FBXO41

Summary

FBXO41 (F-box protein 41, HGNC:29409) is a protein-coding gene on chromosome 2p13.2, encoding F-box only protein 41 (Q8TF61). Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.

This gene encodes a member of the F-box protein family, which is characterized by an approximately 40 amino acid motif, the F-box. F-box proteins constitute one of the four subunits of the SCF ubiquitin protein ligase complex that plays a role in phosphorylation-dependent ubiquitination. F-box proteins are divided into three classes depending on the interaction substrate domain each contains in addition to the F-box motif: FBXW proteins contain WD-40 domains, FBXL proteins contain leucine-rich repeats, and FBXO proteins contain either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the FBXO class.

Source: NCBI Gene 150726 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 150 total
• MANE Select transcript: NM_001371389

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29409
Approved symbol	FBXO41
Name	F-box protein 41
Location	2p13.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1940, Fbx41
Ensembl gene	ENSG00000163013
Ensembl biotype	protein_coding
OMIM	609108
Entrez	150726

Gene structure

Transcript identifiers

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

ENST00000295133, ENST00000519873, ENST00000520186, ENST00000520530, ENST00000521871

RefSeq mRNA: 2 — MANE Select: NM_001371389 NM_001080410, NM_001371389

CCDS: CCDS46337

Canonical transcript exons

ENST00000520530 — 13 exons

Exon	Start	End
ENSE00001070649	73264278	73264519
ENSE00001070651	73263938	73264053
ENSE00001070652	73265282	73265640
ENSE00001070654	73263678	73263830
ENSE00001168563	73266457	73266682
ENSE00001200862	73259181	73259296
ENSE00001200866	73260389	73260547
ENSE00001200870	73260740	73260858
ENSE00001200874	73263213	73263308
ENSE00002096389	73268726	73269768
ENSE00002103292	73254690	73259044
ENSE00003288836	73284160	73284478
ENSE00003578597	73265893	73265966

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 96.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.5363 / max 142.5180, expressed in 1350 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29136	3.3172	1008
29135	1.6157	661
29130	0.8392	332
29133	0.3650	154
29132	0.1768	77
29131	0.1142	59
29134	0.0504	19
29128	0.0256	16
29137	0.0228	10
29129	0.0094	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
CA1 field of hippocampus	UBERON:0003881	96.89	gold quality
orbitofrontal cortex	UBERON:0004167	95.60	gold quality
Brodmann (1909) area 46	UBERON:0006483	95.39	gold quality
cerebellar vermis	UBERON:0004720	95.19	gold quality
superior frontal gyrus	UBERON:0002661	94.75	gold quality
postcentral gyrus	UBERON:0002581	94.63	gold quality
parietal lobe	UBERON:0001872	94.32	gold quality
entorhinal cortex	UBERON:0002728	93.88	gold quality
right frontal lobe	UBERON:0002810	93.73	gold quality
frontal cortex	UBERON:0001870	93.53	gold quality
frontal lobe	UBERON:0016525	93.53	gold quality
prefrontal cortex	UBERON:0000451	93.17	gold quality
cingulate cortex	UBERON:0003027	93.09	gold quality
anterior cingulate cortex	UBERON:0009835	93.08	gold quality
neocortex	UBERON:0001950	92.98	gold quality
cerebral cortex	UBERON:0000956	92.27	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.25	gold quality
temporal lobe	UBERON:0001871	92.12	gold quality
primary visual cortex	UBERON:0002436	92.06	gold quality
occipital lobe	UBERON:0002021	91.92	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.89	gold quality
cerebellum	UBERON:0002037	91.56	gold quality
cerebellar cortex	UBERON:0002129	91.48	gold quality
cerebellar hemisphere	UBERON:0002245	91.41	gold quality
type B pancreatic cell	CL:0000169	91.36	silver quality
amygdala	UBERON:0001876	91.20	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.08	gold quality
middle temporal gyrus	UBERON:0002771	90.90	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.79	gold quality
telencephalon	UBERON:0001893	90.77	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6142	no	28.35
E-CURD-10	no	3.59
E-ANND-3	no	2.48

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

238 targeting FBXO41, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4645-5P	99.98	65.81	1284
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-512-3P	99.97	67.35	1049
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-22-3P	99.93	68.13	917

Literature-anchored findings (GeneRIF, showing 4)

• Our finding suggests that the FBXO41gene may be a non-X chromosome-related Parkinson disease risk factor (PMID:23777664)
• This study show that FBXO41 is a critical factor, not only for neuronal migration in the cerebellum, but also for its long-term integrity. (PMID:26063905)
• F-box protein FBXO41 plays vital role in arsenic trioxide-mediated autophagic death of cancer cells. (PMID:35278439)
• F-box protein FBXO41 suppresses breast cancer growth by inducing autophagic cell death through facilitating proteasomal degradation of oncogene SKP2. (PMID:35598880)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fbxo41	ENSDARG00000078908
mus_musculus	Fbxo41	ENSMUSG00000047013
rattus_norvegicus	Fbxo41	ENSRNOG00000033202

