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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Aarskog-Scott syndrome	XL	General	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	Craniofacial; Genitourinary; Musculoskeletal; Neurologic	5504078; 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 (19 variants)
• Aarskog syndrome (12 variants)
• Inborn genetic diseases (4 variants)
• FGD1-related disorder (2 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	59	14	79
missense	2	7	125	17	4	155
nonsense	10	6	1			17
start loss						0
frameshift	14	8	3			25
inframe indel	1	1	4			6
splice donor/acceptor (+/-2bp)	5	4				9
splice region			5	11	1	17
non coding	1		2	17	20	40
Total	33	26	141	93	38

Variants in FGD1

This is a list of pathogenic ClinVar variants found in the FGD1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-54446073-G-A		not specified • Aarskog syndrome	Benign (Aug 10, 2021)
X-54446122-C-T		Aarskog syndrome	Uncertain significance (Dec 21, 2023)
X-54446123-G-A			Uncertain significance (Nov 14, 2019)
X-54446138-C-T		Inborn genetic diseases	Uncertain significance (Nov 27, 2023)
X-54446141-G-C			Uncertain significance (Jan 18, 2024)
X-54446144-G-A		Inborn genetic diseases	Uncertain significance (Sep 12, 2023)
X-54446144-G-T		Inborn genetic diseases	Uncertain significance (Jun 10, 2024)
X-54446149-G-A			Uncertain significance (Dec 08, 2022)
X-54446161-A-C			Uncertain significance (Nov 07, 2023)
X-54446172-C-G			Likely benign (May 25, 2022)
X-54446172-C-T		Inborn genetic diseases	Likely benign (Oct 23, 2019)
X-54446174-G-A		Inborn genetic diseases	Benign/Likely benign (Nov 24, 2023)
X-54446179-T-G		Inborn genetic diseases • FGD1-related disorder	Conflicting classifications of pathogenicity (Apr 01, 2024)
X-54446190-C-T		Inborn genetic diseases	Likely benign (Jan 19, 2017)
X-54446192-T-C		Aarskog syndrome	Uncertain significance (Jun 22, 2022)
X-54446196-C-T			Likely benign (Mar 21, 2023)
X-54446197-TCAGA-T			Uncertain significance (Dec 21, 2022)
X-54446209-G-A		TSR2-related disorder	Uncertain significance (Dec 10, 2022)
X-54446210-G-GC		Aarskog syndrome	Uncertain significance (May 17, 2023)
X-54446222-A-C			Uncertain significance (Jul 01, 2022)
X-54446224-G-A			Uncertain significance (Apr 08, 2021)
X-54446234-G-A		Aarskog syndrome	Conflicting classifications of pathogenicity (Jun 25, 2024)
X-54446234-G-T			Likely benign (Nov 01, 2022)
X-54446238-C-T		Inborn genetic diseases	Benign/Likely benign (Jan 21, 2024)
X-54446242-C-T		Inborn genetic diseases	Uncertain significance (Apr 07, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FGD1	protein_coding	protein_coding	ENST00000375135	18	50713

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000301	125679	2	3	125684	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.52	215	417	0.515	0.0000357	6169
Missense in Polyphen		40	129.7	0.30839		1847
Synonymous	0.353	164	170	0.966	0.0000143	2000
Loss of Function	4.92	2	32.0	0.0624	0.00000245	505

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000115	0.0000981
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000640	0.0000462
European (Non-Finnish)	0.0000122	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000226	0.000163

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

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

Mouse Genome Informatics

• Gene name: Fgd1

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