FBXO10

Summary

FBXO10 (F-box protein 10, HGNC:13589) is a protein-coding gene on chromosome 9p13.2, encoding F-box only protein 10 (Q9UK96). 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 FBXO10, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603134), 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 26267 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 128 total — 1 pathogenic
• MANE Select transcript: NM_012166

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13589
Approved symbol	FBXO10
Name	F-box protein 10
Location	9p13.2
Locus type	gene with protein product
Status	Approved
Aliases	FBX10
Ensembl gene	ENSG00000147912
Ensembl biotype	protein_coding
OMIM	609092
Entrez	26267

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000276960, ENST00000432825, ENST00000541607, ENST00000543968, ENST00000544208, ENST00000967085, ENST00000967086

RefSeq mRNA: 1 — MANE Select: NM_012166 NM_012166

CCDS: CCDS47966

Canonical transcript exons

ENST00000432825 — 11 exons

Exon	Start	End
ENSE00000982397	37576211	37576380
ENSE00002321830	37510892	37512721
ENSE00003485876	37518125	37518438
ENSE00003485964	37541184	37541774
ENSE00003496668	37529124	37529260
ENSE00003516646	37531909	37532058
ENSE00003569519	37537110	37537943
ENSE00003576790	37522825	37522977
ENSE00003599386	37521569	37521838
ENSE00003623167	37515904	37516085
ENSE00003677306	37525102	37525172

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 93.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.7035 / max 56.2874, expressed in 1413 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100735	1.5166	810
100736	1.4985	869
100737	1.1808	696
100734	0.5076	221

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	93.35	gold quality
tibialis anterior	UBERON:0001385	92.80	silver quality
gastrocnemius	UBERON:0001388	90.01	gold quality
muscle of leg	UBERON:0001383	88.73	gold quality
pituitary gland	UBERON:0000007	86.43	gold quality
adenohypophysis	UBERON:0002196	86.29	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.12	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.38	gold quality
secondary oocyte	CL:0000655	82.76	gold quality
oocyte	CL:0000023	82.54	gold quality
deltoid	UBERON:0001476	82.16	silver quality
stromal cell of endometrium	CL:0002255	81.15	gold quality
right adrenal gland	UBERON:0001233	80.64	gold quality
spleen	UBERON:0002106	80.50	gold quality
right adrenal gland cortex	UBERON:0035827	80.41	gold quality
skeletal muscle tissue	UBERON:0001134	80.14	gold quality
muscle tissue	UBERON:0002385	80.14	gold quality
left ventricle myocardium	UBERON:0006566	79.94	gold quality
adrenal gland	UBERON:0002369	79.92	gold quality
cardiac muscle of right atrium	UBERON:0003379	79.72	gold quality
right frontal lobe	UBERON:0002810	79.47	gold quality
right testis	UBERON:0004534	79.42	gold quality
left adrenal gland cortex	UBERON:0035825	79.33	gold quality
muscle layer of sigmoid colon	UBERON:0035805	79.13	gold quality
left adrenal gland	UBERON:0001234	79.12	gold quality
left testis	UBERON:0004533	79.01	gold quality
prefrontal cortex	UBERON:0000451	78.91	gold quality
adrenal cortex	UBERON:0001235	78.89	gold quality
epithelial cell of pancreas	CL:0000083	78.74	gold quality
testis	UBERON:0000473	78.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.67

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CUX1

miRNA regulators (miRDB)

93 targeting FBXO10, 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-513A-5P	100.00	69.77	2465
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3065-3P	99.87	70.25	1407

Literature-anchored findings (GeneRIF, showing 4)

• Higher Fbxo10 expression in T cells is associated with Mcs5a increased susceptibility alleles (PMID:23138933)
• FBXO10, a protein related to DRE-1, binds BCL2 and promotes its degradation, thereby initiating cell death. Moreover, some diffuse large B-cell lymphomas have inactivating mutations in FBXO10 or express FBXO10 at low levels. (PMID:23431138)
• siRNA-mediated knockdown of FBXO11 facilitated HIF-1alpha expression in various cancer cells and HIF-1alpha-driven gene expressions, but the FBXO10 knockdown did not. (PMID:26187670)
• Recent BCR stimulation induces a negative autoregulatory loop via FBXO10 mediated degradation of HGAL. (PMID:31570756)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	fbxo10	ENSDARG00000061936
mus_musculus	Fbxo10	ENSMUSG00000048232
rattus_norvegicus	Fbxo10	ENSRNOG00000012634
drosophila_melanogaster	FBXO11	FBGN0037760
caenorhabditis_elegans		WBGENE00001089
caenorhabditis_elegans		WBGENE00015268