Paralogs (1): ZNF365 (ENSG00000138311)

Protein

Protein identifiers

F-box only protein 41 — Q8TF61 (reviewed: Q8TF61)

All UniProt accessions (1): Q8TF61

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 (2): NP_001073879, NP_001358318* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001810	F-box_dom	Domain
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR036047	F-box-like_dom_sf	Homologous_superfamily
IPR052283	GenomicStab_NeuMorph_Reg	Family
IPR057038	FBX41/ZN365_Znf-C2H2	Domain

Pfam: PF12937, PF23165

UniProt features (16 total): compositionally biased region 5, modified residue 4, region of interest 3, chain 1, domain 1, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8S1R	X-RAY DIFFRACTION	1.98

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TF61-F1	69.41	0.44

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 (4): 360, 478, 479, 762

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: 170 (showing top): GOBP_DENTATE_GYRUS_DEVELOPMENT, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_NEURON_MATURATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEUROGENESIS, NAGASHIMA_NRG1_SIGNALING_UP, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_CELL_CELL_SIGNALING, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_HIPPOCAMPUS_DEVELOPMENT, GOBP_CELL_MATURATION, GOBP_PALLIUM_DEVELOPMENT, LIAO_METASTASIS

GO Biological Process (6): neuron migration (GO:0001764), chemical synaptic transmission (GO:0007268), gene expression (GO:0010467), dentate gyrus development (GO:0021542), neuron maturation (GO:0042551), hippocampus development (GO:0021766)

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

GO Cellular Component (2): cytosol (GO:0005829), synapse (GO:0045202)

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
anatomical structure development	2
cell migration	1
generation of neurons	1
anterograde trans-synaptic signaling	1
macromolecule biosynthetic process	1
hippocampus development	1
cell maturation	1
neuron development	1
pallium development	1
limbic system development	1
binding	1
cytoplasm	1
cellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

626 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FBXO41	CUL1	Q13616	656
FBXO41	SKP1	P34991	642
FBXO41	FBXO21	O94952	462
FBXO41	SMARCD2	Q92925	456
FBXO41	KLHL42	Q9P2K6	451
FBXO41	FBXO42	Q6P3S6	447
FBXO41	FBXW12	Q6X9E4	423
FBXO41	HSDL1	Q3SXM5	396
FBXO41	ARIH2	O95376	394
FBXO41	FAM219B	Q5XKK7	376
FBXO41	KLHL3	Q9UH77	372
FBXO41	TNPO3	Q9Y5L0	347
FBXO41	PSMC5	P47210	343
FBXO41	FBXO9	Q9UK97	342
FBXO41	DCAKD	Q8WVC6	342

IntAct

6 interactions, top by confidence:

A	B	Type	Score
FBXO41	SKP1	psi-mi:“MI:0915”(physical association)	0.400
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	POM121C	psi-mi:“MI:0914”(association)	0.350
FBXO41	DISC1	psi-mi:“MI:0915”(physical association)	0.000
DISC1	FBXO41	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): FBXO41 (Negative Genetic), SKP1 (Affinity Capture-Western), SKP2 (Affinity Capture-Western), FBXO41 (Affinity Capture-RNA), FBXO41 (Two-hybrid)

ESM2 similar proteins: A0A8I5KY20, A2A9T0, A2IDD5, B0BNK9, B8ZZ34, C9JI98, C9JLR9, F5GYI3, O18734, P0CG25, P84157, Q0IIA6, Q0PHV7, Q0X0E2, Q13387, Q1RMK9, Q2M3D2, Q2TAM9, Q3ZCQ3, Q4VA45, Q673H1, Q69YZ2, Q6NS60, Q6P6N5, Q6PJ61, Q7Z6J2, Q80ZJ8, Q810I0, Q86SX3, Q86UD0, Q86XT2, Q8BNN1, Q8IUW3, Q8N4Y2, Q8N6N2, Q8QZV0, Q8R4T5, Q8TF61, Q8VCR9, Q8WXF8

Diamond homologs: Q6NS60, Q8TF61

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	136
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2239 predictions. Top by Δscore:

Variant	Effect	Δscore
2:73259294:TGC:T	acceptor_gain	1.0000
2:73259297:C:CC	acceptor_gain	1.0000
2:73259297:CTGAG:C	acceptor_loss	1.0000
2:73259298:T:G	acceptor_loss	1.0000
2:73260387:A:AC	donor_gain	1.0000
2:73260388:C:CT	donor_gain	1.0000
2:73260403:AGGG:A	donor_gain	1.0000
2:73260544:CTCG:C	acceptor_gain	1.0000
2:73260545:TCG:T	acceptor_gain	1.0000
2:73260546:CG:C	acceptor_gain	1.0000
2:73260546:CGC:C	acceptor_gain	1.0000
2:73260547:GCTAG:G	acceptor_loss	1.0000
2:73260548:C:CC	acceptor_gain	1.0000
2:73260548:CT:C	acceptor_loss	1.0000
2:73260549:T:A	acceptor_loss	1.0000
2:73260855:CTGG:C	acceptor_gain	1.0000
2:73260859:C:CC	acceptor_gain	1.0000
2:73263304:CACTC:C	acceptor_gain	1.0000
2:73263306:CTC:C	acceptor_gain	1.0000
2:73263307:TCC:T	acceptor_loss	1.0000
2:73263673:CCCA:C	donor_loss	1.0000
2:73263674:CCA:C	donor_loss	1.0000
2:73263675:CACC:C	donor_loss	1.0000
2:73263676:A:AC	donor_gain	1.0000
2:73263676:ACC:A	donor_loss	1.0000
2:73263677:C:CC	donor_gain	1.0000
2:73263677:C:G	donor_loss	1.0000
2:73263826:AGCCC:A	acceptor_gain	1.0000
2:73263827:GCCC:G	acceptor_gain	1.0000
2:73263828:CCC:C	acceptor_gain	1.0000

