FBXW10

Summary

FBXW10 (F-box and WD repeat domain containing 10, HGNC:1211) is a protein-coding gene on chromosome 17p11.2, encoding F-box/WD repeat-containing protein 10 (Q5XX13). Probable substrate-recognition component of a SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.

Members of the F-box protein family, such as FBXW10, 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 10517 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 14 total — 1 pathogenic
• MANE Select transcript: NM_001267585

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1211
Approved symbol	FBXW10
Name	F-box and WD repeat domain containing 10
Location	17p11.2
Locus type	gene with protein product
Status	Approved
Aliases	SM2SH2, HREP, Fbw10
Ensembl gene	ENSG00000171931
Ensembl biotype	protein_coding
OMIM	611679
Entrez	10517

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000301938, ENST00000308799, ENST00000395665, ENST00000573605, ENST00000574478

RefSeq mRNA: 3 — MANE Select: NM_001267585 NM_001267585, NM_001267586, NM_001411059

CCDS: CCDS11199, CCDS58524, CCDS92270

Canonical transcript exons

ENST00000395665 — 14 exons

Exon	Start	End
ENSE00001825335	18778475	18779349
ENSE00002420260	18744054	18744749
ENSE00003497505	18749722	18749922
ENSE00003527030	18756045	18756154
ENSE00003538831	18772412	18772683
ENSE00003584258	18766714	18766862
ENSE00003617890	18750931	18751053
ENSE00003625942	18764742	18764863
ENSE00003634664	18747941	18748105
ENSE00003647830	18750010	18750137
ENSE00003647931	18758305	18758505
ENSE00003655628	18775136	18775192
ENSE00003661481	18768534	18768676
ENSE00003668650	18769927	18770085

Expression profiles

Bgee: expression breadth ubiquitous, 119 present calls, max score 79.93.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0353 / max 27.0525, expressed in 9 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
208086	0.0353	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.93	gold quality
testis	UBERON:0000473	76.99	gold quality
left testis	UBERON:0004533	76.83	gold quality
right testis	UBERON:0004534	76.38	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	68.36	gold quality
right uterine tube	UBERON:0001302	66.14	gold quality
lower esophagus mucosa	UBERON:0035834	64.68	gold quality
right adrenal gland cortex	UBERON:0035827	62.03	gold quality
cerebellar hemisphere	UBERON:0002245	60.92	gold quality
cerebellar cortex	UBERON:0002129	60.89	gold quality
cerebellum	UBERON:0002037	60.83	gold quality
right hemisphere of cerebellum	UBERON:0014890	60.62	gold quality
right lobe of liver	UBERON:0001114	59.61	gold quality
right adrenal gland	UBERON:0001233	59.43	gold quality
gastrocnemius	UBERON:0001388	58.60	gold quality
left adrenal gland	UBERON:0001234	57.85	gold quality
left lobe of thyroid gland	UBERON:0001120	57.57	gold quality
thyroid gland	UBERON:0002046	57.38	gold quality
right lobe of thyroid gland	UBERON:0001119	57.25	gold quality
left adrenal gland cortex	UBERON:0035825	57.05	gold quality
muscle of leg	UBERON:0001383	56.98	gold quality
adrenal gland	UBERON:0002369	56.88	gold quality
apex of heart	UBERON:0002098	54.34	gold quality
esophagus mucosa	UBERON:0002469	53.58	gold quality
hindlimb stylopod muscle	UBERON:0004252	53.52	gold quality
gall bladder	UBERON:0002110	52.59	gold quality
liver	UBERON:0002107	51.92	gold quality
primary visual cortex	UBERON:0002436	51.35	gold quality
fallopian tube	UBERON:0003889	51.13	gold quality
right lung	UBERON:0002167	50.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.04

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 5)

• Mislocalized lamins can induce ubiquitin-mediated proteasomal degradation of certain HP1 isoforms by activation of FBXW10, a member of the F-box family of proteins that is involved in E3 ubiquitin ligase activity. (PMID:20498703)
• O-GlcNAcylation is involved in the regulation of ubiquitination-related genes including FBXW10 (PMID:23899520)
• FBXW10 promotes hepatocarcinogenesis in male patients and mice. (PMID:31400758)
• The E3 ubiquitin ligase SCF (FBXW10)-mediated LATS2 degradation regulates angiogenesis and liver metastasis in colorectal cancer. (PMID:36990424)
• FBXW10: a male-biased E3 ligase in liver cancer. (PMID:37775405)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fbxw10	ENSDARG00000086484
mus_musculus	Fbxw10	ENSMUSG00000090173
rattus_norvegicus	Fbxw10	ENSRNOG00000071275

Paralogs (1): FBXW10B (ENSG00000241322)

Protein

Protein identifiers

F-box/WD repeat-containing protein 10 — Q5XX13 (reviewed: Q5XX13)

Alternative names: F-box and WD-40 domain-containing protein 10, Ubiquitin ligase-specificity factor

All UniProt accessions (2): Q5XX13, J3QLH9

UniProt curated annotations — full annotation on UniProt →

Function. Probable substrate-recognition component of a SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Overexpression is leading to degradation of CBX5 and CBX1.

