FBXO30

Summary

FBXO30 (F-box protein 30, HGNC:15600) is a protein-coding gene on chromosome 6q24.3, encoding F-box only protein 30 (Q8TB52). Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.

This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class and it is upregulated in nasopharyngeal carcinoma.

Source: NCBI Gene 84085 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 8 total
• MANE Select transcript: NM_032145

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15600
Approved symbol	FBXO30
Name	F-box protein 30
Location	6q24.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC21674, Fbx30
Ensembl gene	ENSG00000118496
Ensembl biotype	protein_coding
OMIM	609101
Entrez	84085

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 12 protein_coding

ENST00000237281, ENST00000894020, ENST00000894021, ENST00000894022, ENST00000894023, ENST00000929661, ENST00000929662, ENST00000929663, ENST00000929664, ENST00000929665, ENST00000929666, ENST00000942589

RefSeq mRNA: 2 — MANE Select: NM_032145 NM_001348092, NM_032145

CCDS: CCDS5208

Canonical transcript exons

ENST00000237281 — 3 exons

Exon	Start	End
ENSE00001161068	145804372	145806421
ENSE00001444838	145814603	145814795
ENSE00003697866	145793502	145800309

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 98.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.5499 / max 122.8334, expressed in 1698 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
76075	5.6751	1669
76074	0.8749	461

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.62	gold quality
tibialis anterior	UBERON:0001385	97.49	gold quality
oocyte	CL:0000023	96.87	gold quality
deltoid	UBERON:0001476	95.02	gold quality
left ventricle myocardium	UBERON:0006566	94.50	gold quality
cauda epididymis	UBERON:0004360	94.01	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.15	gold quality
heart right ventricle	UBERON:0002080	93.11	gold quality
myocardium	UBERON:0002349	92.91	gold quality
cartilage tissue	UBERON:0002418	91.57	gold quality
quadriceps femoris	UBERON:0001377	90.33	gold quality
cortical plate	UBERON:0005343	90.31	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.03	gold quality
biceps brachii	UBERON:0001507	89.99	gold quality
vastus lateralis	UBERON:0001379	89.60	gold quality
saphenous vein	UBERON:0007318	88.96	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	88.77	gold quality
skeletal muscle tissue	UBERON:0001134	87.75	gold quality
gingival epithelium	UBERON:0001949	87.71	gold quality
trabecular bone tissue	UBERON:0002483	87.62	gold quality
urethra	UBERON:0000057	87.60	gold quality
lower lobe of lung	UBERON:0008949	87.42	gold quality
muscle tissue	UBERON:0002385	87.31	gold quality
gingiva	UBERON:0001828	87.20	gold quality
ileal mucosa	UBERON:0000331	86.50	gold quality
ileum	UBERON:0002116	86.42	silver quality
upper arm skin	UBERON:0004263	85.94	silver quality
esophagus squamous epithelium	UBERON:0006920	85.94	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.55	gold quality
lower esophagus	UBERON:0013473	85.50	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.68
E-MTAB-6142	no	26.92

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• Results suggest that D6S1581 is highly associated with nasopharyngeal carcinoma, and there may be one or more NPC associated genes near D6S1581, including FBXO30. (PMID:12903040)
• Retinoic acid receptor gamma levels are controlled by FBXO30-mediated ubiquitination and that FBXO30 is a key regulator of BMP signaling. (PMID:31320612)
• FBXO30 functions as a tumor suppressor and an E3 ubiquitin ligase for hZIP1mediated HIF1alpha degradation in renal cell carcinoma. (PMID:36799168)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	fbxo30a	ENSDARG00000058561
mus_musculus	Fbxo30	ENSMUSG00000047648
rattus_norvegicus	Fbxo30	ENSRNOG00000014852
caenorhabditis_elegans		WBGENE00015673

Paralogs (1): FBXO40 (ENSG00000163833)

Protein

Protein identifiers

F-box only protein 30 — Q8TB52 (reviewed: Q8TB52)

All UniProt accessions (1): Q8TB52

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Required for muscle atrophy following denervation.

