FGD3

Summary

FGD3 (FYVE, RhoGEF and PH domain containing 3, HGNC:16027) is a protein-coding gene on chromosome 9q22.31, encoding FYVE, RhoGEF and PH domain-containing protein 3 (Q5JSP0). Promotes the formation of filopodia.

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. Predicted to be located in Golgi apparatus; lamellipodium; and ruffle. Predicted to be active in cytoplasm.

Source: NCBI Gene 89846 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 122 total
• MANE Select transcript: NM_001083536

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16027
Approved symbol	FGD3
Name	FYVE, RhoGEF and PH domain containing 3
Location	9q22.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ00004, ZFYVE5
Ensembl gene	ENSG00000127084
Ensembl biotype	protein_coding
OMIM	617554
Entrez	89846

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 13 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000337352, ENST00000375482, ENST00000416701, ENST00000467786, ENST00000468206, ENST00000488407, ENST00000494553, ENST00000494669, ENST00000854360, ENST00000854361, ENST00000854362, ENST00000854363, ENST00000854364, ENST00000854365, ENST00000941518, ENST00000941519, ENST00000941520

RefSeq mRNA: 5 — MANE Select: NM_001083536 NM_001083536, NM_001286993, NM_001369951, NM_001369952, NM_033086

CCDS: CCDS43849, CCDS69619

Canonical transcript exons

ENST00000375482 — 18 exons

Exon	Start	End
ENSE00000869889	93022327	93022389
ENSE00000869890	93020317	93020424
ENSE00000869891	93019831	93019861
ENSE00000869892	93018136	93018215
ENSE00000869895	93011214	93011272
ENSE00000869896	93010246	93010384
ENSE00000900686	93013852	93013998
ENSE00001091495	93004001	93004137
ENSE00001091498	93006024	93006180
ENSE00001091502	93002925	93003014
ENSE00001337184	93034541	93034681
ENSE00001410773	92975238	92975405
ENSE00001467240	92947523	92947729
ENSE00003555864	93015737	93015829
ENSE00003578837	93029874	93029996
ENSE00003687417	93032769	93032873
ENSE00003838357	92976208	92976709
ENSE00003847335	93035338	93036233

Expression profiles

Bgee: expression breadth ubiquitous, 207 present calls, max score 98.08.

FANTOM5 (CAGE): breadth broad, TPM avg 11.3645 / max 379.9881, expressed in 725 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97369	5.5381	483
97365	3.9070	239
97364	0.8352	186
97367	0.2203	70
97363	0.1947	82
97366	0.1176	57
97368	0.1158	58
97370	0.1115	45
97373	0.0927	40
97372	0.0865	37

Top tissues by expression

244 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.08	gold quality
blood	UBERON:0000178	97.99	gold quality
thymus	UBERON:0002370	94.86	gold quality
leukocyte	CL:0000738	94.75	gold quality
monocyte	CL:0000576	94.56	gold quality
spleen	UBERON:0002106	94.21	gold quality
bone marrow cell	CL:0002092	93.94	gold quality
trabecular bone tissue	UBERON:0002483	93.91	gold quality
bone marrow	UBERON:0002371	93.35	gold quality
pancreatic ductal cell	CL:0002079	93.11	silver quality
lymph node	UBERON:0000029	92.75	gold quality
vermiform appendix	UBERON:0001154	91.89	gold quality
caecum	UBERON:0001153	87.62	gold quality
tonsil	UBERON:0002372	85.64	gold quality
amniotic fluid	UBERON:0000173	84.77	gold quality
colonic epithelium	UBERON:0000397	83.42	gold quality
right lung	UBERON:0002167	83.28	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.07	gold quality
upper lobe of left lung	UBERON:0008952	83.02	gold quality
ileal mucosa	UBERON:0000331	82.70	gold quality
small intestine Peyer’s patch	UBERON:0003454	82.33	gold quality
upper lobe of lung	UBERON:0008948	81.74	gold quality
decidua	UBERON:0002450	81.62	gold quality
upper arm skin	UBERON:0004263	81.52	gold quality
sperm	CL:0000019	81.04	silver quality
small intestine	UBERON:0002108	80.77	gold quality
gingival epithelium	UBERON:0001949	80.40	silver quality
palpebral conjunctiva	UBERON:0001812	80.39	gold quality
epithelium of nasopharynx	UBERON:0001951	79.80	gold quality
urinary bladder	UBERON:0001255	79.79	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	8.37
E-ANND-3	yes	6.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting FGD3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-4691-3P	98.11	66.83	1204
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-5189-5P	97.72	66.96	1814
HSA-MIR-1285-3P	97.72	67.02	1932
HSA-MIR-1227-3P	97.36	66.94	834
HSA-MIR-612	97.26	65.95	1597
HSA-MIR-6860	97.21	66.31	1656
HSA-MIR-8069	97.05	66.79	718
HSA-MIR-4486	96.96	60.61	931
HSA-MIR-9900	96.06	65.48	557
HSA-MIR-3914	94.91	65.77	643
HSA-MIR-371B-3P	94.48	66.59	345
HSA-MIR-6075	93.03	64.73	45

Literature-anchored findings (GeneRIF, showing 1)

• Expression of FGD3 gene as prognostic factor in young breast cancer patients. (PMID:31645624)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000099650
mus_musculus	Fgd3	ENSMUSG00000037946
rattus_norvegicus	Fgd3	ENSRNOG00000016225
caenorhabditis_elegans		WBGENE00001366
caenorhabditis_elegans		WBGENE00001490

Paralogs (10): FARP2 (ENSG00000006607), FGD1 (ENSG00000102302), ARHGEF39 (ENSG00000137135), FGD4 (ENSG00000139132), FGD2 (ENSG00000146192), FARP1 (ENSG00000152767), FGD5 (ENSG00000154783), FRMD7 (ENSG00000165694), FGD6 (ENSG00000180263), ECT2L (ENSG00000203734)

Protein

Protein identifiers

FYVE, RhoGEF and PH domain-containing protein 3 — Q5JSP0 (reviewed: Q5JSP0)

Alternative names: Zinc finger FYVE domain-containing protein 5

All UniProt accessions (1): Q5JSP0

UniProt curated annotations — full annotation on UniProt →

Function. Promotes the formation of filopodia. May activate 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.

Subcellular location. Cytoplasm. Cytoskeleton.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5JSP0-1	1	yes
Q5JSP0-2	2
Q5JSP0-3	3

RefSeq proteins (5): NP_001077005, NP_001273922, NP_001356880, NP_001356881, NP_149077 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000219	DH_dom	Domain
IPR000306	Znf_FYVE	Domain
IPR001849	PH_domain	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017455	Znf_FYVE-rel	Domain
IPR035899	DBL_dom_sf	Homologous_superfamily
IPR035941	FGD1-4_PH2	Domain
IPR051092	FYVE_RhoGEF_PH	Family

Pfam: PF00169, PF00621, PF01363

UniProt features (35 total): strand 9, binding site 8, domain 3, compositionally biased region 3, splice variant 3, region of interest 3, helix 2, chain 1, modified residue 1, sequence variant 1, zinc finger region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2COC	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5JSP0-F1	70.38	0.29

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (8): 538; 541; 555; 558; 563; 566; 580; 583

Post-translational modifications (1): 128

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-193648	NRAGE signals death through JNK
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-9013148	CDC42 GTPase cycle

MSigDB gene sets: 155 (showing top): GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, REACTOME_NRAGE_SIGNALS_DEATH_THROUGH_JNK, GOCC_RUFFLE, GOMF_GTPASE_BINDING, GOBP_REGULATION_OF_HYDROLASE_ACTIVITY, SANSOM_APC_TARGETS_DN, chr9q22, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_FILOPODIUM_ASSEMBLY, GOBP_REGULATION_OF_CELL_SHAPE