Induction. By disease-causing laminin A mutants also inducing CBX5 and CBX1 proteasomal degradation.

Isoforms (4)

UniProt ID	Names	Canonical?
Q5XX13-1	1	yes
Q5XX13-2	2
Q5XX13-3	3
Q5XX13-4	4

RefSeq proteins (3): NP_001254514, NP_001254515, NP_001397988 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
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
IPR051075	SCF_subunit_WD-repeat	Family

Pfam: PF00400

UniProt features (24 total): repeat 7, splice variant 4, sequence conflict 4, sequence variant 3, coiled-coil region 2, chain 1, compositionally biased region 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5XX13-F1	61.90	0.21

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: 60 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, 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, MARSON_BOUND_BY_FOXP3_STIMULATED, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, GOBP_PROTEOLYSIS, GOCC_CULLIN_RING_UBIQUITIN_LIGASE_COMPLEX, GOCC_UBIQUITIN_LIGASE_COMPLEX

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

585 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FBXW10	CUL1	Q13616	650
FBXW10	SKP1	P34991	642
FBXW10	FBXW9	Q5XUX1	512
FBXW10	FBXW4	P57775	483
FBXW10	FBXW12	Q6X9E4	475
FBXW10	CCDC191	Q8NCU4	448
FBXW10	TVP23B	Q9NYZ1	447
FBXW10	FBXL22	Q6P050	431
FBXW10	FBXW5	Q969U6	418
FBXW10	RNF123	Q5XPI4	401
FBXW10	FBXW8	Q8N3Y1	381
FBXW10	TRIM16L	Q309B1	379
FBXW10	FBXO3	Q9UK99	377
FBXW10	TBC1D28	Q2M2D7	372
FBXW10	HECW2	Q9P2P5	371

IntAct

3 interactions, top by confidence:

A	B	Type	Score
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
CUL5	DDX3X	psi-mi:“MI:0914”(association)	0.350

BioGRID (141): FBXW10 (Affinity Capture-MS), FBXW10 (Affinity Capture-MS), FBXW10 (Negative Genetic), LATS2 (Affinity Capture-Western), FBXW10 (Affinity Capture-Western), CUL1 (Affinity Capture-Western), SKP1 (Affinity Capture-Western), RBX1 (Affinity Capture-Western), ANXA2 (Biochemical Activity), UBE2D3 (Biochemical Activity), ANXA2 (Affinity Capture-Western), CRABP2 (Cross-Linking-MS (XL-MS)), GAPDH (Affinity Capture-Western), FBXW10 (Affinity Capture-Western), GAPDH (Affinity Capture-MS)

ESM2 similar proteins: A2VDJ0, A5D791, A9CB18, D3YYM4, D5K8A9, E7FKV8, F1LW30, M0R2J8, O60383, O70173, O75747, Q07105, Q08DV9, Q2F7Z7, Q3MJ13, Q3SXY7, Q3T0Q2, Q3U3D7, Q3U3S3, Q4R8C8, Q5F479, Q5R800, Q5RFQ4, Q5SUS0, Q5XX13, Q6IRU7, Q6P4T1, Q6UXZ4, Q7TP65, Q8BLA1, Q8K1S2, Q8NDB2, Q8NEM2, Q8QHJ9, Q8R526, Q8TDX9, Q920I9, Q96KN7, Q9BXS4, Q9D0L6

Diamond homologs: A0A0D1E015, A0JMD2, A1CEK1, A1DFP5, A8QCE4, A8WGF4, A8XJZ8, A8XXC7, B0G126, D2H5P6, D4A8G9, E1BLZ4, E9Q4P1, O14964, O88387, O95170, P34657, P52734, P98174, Q0CJV3, Q0P4S0, Q0U4Z8, Q0V8S0, Q11176, Q13615, Q17AN2, Q18964, Q22712, Q2GS33, Q2KIY3, Q3TB82, Q4P7Q1, Q4WHN8, Q54CH1, Q54TC3, Q5BBK9, Q5DU37, Q5PQT2, Q5R5R4, Q5RHI5

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
FBXW10	“down-regulates quantity by destabilization”	CBX5	binding
FBXW10	“up-regulates activity”	“Cullin 1-RBX1-Skp1”	binding
FBXW10	“up-regulates activity”	GAPDH	polyubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	3
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
496743	arr[hg19]17p11.2(16,757,111-20,219,651)x3	Pathogenic

SpliceAI

2233 predictions. Top by Δscore:

Variant	Effect	Δscore
17:18749720:A:AG	acceptor_gain	1.0000
17:18749721:G:GG	acceptor_gain	1.0000
17:18749912:G:GG	donor_gain	1.0000
17:18749919:C:CG	donor_gain	1.0000
17:18749923:G:GG	donor_gain	1.0000
17:18750008:A:AG	acceptor_gain	1.0000
17:18750009:G:GG	acceptor_gain	1.0000
17:18750133:TGCAG:T	donor_loss	1.0000
17:18750135:CAG:C	donor_loss	1.0000
17:18750136:AG:A	donor_loss	1.0000
17:18750137:GGTAC:G	donor_loss	1.0000
17:18750138:G:T	donor_loss	1.0000
17:18750139:T:A	donor_loss	1.0000
17:18756155:G:GG	donor_gain	1.0000
17:18763854:G:GT	donor_gain	1.0000
17:18766686:T:G	acceptor_gain	1.0000
17:18766707:T:TA	acceptor_gain	1.0000
17:18766712:A:AG	acceptor_gain	1.0000
17:18766712:AGTAT:A	acceptor_gain	1.0000
17:18766713:G:GC	acceptor_gain	1.0000
17:18766713:GT:G	acceptor_gain	1.0000
17:18766713:GTA:G	acceptor_gain	1.0000
17:18766713:GTAT:G	acceptor_gain	1.0000
17:18766713:GTATG:G	acceptor_gain	1.0000
17:18766863:GT:G	donor_loss	1.0000
17:18768677:G:GG	donor_gain	1.0000
17:18749708:T:TA	acceptor_gain	0.9900
17:18749720:AGAG:A	acceptor_gain	0.9900
17:18749721:GA:G	acceptor_gain	0.9900
17:18749721:GAGG:G	acceptor_gain	0.9900

AlphaMissense

6964 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:18769967:A:C	S630R	0.999
17:18769969:C:A	S630R	0.999
17:18769969:C:G	S630R	0.999
17:18758480:A:C	S470R	0.998
17:18758482:C:A	S470R	0.998
17:18758482:C:G	S470R	0.998
17:18766803:A:C	S549R	0.998
17:18766805:C:A	S549R	0.998
17:18766805:C:G	S549R	0.998
17:18750060:T:A	W308R	0.996
17:18750060:T:C	W308R	0.996
17:18769992:G:C	R638P	0.995
17:18766716:T:A	W520R	0.994
17:18766716:T:C	W520R	0.994
17:18758486:A:C	S472R	0.993
17:18758488:C:A	S472R	0.993
17:18758488:C:G	S472R	0.993
17:18764746:T:A	W480R	0.992
17:18764746:T:C	W480R	0.992
17:18766806:A:C	S550R	0.991
17:18766808:C:A	S550R	0.991
17:18766808:C:G	S550R	0.991
17:18768616:T:A	V596D	0.991
17:18768624:T:A	W599R	0.991
17:18768624:T:C	W599R	0.991
17:18769959:G:C	R627P	0.990
17:18769975:T:G	C632W	0.990
17:18750062:G:C	W308C	0.989
17:18750062:G:T	W308C	0.989
17:18768627:A:C	S600R	0.989

dbSNP variants (sampled 300 via entrez): RS1000431941 (17:18774884 C>T), RS1000438979 (17:18763791 T>C), RS1000731650 (17:18750197 C>G), RS1000781304 (17:18776757 A>G), RS1000891275 (17:18768820 C>T), RS1000985842 (17:18743063 C>T), RS1001045812 (17:18766490 C>A), RS1001190343 (17:18776132 A>G), RS1001240108 (17:18769172 T>C,G), RS1001561607 (17:18746940 G>T), RS1001592660 (17:18755258 C>T), RS1001611443 (17:18763018 G>A), RS1001614296 (17:18763372 G>A), RS1001856318 (17:18742326 T>C), RS1001979429 (17:18749261 G>A,T)

Disease associations

OMIM: gene MIM:611679 | disease phenotypes: MIM:610883

GenCC curated gene-disease

Mondo (1): Potocki-Lupski syndrome (MONDO:0012574)

Orphanet (1): 17p11.2 microduplication syndrome (Orphanet:1713)

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

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Cadmium Chloride	increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
tungsten carbide	affects cotreatment, increases expression	1
bisphenol A	increases methylation	1
2-methyl-4-isothiazolin-3-one	increases expression	1
benzo(e)pyrene	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Poly(amidoamine)	decreases expression	1
NSC 689534	increases expression, affects binding	1
PCI 5002	affects cotreatment, increases expression	1
Cobalt	affects cotreatment, increases expression	1
Copper	affects binding, increases expression	1
Endosulfan	affects cotreatment, increases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
Methapyrilene	increases methylation	1
Phenobarbital	increases expression	1
Silicon Dioxide	affects expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	affects expression	1
Zinc	affects cotreatment, increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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