FBXO40

Summary

FBXO40 (F-box protein 40, HGNC:29816) is a protein-coding gene on chromosome 3q13.33, encoding F-box only protein 40 (Q9UH90). Probable substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex that may function in myogenesis.

Members of the F-box protein family, such as FBXO40, 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 51725 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 110 total — 1 likely-pathogenic
• MANE Select transcript: NM_016298

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29816
Approved symbol	FBXO40
Name	F-box protein 40
Location	3q13.33
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1195, Fbx40
Ensembl gene	ENSG00000163833
Ensembl biotype	protein_coding
OMIM	609107
Entrez	51725

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000338040, ENST00000868808, ENST00000868809, ENST00000868810, ENST00000868811, ENST00000968418, ENST00000968419, ENST00000968420, ENST00000968421, ENST00000968422

RefSeq mRNA: 1 — MANE Select: NM_016298 NM_016298

CCDS: CCDS33835

Canonical transcript exons

ENST00000338040 — 4 exons

Exon	Start	End
ENSE00001078696	121621433	121623343
ENSE00001343958	121626695	121630295
ENSE00001343969	121620546	121620578
ENSE00001729548	121593379	121593502

Expression profiles

Bgee: expression breadth ubiquitous, 125 present calls, max score 98.67.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.0738 / max 263.3742, expressed in 74 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38195	1.0198	74
38196	0.0540	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gluteal muscle	UBERON:0002000	98.67	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.14	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.92	gold quality
biceps brachii	UBERON:0001507	97.73	gold quality
vastus lateralis	UBERON:0001379	97.55	gold quality
triceps brachii	UBERON:0001509	97.43	gold quality
body of tongue	UBERON:0011876	97.03	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.71	gold quality
quadriceps femoris	UBERON:0001377	95.51	gold quality
left ventricle myocardium	UBERON:0006566	95.07	gold quality
apex of heart	UBERON:0002098	94.93	gold quality
myocardium	UBERON:0002349	94.43	gold quality
heart right ventricle	UBERON:0002080	94.27	gold quality
skeletal muscle tissue	UBERON:0001134	94.16	gold quality
cardiac atrium	UBERON:0002081	93.74	gold quality
right atrium auricular region	UBERON:0006631	93.65	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.01	gold quality
cardiac ventricle	UBERON:0002082	92.38	gold quality
vena cava	UBERON:0004087	92.38	gold quality
heart left ventricle	UBERON:0002084	92.27	gold quality
muscle organ	UBERON:0001630	91.44	gold quality
gastrocnemius	UBERON:0001388	90.82	gold quality
muscle tissue	UBERON:0002385	90.67	gold quality
muscle of leg	UBERON:0001383	89.85	gold quality
diaphragm	UBERON:0001103	89.50	gold quality
heart	UBERON:0000948	88.20	gold quality
deltoid	UBERON:0001476	87.65	gold quality
tongue	UBERON:0001723	86.90	gold quality
superior surface of tongue	UBERON:0007371	79.34	gold quality
tibialis anterior	UBERON:0001385	78.82	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

107 targeting FBXO40, 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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
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-98-3P	100.00	74.08	3907
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-489-3P	99.80	66.46	839

Literature-anchored findings (GeneRIF, showing 1)

• FBXO40 may function as a regulator involved in the postnatal myogenesis. (PMID:17928169)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fbxo40.1	ENSDARG00000069775
danio_rerio	fbxo40.2	ENSDARG00000091119
mus_musculus	Fbxo40	ENSMUSG00000047746
rattus_norvegicus	Fbxo40	ENSRNOG00000002459
caenorhabditis_elegans		WBGENE00015673

Paralogs (1): FBXO30 (ENSG00000118496)

Protein

Protein identifiers

F-box only protein 40 — Q9UH90 (reviewed: Q9UH90)

Alternative names: Muscle disease-related protein

All UniProt accessions (1): Q9UH90

UniProt curated annotations — full annotation on UniProt →

Function. Probable substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex that may function in myogenesis.

Subunit / interactions. Directly interacts with SKP1 and CUL1.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed only in heart and skeletal muscle.

Miscellaneous. The expression decreases in the dystrophic muscle of Limb-girdle muscular dystrophy (LGMD) patient.