Subunit / interactions. Part of a SCF (SKP1-cullin-F-box) protein ligase complex. Interacts with SKP1, CUL1 and RBX1/ROC1.

Post-translational modifications. Auto-ubiquitinated. May be neddylated. Neddylation may be required for E3 ligase activity.

Pathway. Protein modification; protein ubiquitination.

RefSeq proteins (2): NP_001335021, NP_115521* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001293	Znf_TRAF	Domain
IPR001810	F-box_dom	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR031890	Fbxo30/Fbxo40	Family
IPR036047	F-box-like_dom_sf	Homologous_superfamily
IPR043013	Znf_TRAF_N	Homologous_superfamily

Pfam: PF15965, PF15966

UniProt features (21 total): sequence variant 4, helix 4, strand 4, turn 2, region of interest 2, compositionally biased region 2, chain 1, domain 1, zinc finger region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2YRE	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TB52-F1	61.94	0.30

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-8951664	Neddylation
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation

MSigDB gene sets: 197 (showing top): GOBP_CHROMOSOME_ORGANIZATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, RORA1_01, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, ATACCTC_MIR202, GCM_ZNF198, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, TGACCTY_ERR1_Q2, GOBP_CHROMOSOME_CONDENSATION, TGTGTGA_MIR377, TGANTCA_AP1_C, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GCM_SUFU, NRF2_Q4

GO Biological Process (5): chromatin organization (GO:0006325), chromosome segregation (GO:0007059), gene expression (GO:0010467), protein ubiquitination (GO:0016567), chromosome condensation (GO:0030261)

GO Molecular Function (4): zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (1): cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Post-translational protein modification	1
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular component organization	1
cell cycle process	1
macromolecule biosynthetic process	1
protein modification by small protein conjugation	1
chromosome organization	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
cation binding	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1046 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FBXO30	SHPRH	Q149N8	616
FBXO30	TRAF1	Q13077	586
FBXO30	EPM2A	O95278	516
FBXO30	CUL1	Q13616	511
FBXO30	SKP1	P34991	497
FBXO30	MOB3B	Q86TA1	473
FBXO30	PPP1R11	O60927	372
FBXO30	AKAP19	P0C876	357
FBXO30	HIF3A	Q9Y2N7	337
FBXO30	ZNRF1	Q8ND25	316
FBXO30	RNF39	Q9H2S5	300
FBXO30	PDC	P20941	298
FBXO30	UBA2	Q9UBT2	288
FBXO30	DOCK2	Q92608	287
FBXO30	TPM4	P07226	283

IntAct

64 interactions, top by confidence:

A	B	Type	Score
NFE2L2	MAFG	psi-mi:“MI:0914”(association)	0.940
SKP1	TTC9C	psi-mi:“MI:0914”(association)	0.870
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
FLII	TMOD1	psi-mi:“MI:0914”(association)	0.640
SKP1	MYCBP2	psi-mi:“MI:0914”(association)	0.640
CUL1	FBXO21	psi-mi:“MI:0914”(association)	0.600
FBXO30	MYO6	psi-mi:“MI:0915”(physical association)	0.560
SETDB1	CCDC85C	psi-mi:“MI:0914”(association)	0.530
PHAF1	PSMG1	psi-mi:“MI:0914”(association)	0.530
MYO1C	TMOD1	psi-mi:“MI:0914”(association)	0.530
DNALI1	GSN	psi-mi:“MI:0914”(association)	0.510
Dynll1		psi-mi:“MI:0915”(physical association)	0.400
Skp1	XPO1	psi-mi:“MI:0914”(association)	0.350
MYO1C	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Trappc11	TRAPPC3	psi-mi:“MI:0914”(association)	0.350
QSOX2	NAP1L1	psi-mi:“MI:0914”(association)	0.350
PB2	SEC15L3	psi-mi:“MI:0914”(association)	0.350
CUL1	LGALS8	psi-mi:“MI:0914”(association)	0.350
SETDB1	CCDC85C	psi-mi:“MI:0914”(association)	0.350
PNKD	EXOC5	psi-mi:“MI:0914”(association)	0.350
DQX1	MYO9A	psi-mi:“MI:0914”(association)	0.350
FBXO34	GSN	psi-mi:“MI:0914”(association)	0.350

