FBXW9

Summary

FBXW9 (F-box and WD repeat domain containing 9, HGNC:28136) is a protein-coding gene on chromosome 19p13.13, encoding F-box/WD repeat-containing protein 9 (Q5XUX1). Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.

Members of the F-box protein family, such as FBXW9, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603034), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).

Source: NCBI Gene 84261 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 92 total
• MANE Select transcript: NM_032301

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28136
Approved symbol	FBXW9
Name	F-box and WD repeat domain containing 9
Location	19p13.13
Locus type	gene with protein product
Status	Approved
Aliases	MGC10870, Fbw9, MEC-15
Ensembl gene	ENSG00000132004
Ensembl biotype	protein_coding
OMIM	609074
Entrez	84261

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 nonsense_mediated_decay

ENST00000393261, ENST00000587296, ENST00000587955, ENST00000872815, ENST00000872816, ENST00000915317, ENST00000915318, ENST00000963589, ENST00000963590

RefSeq mRNA: 1 — MANE Select: NM_032301 NM_032301

CCDS: CCDS12278

Canonical transcript exons

ENST00000393261 — 10 exons

Exon	Start	End
ENSE00001514656	12688916	12689290
ENSE00001788153	12694799	12694938
ENSE00001797866	12696173	12696631
ENSE00001806609	12691342	12691454
ENSE00003487928	12694594	12694722
ENSE00003539760	12691166	12691257
ENSE00003546385	12689541	12689630
ENSE00003604794	12689761	12689874
ENSE00003637337	12689962	12690110
ENSE00003683628	12689372	12689437

Expression profiles

Bgee: expression breadth ubiquitous, 196 present calls, max score 90.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.4110 / max 86.1642, expressed in 1726 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179331	8.3611	1714
179330	1.0499	618

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	90.60	gold quality
pancreatic ductal cell	CL:0002079	89.76	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.50	gold quality
bronchial epithelial cell	CL:0002328	85.64	gold quality
bronchus	UBERON:0002185	84.74	gold quality
tibialis anterior	UBERON:0001385	82.32	silver quality
ileal mucosa	UBERON:0000331	82.05	gold quality
left testis	UBERON:0004533	81.48	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.29	gold quality
right testis	UBERON:0004534	80.87	gold quality
mucosa of transverse colon	UBERON:0004991	79.81	gold quality
testis	UBERON:0000473	79.50	gold quality
ventricular zone	UBERON:0003053	79.48	gold quality
right adrenal gland cortex	UBERON:0035827	79.13	gold quality
right adrenal gland	UBERON:0001233	79.06	gold quality
esophagus mucosa	UBERON:0002469	78.90	gold quality
nasal cavity mucosa	UBERON:0001826	78.52	gold quality
left adrenal gland	UBERON:0001234	78.44	gold quality
skin of leg	UBERON:0001511	78.27	gold quality
left adrenal gland cortex	UBERON:0035825	78.11	gold quality
prefrontal cortex	UBERON:0000451	77.97	gold quality
cortical plate	UBERON:0005343	77.69	gold quality
metanephros cortex	UBERON:0010533	77.57	gold quality
lower esophagus mucosa	UBERON:0035834	77.56	gold quality
skin of abdomen	UBERON:0001416	77.29	gold quality
adrenal cortex	UBERON:0001235	77.28	gold quality
right lobe of thyroid gland	UBERON:0001119	76.87	gold quality
mucosa of paranasal sinus	UBERON:0005030	76.77	gold quality
stromal cell of endometrium	CL:0002255	76.68	gold quality
adenohypophysis	UBERON:0002196	76.68	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.35
E-MTAB-7303	no	254.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting FBXW9, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-6849-3P	97.25	64.57	1371
HSA-MIR-7160-3P	96.40	64.15	462
HSA-MIR-744-5P	93.78	65.29	230
HSA-MIR-10396A-5P	93.49	65.54	172

Literature-anchored findings (GeneRIF, showing 1)

• A Comprehensive Analysis Revealing FBXW9 as a Potential Prognostic and Immunological Biomarker in Breast Cancer. (PMID:36982338)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fbxw9	ENSDARG00000058020
mus_musculus	Fbxw9	ENSMUSG00000008167
rattus_norvegicus	Fbxw9	ENSRNOG00000004212

Paralogs (14): WDR54 (ENSG00000005448), FBXW11 (ENSG00000072803), FBXW7 (ENSG00000109670), TRAF7 (ENSG00000131653), FBXO36 (ENSG00000153832), WDR64 (ENSG00000162843), FBXW12 (ENSG00000164049), BTRC (ENSG00000166167), WDR49 (ENSG00000174776), FBXW8 (ENSG00000174989), PAAF1 (ENSG00000175575), WDR86 (ENSG00000187260), FBXO16 (ENSG00000214050), EFCAB8 (ENSG00000215529)

Protein

Protein identifiers

F-box/WD repeat-containing protein 9 — Q5XUX1 (reviewed: Q5XUX1)

Alternative names: F-box and WD-40 domain-containing protein 9

All UniProt accessions (2): Q5XUX1, K7EL01

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.

Subunit / interactions. Interacts with SKP1 and CUL1.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5XUX1-3	1	yes
Q5XUX1-2	2

RefSeq proteins (1): NP_115677* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR001810	F-box_dom	Domain
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR020472	WD40_PAC1	Repeat
IPR036047	F-box-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily

Pfam: PF00400, PF12937

UniProt features (20 total): repeat 7, modified residue 4, region of interest 2, splice variant 2, sequence variant 2, chain 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5XUX1-F1	85.42	0.67

Functional residue map

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

Post-translational modifications (4): 1, 18, 55, 59

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-390471	Association of TriC/CCT with target proteins during biosynthesis
R-HSA-8951664	Neddylation
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation

MSigDB gene sets: 94 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_SCF_DEPENDENT_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, CREB_Q3, NRF2_01, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, MARTORIATI_MDM4_TARGETS_FETAL_LIVER_UP, GOBP_PROTEIN_CATABOLIC_PROCESS, GOCC_SCF_UBIQUITIN_LIGASE_COMPLEX, GOCC_TRANSFERASE_COMPLEX, YGCGYRCGC_UNKNOWN

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

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

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Chaperonin-mediated protein folding	1
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
binding	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

579 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FBXW9	SKP1	P34991	815
FBXW9	CUL1	Q13616	664
FBXW9	FBXW5	Q969U6	634
FBXW9	FBXW12	Q6X9E4	544
FBXW9	FBXW4	P57775	532
FBXW9	FBXW10	Q5XX13	512
FBXW9	NPAS3	Q8IXF0	488
FBXW9	FBXW2	Q9UKT8	485
FBXW9	FBXL5	Q9UKA1	477
FBXW9	INTS1	Q8N201	473
FBXW9	FBXW8	Q8N3Y1	455
FBXW9	SFI1	A8K8P3	454
FBXW9	AP2A2	O94973	435
FBXW9	ACVR1	Q04771	415
FBXW9	CCDC97	Q96F63	399

IntAct

27 interactions, top by confidence:

A	B	Type	Score
SKP1	FBXW9	psi-mi:“MI:0915”(physical association)	0.780
FBXW9	SKP1	psi-mi:“MI:0915”(physical association)	0.780
COPS6	RHOBTB1	psi-mi:“MI:0914”(association)	0.730
CCT2	TXNDC9	psi-mi:“MI:0914”(association)	0.730
CCT3	TXNDC9	psi-mi:“MI:0914”(association)	0.640
CCT5	TXNDC9	psi-mi:“MI:0914”(association)	0.640
SKP1	MYCBP2	psi-mi:“MI:0914”(association)	0.640
CCT7	PEX7	psi-mi:“MI:0914”(association)	0.530
CUL1	LGALS8	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
COPS6	DDX3X	psi-mi:“MI:0914”(association)	0.350
COPS6		psi-mi:“MI:0914”(association)	0.350
CCT2	WDR91	psi-mi:“MI:0914”(association)	0.350
DNAJA2	DENND11	psi-mi:“MI:0914”(association)	0.350
CCT5	TUBAL3	psi-mi:“MI:0914”(association)	0.350
SKP1	BHLHE40	psi-mi:“MI:0914”(association)	0.350
FBXW9	TXNDC9	psi-mi:“MI:0914”(association)	0.350
TTC9C	PLD2	psi-mi:“MI:0914”(association)	0.350
SKP1	RNASET2	psi-mi:“MI:0914”(association)	0.350
SKP1	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
SKP1	NDC80	psi-mi:“MI:0914”(association)	0.350

BioGRID (34): FBXW9 (Affinity Capture-MS), FBXW9 (Affinity Capture-MS), FBXW9 (Affinity Capture-MS), SKP1 (Affinity Capture-Western), CCT8 (Affinity Capture-MS), CCT6B (Affinity Capture-MS), CCT3 (Affinity Capture-MS), FBXW9 (Affinity Capture-MS), FBXW9 (Affinity Capture-MS), FBXW9 (Affinity Capture-MS), CCT6A (Affinity Capture-MS), TCP1 (Affinity Capture-MS), FBXW9 (Affinity Capture-MS), CUL1 (Affinity Capture-MS), CCT7 (Affinity Capture-MS)

ESM2 similar proteins: A5DNK9, A8ID74, A8IF44, A8IRK7, A8J1V4, A8JAF2, A8JAN3, A8JFU2, A9UP22, C4YBE4, D3ZX63, O75843, P0DKL4, P0DKL6, P93043, P93231, Q09417, Q15269, Q1LVE8, Q24314, Q28205, Q2TAF3, Q3V3N7, Q57WH1, Q5DM57, Q5RFQ3, Q5TTP0, Q5XUX1, Q5ZHX9, Q6C462, Q6C953, Q6CAH5, Q74ZJ1, Q7TT37, Q8BU03, Q8CFJ9, Q8NFJ9, Q8R307, Q96S15, Q9H977

Diamond homologs: A1CH75, A1CXL0, A2QI22, A3LQ86, A4R2Q6, A5DL92, A5DST9, A6R3K5, A6S0T8, A6ZPA9, A7ECP3, A7TMF9, B0Y5V6, B2B5V0, B2VZH2, B3RQN1, G0SFB5, P41318, Q0CLJ4, Q0UXP3, Q12024, Q1DJF7, Q2GXT0, Q2UGK1, Q4WP10, Q54S59, Q5APF0, Q5B4R1, Q5XUX1, Q6BLS5, Q6CEW7, Q6CU59, Q6FKK3, Q756D0, Q9AYE4, Q9C2I5, Q9LV27, Q9URY0, A8IR43, O74184

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 25 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
Formation of tubulin folding intermediates by CCT/TriC	5	111.3×	8e-08
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	5	107.3×	8e-08
Chaperonin-mediated protein folding	5	79.1×	2e-07
Protein folding	5	68.3×	3e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	83
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1496 predictions. Top by Δscore:

Variant	Effect	Δscore
19:12689286:CAGAC:C	acceptor_gain	1.0000
19:12689290:CCTGG:C	acceptor_loss	1.0000
19:12689291:C:CA	acceptor_loss	1.0000
19:12689292:T:G	acceptor_loss	1.0000
19:12689535:CCTCA:C	donor_loss	1.0000
19:12689536:CTCA:C	donor_loss	1.0000
19:12689537:TCACC:T	donor_loss	1.0000
19:12689538:CA:C	donor_loss	1.0000
19:12689539:A:T	donor_loss	1.0000
19:12689539:AC:A	donor_gain	1.0000
19:12689540:C:CA	donor_loss	1.0000
19:12689540:CC:C	donor_gain	1.0000
19:12689626:AAGGA:A	acceptor_gain	1.0000
19:12689627:AGGA:A	acceptor_gain	1.0000
19:12689628:GGA:G	acceptor_gain	1.0000
19:12689629:GA:G	acceptor_gain	1.0000
19:12689630:ACT:A	acceptor_loss	1.0000
19:12689631:C:CC	acceptor_gain	1.0000
19:12689631:CTGCA:C	acceptor_loss	1.0000
19:12689958:CCACC:C	donor_loss	1.0000
19:12689959:CACCT:C	donor_loss	1.0000
19:12689961:C:G	donor_loss	1.0000
19:12690108:CGG:C	acceptor_gain	1.0000
19:12690114:C:CT	acceptor_gain	1.0000
19:12690115:A:C	acceptor_gain	1.0000
19:12690119:G:GC	acceptor_gain	1.0000
19:12690128:C:CT	acceptor_gain	1.0000
19:12690129:G:T	acceptor_gain	1.0000
19:12691161:CCCA:C	donor_loss	1.0000
19:12691162:CCA:C	donor_loss	1.0000

AlphaMissense

2922 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:12691382:A:G	W251R	0.995
19:12691382:A:T	W251R	0.995
19:12691380:C:A	W251C	0.994
19:12691380:C:G	W251C	0.994
19:12690022:G:C	S324R	0.993
19:12690022:G:T	S324R	0.993
19:12690024:T:G	S324R	0.993
19:12690023:C:A	S324I	0.992
19:12691400:C:G	D245H	0.992
19:12691451:A:G	W228R	0.991
19:12691451:A:T	W228R	0.991
19:12691398:G:C	D245E	0.990
19:12691398:G:T	D245E	0.990
19:12690018:C:G	D326H	0.989
19:12691399:T:A	D245V	0.989
19:12691406:A:G	S243P	0.989
19:12691411:G:T	S241Y	0.988
19:12694682:A:T	V197D	0.988
19:12694700:C:T	G191D	0.988
19:12696224:A:G	W120R	0.988
19:12696224:A:T	W120R	0.988
19:12689542:C:G	R412P	0.987
19:12689829:A:G	W360R	0.987
19:12689829:A:T	W360R	0.987
19:12691408:C:T	G242D	0.987
19:12691411:G:A	S241F	0.987
19:12694698:A:G	S192P	0.987
19:12689561:A:G	S406P	0.986
19:12691399:T:G	D245A	0.986
19:12691412:A:G	S241P	0.986

dbSNP variants (sampled 300 via entrez): RS1000547606 (19:12698323 C>G,T), RS1000819108 (19:12691957 T>C), RS1000884436 (19:12691185 C>T), RS1000941216 (19:12690915 G>A), RS1001284597 (19:12697142 A>G), RS1001428950 (19:12698118 A>G), RS1001601805 (19:12694394 C>T), RS1002222938 (19:12698050 G>A), RS1002248998 (19:12691146 C>T), RS1002572463 (19:12688551 C>G,T), RS1002595370 (19:12697809 T>C), RS1002676136 (19:12690435 C>T), RS1002680070 (19:12696765 G>A), RS1003686822 (19:12695874 T>A), RS1003942061 (19:12697972 T>C)

Disease associations

OMIM: gene MIM:609074 | 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

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Cadmium Chloride	decreases expression	2
pirinixic acid	affects binding, decreases expression, increases activity	1
di-n-butylphosphoric acid	affects expression	1
corosolic acid	increases expression	1
abrine	increases expression	1
Sunitinib	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Ethanol	decreases expression	1
Arsenic	affects methylation	1
Benzene	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Palmitic Acid	decreases phosphorylation	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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