FBXO34

Summary

FBXO34 (F-box protein 34, HGNC:20201) is a protein-coding gene on chromosome 14q22.3, encoding F-box only protein 34 (Q9NWN3). Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex promoting ubiquitination and proteasomal degradation of specific target proteins including HNRNPU.

Members of the F-box protein family, such as FBXO34, 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 55030 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 154 total
• MANE Select transcript: NM_017943

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20201
Approved symbol	FBXO34
Name	F-box protein 34
Location	14q22.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20725, Fbx34
Ensembl gene	ENSG00000178974
Ensembl biotype	protein_coding
OMIM	609104
Entrez	55030

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 14 protein_coding, 4 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000313833, ENST00000440021, ENST00000554940, ENST00000555087, ENST00000555280, ENST00000557647, ENST00000679934, ENST00000680658, ENST00000680682, ENST00000681074, ENST00000681400, ENST00000681904, ENST00000855357, ENST00000855358, ENST00000855359, ENST00000855360, ENST00000855361, ENST00000918751, ENST00000918752, ENST00000969173, ENST00000969174

RefSeq mRNA: 2 — MANE Select: NM_017943 NM_017943, NM_152231

CCDS: CCDS32086

Canonical transcript exons

ENST00000313833 — 2 exons

Exon	Start	End
ENSE00001232707	55271421	55271537
ENSE00001232716	55350381	55353611

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 96.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.6885 / max 227.7363, expressed in 1817 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
139724	23.6464	1816
139725	0.8275	401
139723	0.2146	88

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	96.96	gold quality
esophagus squamous epithelium	UBERON:0006920	96.85	gold quality
epithelium of esophagus	UBERON:0001976	96.80	gold quality
tongue squamous epithelium	UBERON:0006919	96.69	gold quality
squamous epithelium	UBERON:0006914	95.03	gold quality
cervix squamous epithelium	UBERON:0006922	95.00	gold quality
nasal cavity epithelium	UBERON:0005384	94.97	gold quality
orbitofrontal cortex	UBERON:0004167	94.88	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.80	gold quality
pharyngeal mucosa	UBERON:0000355	94.78	gold quality
postcentral gyrus	UBERON:0002581	94.31	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.17	gold quality
epithelium of nasopharynx	UBERON:0001951	94.12	gold quality
middle temporal gyrus	UBERON:0002771	94.06	gold quality
amniotic fluid	UBERON:0000173	94.00	gold quality
cervix epithelium	UBERON:0004801	93.85	gold quality
parietal lobe	UBERON:0001872	93.70	gold quality
oocyte	CL:0000023	93.65	gold quality
colonic mucosa	UBERON:0000317	93.55	gold quality
superior frontal gyrus	UBERON:0002661	93.23	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.22	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.20	gold quality
biceps brachii	UBERON:0001507	93.18	gold quality
quadriceps femoris	UBERON:0001377	93.17	gold quality
triceps brachii	UBERON:0001509	93.16	gold quality
body of tongue	UBERON:0011876	93.10	gold quality
vastus lateralis	UBERON:0001379	93.07	gold quality
gluteal muscle	UBERON:0002000	92.98	gold quality
deltoid	UBERON:0001476	92.77	gold quality
lower esophagus mucosa	UBERON:0035834	92.74	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.90

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

85 targeting FBXO34, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
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-4789-5P	99.98	70.76	2721
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-499A-5P	99.98	70.79	1323

Literature-anchored findings (GeneRIF, showing 1)

• FBXO34 promotes latent HIV-1 activation by post-transcriptional modulation. (PMID:36285453)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fbxo34	ENSDARG00000071259
mus_musculus	Fbxo34	ENSMUSG00000037536
rattus_norvegicus	Fbxo34	ENSRNOG00000011704

Paralogs (1): FBXO46 (ENSG00000177051)

Protein

Protein identifiers

F-box only protein 34 — Q9NWN3 (reviewed: Q9NWN3)

All UniProt accessions (2): Q9NWN3, G3V2U9

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex promoting ubiquitination and proteasomal degradation of specific target proteins including HNRNPU. Regulates both the G2/M transition and anaphase entry in meiotic oocytes. (Microbial infection) Plays a positive role in latent HIV-1 activation. Mechanistically, promotes hnRNP U/HNRNPU ubiquitination, which leads to its degradation and abolishment of the interaction between hnRNP U and HIV-1 Rev mRNA.

Subunit / interactions. Directly interacts with SKP1 and CUL1.

