FGD1 FYVE, RhoGEF and PH domain containing 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: FGD1provided by HGNC
Official Full Name: FYVE, RhoGEF and PH domain containing 1provided by HGNC
Primary source: HGNC:HGNC:3663
See related: Ensembl:ENSG00000102302 MIM:300546; AllianceGenome:HGNC:3663
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: AAS; FGDY; MRXS16; ZFYVE3
Summary: This gene encodes a protein that contains Dbl (DH) and pleckstrin (PH) homology domains and is similar to the Rho family of small GTP-binding proteins. The encoded protein specifically binds to the Rho family GTPase Cdc42Hs and can stimulate the GDP-GTP exchange of the isoprenylated form of Cdc42Hs. It also stimulates the mitogen activated protein kinase cascade leading to c-Jun kinase SAPK/JNK1 activation. Defects in this gene are the cause of the faciogenital dysplasia in Aarskog-Scott syndrome and a syndromatic form of X-linked cognitive disability. [provided by RefSeq, Jul 2017]
Expression: Ubiquitous expression in endometrium (RPKM 4.2), brain (RPKM 3.6) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: Xp11.22

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	X	NC_000023.11 (54445454..54496234, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	X	NC_060947.1 (53736310..53787092, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (54471887..54522667, complement)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Novel truncating variants in FGD1 detected in two Danish families with Aarskog-Scott syndrome and myopathic features.
Title: Novel truncating variants in FGD1 detected in two Danish families with Aarskog-Scott syndrome and myopathic features.
Silencing FYVE, RhoGEF, and PH domain containing 1 (FGD1) suppresses melanoma progression by inhibiting PI3K/AKT signaling pathway.
Title: Silencing FYVE, RhoGEF, and PH domain containing 1 (FGD1) suppresses melanoma progression by inhibiting PI3K/AKT signaling pathway.
A novel truncating variant in the FGD1 gene associated with Aarskog-Scott syndrome in a family previously diagnosed with Tel Hashomer camptodactyly.
Title: A novel truncating variant in the FGD1 gene associated with Aarskog-Scott syndrome in a family previously diagnosed with Tel Hashomer camptodactyly.
Xp11.22 duplications in four unrelated Chinese families: delineating the genotype-phenotype relationship for HSD17B10 and FGD1.
Title: Xp11.22 duplications in four unrelated Chinese families: delineating the genotype-phenotype relationship for HSD17B10 and FGD1.
FGD1 promotes tumor progression and regulates tumor immune response in osteosarcoma via inhibiting PTEN activity.
Title: FGD1 promotes tumor progression and regulates tumor immune response in osteosarcoma via inhibiting PTEN activity.
Intersection of TKS5 and FGD1/CDC42 signaling cascades directs the formation of invadopodia.
Title: Intersection of TKS5 and FGD1/CDC42 signaling cascades directs the formation of invadopodia.
Sequencing analyses in numerous types of cancer have found missense mutations in the FGD1 gene in metastatic tumors.
Title: Minireview: Role of genetic changes of faciogenital dysplasia protein 1 in human disease.
A novel variant in FGD1 (a novel hemizygous mutation in FGD1 c.53del (p.Pro18Argfs*106) for which the mother is heterozygous) was found in an Emirati family with two brothers suffering from Aarskog-Scott syndrome. The variant is predicted to be a null mutation, and this is the first report of its kind from the United Arab Emirates.
Title: A novel, putatively null, FGD1 variant leading to Aarskog-Scott syndrome in a family from UAE.
Splice site mutation of FGD1 gene is associated with Aarskog-Scott syndrome patient with a large anterior fontanel.
Title: A novel splice site mutation of FGD1 gene in an Aarskog-Scott syndrome patient with a large anterior fontanel.
Results identify a novel mutation of FDG1 in a family with Aarskog syndrome and underscore the phenotypical variability of this condition.
Title: Aarskog-Scott syndrome: a novel mutation in the FGD1 gene associated with severe craniofacial dysplasia.

Submit: New GeneRIF Correction See all GeneRIFs (29)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Aarskog syndrome MedGen: C0175701 OMIM: 305400 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2021-05-26) ClinGen Genome Curation PagePubMed Triplosensitivity No evidence available (Last evaluated 2021-05-26) ClinGen Genome Curation Page

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SGC30464 (e-PCR)
- UniSTS:7

DXS1044 (e-PCR)
- UniSTS:8207

RH75708 (e-PCR)
- UniSTS:87311

FGD1 (e-PCR)
- UniSTS:99395

G35013 (e-PCR)
- UniSTS:68686

RH98842 (e-PCR)
- UniSTS:84567

DXS7573E (e-PCR)
- UniSTS:154056

FGD1 (e-PCR)
- UniSTS:506596

FGD1_8347 (e-PCR)
- UniSTS:467689

SHGC-24021 (e-PCR)
- UniSTS:74988

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables guanyl-nucleotide exchange factor activity	IBA Inferred from Biological aspect of Ancestor more info
enables guanyl-nucleotide exchange factor activity	IDA Inferred from Direct Assay more info	PubMed
enables guanyl-nucleotide exchange factor activity	TAS Traceable Author Statement more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables small GTPase binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in actin cytoskeleton organization	IDA Inferred from Direct Assay more info	PubMed
involved_in animal organ morphogenesis	TAS Traceable Author Statement more info	PubMed
involved_in cytoskeleton organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in cytoskeleton organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in filopodium assembly	IBA Inferred from Biological aspect of Ancestor more info
involved_in filopodium assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of GTPase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cell shape	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of small GTPase mediated signal transduction	TAS Traceable Author Statement more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	ISS Inferred from Sequence or Structural Similarity more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in cytoskeleton	IEA Inferred from Electronic Annotation more info
located_in cytosol	TAS Traceable Author Statement more info
located_in lamellipodium	ISS Inferred from Sequence or Structural Similarity more info
located_in ruffle	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: FYVE, RhoGEF and PH domain-containing protein 1

Names: faciogenital dysplasia 1 protein; rho/Rac GEF; rho/Rac guanine nucleotide exchange factor FGD1; zinc finger FYVE domain-containing protein 3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008054.1 RefSeqGene

Range

4933..55713

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_004463.3 → NP_004454.2 FYVE, RhoGEF and PH domain-containing protein 1

See identical proteins and their annotated locations for NP_004454.2

Status: REVIEWED

Source sequence(s)

Z85987

Consensus CDS

CCDS14359.1

UniProtKB/Swiss-Prot

P98174, Q5H999, Q8N4D9

UniProtKB/TrEMBL

A0A2X0SFE1

Related

ENSP00000364277.3, ENST00000375135.4

Conserved Domains (5) summary

cd00160
Location:376 → 559

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.

cd13236
Location:815 → 920

PH2_FGD1-4; FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins pleckstrin homology (PH) domain, C-terminus

cd01219
Location:591 → 698

PH1_FGD1; FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 1, N-terminal Pleckstrin homology (PH) domain

cd15741
Location:725 → 789

FYVE_FGD1_2_4; FYVE domain found in FYVE, RhoGEF and PH domain-containing protein facio-genital dysplasia FGD1, FGD2, FGD4

pfam00169
Location:591 → 688

PH; PH domain