GO Biological Process (6): cytoskeleton organization (GO:0007010), regulation of cell shape (GO:0008360), actin cytoskeleton organization (GO:0030036), regulation of GTPase activity (GO:0043087), filopodium assembly (GO:0046847), regulation of small GTPase mediated signal transduction (GO:0051056)

GO Molecular Function (4): guanyl-nucleotide exchange factor activity (GO:0005085), zinc ion binding (GO:0008270), small GTPase binding (GO:0031267), metal ion binding (GO:0046872)

GO Cellular Component (6): ruffle (GO:0001726), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), cytoskeleton (GO:0005856), lamellipodium (GO:0030027)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cell death signalling via NRAGE, NRIF and NADE	1
GPCR downstream signalling	1
RHO GTPase cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell leading edge	2
plasma membrane bounded cell projection	2
cellular anatomical structure	2
cytoplasm	2
organelle organization	1
regulation of cell morphogenesis	1
regulation of biological quality	1
cytoskeleton organization	1
actin filament-based process	1
GTPase activity	1
regulation of hydrolase activity	1
plasma membrane bounded cell projection assembly	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
transition metal ion binding	1
GTPase binding	1
cation binding	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

922 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FGD3	MRAP	Q8TCY5	808
FGD3	WNK2	Q9Y3S1	761
FGD3	WNK3	Q9BYP7	710
FGD3	MC2R	Q01718	678
FGD3	SUSD3	Q96L08	540
FGD3	RABGGTA	Q92696	492
FGD3	IDI2	Q9BXS1	479
FGD3	SLC12A4	Q9UP95	470
FGD3	SLC12A5	Q9H2X9	468
FGD3	NOC3L	Q8WTT2	441
FGD3	ARHGEF33	A8MVX0	438
FGD3	SLC12A2	P55011	425
FGD3	RAB23	Q9ULC3	425
FGD3	RND2	P52198	424
FGD3	SLC12A1	Q13621	424

IntAct

6 interactions, top by confidence:

A	B	Type	Score
FGD3	ARHGAP22	psi-mi:“MI:0915”(physical association)	0.400
FGD4	FGD3	psi-mi:“MI:0915”(physical association)	0.400
FGD3	DDX39A	psi-mi:“MI:0914”(association)	0.350
RASGRF2	SNRPA	psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350

BioGRID (11): FGD3 (Affinity Capture-MS), ARHGAP22 (Affinity Capture-Western), FGD3 (FRET), ARHGAP22 (Affinity Capture-MS), DDX39A (Affinity Capture-MS), DNAJB6 (Affinity Capture-MS), FGD3 (Affinity Capture-MS), FGD3 (Affinity Capture-MS), FGD3 (Affinity Capture-RNA), FGD3 (Affinity Capture-Western), FGD3 (Reconstituted Complex)

ESM2 similar proteins: A0A0G2JXN2, A2AWP8, O88842, O95267, P29590, P52734, P98174, Q1LY10, Q29RM4, Q2TBA3, Q3TAA7, Q3U0J8, Q3UTZ3, Q496Y0, Q4VX76, Q568M3, Q58D15, Q5BIM1, Q5JSP0, Q5R5M3, Q5R5T1, Q5REJ9, Q5W0U4, Q68FF6, Q69Z89, Q69ZK0, Q6PFY8, Q7TNM2, Q7Z4K8, Q7Z5H3, Q7Z6J4, Q80V85, Q8BY35, Q8BZ52, Q8C190, Q8N1F8, Q8TCU6, Q8WVR3, Q96JH8, Q99N48

