FBXO16

Summary

FBXO16 (F-box protein 16, HGNC:13618) is a protein-coding gene on chromosome 8p21.1, encoding F-box only protein 16 (Q8IX29). Substrate recognition component of an SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins.

This gene encodes a member of the F-box protein family, members of which are characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into three 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 Fbx class. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 157574 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 65 total
• MANE Select transcript: NM_172366

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13618
Approved symbol	FBXO16
Name	F-box protein 16
Location	8p21.1
Locus type	gene with protein product
Status	Approved
Aliases	FBX16
Ensembl gene	ENSG00000214050
Ensembl biotype	protein_coding
OMIM	608519
Entrez	157574

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000346498, ENST00000380254, ENST00000517436, ENST00000517673, ENST00000518016, ENST00000518248, ENST00000518734, ENST00000519471, ENST00000520481, ENST00000521548, ENST00000522609, ENST00000902912

RefSeq mRNA: 2 — MANE Select: NM_172366 NM_001258211, NM_172366

CCDS: CCDS59099, CCDS6068

Canonical transcript exons

ENST00000380254 — 9 exons

Exon	Start	End
ENSE00001043031	28447171	28447273
ENSE00001307038	28428412	28428736
ENSE00001316191	28429378	28429403
ENSE00001394282	28483348	28483462
ENSE00001484373	28490186	28490229
ENSE00003592993	28463612	28463818
ENSE00003608691	28473772	28473807
ENSE00003623540	28456766	28456930
ENSE00003678727	28452244	28452476

Expression profiles

Bgee: expression breadth ubiquitous, 181 present calls, max score 89.96.

FANTOM5 (CAGE): breadth broad, TPM avg 3.6961 / max 373.1940, expressed in 849 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92538	3.3829	838
92537	0.3132	58

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adenohypophysis	UBERON:0002196	89.96	gold quality
pituitary gland	UBERON:0000007	89.41	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.86	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.65	gold quality
right hemisphere of cerebellum	UBERON:0014890	81.65	gold quality
nucleus accumbens	UBERON:0001882	81.63	gold quality
cerebellar hemisphere	UBERON:0002245	81.40	gold quality
right frontal lobe	UBERON:0002810	81.40	gold quality
islet of Langerhans	UBERON:0000006	81.31	gold quality
cerebellar cortex	UBERON:0002129	81.23	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.10	gold quality
prefrontal cortex	UBERON:0000451	80.91	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.11	gold quality
cortical plate	UBERON:0005343	80.06	gold quality
right uterine tube	UBERON:0001302	79.95	gold quality
popliteal artery	UBERON:0002250	79.91	gold quality
tibial artery	UBERON:0007610	79.87	gold quality
cerebellum	UBERON:0002037	79.80	gold quality
corpus epididymis	UBERON:0004359	79.47	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	79.33	gold quality
caudate nucleus	UBERON:0001873	79.29	gold quality
anterior cingulate cortex	UBERON:0009835	79.01	gold quality
ventricular zone	UBERON:0003053	78.95	gold quality
right lobe of thyroid gland	UBERON:0001119	78.41	gold quality
neocortex	UBERON:0001950	78.05	gold quality
frontal cortex	UBERON:0001870	77.94	gold quality
putamen	UBERON:0001874	77.92	gold quality
hypothalamus	UBERON:0001898	77.30	gold quality
left lobe of thyroid gland	UBERON:0001120	77.28	gold quality
thyroid gland	UBERON:0002046	76.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting FBXO16, 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-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-4480	99.42	66.02	735
HSA-MIR-4999-3P	99.11	65.55	424
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-490-3P	97.79	65.54	606
HSA-MIR-616-3P	96.82	66.99	784
HSA-MIR-6726-5P	95.97	63.72	841
HSA-MIR-920	95.97	63.95	811
HSA-MIR-4300	95.85	64.56	1003
HSA-MIR-5591-5P	95.85	64.76	1002
HSA-MIR-6090	91.01	62.65	222

Literature-anchored findings (GeneRIF, showing 5)

• FBXO16 was localized to the human chromosome 8p12. The FBXO16 gene consisted of 9 exons that spanned 67,816 bp of human genomic DNA (PMID:12243353)
• we show that due to low expression of FBXO16, the beta-catenin is not targeted in glioma cells leading to its nuclear accumulation resulting in active Wnt signaling. Activated Wnt signaling potentiates the glioma cells toward a highly proliferative and malignant state. (PMID:30530053)
• that FBXO16 functions as a putative tumor suppressor by forming an SCF(FBXO16) complex that targets nuclear beta-catenin in a unique manner for ubiquitination and subsequent proteasomal degradation to prevent malignancy (PMID:30714168)
• FBXO16-mediated hnRNPL ubiquitination and degradation plays a tumor suppressor role in ovarian cancer. (PMID:34333526)
• MIR937 amplification potentiates ovarian cancer progression by attenuating FBXO16 inhibition on ULK1-mediated autophagy. (PMID:39384743)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fbxo16	ENSDARG00000033949
mus_musculus	Fbxo16	ENSMUSG00000034532
rattus_norvegicus	Fbxo16	ENSRNOG00000014003

Paralogs (14): WDR54 (ENSG00000005448), FBXW11 (ENSG00000072803), FBXW7 (ENSG00000109670), TRAF7 (ENSG00000131653), FBXW9 (ENSG00000132004), FBXO36 (ENSG00000153832), WDR64 (ENSG00000162843), FBXW12 (ENSG00000164049), BTRC (ENSG00000166167), WDR49 (ENSG00000174776), FBXW8 (ENSG00000174989), PAAF1 (ENSG00000175575), WDR86 (ENSG00000187260), EFCAB8 (ENSG00000215529)

Protein

Protein identifiers

F-box only protein 16 — Q8IX29 (reviewed: Q8IX29)

All UniProt accessions (6): E5RFF8, E5RIL5, G3V0Z8, H0YC72, J3KNU2, Q8IX29

UniProt curated annotations — full annotation on UniProt →

Function. Substrate recognition component of an SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Functions as a putative tumor suppressor by targeting nuclear beta-catenin/CTNNB1 for degradation independently of upstream activating signals, thereby inhibiting epithelial-to-mesenchymal transition. Controls the ubiquitination and degradation of hnRNPL. Negatively regulates NF-kappa-B signaling by mediating the polyubiquitination and degradation of RELA. Inhibits autophagy by promoting ‘Lys-48’-linked polyubiquitination of the serine/threonine-protein kinase ULK1.

Subunit / interactions. Part of a SCF (SKP1-cullin-F-box) protein ligase complex. Interacts with CTNNB1. Interacts with HNRNPL. Interacts with RELA. Interacts with ULK1.

Tissue specificity. Expressed in heart, spleen and colon.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IX29-1	1	yes
Q8IX29-2	2

RefSeq proteins (2): NP_001245140, NP_758954* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001810	F-box_dom	Domain
IPR036047	F-box-like_dom_sf	Homologous_superfamily
IPR052805	GEF_Ubiquitin-Prot_Reg	Family

Pfam: PF12937

UniProt features (11 total): sequence variant 3, region of interest 2, compositionally biased region 2, chain 1, domain 1, sequence conflict 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IX29-F1	71.51	0.42

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 75 (showing top): GOBP_MACROMOLECULE_CATABOLIC_PROCESS, TAL1ALPHAE47_01, CCANNAGRKGGC_UNKNOWN, chr8p21, GOBP_SCF_DEPENDENT_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOBP_PROTEIN_CATABOLIC_PROCESS, SHAFFER_IRF4_MULTIPLE_MYELOMA_PROGRAM, GOCC_SCF_UBIQUITIN_LIGASE_COMPLEX, GOCC_TRANSFERASE_COMPLEX, GOBP_PROTEOLYSIS, GOCC_CULLIN_RING_UBIQUITIN_LIGASE_COMPLEX, GOCC_UBIQUITIN_LIGASE_COMPLEX, TAL1BETAITF2_01, MIKKELSEN_ES_ICP_WITH_H3K4ME3

GO Biological Process (0):