Paralogs (1): FBXO11 (ENSG00000138081)

Protein

Protein identifiers

F-box only protein 10 — Q9UK96 (reviewed: Q9UK96)

All UniProt accessions (3): Q9UK96, F5GXN9, J3KN78

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Mediates the ubiquitination and degradation of BCL2, an antiapoptotic protein, thereby playing a role in apoptosis by controlling the stability of BCL2. Targets also the receptor for advanced glycation end products RAGE for ubiquitination and subsequent lysosomal degradation. Directly controls HGAL/GCSAM ubiquitination and degradation and thereby decreases BCR signaling.

Subunit / interactions. Component of the SCF(FBXO10) complex consisting of CUL1, SKP1 and FBXO10. Interacts with BCL2. Interacts with PRDM1.

Subcellular location. Cytoplasm.

Disease relevance. Defects in FBXO10 may be a cause of diffuse large B-cell lymphoma by allowing the accumulation of BCL2, an oncoprotein that has a critical role in lymphomas.

Pathway. Protein modification; protein ubiquitination.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UK96-1	1	yes
Q9UK96-2	2

RefSeq proteins (1): NP_036298* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001810	F-box_dom	Domain
IPR006626	PbH1	Repeat
IPR006633	Carb-bd_sugar_hydrolysis-dom	Domain
IPR007742	NosD_dom	Domain
IPR011050	Pectin_lyase_fold/virulence	Homologous_superfamily
IPR012334	Pectin_lyas_fold	Homologous_superfamily
IPR022441	Para_beta_helix_rpt-2	Repeat
IPR036047	F-box-like_dom_sf	Homologous_superfamily
IPR039448	Beta_helix	Domain
IPR051550	SCF-Subunits/Alg-Epimerases	Family

Pfam: PF05048, PF12937, PF13229

UniProt features (29 total): repeat 17, sequence variant 4, compositionally biased region 2, modified residue 2, chain 1, domain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UK96-F1	75.79	0.53

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 (2): 321, 326

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: 80 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, chr9p13, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_SCF_DEPENDENT_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOBP_PROTEIN_CATABOLIC_PROCESS, GOCC_SCF_UBIQUITIN_LIGASE_COMPLEX, GOCC_TRANSFERASE_COMPLEX, GOBP_PROTEOLYSIS, GOCC_CULLIN_RING_UBIQUITIN_LIGASE_COMPLEX, GOMF_ACYLTRANSFERASE_ACTIVITY

GO Biological Process (4): ubiquitin-dependent protein catabolic process (GO:0006511), apoptotic process (GO:0006915), protein ubiquitination (GO:0016567), regulation of apoptotic process (GO:0042981)

GO Molecular Function (2): ubiquitin-protein transferase activity (GO:0004842), protein binding (GO:0005515)

GO Cellular Component (3): ubiquitin ligase complex (GO:0000151), cytoplasm (GO:0005737), 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 anatomical structure	2
protein ubiquitination	1
modification-dependent protein catabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
protein modification by small protein conjugation	1
apoptotic process	1
regulation of programmed cell death	1
ubiquitin-like protein transferase activity	1
binding	1
intracellular protein-containing complex	1
transferase complex	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

504 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FBXO10	BCL2	P10415	776
FBXO10	FRMPD1	Q5SYB0	669
FBXO10	PRMT9	Q6P2P2	666
FBXO10	CUL1	Q13616	654
FBXO10	SKP1	P34991	634
FBXO10	TRIP12	Q14669	512
FBXO10	PRMT7	Q9NVM4	461
FBXO10	TRIM50	Q86XT4	459
FBXO10	FRMD5	Q7Z6J6	453
FBXO10	FBXO9	Q9UK97	449
FBXO10	PRMT1	Q99873	449
FBXO10	PRMT5	O14744	447
FBXO10	PRMT8	Q9NR22	439
FBXO10	PRMT3	O60678	431
FBXO10	OR13C9	Q8NGT0	418
FBXO10	PRMT2	P55345	418