RefSeq proteins (1): NP_057382* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001293	Znf_TRAF	Domain
IPR001810	F-box_dom	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR031890	Fbxo30/Fbxo40	Family
IPR036047	F-box-like_dom_sf	Homologous_superfamily
IPR043013	Znf_TRAF_N	Homologous_superfamily

Pfam: PF15965, PF15966

UniProt features (10 total): sequence conflict 3, compositionally biased region 2, chain 1, domain 1, zinc finger region 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UH90-F1	74.32	0.39

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: 81 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, AP4_Q6, MEF2_02, CHX10_01, CAGCTG_AP4_Q5, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, FREAC3_01, GOBP_SCF_DEPENDENT_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, PTF1BETA_Q6, CTAWWWATA_RSRFC4_Q2, HOXA4_Q2

GO Biological Process (1): muscle cell differentiation (GO:0042692)

GO Molecular Function (4): zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

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
cellular anatomical structure	2
cell differentiation	1
muscle structure development	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
cation binding	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1676 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FBXO40	COP1	Q8NHY2	839
FBXO40	ASTN2	O75129	763
FBXO40	NLGN1	Q8N2Q7	696
FBXO40	SKP1	P34991	693
FBXO40	CDH9	Q9ULB4	691
FBXO40	CNTN4	Q8IWV2	682
FBXO40	NLGN4X	Q8N0W4	657
FBXO40	NLGN3	Q9NZ94	639
FBXO40	CDH10	Q9Y6N8	631
FBXO40	TAS2R1	Q9NYW7	620
FBXO40	UBE3A	P78355	594
FBXO40	PRKN	O60260	567
FBXO40	NRXN1	Q9ULB1	561
FBXO40	SEMA5A	Q13591	558
FBXO40	ATP1A2	P50993	555

IntAct

5 interactions, top by confidence:

A	B	Type	Score
FBXO40	MYO1D	psi-mi:“MI:0914”(association)	0.530
HSP90AB1	FBXO40	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (19): CUL1 (Affinity Capture-MS), ACTBL2 (Affinity Capture-MS), MYO1D (Affinity Capture-MS), GSN (Affinity Capture-MS), SKP1 (Affinity Capture-MS), CUL1 (Affinity Capture-MS), GSN (Affinity Capture-MS), MYO1D (Affinity Capture-MS), SKP1 (Affinity Capture-MS), ACTBL2 (Affinity Capture-MS), ACTB (Affinity Capture-MS), FLII (Affinity Capture-MS), DYNLL2 (Affinity Capture-MS), ACTC1 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8HBI7, A0A1L8HJK9, A0A1L8HTT5, A6NP61, A7E2V4, B2RVL6, C0SPG1, C3VD30, K7SGN7, P56163, P56198, P62932, Q1XFL1, Q29RJ0, Q32L09, Q3UHH1, Q3V0J4, Q497M3, Q4R739, Q58D79, Q5EA86, Q5R8D5, Q5TKR9, Q5VWQ0, Q5XI33, Q6DMN8, Q768S4, Q7T3T8, Q7T3T9, Q7T3U0, Q80T69, Q8BV79, Q8BZ21, Q8CAK3, Q8CDN1, Q8HXK7, Q8K3Y6, Q8N2G6, Q8N9V6, Q8ND61

Diamond homologs: P62932, Q5XI67, Q8BJL1, Q8TB52, Q9UH90

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	100
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
253332	GRCh37/hg19 3q13.33-21.1(chr3:119749810-122459323)x3	Likely pathogenic

SpliceAI

614 predictions. Top by Δscore:

Variant	Effect	Δscore
3:121623342:AGGT:A	donor_loss	1.0000
3:121593501:AG:A	donor_gain	0.9900
3:121593501:AGG:A	donor_loss	0.9900
3:121593502:GG:G	donor_gain	0.9900
3:121593503:G:GA	donor_loss	0.9900
3:121593503:G:GG	donor_gain	0.9900
3:121621421:T:TA	acceptor_gain	0.9900
3:121623339:GAGAG:G	donor_gain	0.9900
3:121623340:AGAG:A	donor_gain	0.9900
3:121623341:GAG:G	donor_gain	0.9900
3:121623341:GAGG:G	donor_gain	0.9900
3:121623342:AG:A	donor_gain	0.9900
3:121623343:GG:G	donor_gain	0.9900
3:121623344:G:GG	donor_gain	0.9900
3:121593498:TTAAG:T	donor_gain	0.9800
3:121620544:A:AG	acceptor_gain	0.9800
3:121620545:G:GG	acceptor_gain	0.9800
3:121623345:T:G	donor_loss	0.9800
3:121593499:TAAG:T	donor_gain	0.9700
3:121593500:AAG:A	donor_gain	0.9700
3:121620545:GA:G	acceptor_gain	0.9700
3:121626894:G:GT	donor_gain	0.9700
3:121620619:TCC:T	donor_gain	0.9500
3:121620625:T:TA	donor_gain	0.9500
3:121621422:G:A	acceptor_gain	0.9500
3:121626772:G:GT	donor_gain	0.9500
3:121593174:G:T	donor_gain	0.9300
3:121593175:A:T	donor_gain	0.9200
3:121620545:G:C	acceptor_gain	0.9200
3:121620540:CCGTA:C	acceptor_loss	0.9100

AlphaMissense

4719 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:121622960:T:C	C511R	0.999
3:121621712:T:C	C95R	0.998
3:121621731:G:C	R101P	0.998
3:121622981:T:C	C518R	0.998
3:121623290:T:A	W621R	0.998
3:121623290:T:C	W621R	0.998
3:121621691:T:C	C88R	0.997
3:121621724:T:A	W99R	0.997
3:121621724:T:C	W99R	0.997
3:121622297:T:A	W290R	0.997
3:121622297:T:C	W290R	0.997
3:121622962:C:G	C511W	0.997
3:121623292:G:C	W621C	0.997
3:121623292:G:T	W621C	0.997
3:121626734:T:A	W652R	0.997
3:121626734:T:C	W652R	0.997
3:121621601:T:C	C58R	0.996
3:121621622:T:C	C65R	0.996
3:121621643:T:C	C72R	0.996
3:121621714:C:G	C95W	0.996
3:121621730:C:A	R101S	0.996
3:121622981:T:A	C518S	0.996
3:121622982:G:C	C518S	0.996
3:121622983:T:G	C518W	0.996
3:121626779:T:C	C667R	0.996
3:121621726:G:C	W99C	0.995
3:121621726:G:T	W99C	0.995
3:121621733:T:A	W102R	0.995
3:121621733:T:C	W102R	0.995
3:121622429:T:C	F334L	0.995

dbSNP variants (sampled 300 via entrez): RS1000003261 (3:121612333 G>A), RS1000061197 (3:121618448 G>A,T), RS1000116804 (3:121602277 C>T), RS1000138860 (3:121627148 T>C), RS1000205196 (3:121594686 T>C), RS1000248630 (3:121627106 G>A), RS1000330809 (3:121614384 G>A), RS1000336603 (3:121609319 T>C), RS1000427372 (3:121630580 C>T), RS1000493104 (3:121608709 G>A), RS1000596775 (3:121620448 A>G), RS1000641475 (3:121597339 T>C), RS1000650060 (3:121608263 G>C), RS1000695465 (3:121601632 A>T), RS1000813693 (3:121624386 G>A)

Disease associations

OMIM: gene MIM:609107 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000477_23	Cognitive performance	6.000000e-06
GCST001767_1	Aging (facial)	2.000000e-08
GCST001767_2	Aging (facial)	6.000000e-09
GCST001767_3	Aging (facial)	4.000000e-09
GCST001767_4	Aging (facial)	1.000000e-09
GCST002813_3	Alzheimer’s disease in APOE e4+ carriers	3.000000e-06
GCST008522_24	Bitter alcoholic beverage consumption	4.000000e-07
GCST012489_128	Heel bone mineral density x serum urate levels interaction	7.000000e-10
GCST90002397_657	Mean spheric corpuscular volume	4.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0003926	neuropsychological test
EFO:0022597	aging
EFO:0010092	bitter alcoholic beverage consumption measurement
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Doxorubicin	decreases expression	2
testosterone enanthate	affects expression	1
bisphenol A	affects cotreatment, decreases methylation	1
maleic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Air Pollutants	increases expression	1
Copper	affects cotreatment, decreases expression	1
Triclosan	decreases expression	1

Clinical trials (associated diseases)

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