RefSeq proteins (2): NP_060413, NP_689417 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001810	F-box_dom	Domain
IPR036047	F-box-like_dom_sf	Homologous_superfamily
IPR039594	FBXO34/46	Family

Pfam: PF12937

UniProt features (12 total): sequence variant 4, region of interest 4, compositionally biased region 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NWN3-F1	49.31	0.01

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 146 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, CMYB_01, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_MATURE_CELL, SP1_Q2_01, GOBP_SCF_DEPENDENT_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, MODULE_207, GOBP_PROTEIN_CATABOLIC_PROCESS, AP2GAMMA_01, SAFFORD_T_LYMPHOCYTE_ANERGY, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, GOCC_SCF_UBIQUITIN_LIGASE_COMPLEX, GOCC_TRANSFERASE_COMPLEX

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

446 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FBXO34	CUL1	Q13616	638
FBXO34	SKP1	P34991	637
FBXO34	FBXO42	Q6P3S6	494
FBXO34	FBXO36	Q8NEA4	475
FBXO34	FBXO5	Q9UKT4	452
FBXO34	FBXO22	Q8NEZ5	435
FBXO34	FBXO28	Q9NVF7	434
FBXO34	FBXO31	Q5XUX0	405
FBXO34	FBXW12	Q6X9E4	400
FBXO34	MYO15B	Q96JP2	396
FBXO34	NCCRP1	Q6ZVX7	355
FBXO34	ECT2L	Q008S8	353
FBXO34	TIMM9	Q9Y5J7	349
FBXO34	FBXO47	Q5MNV8	343
FBXO34	FBXO17	Q96EF6	332

IntAct

84 interactions, top by confidence:

A	B	Type	Score
YEATS4	ZNHIT1	psi-mi:“MI:0914”(association)	0.790
FBXO34	MTUS2	psi-mi:“MI:0915”(physical association)	0.670
MTUS2	FBXO34	psi-mi:“MI:0915”(physical association)	0.670
KRTAP12-4	FBXO34	psi-mi:“MI:0915”(physical association)	0.600
FBXO34	KRTAP12-4	psi-mi:“MI:0915”(physical association)	0.600
FBXO34	MTUS2	psi-mi:“MI:0915”(physical association)	0.560
KRT40	FBXO34	psi-mi:“MI:0915”(physical association)	0.560
MDFI	FBXO34	psi-mi:“MI:0915”(physical association)	0.560
FBXO34	KRT40	psi-mi:“MI:0915”(physical association)	0.560
FBXO34	MDFI	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	FBXO34	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-11	FBXO34	psi-mi:“MI:0915”(physical association)	0.560
KRTAP9-2	FBXO34	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-5	FBXO34	psi-mi:“MI:0915”(physical association)	0.560
OIT3	FBXO34	psi-mi:“MI:0915”(physical association)	0.560
DISC1	FBXO34	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-5	FBXO34	psi-mi:“MI:0915”(physical association)	0.560
KRTAP9-3	FBXO34	psi-mi:“MI:0915”(physical association)	0.560
KRTAP9-8	FBXO34	psi-mi:“MI:0915”(physical association)	0.560
	FBXO34	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-12	FBXO34	psi-mi:“MI:0915”(physical association)	0.560
COL8A1	FBXO34	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (66): FBXO34 (Two-hybrid), FBXO34 (Two-hybrid), KRT40 (Two-hybrid), FBXO34 (Affinity Capture-MS), SKP1 (Affinity Capture-Western), FBXO34 (Affinity Capture-MS), MYO6 (Affinity Capture-MS), FBXO30 (Affinity Capture-MS), GSN (Affinity Capture-MS), TMOD3 (Affinity Capture-MS), CUL1 (Affinity Capture-MS), FBXO34 (Affinity Capture-MS), FBXO34 (Affinity Capture-MS), FBXO34 (Affinity Capture-MS), FBXO34 (Affinity Capture-MS)

ESM2 similar proteins: A0A0A6YY25, A0A5K7RLP0, A6NMK8, A8MVX0, B2RQL2, B2RXH4, C9JSJ3, D2J0Y4, O54824, P97303, Q01954, Q05AH6, Q0VET5, Q14005, Q1W617, Q2YDE2, Q3MHT3, Q3U0P1, Q3ULM6, Q3UXL4, Q4R7L6, Q5RC05, Q5T0L3, Q68CR7, Q6GQV1, Q6NS69, Q6NZK5, Q6P1D7, Q6PG16, Q6ZVT6, Q7Z4V0, Q80W88, Q80XI1, Q811R2, Q86T90, Q86YN6, Q8BHP2, Q8BLK9, Q8BP99, Q8BW86

Diamond homologs: Q4KLY2, Q6PJ61, Q80XI1, Q8BG80, Q9NWN3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 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
Keratinization	11	25.5×	3e-11

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	131
Likely benign	15
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1193 predictions. Top by Δscore:

Variant	Effect	Δscore
14:55350377:ATAG:A	acceptor_gain	1.0000
14:55350379:AG:A	acceptor_gain	1.0000
14:55350379:AGG:A	acceptor_gain	1.0000
14:55350380:GG:G	acceptor_gain	1.0000
14:55350380:GGG:G	acceptor_gain	1.0000
14:55271535:CAGG:C	donor_loss	0.9900
14:55271537:GG:G	donor_loss	0.9900
14:55271538:GTG:G	donor_loss	0.9900
14:55271539:T:A	donor_loss	0.9900
14:55315377:GTTT:G	donor_gain	0.9900
14:55315378:TTTT:T	donor_gain	0.9900
14:55350376:TATA:T	acceptor_loss	0.9900
14:55350377:ATAGG:A	acceptor_gain	0.9900
14:55350378:TAG:T	acceptor_loss	0.9900
14:55350379:A:AG	acceptor_gain	0.9900
14:55350380:G:A	acceptor_loss	0.9900
14:55350380:G:GG	acceptor_gain	0.9900
14:55369921:CTGAC:C	acceptor_gain	0.9900
14:55369923:GACCT:G	acceptor_loss	0.9900
14:55369924:ACC:A	acceptor_loss	0.9900
14:55369925:CC:C	acceptor_loss	0.9900
14:55369926:C:CA	acceptor_loss	0.9900
14:55369927:T:G	acceptor_loss	0.9900
14:55307337:A:AG	acceptor_gain	0.9800
14:55307338:A:G	acceptor_gain	0.9800
14:55350379:AGGG:A	acceptor_gain	0.9800
14:55350380:GGGG:G	acceptor_gain	0.9800
14:55350380:GGGGC:G	acceptor_gain	0.9800
14:55369923:GACC:G	acceptor_gain	0.9800
14:55369926:C:CC	acceptor_gain	0.9800

AlphaMissense

4705 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:55352251:T:A	W621R	1.000
14:55352251:T:C	W621R	1.000
14:55352253:G:C	W621C	1.000
14:55352253:G:T	W621C	1.000
14:55352284:T:C	C632R	1.000
14:55352293:T:A	C635S	1.000
14:55352293:T:C	C635R	1.000
14:55352294:G:C	C635S	1.000
14:55352329:T:C	C647R	1.000
14:55352159:T:C	L590P	0.999
14:55352183:T:C	L598P	0.999
14:55352284:T:A	C632S	0.999
14:55352285:G:A	C632Y	0.999
14:55352285:G:C	C632S	0.999
14:55352286:C:G	C632W	0.999
14:55352289:A:C	K633N	0.999
14:55352289:A:T	K633N	0.999
14:55352294:G:A	C635Y	0.999
14:55352295:C:G	C635W	0.999
14:55352329:T:A	C647S	0.999
14:55352330:G:A	C647Y	0.999
14:55352330:G:C	C647S	0.999
14:55352331:C:G	C647W	0.999
14:55352335:T:A	W649R	0.999
14:55352335:T:C	W649R	0.999
14:55352338:C:G	H650D	0.999
14:55352340:C:A	H650Q	0.999
14:55352340:C:G	H650Q	0.999
14:55352383:T:A	W665R	0.999
14:55352383:T:C	W665R	0.999

dbSNP variants (sampled 300 via entrez): RS1000028849 (14:55280247 A>G), RS1000043192 (14:55383617 TAAC>T), RS1000054702 (14:55405807 A>C), RS1000078009 (14:55324354 G>A), RS1000099990 (14:55383421 G>A), RS1000125222 (14:55285874 A>G), RS1000139506 (14:55324612 A>C,G), RS1000150287 (14:55270779 T>A,C), RS1000156089 (14:55370067 G>A,T), RS1000175448 (14:55317318 G>C), RS1000191279 (14:55287201 C>T), RS1000198564 (14:55291467 C>A), RS1000229086 (14:55442680 A>C), RS1000235421 (14:55398498 T>G), RS1000243152 (14:55357309 T>G)

Disease associations

OMIM: gene MIM:609104 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004635_27	Testicular germ cell tumor	3.000000e-08
GCST008971_4	Urate levels	2.000000e-06
GCST008972_81	Urate levels	2.000000e-08
GCST90002385_25	High light scatter reticulocyte count	2.000000e-09
GCST90002386_168	High light scatter reticulocyte percentage of red cells	2.000000e-11
GCST90002387_142	Immature fraction of reticulocytes	2.000000e-12
GCST90002395_197	Mean platelet volume	2.000000e-24
GCST90002407_621	White blood cell count	1.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases methylation	2
Acetaminophen	increases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
Tretinoin	increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Atrazine	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Cisplatin	increases expression	1
Estradiol	affects expression	1
Formaldehyde	decreases expression	1
Phenobarbital	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Valproic Acid	decreases methylation	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1
Cadmium Chloride	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SN24	HAP1 FBXO34 (-) 1	Cancer cell line	Male
CVCL_SN25	HAP1 FBXO34 (-) 2	Cancer cell line	Male
CVCL_SN26	HAP1 FBXO34 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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