AlphaMissense

5561 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:73259010:A:G	L867P	1.000
2:73259040:A:G	L857P	1.000
2:73259185:A:G	L854P	1.000
2:73259266:A:T	V827D	1.000
2:73259281:A:T	L822H	1.000
2:73259289:G:C	C819W	1.000
2:73259291:A:G	C819R	1.000
2:73260394:A:G	F815S	1.000
2:73260400:A:G	L813P	1.000
2:73260403:A:G	L812P	1.000
2:73260418:A:T	V807D	1.000
2:73260433:A:G	L802P	1.000
2:73260439:A:G	L800P	1.000
2:73260514:A:G	L775P	1.000
2:73260514:A:T	L775H	1.000
2:73260520:A:G	L773P	1.000
2:73260537:G:C	C767W	1.000
2:73260538:C:T	C767Y	1.000
2:73260539:A:G	C767R	1.000
2:73260755:C:G	G759R	1.000
2:73260778:C:T	G751E	1.000
2:73260779:C:A	G751W	1.000
2:73260779:C:G	G751R	1.000
2:73260779:C:T	G751R	1.000
2:73260787:A:G	L748P	1.000
2:73260796:A:G	L745P	1.000
2:73260806:A:G	W742R	1.000
2:73260806:A:T	W742R	1.000
2:73260814:C:T	G739D	1.000
2:73260815:C:G	G739R	1.000

dbSNP variants (sampled 300 via entrez): RS1000419745 (2:73274084 C>T), RS1000443042 (2:73262352 T>C), RS1000499761 (2:73274329 C>T), RS1000551221 (2:73263093 T>G), RS1000557266 (2:73256962 A>G), RS1000609667 (2:73257326 A>G), RS1000624308 (2:73280234 T>C), RS1000720328 (2:73280540 G>C), RS1000861149 (2:73268707 G>C,T), RS1000884341 (2:73254934 C>G,T), RS1001024269 (2:73266851 A>G), RS1001222255 (2:73274050 A>G), RS1001229644 (2:73285320 A>C,G), RS1001439570 (2:73255989 A>C), RS1001492977 (2:73256155 C>G)

Disease associations

OMIM: gene MIM:609108 | disease phenotypes: MIM:203800

GenCC curated gene-disease

Mondo (1): Alstrom syndrome (MONDO:0008763)

Orphanet (1): Alström syndrome (Orphanet:64)

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST005316_334	Intelligence (MTAG)	6.000000e-11
GCST006879_10	Blood metabolite levels	6.000000e-09
GCST006879_11	Blood metabolite levels	1.000000e-12
GCST006879_6	Blood metabolite levels	5.000000e-14
GCST006879_7	Blood metabolite levels	2.000000e-15
GCST006879_8	Blood metabolite levels	4.000000e-08
GCST006879_9	Blood metabolite levels	2.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D056769	Alstrom Syndrome	C10.500.300.099; C10.574.500.495.099; C10.668.829.800.300.099; C11.270.684.249; C16.131.077.245.063; C16.131.666.300.099; C16.320.184.063; C16.320.290.684.249; C16.320.400.375.099

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
pentanal	increases expression	1
phenethyl isothiocyanate	affects binding	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Decitabine	decreases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cisplatin	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Lead	affects expression	1
Methotrexate	increases expression	1
Methyl Methanesulfonate	decreases expression	1
Quercetin	increases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	affects expression	1
Urethane	decreases expression	1
Vanadium	increases abundance, increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03746522	PHASE3	COMPLETED	Setmelanotide (RM-493), Melanocortin-4 Receptor (MC4R) Agonist, in Bardet-Biedl Syndrome (BBS) and Alström Syndrome (AS) Participants With Moderate to Severe Obesity
NCT03184584	PHASE2/PHASE3	TERMINATED	Open-Label Rollover Study of PBI 4050 in Subjects With Alström Syndrome
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT02890550	Not specified	TERMINATED	Clinical Study of a Single Ciliopathy: Alström Syndrome
NCT04461444	Not specified	RECRUITING	COhort for Bardet-Bield Syndrome and Alström Syndrome for Translational Research Monocentric Interventional Study