FBXO32

Summary

FBXO32 (F-box protein 32, HGNC:16731) is a protein-coding gene on chromosome 8q24.13, encoding F-box only protein 32 (Q969P5). Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.

This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 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 Fbxs class and contains an F-box domain. This protein is highly expressed during muscle atrophy, whereas mice deficient in this gene were found to be resistant to atrophy. This protein is thus a potential drug target for the treatment of muscle atrophy. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 114907 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dilated cardiomyopathy (Limited, ClinGen)
• GWAS associations: 20
• Clinical variants (ClinVar): 64 total — 1 likely-pathogenic
• MANE Select transcript: NM_058229

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16731
Approved symbol	FBXO32
Name	F-box protein 32
Location	8q24.13
Locus type	gene with protein product
Status	Approved
Aliases	MAFbx, ATROGIN1, Fbx32
Ensembl gene	ENSG00000156804
Ensembl biotype	protein_coding
OMIM	606604
Entrez	114907

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 retained_intron, 4 protein_coding

ENST00000287396, ENST00000443022, ENST00000517956, ENST00000520511, ENST00000521719, ENST00000524000, ENST00000889272, ENST00000889273

RefSeq mRNA: 3 — MANE Select: NM_058229 NM_001242463, NM_058229, NM_148177

CCDS: CCDS56553, CCDS6345

Canonical transcript exons

ENST00000517956 — 9 exons

Exon	Start	End
ENSE00001090851	123540899	123541206
ENSE00002136185	123497889	123503462
ENSE00003460761	123533191	123533240
ENSE00003465283	123504604	123504747
ENSE00003495714	123514240	123514333
ENSE00003539010	123534702	123534814
ENSE00003557203	123513198	123513382
ENSE00003609039	123531898	123531990
ENSE00003629790	123506392	123506574

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 99.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.9946 / max 2499.6126, expressed in 1545 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
94729	41.4357	1540
94726	0.4203	131
94727	0.1387	54

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cardiac muscle of right atrium	UBERON:0003379	99.69	gold quality
deltoid	UBERON:0001476	99.53	gold quality
tibialis anterior	UBERON:0001385	99.47	gold quality
left ventricle myocardium	UBERON:0006566	99.23	gold quality
gastrocnemius	UBERON:0001388	99.20	gold quality
quadriceps femoris	UBERON:0001377	99.13	gold quality
skeletal muscle tissue	UBERON:0001134	99.08	gold quality
vastus lateralis	UBERON:0001379	99.05	gold quality
muscle tissue	UBERON:0002385	98.90	gold quality
skeletal muscle organ	UBERON:0014892	98.85	gold quality
muscle of leg	UBERON:0001383	98.79	gold quality
mucosa of stomach	UBERON:0001199	98.69	gold quality
biceps brachii	UBERON:0001507	98.62	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.58	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.53	gold quality
popliteal artery	UBERON:0002250	98.48	gold quality
tibial artery	UBERON:0007610	98.48	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.47	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.33	gold quality
body of tongue	UBERON:0011876	98.19	gold quality
artery	UBERON:0001637	98.02	gold quality
descending thoracic aorta	UBERON:0002345	97.81	gold quality
aorta	UBERON:0000947	97.80	gold quality
decidua	UBERON:0002450	97.79	gold quality
smooth muscle tissue	UBERON:0001135	97.75	gold quality
myocardium	UBERON:0002349	97.54	gold quality
body of uterus	UBERON:0009853	97.52	gold quality
lower esophagus	UBERON:0013473	97.36	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.36	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.11	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ENAD-21	yes	5507.36
E-CURD-7	yes	5324.07
E-GEOD-99795	no	39.50
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EZH2, FOXO1, FOXO3, FOXO4, FOXO6, MAF, MYOG, NR3C1, SMAD4, STAT3, TP53, TP63

miRNA regulators (miRDB)

255 targeting FBXO32, 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-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-6798-5P	100.00	65.77	699
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588