Diamond homologs: A2AWP8, O15013, P52734, P98174, Q1ZXH8, Q29RM4, Q5JSP0, Q5R5M3, Q5R5T1, Q8BY35, Q8C033, Q9HCE6, A0A0D1E015, A0JMD2, A8QCE4, A8XJZ8, B0G126, B0WAQ0, B3MT31, B3P851, B4G2G5, B4IC49, B4JHI7, B4K982, B4M140, B4NFJ7, B4PRU6, D2H5P6, D4A8G9, E1BLZ4, E9Q4P1, O13786, O13821, O14964, O88387, O88842, O95405, O96838, Q0P4S0, Q0U4Z8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
FGD3	“up-regulates activity”	CDC42	“guanine nucleotide exchange factor”

Disease & clinical

Clinical variants and AI predictions

ClinVar

122 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	96
Likely benign	8
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3290 predictions. Top by Δscore:

Variant	Effect	Δscore
9:93004133:GAGTG:G	donor_gain	1.0000
9:93004134:AGTG:A	donor_gain	1.0000
9:93004135:GTG:G	donor_gain	1.0000
9:93004135:GTGG:G	donor_gain	1.0000
9:93004136:TG:T	donor_gain	1.0000
9:93004136:TGG:T	donor_loss	1.0000
9:93004136:TGGT:T	donor_gain	1.0000
9:93004137:GG:G	donor_gain	1.0000
9:93004137:GGTG:G	donor_gain	1.0000
9:93004138:G:GG	donor_gain	1.0000
9:93004139:TGAG:T	donor_loss	1.0000
9:93006019:C:CA	acceptor_gain	1.0000
9:93006179:AGG:A	donor_loss	1.0000
9:93006181:G:GC	donor_loss	1.0000
9:93006182:T:A	donor_loss	1.0000
9:93010244:A:AG	acceptor_gain	1.0000
9:93010245:G:GG	acceptor_gain	1.0000
9:93010245:GA:G	acceptor_gain	1.0000
9:93010245:GAA:G	acceptor_gain	1.0000
9:93010357:G:GT	donor_gain	1.0000
9:93010371:G:GT	donor_gain	1.0000
9:93010372:A:T	donor_gain	1.0000
9:93010375:GA:G	donor_gain	1.0000
9:93010380:GGAGA:G	donor_gain	1.0000
9:93010381:GAGA:G	donor_gain	1.0000
9:93010381:GAGAG:G	donor_gain	1.0000
9:93010382:A:T	donor_gain	1.0000
9:93010382:AGA:A	donor_gain	1.0000
9:93010383:GA:G	donor_gain	1.0000
9:93010383:GAG:G	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000065343 (9:93026167 G>A,T), RS1000077724 (9:93023415 A>G), RS1000115473 (9:92982482 T>G), RS1000119855 (9:92975305 G>A), RS1000158829 (9:93011074 T>C), RS1000181289 (9:92980976 A>C,G), RS1000184867 (9:92999921 A>C), RS1000258669 (9:92999673 A>T), RS1000273792 (9:93010868 C>A), RS1000308921 (9:92989887 G>C,T), RS1000369135 (9:93006644 A>G), RS1000384893 (9:92971094 A>T), RS1000407291 (9:92953071 G>A), RS1000416940 (9:93017865 G>A), RS1000484598 (9:92970725 C>T)

Disease associations

OMIM: gene MIM:617554 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST012210_5	Longevity	4.000000e-06
GCST90002395_55	Mean platelet volume	1.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

50 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	2
sodium arsenite	decreases expression, increases abundance, increases expression	2
(+)-JQ1 compound	decreases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Estradiol	affects cotreatment, decreases expression	2
Nickel	increases expression	2
Valproic Acid	affects cotreatment, increases expression	2
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
decabromobiphenyl ether	decreases expression	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	decreases expression	1
ferrous chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment, decreases expression, affects response to substance	1
gallium arsenide	decreases expression	1
pentanal	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	decreases expression	1
quinocetone	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Temozolomide	decreases expression	1
Aldehydes	increases expression	1
Arsenic	increases expression, increases abundance	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.