IntAct

37 interactions, top by confidence:

A	B	Type	Score
PDE6D	ARL3	psi-mi:“MI:0914”(association)	0.920
SKP1	MYCBP2	psi-mi:“MI:0914”(association)	0.640
ARL15	SLC25A20	psi-mi:“MI:0914”(association)	0.530
TPCN2	AP3B1	psi-mi:“MI:0914”(association)	0.530
PSME1	POLR3A	psi-mi:“MI:0914”(association)	0.530
NECTIN4	EIF2B2	psi-mi:“MI:0914”(association)	0.530
AGER	FBXO10	psi-mi:“MI:0915”(physical association)	0.400
FBXO10	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
FBXO10	PRDM1	psi-mi:“MI:0915”(physical association)	0.400
CUL1	LGALS8	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
TPCN2	DDX11L8	psi-mi:“MI:0914”(association)	0.350
FAM219A	NBN	psi-mi:“MI:0914”(association)	0.350
NECTIN4	GLB1	psi-mi:“MI:0914”(association)	0.350
PPP4R1L	IFT56	psi-mi:“MI:0914”(association)	0.350
ANKRD39	UBA6	psi-mi:“MI:0914”(association)	0.350
FBXO10	BLTP3B	psi-mi:“MI:0914”(association)	0.350
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
DPP8	KRBA1	psi-mi:“MI:0914”(association)	0.350
SYCE1	RABGAP1L	psi-mi:“MI:0914”(association)	0.350
KCNE3	PIK3R2	psi-mi:“MI:0914”(association)	0.350
PRPS2	SMCHD1	psi-mi:“MI:0914”(association)	0.350
DNAJB3	MEIS1	psi-mi:“MI:0914”(association)	0.350
SKP1	BHLHE40	psi-mi:“MI:0914”(association)	0.350
TTC9C	PLD2	psi-mi:“MI:0914”(association)	0.350
GPS1	HSPA12A	psi-mi:“MI:0914”(association)	0.350
LARP4	TPST2	psi-mi:“MI:0914”(association)	0.350
PDE6D	SUN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (89): FBXO10 (Affinity Capture-MS), FBXO10 (Affinity Capture-MS), FBXO10 (Affinity Capture-MS), FBXO10 (Affinity Capture-MS), FBXO10 (Affinity Capture-MS), FBXO10 (Affinity Capture-MS), FBXO10 (Affinity Capture-MS), FBXO10 (Affinity Capture-MS), FBXO10 (Affinity Capture-MS), FBXO10 (Affinity Capture-RNA), FBXO10 (Affinity Capture-MS), ZYX (Affinity Capture-MS), FBXO10 (Affinity Capture-MS), FBXO10 (Affinity Capture-MS), FBXO10 (Affinity Capture-MS)

ESM2 similar proteins: A5PK16, D3YYM4, F1LW30, F1QGZ6, H2LP95, O13034, O15040, O95714, P41002, P51944, P97573, Q00IB7, Q13309, Q2HJ90, Q3UMR0, Q4KM95, Q4U2R1, Q5F479, Q5M9H0, Q5REW9, Q5XGG5, Q641X6, Q6P549, Q6UXZ4, Q6ZWE6, Q7TNH6, Q7TQF2, Q7Z494, Q80TI1, Q8C0W1, Q8C2S5, Q8IY22, Q8IZ02, Q8JZL1, Q8K1S2, Q8K4F8, Q8NFM7, Q8R2U7, Q92835, Q96M69

Diamond homologs: Q7TQF2, Q9UK96

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	97
Likely benign	5
Benign	5

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
664453	NC_000009.12:g.(?37422741)(37785054_?)del	Pathogenic

SpliceAI

2485 predictions. Top by Δscore:

Variant	Effect	Δscore
9:37515902:A:AC	donor_gain	1.0000
9:37515903:C:CA	donor_gain	1.0000
9:37515903:CT:C	donor_gain	1.0000
9:37518123:A:AC	donor_gain	1.0000
9:37518124:C:CC	donor_gain	1.0000
9:37522973:ATTTT:A	acceptor_gain	1.0000
9:37522974:TTTT:T	acceptor_gain	1.0000
9:37522975:TTT:T	acceptor_gain	1.0000
9:37522975:TTTC:T	acceptor_loss	1.0000
9:37522976:TT:T	acceptor_gain	1.0000
9:37522977:TC:T	acceptor_loss	1.0000
9:37522978:C:CC	acceptor_gain	1.0000
9:37522980:A:C	acceptor_gain	1.0000
9:37525168:TCCCG:T	acceptor_gain	1.0000
9:37525169:CCCG:C	acceptor_gain	1.0000
9:37525169:CCCGC:C	acceptor_gain	1.0000
9:37525170:CCG:C	acceptor_gain	1.0000
9:37525170:CCGC:C	acceptor_gain	1.0000
9:37525171:CG:C	acceptor_gain	1.0000
9:37525171:CGC:C	acceptor_gain	1.0000
9:37525172:GCT:G	acceptor_loss	1.0000
9:37525173:C:CC	acceptor_gain	1.0000
9:37525173:CTAA:C	acceptor_loss	1.0000
9:37525174:T:C	acceptor_loss	1.0000
9:37525178:G:C	acceptor_gain	1.0000
9:37525178:G:GC	acceptor_gain	1.0000
9:37529166:T:TA	donor_gain	1.0000
9:37531905:GTA:G	donor_loss	1.0000
9:37531906:TAC:T	donor_loss	1.0000
9:37531932:T:A	donor_gain	1.0000

AlphaMissense

6307 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:37522835:A:C	N640K	1.000
9:37522835:A:T	N640K	1.000
9:37522904:G:C	N617K	1.000
9:37522904:G:T	N617K	1.000
9:37522973:A:C	N594K	1.000
9:37522973:A:T	N594K	1.000
9:37525166:G:C	N571K	1.000
9:37525166:G:T	N571K	1.000
9:37529186:A:C	N548K	1.000
9:37529186:A:T	N548K	1.000
9:37529209:C:A	G541W	1.000
9:37531972:G:C	N502K	1.000
9:37531972:G:T	N502K	1.000
9:37516005:G:C	N865K	0.999
9:37516005:G:T	N865K	0.999
9:37518182:G:C	N819K	0.999
9:37518182:G:T	N819K	0.999
9:37521780:G:C	N663K	0.999
9:37521780:G:T	N663K	0.999
9:37522920:G:T	P612H	0.999
9:37525114:C:G	G589R	0.999
9:37525119:C:T	G587D	0.999
9:37525137:A:C	I581R	0.999
9:37525137:A:T	I581K	0.999
9:37529127:A:T	V568E	0.999
9:37529133:G:C	P566R	0.999
9:37529133:G:T	P566H	0.999
9:37529193:C:G	R546P	0.999
9:37529203:C:G	G543R	0.999
9:37529208:C:T	G541E	0.999

dbSNP variants (sampled 300 via entrez): RS1000013762 (9:37570212 G>A), RS1000135741 (9:37571526 C>T), RS1000169165 (9:37533118 G>T), RS1000175726 (9:37521310 C>A), RS1000222462 (9:37532730 T>C), RS1000278492 (9:37520335 C>T), RS1000303431 (9:37577075 T>C,G), RS1000349190 (9:37534156 T>A), RS1000373670 (9:37538420 G>T), RS1000374431 (9:37515214 A>T), RS1000439202 (9:37538767 A>C), RS1000469132 (9:37570112 C>T), RS1000566949 (9:37545322 G>A), RS1000568987 (9:37576840 C>T), RS1000595099 (9:37527771 G>A)

Disease associations

OMIM: gene MIM:609092 | 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
GCST002818_5	HIV-1 susceptibility	4.000000e-07
GCST002818_7	HIV-1 susceptibility	5.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0000180	HIV-1 infection

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 2.1.1.- Protein arginine N-methyltransferases

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression	2
Estradiol	increases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol A	decreases methylation	1
manganese chloride	decreases expression, increases abundance	1
abrine	increases expression	1
Acetylglucosamine	increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Doxorubicin	decreases expression	1
Glucose	increases expression	1
Manganese	decreases expression, increases abundance	1
Quercetin	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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