Literature-anchored findings (GeneRIF, showing 40)

• Human skeletal muscle atrophy in the amyotrophic lateral sclerosis shows an increase in atrogin-1 & a decrease in Akt. The transcriptional regulation of human atrogin-1 may be controlled by an Akt-mediated transcription factor other than FKHR. (PMID:16507768)
• results suggest that Cbl-b- or atrogin-1-mediated ubiquitination plays an important role in unloading-induced muscle atrophy, and that unloading stress may preferentially inhibit transcriptional responses in skeletal muscle (PMID:16868939)
• Atrogin-1 mRNA expression was significantly increased in quadriceps of patients with COPD; transcriptional regulation of atrogin-1 and MuRF1 may occur via FoxO-1, but independently of AKT (PMID:17478621)
• CSRP3, MUSTN1, SIX1, and FBXO32 expression changes in response to lengthening and shortening contractions in human muscle (PMID:17519359)
• We conclude that smoking impairs the muscle protein synthesis process and increases the expression of genes associated with impaired muscle maintenance; smoking therefore likely increases the risk of sarcopenia. (PMID:17609255)
• Expression of mRNA for MuRF-1 increased approximately 3-fold at 10 days without changes in MAFbx or tripeptidyl peptidase II mRNA, but all decreased between 10 and 21 days of muscle disuse. (PMID:17901116)
• MuRF-1 and MAFbx, are differently affected by the exercise as well as by repeated exercise (PMID:17971512)
• Results showed upregulation of MuRf1 and MAFbx in atrophies muscle and support their role as regulatory peptides in various conditions which lead to muscle atrophy. (PMID:17977773)
• atrogin-1 may be a critical mediator of the muscle damage induced by statins. (PMID:17992259)
• Testosterone represses MAFbx expression via interactions of the AR with Oct-1. (PMID:18599544)
• Review discusses findings implicating atrogin-1, a gene required for muscle atrophy, in the pathophysiology of statin-induced muscle injury. (PMID:18681786)
• atrogin-1 specifically targets truncated M7t-cMyBP-C, but not WT-cMyBP-C, for proteasomal degradation and that MuRF1 indirectly reduces cMyBP-C levels by regulating the transcription of myosin heavy chain. (PMID:19850579)
• Reduced expression of MuRF1 and MAFbx in the myocardium might permit hypertrophy characteristic of the early post-infarction remodeling phase. (PMID:19859778)
• The novel tumor suppressor FBXO32 is epigenetically silenced in ovarian cancer cell lines with disrupted TGF-beta/SMAD4 signaling, and FBXO32 methylation status predicts survival in patients with ovarian cancer. (PMID:20065949)
• atrophic AKT-FOXO signaling play major roles in eliciting pathological changes associated with diaphragm disuse. (PMID:20833824)
• 11beta-HSD1 controls glucocorticoid-induced protein degradation in human and murine skeletal muscle via regulation of the E3 ubiquitin ligases Atrogin-1 and MuRF-1. (PMID:21304964)
• SerpinB5 interacts with KHDRBS3 and FBXO32, and KHDRBS3 can interact with FBXO32 mRNA. (PMID:21725612)
• investigation of factors regulating expression of two ubiquitin ligases (MAFbx and MURF1) in skeletal muscle (i.e., vastus lateralis): effects of resistance exercise and anabolic dietary supplement (i.e., branched-chain amino acids) (PMID:22127230)
• MAFbx contains two functional nuclear localization signals (NLS). Mutation or deletion of only one NLS induced cytoplasmic localization of MAFbx. (PMID:22249105)
• Cardiac and vascular atrogin-1 mRNA expression is not associated with dexamethasone efficacy in the monocrotaline model of pulmonary hypertension. (PMID:22311109)
• Resistance exercise resulted in a significant downregulation of MSTN and FBXO32 mRNA expression and a significant upregulation in FSTL3 and SMURF1 mRNA expression, and carbohydrate and protein feeding have little influence on the these markers expression. (PMID:22476926)
