FGD5
protein-codingFYVE, RhoGEF and PH domain containing 5, the group of Pleckstrin homology domain containing|Dbl family Rho GEFs|Zinc fingers FYVE-type
Gene summary
Predicted to enable guanyl-nucleotide exchange factor activity and small GTPase binding activity. Predicted to be involved in actin cytoskeleton organization; filopodium assembly; and regulation of cell shape. Located in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~123.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to FGD5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_152536.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 7 | 4 | 12 | ||
| missense | 247 | 17 | 4 | 268 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 254 | 24 | 8 | 286 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_689749.3 | 20 | MANE Select | |
| Ensembl | ENSP00000285046.5 | 20 | MANE Select | |
| RefSeq | NP_001307205.1 | 19 | Standard | |
| Ensembl | ENSP00000394827.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- cytoskeleton organization
- regulation of cell shape
- actin cytoskeleton organization
- regulation of Rho protein signal transduction
- regulation of GTPase activity
Molecular Function
- guanyl-nucleotide exchange factor activity
- Rho guanyl-nucleotide exchange factor activity
- protein binding
- small GTPase binding
- metal ion binding
Cellular Component
- ruffle
- cytoplasm
- early endosome
- endoplasmic reticulum
- Golgi apparatus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000285046
- Coding exons
- 20
- Length
- 115427
- Individuals with no LoFs
- 124643
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 124649
- p
- 0.0000241
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.167 | 830 | 844 | 0.984 | 0.0000513 | 9466 |
| Missense (PolyPhen) | 275 | 304.19 | 0.90403 | 3322 | ||
| Synonymous | -0.361 | 376 | 367 | 1.02 | 0.0000254 | 2928 |
| Loss of Function | 6.46 | 4 | 56.4 | 0.0710 | 0.00000257 | 731 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000093 | 0.000093 | rare |
| European (Non-Finnish) | 0.000027 | 0.000027 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00017 | 0.00017 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. Mediates VEGF-induced CDC42 activation. May regulate proangiogenic action of VEGF in vascular endothelial cells, including network formation, directional movement and proliferation. May play a role in regulating the actin cytoskeleton and cell shape. {ECO:0000269|PubMed:22328776}.;
Intolerance Scores
- LoFtool
- 0.172
- RVIS EVS
- 1.02
- RVIS percentile EVS
- 90.87
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.177
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |