FBXO39

Summary

FBXO39 (F-box protein 39, HGNC:28565) is a protein-coding gene on chromosome 17p13.1, encoding F-box only protein 39 (Q8N4B4). 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 FBXO39, 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 162517 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 76 total
• MANE Select transcript: NM_153230

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28565
Approved symbol	FBXO39
Name	F-box protein 39
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC35179, Fbx39, CT144
Ensembl gene	ENSG00000177294
Ensembl biotype	protein_coding
OMIM	609106
Entrez	162517

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 nonsense_mediated_decay, 1 protein_coding

ENST00000321535, ENST00000572251, ENST00000575022

RefSeq mRNA: 1 — MANE Select: NM_153230 NM_153230

CCDS: CCDS11082

Canonical transcript exons

ENST00000321535 — 4 exons

Exon	Start	End
ENSE00001223273	6786780	6786956
ENSE00001223277	6787300	6787646
ENSE00001223285	6779789	6780891
ENSE00001327051	6776215	6776272

Expression profiles

Bgee: expression breadth ubiquitous, 142 present calls, max score 87.67.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1352 / max 58.1900, expressed in 35 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159073	0.0674	32
159071	0.0540	3
159072	0.0138	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	87.67	gold quality
left testis	UBERON:0004533	87.57	gold quality
testis	UBERON:0000473	84.69	gold quality
sperm	CL:0000019	76.15	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.38	silver quality
lower esophagus mucosa	UBERON:0035834	67.21	gold quality
right ovary	UBERON:0002118	64.63	gold quality
oocyte	CL:0000023	64.07	gold quality
right lobe of liver	UBERON:0001114	63.71	gold quality
left ovary	UBERON:0002119	62.59	gold quality
adult organism	UBERON:0007023	62.42	gold quality
esophagus mucosa	UBERON:0002469	61.21	gold quality
ovary	UBERON:0000992	59.31	gold quality
left uterine tube	UBERON:0001303	59.17	gold quality
mucosa of stomach	UBERON:0001199	58.92	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	58.82	gold quality
smooth muscle tissue	UBERON:0001135	58.62	gold quality
right uterine tube	UBERON:0001302	58.53	gold quality
superficial temporal artery	UBERON:0001614	58.50	gold quality
omental fat pad	UBERON:0010414	58.27	gold quality
peritoneum	UBERON:0002358	58.22	gold quality
adipose tissue of abdominal region	UBERON:0007808	57.30	gold quality
endocervix	UBERON:0000458	56.42	gold quality
ectocervix	UBERON:0012249	56.34	gold quality
parietal pleura	UBERON:0002400	56.15	gold quality
gall bladder	UBERON:0002110	55.98	gold quality
visceral pleura	UBERON:0002401	55.71	gold quality
subcutaneous adipose tissue	UBERON:0002190	55.67	gold quality
stromal cell of endometrium	CL:0002255	55.27	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	55.16	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.06

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting FBXO39, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-3168	99.08	67.75	1384
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914
HSA-MIR-11399	98.71	65.69	869
HSA-MIR-6755-3P	98.61	66.90	834
HSA-MIR-3614-3P	97.81	67.15	582
HSA-MIR-6787-3P	97.75	66.17	1233
HSA-MIR-6131	97.22	66.72	960

Literature-anchored findings (GeneRIF, showing 6)

• These data suggest that the BCP-20 (FBXO39) gene is a new Cancer/Testis antigen and may be useful for diagnosis and immunotherapy. (PMID:21338577)
• FBXO39 showed significant up-regulation in invasive ductal breast carcinoma. (PMID:24377578)
• High FBXO39 expression is associated with Colorectal Cancer. (PMID:29802700)
• Aberrant Expression of Cancer-Testis Antigen FBXO39 in Breast Cancer and its Clinical Significance. (PMID:32902238)
• Significance of cancer testis-associated antigens (SPAG9 and FBXO39) in colon cancer. (PMID:34380828)
• The cancer-testis antigen FBXO39 predicts poor prognosis and is associated with stemness and aggressiveness in glioma. (PMID:36244247)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fbxo39	ENSMUSG00000070388
rattus_norvegicus	Fbxo39	ENSRNOG00000014953

Paralogs (1): FBXO31 (ENSG00000103264)

Protein

Protein identifiers

F-box only protein 39 — Q8N4B4 (reviewed: Q8N4B4)

All UniProt accessions (3): Q8N4B4, I3L1J5, I3L210

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. Directly interacts with SKP1 and CUL1.

RefSeq proteins (1): NP_694962* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR001810	F-box_dom	Domain
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR036047	F-box-like_dom_sf	Homologous_superfamily
IPR045048	FBXO31/39	Family

Pfam: PF12937

UniProt features (7 total): sequence variant 5, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N4B4-F1	92.55	0.84

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 34 (showing top): 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, GOBP_PROTEOLYSIS, GOCC_CULLIN_RING_UBIQUITIN_LIGASE_COMPLEX, GOCC_UBIQUITIN_LIGASE_COMPLEX, HATADA_METHYLATED_IN_LUNG_CANCER_UP, MIKKELSEN_ES_LCP_WITH_H3K4ME3, BOSCO_TH1_CYTOTOXIC_MODULE, ZSCAN2_TARGET_GENES, MIR3168, MIR452_3P

GO Biological Process (1): SCF-dependent proteasomal ubiquitin-dependent protein catabolic process (GO:0031146)

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

GO Cellular Component (1): SCF ubiquitin ligase complex (GO:0019005)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
proteasome-mediated ubiquitin-dependent protein catabolic process	1
binding	1
cullin-RING ubiquitin ligase complex	1

Protein interactions and networks

STRING

540 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FBXO39	RNH1	P13489	826
FBXO39	SPAG8	Q99932	609
FBXO39	CUL1	Q13616	544
FBXO39	SKP1	P34991	543
FBXO39	SPAG17	Q6Q759	540
FBXO39	SH2D4B	Q5SQS7	527
FBXO39	UBOX5	O94941	509
FBXO39	CDRT15L2	A8MXV6	507
FBXO39	TBC1D28	Q2M2D7	445
FBXO39	SLC35G3	Q8N808	418
FBXO39	SLC35G6	P0C7Q6	418
FBXO39	CT55	Q8WUE5	417
FBXO39	CCDC144A	A2RUR9	416
FBXO39	CHCT1	Q86WR6	411
FBXO39	LONP2	Q86WA8	411

IntAct

4 interactions, top by confidence:

A	B	Type	Score
MEOX2	FBXO39	psi-mi:“MI:0915”(physical association)	0.560
FBXO39	MEOX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): FBXO39 (Two-hybrid), FBXO39 (Affinity Capture-MS), FBXO39 (Affinity Capture-MS)

ESM2 similar proteins: A2RT62, A4IIK1, B3FL73, F4I9T0, I1SSI5, I1SSI6, O22161, O22243, O74991, P21541, Q09299, Q09562, Q0DKP3, Q1EHT7, Q1L8H0, Q2R3K5, Q32LM4, Q38SD2, Q3UHC2, Q3ZBA7, Q570C0, Q5MJ12, Q5NBU5, Q5RE08, Q66H10, Q75A03, Q7KLI1, Q7XVM8, Q8BFZ4, Q8C4V4, Q8N4B4, Q8NEZ5, Q8RWQ8, Q8VYT5, Q8W104, Q96ME1, Q9FJ32, Q9FJ57, Q9LPW7, Q9LTX2

Diamond homologs: Q32LM4, Q5NBU5, Q66H10, Q8N4B4, Q3ZBA7, Q8BFZ4, A8QGZ7, B3FL73, Q32PG9, Q7Z6M2, Q8C4V4, Q8VE08, Q9EPX5, Q9NXK8, Q9UKT6, Q9UKT7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

387 predictions. Top by Δscore:

Variant	Effect	Δscore
17:6776268:AGCAG:A	donor_loss	1.0000
17:6776270:CAGG:C	donor_loss	1.0000
17:6776271:AG:A	donor_loss	1.0000
17:6776272:GGT:G	donor_loss	1.0000
17:6776274:T:G	donor_loss	1.0000
17:6786779:GA:G	acceptor_gain	1.0000
17:6786953:CAAGG:C	donor_loss	1.0000
17:6786954:AAGGT:A	donor_loss	1.0000
17:6786957:G:GC	donor_loss	1.0000
17:6786958:T:A	donor_loss	1.0000
17:6776269:GCAG:G	donor_gain	0.9900
17:6779787:A:AG	acceptor_gain	0.9900
17:6779788:G:GG	acceptor_gain	0.9900
17:6779788:GAAA:G	acceptor_gain	0.9900
17:6779821:T:A	acceptor_gain	0.9900
17:6786766:T:TA	acceptor_gain	0.9900
17:6786774:TTCCA:T	acceptor_loss	0.9900
17:6786775:TCCA:T	acceptor_loss	0.9900
17:6786776:CCA:C	acceptor_loss	0.9900
17:6786777:CA:C	acceptor_loss	0.9900
17:6786778:A:AG	acceptor_gain	0.9900
17:6786778:AG:A	acceptor_loss	0.9900
17:6786779:G:GA	acceptor_gain	0.9900
17:6786779:GAA:G	acceptor_gain	0.9900
17:6786779:GAAA:G	acceptor_gain	0.9900
17:6786779:GAAAT:G	acceptor_gain	0.9900
17:6786854:G:GT	donor_gain	0.9800
17:6777680:GTT:G	donor_gain	0.9700
17:6777681:TTT:T	donor_gain	0.9700
17:6786767:G:A	acceptor_gain	0.9700

AlphaMissense

2958 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:6780004:T:A	W46R	0.999
17:6780004:T:C	W46R	0.999
17:6780034:T:A	W56R	0.997
17:6780034:T:C	W56R	0.997
17:6779976:G:C	R36S	0.996
17:6779976:G:T	R36S	0.996
17:6780006:G:C	W46C	0.996
17:6780006:G:T	W46C	0.996
17:6779984:C:A	A39D	0.995
17:6780289:T:A	W141R	0.995
17:6780289:T:C	W141R	0.995
17:6780685:T:A	W273R	0.994
17:6780685:T:C	W273R	0.994
17:6780036:G:C	W56C	0.993
17:6780036:G:T	W56C	0.993
17:6780005:G:C	W46S	0.992
17:6779975:G:C	R36T	0.991
17:6779983:G:C	A39P	0.991
17:6779995:T:C	C43R	0.990
17:6780143:T:C	L92P	0.990
17:6780035:G:C	W56S	0.989
17:6780403:G:C	G179R	0.989
17:6779960:T:C	L31P	0.987
17:6779974:A:G	R36G	0.985
17:6779997:C:G	C43W	0.985
17:6780291:G:C	W141C	0.985
17:6780291:G:T	W141C	0.985
17:6780687:G:C	W273C	0.985
17:6780687:G:T	W273C	0.985
17:6779975:G:T	R36M	0.984

dbSNP variants (sampled 300 via entrez): RS1000028121 (17:6783413 A>G), RS1000058173 (17:6776708 T>C), RS1000063722 (17:6781709 T>C), RS1000160957 (17:6777194 A>G), RS1000299392 (17:6776904 A>C), RS1000490335 (17:6775389 C>T), RS1000640010 (17:6778006 G>A,C), RS1000767297 (17:6787266 G>A,C), RS1000820303 (17:6787682 T>C), RS1001490532 (17:6774215 C>G), RS1001722307 (17:6779210 A>G), RS1001794051 (17:6784935 G>A,C), RS1001820255 (17:6786061 A>G), RS1002046687 (17:6774588 T>C), RS1002050563 (17:6779552 C>A,T)

Disease associations

OMIM: gene MIM:609106 | 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

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	2
bisphenol A	increases methylation, affects cotreatment	1
lead acetate	increases expression	1
arsenite	increases methylation	1
sodium arsenite	increases expression	1
N-acetyl-4-benzoquinoneimine	affects response to substance	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
perfluorooctane sulfonic acid	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
perfluorohexanesulfonic acid	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Lipopolysaccharides	decreases reaction, increases expression	1
N-Nitrosopyrrolidine	increases expression	1

Clinical trials (associated diseases)

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