• In a transgenic mouse model of autoimmune myositis, cellular inflammation is associated with FOXO3A translocation and Atrogin-1 induction. (PMID:22590725)
• Data suggest expression of atrogin-1 and MuRF-1 (muscle-specific RING finger protein 1) play role in aging-related decrease in muscle mass (i.e., sarcopenia); up-regulation of atrogin-1/MuRF-1 has potential to prevent/reverse sarcopenia. [REVIEW] (PMID:22815045)
• ATROGIN1 gene expression is increased in patients with severe burn injury. (PMID:23816995)
• Quadriceps muscle atrogin-1 levels were lower in COPD patients than controls, but similar in patients with a low and normal fat-free mass index. Atrogin1 levels were not associated with quadriceps fiber cross-sectional area or strength in patients. (PMID:23844868)
• EZH2 is a key factor in the proliferation and survival of PAX3-FOXO1 alveolar RMS cells working, at least in part, by repressing FBXO32 (PMID:24213577)
• In conclusion, atrogin-1, MuRF1, FOXO1/3A, and eIF3-f mRNA, and protein levels, are differentially regulated by exercise contraction mode but not WPH supplementation combined with hypertrophy-inducing training. (PMID:24458747)
• MAFbx not only regulates protein degradation, but also reduces protein synthesis, exerting a dual role in regulating cardiac mass and preventing from cardiac hypertrophy. (PMID:24650875)
• FBXO32 methylation status and protein expression were independently associated with survival in ESCC. FBXO32 may be a functional tumor suppressor. Its inactivation through promoter methylation could play an important role in ESCC carcinogenesis. (PMID:24798237)
• both MuRF1 and MAFbx are enriched in skeletal, cardiac, and smooth muscle–REVIEW (PMID:25096180)
• Atrogin-1 expression tended to be increased in the skeletal muscle of patients with malignant disease even before cancer related cachexia weight loss. (PMID:25760630)
• Vitamin D3 might have an inhibitory effect on the expression of MAFbx and MuRF1 in skeletal muscle. (PMID:25876656)
• FBXO32 targets Lys-326 of c-Myc to form polyubiquitin chains, resulting in inhibition of cell proliferation. (PMID:25944903)
• Expression of USP19 correlates with that of MuRF1 and MAFbx/atrogin-1 in skeletal muscles (PMID:26048142)
• role of the muscle specific E3s MuRF-1 and MAFbx in skeletal muscle wasting during various pathologies, as well as their regulation by modifiable lifestyle factors, were explored (review) (PMID:26738803)
• Our results indicate that abnormal SCF activity with subsequent impairment of the autophagic flux due to a novel FBXO32 mutation is implicated in the pathogenesis of Dilated cardiomyopathy . (PMID:26753747)
• Our data suggest that FBXO32 is a candidate gene for recessive familial dilated cardiomyopathy. Acting as a cardiac ubiquitin ligase, mutated FBXO32 could perturb the degradation of target proteins in the ubiquitin proteasome system. (PMID:26768247)
• These results have revealed the roles for atrogin-1 in the regulation of smooth muscle contractility through enhancement of myocardin ubiquitylation/degradation and its transcriptional activity. (PMID:27403897)
• the involvement of oxidative stress in the atrophy of COPD peripheral muscle cells in vitro, via the FoxO1/MuRF1/atrogin-1 signaling pathway of the ubiquitin/proteasome system (PMID:27526027)
• Transcriptional analysis of endophilin-A mutant mice, complemented by proteomics, highlighted ataxia- and protein-homeostasis-related genes and revealed upregulation of the E3-ubiquitin ligase FBXO32/atrogin-1 and its transcription factor FOXO3A. (PMID:27720640)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fbxo32	ENSDARG00000040277
mus_musculus	Fbxo32	ENSMUSG00000022358
rattus_norvegicus	Fbxo32	ENSRNOG00000006738
drosophila_melanogaster	CG11658	FBGN0036196
caenorhabditis_elegans	mfb-1	WBGENE00008439

Paralogs (1): FBXO25 (ENSG00000147364)

Protein

Protein identifiers

F-box only protein 32 — Q969P5 (reviewed: Q969P5)

Alternative names: Atrogin-1, Muscle atrophy F-box protein

All UniProt accessions (1): Q969P5

UniProt curated annotations — full annotation on UniProt →

Function. Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Probably recognizes and binds to phosphorylated target proteins during skeletal muscle atrophy. Recognizes TERF1. Negatively regulates macrophage efferocytosis by promoting the ubiquitination of the transcription factor KLF4, suppressing the receptor tyrosine kinase MERTK transcription. Regulates LPS-induced apoptosis and mitochondrial dysfunction through ANXA1 ubiquitination and degradation. Mediates cyclin D1 protein stabilization via ‘Lys-27’-linked ubiquitination.

Subunit / interactions. Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXO32) formed of CUL1, SKP1, RBX1 and FBXO32. Interacts with cyclin D1/CCND1.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Specifically expressed in cardiac and skeletal muscle.

Disease relevance. Defects in FBXO32 are associated with susceptibility to dilated cardiomyopathy (DCM). A disorder characterized by ventricular and impaired systolic function, resulting in heart failure and arrhythmia. Patient are at risk of premature death.

Pathway. Protein modification; protein ubiquitination.

Isoforms (2)

UniProt ID	Names	Canonical?
Q969P5-1	1	yes
Q969P5-2	2

RefSeq proteins (3): NP_001229392, NP_478136, NP_680482 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR036047	F-box-like_dom_sf	Homologous_superfamily
IPR040394	FBX25/32	Family

UniProt features (10 total): short sequence motif 3, sequence variant 3, chain 1, domain 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q969P5-F1	80.15	0.53

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (1):

Position	Phenotype
169	significantly increases nuclear localization.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8951664	Neddylation
R-HSA-9615017	FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation

MSigDB gene sets: 309 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GSE45365_NK_CELL_VS_CD8A_DC_DN, SHEPARD_BMYB_MORPHOLINO_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HORIUCHI_WTAP_TARGETS_DN, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_CELLULAR_RESPONSE_TO_LIPID, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_RESPONSE_TO_CORTICOSTEROID, GCANCTGNY_MYOD_Q6, GOZGIT_ESR1_TARGETS_DN

GO Biological Process (4): response to denervation involved in regulation of muscle adaptation (GO:0014894), protein ubiquitination (GO:0016567), negative regulation of SCF-dependent proteasomal ubiquitin-dependent catabolic process (GO:0062026), cellular response to dexamethasone stimulus (GO:0071549)

GO Molecular Function (2): ubiquitin-like ligase-substrate adaptor activity (GO:1990756), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), SCF ubiquitin ligase complex (GO:0019005), Z disc (GO:0030018)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Post-translational protein modification	1
FOXO-mediated transcription	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	4
response to muscle inactivity	1
regulation of muscle adaptation	1
protein modification by small protein conjugation	1
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	1
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	1
regulation of SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	1
cellular response to glucocorticoid stimulus	1
response to dexamethasone	1
cellular response to ketone	1
enzyme-substrate adaptor activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
cullin-RING ubiquitin ligase complex	1
I band	1

Protein interactions and networks

STRING

2228 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FBXO32	TRIM63	Q969Q1	958
FBXO32	YIPF1	Q9Y548	946
FBXO32	CUL1	Q13616	932
FBXO32	SKP1	P34991	894
FBXO32	MSTN	O14793	873
FBXO32	FOXO3	O43524	869
FBXO32	MYOD1	P15172	858
FBXO32	FOXO1	Q12778	837
FBXO32	TRIM54	Q9BYV2	801
FBXO32	MYOG	P15173	779
FBXO32	IGF1	P01343	720
FBXO32	RPS6KB1	P23443	706
FBXO32	AKT1	P31749	703
FBXO32	FOXO4	P98177	690
FBXO32	PPARGC1A	Q9UBK2	664