BioGRID (82): FBXO30 (Affinity Capture-RNA), FBXO30 (Affinity Capture-RNA), FBXO30 (Affinity Capture-MS), FBXO30 (Affinity Capture-MS), FBXO30 (Affinity Capture-MS), FBXO30 (Affinity Capture-MS), FBXO30 (Affinity Capture-MS), FBXO30 (Affinity Capture-MS), FBXO30 (Affinity Capture-MS), FBXO30 (Affinity Capture-MS), FBXO30 (Affinity Capture-MS), FBXO30 (Affinity Capture-MS), FBXO30 (Affinity Capture-MS), FBXO30 (Affinity Capture-MS), SKP1 (Affinity Capture-Western)

ESM2 similar proteins: A0A2R6W1B1, A0FKI7, A2XC52, A2XTW9, A2Y0Q2, B8AMA8, B8B8I3, F4I9G2, O94972, P07106, P20067, P41135, P85828, Q5EAE9, Q5EAH9, Q5R7V3, Q5T8D3, Q5XEM9, Q5XG73, Q5XI67, Q6EPZ2, Q6GPE9, Q6IE24, Q6PCX9, Q70EL1, Q75IR6, Q76N89, Q7XUW3, Q84TV4, Q86UB2, Q8BJL1, Q8BL06, Q8CBX9, Q8H383, Q8H8C6, Q8K3A6, Q8K4P8, Q8LA16, Q8TB52, Q96S38

Diamond homologs: P62932, Q5XI67, Q8BJL1, Q8TB52, Q9UH90

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SMAD1/5/8/SMAD4	down-regulates	FBXO30
FBXO30	up-regulates	Muscle_atrophy

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 76 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2	5	24.3×	4e-04
Degradation of beta-catenin by the destruction complex	5	17.0×	1e-03
Translocation of SLC2A4 (GLUT4) to the plasma membrane	5	15.1×	1e-03
Macroautophagy	6	13.6×	8e-04
Regulation of PLK1 Activity at G2/M Transition	5	12.4×	2e-03
KEAP1-NFE2L2 pathway	5	11.8×	2e-03
RHO GTPases Activate Formins	6	9.1×	2e-03
Diseases of signal transduction by growth factor receptors and second messengers	6	6.7×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein localization to phagophore assembly site	5	75.1×	3e-06
axonogenesis	5	12.2×	5e-03
actin filament organization	6	10.8×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	7
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

806 predictions. Top by Δscore:

Variant	Effect	Δscore
6:145800142:T:TA	donor_gain	1.0000
6:145800194:T:TA	donor_gain	1.0000
6:145806429:A:AC	acceptor_gain	1.0000
6:145806429:A:C	acceptor_gain	1.0000
6:145809023:A:C	acceptor_gain	1.0000
6:145806417:CAGCT:C	acceptor_gain	0.9900
6:145806420:CT:C	acceptor_gain	0.9900
6:145806421:TCTG:T	acceptor_gain	0.9900
6:145806422:C:CC	acceptor_gain	0.9900
6:145806434:A:AC	acceptor_gain	0.9900
6:145806434:A:C	acceptor_gain	0.9900
6:145809023:A:AC	acceptor_gain	0.9900
6:145809266:A:AC	donor_gain	0.9900
6:145809267:C:CC	donor_gain	0.9900
6:145814594:GTCAC:G	donor_loss	0.9900
6:145814595:TCACT:T	donor_loss	0.9900
6:145814596:CACT:C	donor_loss	0.9900
6:145814597:ACTC:A	donor_loss	0.9900
6:145814598:CTCA:C	donor_loss	0.9900
6:145814599:T:TC	donor_loss	0.9900
6:145814600:CACC:C	donor_loss	0.9900
6:145814601:A:AC	donor_gain	0.9900
6:145814601:ACC:A	donor_loss	0.9900
6:145814601:ACCGG:A	donor_gain	0.9900
6:145814602:C:CC	donor_gain	0.9900
6:145814602:CCGG:C	donor_gain	0.9900
6:145814602:CCGGC:C	donor_gain	0.9900
6:145806418:AGCTC:A	acceptor_loss	0.9800
6:145806419:GCT:G	acceptor_gain	0.9800
6:145806420:CTC:C	acceptor_gain	0.9800