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

524 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FBXO16	SKP1	P34991	655
FBXO16	CUL1	Q13616	638
FBXO16	FBXL16	Q8N461	593
FBXO16	UBE2K	P27924	592
FBXO16	TNFRSF17	Q02223	575
FBXO16	UBE2S	Q16763	552
FBXO16	FBXO2	Q9UK22	521
FBXO16	FBXO6	Q9NRD1	498
FBXO16	FBXL7	Q9UJT9	496
FBXO16	FBXL6	Q8N531	493
FBXO16	GLYAT	Q6IB77	434
FBXO16	FBXL3	Q9UKT7	432
FBXO16	ZNF280B	Q86YH2	432
FBXO16	FBXL13	Q8NEE6	410
FBXO16	FBXO17	Q96EF6	376

IntAct

26 interactions, top by confidence:

A	B	Type	Score
CETN1	SFI1	psi-mi:“MI:0914”(association)	0.640
SKP1	MYCBP2	psi-mi:“MI:0914”(association)	0.640
FBXO16	NXT1	psi-mi:“MI:0915”(physical association)	0.560
FBXO16	TRIM54	psi-mi:“MI:0915”(physical association)	0.560
MORF4L2	FBXO16	psi-mi:“MI:0915”(physical association)	0.560
LMO1	FBXO16	psi-mi:“MI:0915”(physical association)	0.560
FBXO16	MORF4L1	psi-mi:“MI:0915”(physical association)	0.560
FBXO16	CETN3	psi-mi:“MI:0914”(association)	0.530
SKP1	BHLHE40	psi-mi:“MI:0914”(association)	0.350
FBXO16	NXT1	psi-mi:“MI:0915”(physical association)	0.000
FBXO16	TRIM54	psi-mi:“MI:0915”(physical association)	0.000
MORF4L2	FBXO16	psi-mi:“MI:0915”(physical association)	0.000
LMO1	FBXO16	psi-mi:“MI:0915”(physical association)	0.000
MORF4L1	FBXO16	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (28): FBXO16 (Affinity Capture-MS), FBXO16 (Affinity Capture-RNA), SKP1 (Affinity Capture-Western), FBXO16 (Synthetic Lethality), SKP1 (Affinity Capture-Western), CTNNB1 (Affinity Capture-Western), FBXO16 (Affinity Capture-Western), CUL1 (Affinity Capture-Western), FBXO16 (Two-hybrid), FBXO16 (Two-hybrid), FBXO16 (Two-hybrid), FBXO16 (Two-hybrid), FBXO16 (Two-hybrid), CETN2 (Affinity Capture-MS), FBXO16 (Affinity Capture-MS)

ESM2 similar proteins: A1A5Q7, A6NFY4, A6QNT4, D4A6L0, F1RCP1, O14772, O43379, P0C7A6, P50747, Q08BI9, Q08CB3, Q1LVW0, Q1RMS8, Q2HJ93, Q2KHT6, Q3SX24, Q3U3T8, Q4R372, Q5M7V7, Q5R776, Q5R796, Q5T848, Q641X7, Q6GQ33, Q7T0P6, Q7ZU92, Q8C419, Q8HXL3, Q8IWF6, Q8IX29, Q8K2I9, Q8NEA4, Q8NEA9, Q8NFZ0, Q8TCJ0, Q8VDG3, Q8VDV3, Q91W78, Q91WM6, Q91Z62

Diamond homologs: A1C7E4, A1CBP8, A1CUD6, A1DDL6, A1DHW6, A1DP19, A2QCU8, A2R3Z3, A3LNI7, A4RJV3, A5D7H2, A7EKM8, B0XM00, B0XTS1, B2VWG7, B6GZA1, B6Q4Z5, B6QC06, B6QC56, B8M0Q1, B8M7Q5, B8NGT5, C0S902, C1GB49, C5FP68, C5GVJ9, C5JD40, D1ZEM6, D4AM37, D4D8P3, L7N1X6, O43815, O55106, P0DL28, P39014, P58404, P58405, P70483, P87053, Q00659

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	14
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3823 predictions. Top by Δscore:

Variant	Effect	Δscore
8:28348826:CTTTC:C	acceptor_gain	1.0000
8:28349227:ACC:A	acceptor_loss	1.0000
8:28349234:C:CT	acceptor_gain	1.0000
8:28351739:T:TA	donor_gain	1.0000
8:28351807:CCTG:C	acceptor_gain	1.0000
8:28352570:TA:T	donor_loss	1.0000
8:28352571:A:C	donor_loss	1.0000
8:28352571:AC:A	donor_gain	1.0000
8:28352571:ACC:A	donor_gain	1.0000
8:28352572:CC:C	donor_gain	1.0000
8:28352572:CCC:C	donor_gain	1.0000
8:28352669:GAGTT:G	acceptor_gain	1.0000
8:28352670:AGTT:A	acceptor_gain	1.0000
8:28352671:GTT:G	acceptor_gain	1.0000
8:28352672:TT:T	acceptor_gain	1.0000
8:28352672:TTCTA:T	acceptor_loss	1.0000
8:28352674:C:CA	acceptor_loss	1.0000
8:28352674:C:CC	acceptor_gain	1.0000
8:28356787:C:CT	acceptor_gain	1.0000
8:28359591:CCT:C	donor_gain	1.0000
8:28359820:TAAAC:T	acceptor_gain	1.0000
8:28359821:AAAC:A	acceptor_gain	1.0000
8:28359822:AAC:A	acceptor_gain	1.0000
8:28359823:AC:A	acceptor_gain	1.0000
8:28359824:CC:C	acceptor_gain	1.0000
8:28359824:CCT:C	acceptor_loss	1.0000
8:28359825:C:CA	acceptor_loss	1.0000
8:28359825:C:CC	acceptor_gain	1.0000
8:28360946:T:TA	donor_gain	1.0000
8:28452242:AC:A	donor_gain	1.0000

AlphaMissense

1930 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:28463809:A:G	W49R	0.999
8:28463809:A:T	W49R	0.999
8:28456888:A:G	W129R	0.998
8:28456888:A:T	W129R	0.998
8:28456918:A:G	W119R	0.997
8:28456918:A:T	W119R	0.997
8:28483383:A:G	W22R	0.997
8:28483383:A:T	W22R	0.997
8:28473774:A:G	W45R	0.996
8:28473774:A:T	W45R	0.996
8:28456819:A:G	W152R	0.995
8:28456819:A:T	W152R	0.995
8:28456886:C:A	W129C	0.995
8:28456886:C:G	W129C	0.995
8:28463630:G:C	S108R	0.995
8:28463630:G:T	S108R	0.995
8:28463632:T:G	S108R	0.995
8:28473793:T:A	R38S	0.995
8:28473793:T:G	R38S	0.995
8:28483387:G:C	S20R	0.995
8:28483387:G:T	S20R	0.995
8:28483389:T:G	S20R	0.995
8:28456814:C:A	K153N	0.994
8:28456814:C:G	K153N	0.994
8:28452329:A:G	W219R	0.993
8:28452329:A:T	W219R	0.993
8:28456874:A:C	C133W	0.993
8:28456876:A:G	C133R	0.993
8:28473802:A:C	F35L	0.993
8:28473802:A:T	F35L	0.993

dbSNP variants (sampled 300 via entrez): RS1000003945 (8:28436654 T>C), RS1000010036 (8:28465817 T>G), RS1000128817 (8:28469011 A>C), RS1000159683 (8:28488930 A>G), RS1000161621 (8:28433567 T>G), RS1000208977 (8:28446529 C>T), RS1000307208 (8:28432027 A>G), RS1000361958 (8:28437047 T>C), RS1000403067 (8:28466536 A>T), RS1000466359 (8:28466014 T>C,G), RS1000556621 (8:28462008 T>C), RS1000559413 (8:28484742 C>A,T), RS1000618109 (8:28488563 A>G), RS1000631241 (8:28472470 C>T), RS1000666013 (8:28455606 T>C)

Disease associations

OMIM: gene MIM:608519 | 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation, increases expression	5
trichostatin A	affects expression, affects cotreatment, decreases expression	4
Cyclosporine	increases expression	4
Vorinostat	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
kojic acid	increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
tetraarsenic tetrasulfide	increases expression, affects cotreatment	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Imatinib Mesylate	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	increases abundance, increases expression	1
Amiodarone	increases expression	1
Arbutin	increases expression	1
Estradiol	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	decreases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Phenylmercuric Acetate	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

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