GeneBe

FGD1

FYVE, RhoGEF and PH domain containing 1, the group of Dbl family Rho GEFs|Zinc fingers FYVE-type|Pleckstrin homology domain containing

Basic information

Region (hg38): X:54445454-54496234

Previous symbols: [ "FGDY" ]

Links

ENSG00000102302 ∙ NCBI:2245 ∙ OMIM:300546 ∙ HGNC:3663 ∙ Uniprot:P98174 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • Aarskog-Scott syndrome, X-linked (Supportive), mode of inheritance: AD
  • Aarskog-Scott syndrome, X-linked (Strong), mode of inheritance: XL
  • Aarskog-Scott syndrome, X-linked (Definitive), mode of inheritance: XL
  • Aarskog-Scott syndrome, X-linked (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Aarskog-Scott syndromeXLGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Genitourinary; Musculoskeletal; Neurologic5504078; 5173168; 7954831; 10930571; 11093277; 15809997; 17152066; 17847065; 19110080; 20082460; 21654724; 21739585; 22876573

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FGD1 gene.

  • not_provided (338 variants)
  • Inborn_genetic_diseases (103 variants)
  • Aarskog_syndrome (80 variants)
  • FGD1-related_disorder (33 variants)
  • not_specified (19 variants)
  • Intellectual_disability (12 variants)
  • Syndromic_X-linked_intellectual_disability_Claes-Jensen_type (2 variants)
  • History_of_neurodevelopmental_disorder (2 variants)
  • TSR2-related_disorder (2 variants)
  • Russell-Silver_syndrome (1 variants)
  • Polyhydramnios (1 variants)
  • Neurodevelopmental_delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FGD1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004463.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
8
clinvar
75
clinvar
12
clinvar
 95
missense
5
clinvar
11
clinvar
174
clinvar
40
clinvar
4
clinvar
 234
nonsense
10
clinvar
8
clinvar
2
clinvar
 20
start loss
0
frameshift
24
clinvar
11
clinvar
4
clinvar
 39
splice donor/acceptor (+/-2bp)
6
clinvar
7
clinvar
 13
Total 45 37 188 115 16

Highest pathogenic variant AF is 0.00249395

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
FGD1protein_codingprotein_codingENST00000375135 1850713
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.000.000301125679231256840.0000199
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense3.522154170.5150.00003576169
Missense in Polyphen40129.70.308391847
Synonymous0.3531641700.9660.00001432000
Loss of Function4.92232.00.06240.00000245505

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001150.0000981
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.00006400.0000462
European (Non-Finnish)0.00001220.00000879
Middle Eastern0.000.00
South Asian0.000.00
Other0.0002260.000163

dbNSFP

Source: dbNSFP

Function
FUNCTION: Activates 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. {ECO:0000269|PubMed:8969170}.;
Disease
DISEASE: Aarskog-Scott syndrome (AAS) [MIM:305400]: An X-linked recessive, rare multisystemic disorder characterized by disproportionately short stature, and by facial, skeletal and urogenital anomalies. Some patients manifest mental retardation, attention deficit disorder and hyperactivity. {ECO:0000269|PubMed:10930571, ECO:0000269|PubMed:11093277, ECO:0000269|PubMed:14560308}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Defects in FGD1 are found in a patient with non- syndromal X-linked mental retardation. {ECO:0000269|PubMed:11940089}.;
Pathway
Regulation of actin cytoskeleton - Homo sapiens (human);Regulation of Actin Cytoskeleton;Signaling by GPCR;Signal Transduction;Rho GTPase cycle;Signaling by Rho GTPases;NRAGE signals death through JNK;Death Receptor Signalling;p75 NTR receptor-mediated signalling;G alpha (12/13) signalling events;GPCR downstream signalling;Regulation of CDC42 activity;Cell death signalling via NRAGE, NRIF and NADE (Consensus)

Recessive Scores

pRec
0.287

Intolerance Scores

loftool
0.132
rvis_EVS
-0.51
rvis_percentile_EVS
21.56

Haploinsufficiency Scores

pHI
0.323
hipred
Y
hipred_score
0.809
ghis
0.552

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.506

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Fgd1
Phenotype

Gene ontology

Biological process
cytoskeleton organization;signal transduction;G protein-coupled receptor signaling pathway;multicellular organism development;regulation of cell shape;animal organ morphogenesis;actin cytoskeleton organization;regulation of Rho protein signal transduction;positive regulation of apoptotic process;regulation of GTPase activity;filopodium assembly;regulation of small GTPase mediated signal transduction
Cellular component
ruffle;cytoplasm;Golgi apparatus;cytosol;cytoskeleton;lamellipodium
Molecular function
guanyl-nucleotide exchange factor activity;Rho guanyl-nucleotide exchange factor activity;small GTPase binding;metal ion binding