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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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FGD1
FYVE, RhoGEF and PH domain containing 1
Chromosome X Β· Xp11.22
NCBI Gene: 2245Ensembl: ENSG00000102302.9HGNC: HGNC:3663UniProt: P98174
67PubMed Papers
21Diseases
0Drugs
86Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
guanyl-nucleotide exchange factor activitysmall GTPase bindingactin cytoskeleton organizationregulation of GTPase activityAarskog-Scott syndrome, X-linkedfaciodigitogenital syndromegenetic disorderneurodegenerative disease
✦AI Summary

FGD1 (FYVE, RhoGEF and PH domain containing 1) is a guanine nucleotide exchange factor that specifically activates CDC42, a Rho-family GTPase, by catalyzing the exchange of bound GDP for GTP 1. This activation regulates actin cytoskeleton organization, filopodium assembly, and cell shape through RhoGEF-mediated signal transduction 2. FGD1 contains functionally critical domains including RhoGEF, pleckstrin homology (PH), and FYVE domains that form a canonical signaling architecture conserved across the FGD family 1. Mutations in FGD1 cause Aarskog-Scott syndrome (AAS), an X-linked developmental disorder characterized by short stature, facial anomalies, skeletal deformities, and genitourinary malformations 3. A large patient cohort of 111 males with FGD1 variants revealed that short stature has prenatal onset and shows catch-up growth during the first decade, with most patients achieving low-normal adult stature 4. Intellectual disability is rare, though specific learning difficulties and attention-deficit hyperactivity disorder occur at elevated prevalence 4. Growth hormone treatment improved height outcomes in FGD1-related AAS patients with growth hormone deficiency 3. Beyond AAS, FGD1 was identified as one of 15 common differentially expressed genes shared between sarcopenia and type 2 diabetes mellitus, suggesting potential roles in muscle metabolism 5.

Sources cited
1
FGD1 encodes a guanine nucleotide exchange factor that specifically activates Cdc42 and contains RhoGEF, PH, and FYVE domains
PMID: 10458911
2
FGD1 regulates actin cytoskeleton and activates c-Jun N-terminal kinase signaling; FGD1 family members contain conserved RhoGEF, PH, and FYVE domains
PMID: 10721717
3
FGD1 mutations cause Aarskog-Scott syndrome with short stature, facial anomalies, skeletal deformities, and genitourinary malformations; growth hormone treatment improved height in FGD1-related AAS patients
PMID: 38411716
4
Large cohort of 111 AAS patients with FGD1 variants showed short stature with prenatal onset, catch-up growth in first decade, rare intellectual disability but high prevalence of learning difficulties and ADHD
PMID: 39798962
5
FGD1 identified as one of 15 common differentially expressed genes in both sarcopenia and type 2 diabetes mellitus
PMID: 35271662
Disease Associationsβ“˜21
Aarskog-Scott syndrome, X-linkedOpen Targets
0.81Strong
faciodigitogenital syndromeOpen Targets
0.69Moderate
genetic disorderOpen Targets
0.53Moderate
neurodegenerative diseaseOpen Targets
0.46Moderate
X-linked intellectual disability, Siderius typeOpen Targets
0.46Moderate
Intellectual disabilityOpen Targets
0.43Moderate
Abnormality of the skeletal systemOpen Targets
0.39Weak
Neurodevelopmental delayOpen Targets
0.34Weak
PolyhydramniosOpen Targets
0.34Weak
syndromic X-linked intellectual disability Claes-Jensen typeOpen Targets
0.30Weak
prostate adenocarcinomaOpen Targets
0.28Weak
spinal muscular atrophyOpen Targets
0.12Weak
neoplasmOpen Targets
0.08Suggestive
melanomaOpen Targets
0.08Suggestive
osteosarcomaOpen Targets
0.08Suggestive
Atrophy/Degeneration affecting the central nervous systemOpen Targets
0.05Suggestive
hepatocellular carcinomaOpen Targets
0.04Suggestive
prostate carcinomaOpen Targets
0.04Suggestive
thyroid cancerOpen Targets
0.02Suggestive
alopeciaOpen Targets
0.02Suggestive
Aarskog-Scott syndromeUniProt
Pathogenic Variants86
NM_004463.3(FGD1):c.1699C>T (p.Arg567Ter)Pathogenic
