24

FUZ-related disorderTotal: 7

Neural tube defects, susceptibility toTotal: 4

Neural tube defectTotal: 2

See casesTotal: 2

Jeune thoracic dystrophyTotal: 1

Short-rib thoracic dysplasia 6 with or without polydactylyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_025129.5. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	16 clinvar	2 clinvar	19
missense		1 clinvar	56 clinvar	4 clinvar	3 clinvar	64
nonsense						0
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)		1 clinvar	4 clinvar			5
Total	0	2	63	20	5	90

Highest pathogenic variant AF is 0.00003867795

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 92 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_025129.5	RefSeq	NP_079405.2	11	MANE Select
ENST00000313777.9	Ensembl	ENSP00000313309.4	11	MANE Select
NM_001171937.2	RefSeq	NP_001165408.1	10	Standard
NM_001352262.2	RefSeq	NP_001339191.1	11	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
fuz	Danio rerio	Structure: pronephros Quality: cystic abnormal

Gene / Model

Organism

Observed Phenotype

fuz

Danio rerio

Structure: pronephros

Quality: cystic

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

establishment of planar polarity
neural tube closure
hair follicle development
negative regulation of cell population proliferation
regulation of smoothened signaling pathway

Molecular Function

protein binding

Cellular Component

cytoplasm
cytoskeleton
cell projection
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000313777
Coding exons: 11
Length: 10508
Individuals with no LoFs: 125723
Homozygous LoFs: 0
Heterozygous LoFs: 25
Defined: 125748
p: 0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.440	216	235	0.919	0.0000132	2588
Missense (PolyPhen)		127	132.8	0.95634		1488
Synonymous	0.908	97	109	0.889	0.00000580	944
Loss of Function	1.87	11	20.0	0.550	9.65e-7	222

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00044	0.00044	rare
Finnish	0.00018	0.00018	rare
European (Non-Finnish)	0.000073	0.000070	rare
South Asian	0.000099	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable planar cell polarity effector involved in cilium biogenesis. May regulate protein and membrane transport to the cilium. Proposed to function as core component of the CPLANE (ciliogenesis and planar polarity effectors) complex involved in the recruitment of peripheral IFT-A proteins to basal bodies. May regulate the morphogenesis of hair follicles which depends on functional primary cilia (By similarity). {ECO:0000250|UniProtKB:Q3UYI6}.;

Recessive Scores

pRec: 0.249

Intolerance Scores

LoFtool: 0.796
RVIS EVS: 0.02
RVIS percentile EVS: 55.45

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.940

Gene Damage Prediction

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