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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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FGD2
FYVE, RhoGEF and PH domain containing 2
Chromosome 6 · 6p21.2
NCBI Gene: 221472Ensembl: ENSG00000146192.16HGNC: HGNC:3664UniProt: A0ABB0MVF6
21PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingsmall GTPase bindingguanyl-nucleotide exchange factor activitycytoskeleton organizationhypothyroidismthyroid diseaseThyrotoxicosisseptic shock
✦AI Summary

FGD2 is a guanine nucleotide exchange factor that specifically activates CDC42, a member of the Rho family of small GTPases, by catalyzing the exchange of bound GDP for GTP 12. The protein contains a conserved domain architecture including adjacent RhoGEF and PH domains, a second C-terminal PH domain, and a distinctive FYVE domain 1. FGD2 demonstrates complex subcellular localization, concentrating in membrane ruffles and early endosomes, with the FYVE domain mediating endosomal targeting and the C-terminal PH domain directing recruitment to membrane ruffles 2. Functionally, FGD2 overexpression promotes CDC42 activation and elevates JNK1 activity in a CDC42-dependent manner 2. The protein is preferentially expressed in antigen-presenting cells including B lymphocytes, macrophages, and dendritic cells, with expression levels varying during B cell development and being suppressed upon B cell receptor activation 2. This suggests FGD2 plays important roles in leukocyte signaling and vesicle trafficking within immune system cells. Additionally, FGD2 appears to couple actin cytoskeleton dynamics with plasma membrane organization, contributing to cellular processes such as filopodium and lamellipodium formation 3. The gene maps to human chromosome 6.2 1.

Sources cited
1
FGD2 encodes a CDC42-specific guanine nucleotide exchange factor with conserved RhoGEF, PH, and FYVE domains
PMID: 10458911
2
FGD2 is expressed in antigen-presenting cells, localizes to membrane ruffles and early endosomes, and activates CDC42 leading to JNK1 activation
PMID: 18838382
3
FGD2 family members couple the actin cytoskeleton with plasma membrane and contribute to filopodium/lamellipodium formation
PMID: 18410521
⚠Limited data available — This gene has 3 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
hypothyroidismOpen Targets
0.47Moderate
thyroid diseaseOpen Targets
0.35Weak
ThyrotoxicosisOpen Targets
0.34Weak
septic shockOpen Targets
0.31Weak
pernicious anemiaOpen Targets
0.30Weak
seborrheic keratosisOpen Targets
0.18Weak
psoriatic arthritisOpen Targets
0.13Weak
Familial prostate cancerOpen Targets
0.11Weak
prostate cancerOpen Targets
0.11Weak
spondyloarthropathyOpen Targets
0.06Suggestive
abnormality of serum enzyme levelsOpen Targets
0.05Suggestive
melanomaOpen Targets
0.03Suggestive
fracture of pelvisOpen Targets
0.03Suggestive
juvenile idiopathic arthritisOpen Targets
0.02Suggestive
osteosarcomaOpen Targets
0.02Suggestive
tuberculosisOpen Targets
0.02Suggestive
Acute hepatic failureOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.02Suggestive
cancerOpen Targets
0.01Suggestive
asthmaOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
FGD4Shared pathway100%FGD5Shared pathway100%FGD1Shared pathway86%FGD6Shared pathway83%FGD3Shared pathway68%FMNL3Shared pathway44%
Tissue Expression6 tissues
Lung
100%
Bone Marrow
25%
Liver
20%
Heart
11%
Ovary
9%
Brain
6%
Gene Interaction Network
Click a node to explore
FGD2FGD4FGD5FGD1FGD6FGD3FMNL3
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q7Z6J4
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.89LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.71 [0.57–0.89]
RankingsWhere FGD2 stands among ~20K protein-coding genes
  • #13,905of 20,598
    Most Researched21
  • #8,024of 17,882
    Most Constrained (LOEUF)0.89
Genes detectedFGD2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Isolation, characterization, and mapping of the mouse and human Fgd2 genes, faciogenital dysplasia (FGD1; Aarskog syndrome) gene homologues.
PMID: 10458911
Genomics · 1999
1.00
2
Linkage of one gene for familial glucocorticoid deficiency type 2 (FGD2) to chromosome 8q and further evidence of heterogeneity.
PMID: 12384787
Hum Genet · 2002
0.90
3
Characterization of guanine nucleotide exchange activity of DH domain of human FGD2.
PMID: 32681954
Protein Expr Purif · 2020
0.80
4
Isolated glucocorticoid deficiency: Genetic causes and animal models.
PMID: 30817990
J Steroid Biochem Mol Biol · 2019
0.70
5
FGD2, a CDC42-specific exchange factor expressed by antigen-presenting cells, localizes to early endosomes and active membrane ruffles.
PMID: 18838382
J Biol Chem · 2008
0.60