not provided|FGD1-related disorder|Intellectual disability
β˜…β˜…β˜†β˜†2025β†’ Residue 567
NM_004463.3(FGD1):c.577C>T (p.Arg193Ter)Pathogenic
not provided|FGD1-related disorder|Aarskog syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 193
NM_004463.3(FGD1):c.1565G>A (p.Arg522His)Pathogenic
Aarskog syndrome|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 522
NM_004463.3(FGD1):c.26dup (p.Ala10fs)Pathogenic
not provided|Inborn genetic diseases|FGD1-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 10
NM_004463.3(FGD1):c.1829G>A (p.Arg610Gln)Pathogenic
Aarskog syndrome|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 610
NM_004463.3(FGD1):c.2020GAG[2] (p.Glu676del)Likely pathogenic
Inborn genetic diseases|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 676
NM_004463.3(FGD1):c.527del (p.Pro176fs)Pathogenic
Aarskog syndrome|Inborn genetic diseases|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 176
NM_004463.3(FGD1):c.1966C>T (p.Arg656Ter)Pathogenic
Aarskog syndrome|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 656
NM_004463.3(FGD1):c.1555C>T (p.Arg519Cys)Likely pathogenic
Inborn genetic diseases|FGD1-related disorder|Aarskog syndrome
β˜…β˜…β˜†β˜†2023β†’ Residue 519
NM_004463.3(FGD1):c.277dup (p.Tyr93fs)Pathogenic
Aarskog syndrome
β˜…β˜…β˜†β˜†2022β†’ Residue 93
NM_004463.3(FGD1):c.2728C>T (p.Arg910Ter)Pathogenic
Aarskog syndrome|FGD1-related disorder
β˜…β˜…β˜†β˜†2022β†’ Residue 910
NM_004463.3(FGD1):c.1637-679G>ALikely pathogenic
Aarskog syndrome
β˜…β˜†β˜†β˜†2026
NM_004463.3(FGD1):c.278_285del (p.Ser92_Tyr93insTer)Pathogenic
not provided
β˜…β˜†β˜†β˜†2026β†’ Residue 92
NM_004463.3(FGD1):c.1489G>T (p.Glu497Ter)Pathogenic
Thyroid cancer, nonmedullary, 1|not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 497
NM_004463.3(FGD1):c.2336dup (p.Asn779fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 779
NM_004463.3(FGD1):c.2275-1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_004463.3(FGD1):c.1068del (p.Val357fs)Pathogenic
Aarskog syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 357
NM_004463.3(FGD1):c.1226del (p.Asn409fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 409
NM_004463.3(FGD1):c.2437A>T (p.Lys813Ter)Likely pathogenic
Aarskog syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 813
NM_004463.3(FGD1):c.918del (p.Ser307fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 307
View on ClinVar β†—
Related Genes
CDC42Protein interaction97%FGD3Protein interaction90%GNG12Protein interaction90%FGD2Shared pathway86%FGD5Shared pathway86%FGD4Shared pathway86%
Tissue Expression6 tissues
Ovary
100%
Heart
70%
Brain
64%
Lung
32%
Bone Marrow
19%
Liver
18%
Gene Interaction Network
Click a node to explore
FGD1CDC42FGD3GNG12FGD2FGD5FGD4
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt P98174
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.30Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.18 [0.12–0.30]
RankingsWhere FGD1 stands among ~20K protein-coding genes
  • #6,980of 20,598
    Most Researched67
  • #874of 5,498
    Most Pathogenic Variants86 Β· top quartile
  • #1,136of 17,882
    Most Constrained (LOEUF)0.30 Β· top 10%
Genes detectedFGD1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Identification of the shared gene signatures and pathways between sarcopenia and type 2 diabetes mellitus.
PMID: 35271662
PLoS One Β· 2022
1.00
2
FGD1-related Aarskog-Scott syndrome: Identification of four novel variations and a literature review of clinical and molecular aspects.
PMID: 38411716
Eur J Pediatr Β· 2024
0.90
3
Systematic review of mutations associated with resistance to the new and repurposed Mycobacterium tuberculosis drugs bedaquiline, clofazimine, linezolid, delamanid and pretomanid.
PMID: 32361756
J Antimicrob Chemother Β· 2020
0.80
4
Aarskog-Scott syndrome: a clinical study based on a large series of 111 male patients with a pathogenic variant in
PMID: 39798962
J Med Genet Β· 2025
0.70
5
No association between FGD1 gene polymorphisms and intellectual developmental disability in the Qinba mountain area.
PMID: 24446295
Genet Mol Res Β· 2014
0.60