FGD3

protein-coding

FYVE, RhoGEF and PH domain containing 3, the group of Dbl family Rho GEFs|Zinc fingers FYVE-type|Pleckstrin homology domain containing

Gene summary

Predicted to enable guanyl-nucleotide exchange factor activity and small GTPase binding activity. Predicted to be involved in actin cytoskeleton organization; filopodium assembly; and regulation of cell shape. Predicted to be located in Golgi apparatus; lamellipodium; and ruffle. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001083536.2

Inheritance

—

ClinVar variants

U:107B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.48

Max pathogenic AF

—

Genomic locus

chr9:92,947,523-93,036,236

External References & Databases

Ensembl (ENSG00000127084)

Transcript & Mutation Effects

hg38 • Region Span ~88.7 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 FGD3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 104

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001083536.2. 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			2 clinvar	2 clinvar	2 clinvar	6
missense			99 clinvar	6 clinvar		105
nonsense			3 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	107	8	2	117

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001083536.2	RefSeq	NP_001077005.1	16	MANE Select
ENST00000375482.8	Ensembl	ENSP00000364631.3	16	MANE Select
NM_001286993.2	RefSeq	NP_001273922.1	16	Standard
NM_001369951.1	RefSeq	NP_001356880.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Regulation of actin cytoskeleton - Homo sapiens (human)
Signaling by GPCR
Signal Transduction
Rho GTPase cycle
Signaling by Rho GTPases

Biological Process

cytoskeleton organization
G protein-coupled receptor signaling pathway
regulation of cell shape
actin cytoskeleton organization
regulation of Rho protein signal transduction

Molecular Function

guanyl-nucleotide exchange factor activity
Rho guanyl-nucleotide exchange factor activity
small GTPase binding
metal ion binding

Cellular Component

ruffle
cytoplasm
Golgi apparatus
cytosol
cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000375482
Coding exons: 16
Length: 88786
Individuals with no LoFs: 124797
Homozygous LoFs: 0
Heterozygous LoFs: 29
Defined: 124826
p: 0.000116

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.65	345	443	0.779	0.0000273	4715
Missense (PolyPhen)		113	171.02	0.66073		1884
Synonymous	0.535	186	196	0.951	0.0000133	1451
Loss of Function	2.73	15	31.5	0.476	0.00000142	366

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000056	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.00013	0.00013	rare
Other	0.00034	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Promotes the formation of filopodia. May activate CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. Plays a role in regulating the actin cytoskeleton and cell shape (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.149

Intolerance Scores

LoFtool: 0.417
RVIS EVS: -1.08
RVIS percentile EVS: 7.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.456

Gene Damage Prediction

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