AlphaMissense

4915 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:145800225:A:G	C707R	1.000
6:145800268:C:A	W692C	1.000
6:145800268:C:G	W692C	1.000
6:145800270:A:G	W692R	1.000
6:145800270:A:T	W692R	1.000
6:145800306:A:G	W680R	1.000
6:145800306:A:T	W680R	1.000
6:145804425:A:G	W661R	1.000
6:145804425:A:T	W661R	1.000
6:145804720:A:C	C562W	1.000
6:145804722:A:G	C562R	1.000
6:145804741:G:C	C555W	1.000
6:145804743:A:G	C555R	1.000
6:145804843:A:C	F521L	1.000
6:145804843:A:T	F521L	1.000
6:145804845:A:G	F521L	1.000
6:145806011:A:G	L132P	1.000
6:145806023:T:A	D128V	1.000
6:145806023:T:G	D128A	1.000
6:145806024:C:G	D128H	1.000
6:145806124:C:A	W94C	1.000
6:145806124:C:G	W94C	1.000
6:145806126:A:G	W94R	1.000
6:145806126:A:T	W94R	1.000
6:145806159:A:G	C83R	1.000
6:145800223:G:C	C707W	0.999
6:145800269:C:G	W692S	0.999
6:145800298:A:C	F682L	0.999
6:145800298:A:T	F682L	0.999
6:145800299:A:G	F682S	0.999

dbSNP variants (sampled 300 via entrez): RS1000176436 (6:145806660 A>G,T), RS1000534214 (6:145812251 T>C), RS1001052102 (6:145807595 G>A), RS1001162482 (6:145800657 T>A), RS1001224179 (6:145816756 G>T), RS1001426945 (6:145800162 G>A,C,T), RS1001571793 (6:145811377 A>G), RS1001829663 (6:145811072 T>G), RS1001835247 (6:145797049 T>C), RS1002305504 (6:145813078 A>G), RS1002719993 (6:145802550 A>G), RS1002726141 (6:145804102 T>A,C), RS1002817859 (6:145816764 C>G,T), RS1002829377 (6:145799012 T>C), RS1003289859 (6:145802980 T>C)

Disease associations

OMIM: gene MIM:609101 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, increases expression	5
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Tobacco Smoke Pollution	increases expression	3
Valproic Acid	affects expression, decreases expression, increases expression	3
Cyclosporine	increases expression	3
Cadmium Chloride	decreases expression, increases expression	3
Cisplatin	decreases expression	2
Estradiol	affects expression, increases expression	2
Hydrogen Peroxide	affects expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
chloroacetaldehyde	decreases expression	1
hydroxyethyl methacrylate	increases expression	1
triphenyl phosphate	affects expression	1
bis(tri-n-butyltin)oxide	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
cresidine	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
2-amino-3-methylimidazo(4,5-f)quinoline	decreases expression	1
resorcinol	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
ethyl acrylate	increases expression	1
K 7174	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression	1
jinfukang	decreases expression	1
NSC 689534	affects binding, increases expression	1

Clinical trials (associated diseases)

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