IntAct

15 interactions, top by confidence:

A	B	Type	Score
EIF3F	FBXO32	psi-mi:“MI:0915”(physical association)	0.600
FBXO32	EIF3F	psi-mi:“MI:0915”(physical association)	0.600
FBXO32	EIF3F	psi-mi:“MI:0403”(colocalization)	0.600
EIF2AK2	ZC3H11A	psi-mi:“MI:0914”(association)	0.480
FBXO32	YTHDC1	psi-mi:“MI:0915”(physical association)	0.400
FBXO32	MLH1	psi-mi:“MI:0915”(physical association)	0.370
CFL1	PML	psi-mi:“MI:0914”(association)	0.350
KDM2A	FBXO32	psi-mi:“MI:0915”(physical association)	0.000
FBXO32	MYOG	psi-mi:“MI:0915”(physical association)	0.000
FBXO32	SKP1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (276): FBXO32 (Two-hybrid), FBXO32 (Affinity Capture-Western), MYOD1 (Biochemical Activity), FBXO32 (Affinity Capture-Western), EIF3F (Reconstituted Complex), FBXO32 (Affinity Capture-Western), KLF4 (Affinity Capture-Western), CUL1 (Affinity Capture-Western), RBX1 (Affinity Capture-Western), SKP1 (Affinity Capture-Western), FBXO32 (Affinity Capture-Western), FBXO32 (Affinity Capture-Western), FBXO32 (Affinity Capture-Western), FBXO32 (Affinity Capture-Western), SH3GL2 (Reconstituted Complex)

ESM2 similar proteins: A4IFQ0, A6QQW8, P48553, Q08BT5, Q0VA03, Q13769, Q14161, Q1A730, Q1RMS8, Q2KHT6, Q3B7L5, Q3T0J1, Q3TLI0, Q4R372, Q5M7Q1, Q5RAQ5, Q5REX9, Q5RFL7, Q5ZJK1, Q5ZML0, Q62784, Q641X7, Q66H91, Q68FX7, Q6P7Q1, Q6SP92, Q6ZPY2, Q76JQ2, Q8BIK4, Q8BKT7, Q8BXK4, Q8IWV8, Q8K3W0, Q8NFG4, Q8QZS3, Q8TCJ0, Q8WN69, Q8WN70, Q91W96, Q91Z62

Diamond homologs: Q1A730, Q1RMS8, Q2KHT6, Q2T9S7, Q4R372, Q641X7, Q8TCJ0, Q91Z62, Q969P5, Q9CPU7, Q9D2Y6

SIGNOR signaling

23 interactions.

A	Effect	B	Mechanism
FBXO32	“down-regulates quantity by destabilization”	MYOD1	ubiquitination
YAP1	down-regulates	FBXO32
FOXO3	“up-regulates quantity by expression”	FBXO32	“transcriptional regulation”
FOXO1	“up-regulates quantity by expression”	FBXO32	“transcriptional regulation”
FOXO4	“up-regulates quantity by expression”	FBXO32	“transcriptional regulation”
FOXO6	“up-regulates quantity by expression”	FBXO32	“transcriptional regulation”
FOXO	“up-regulates quantity by expression”	FBXO32	“transcriptional regulation”
FBXO32	up-regulates	Muscle_atrophy
FBXO32	“up-regulates activity”	Muscle_atrophy
STAT3	“up-regulates quantity by expression”	FBXO32	“transcriptional regulation”
FBXO32	up-regulates	Protein_degradation
FBXO32	“down-regulates quantity by destabilization”	MYOD1	binding
FBXO32	“up-regulates activity”	“Cullin 1-RBX1-Skp1”	binding
MYOG	“down-regulates activity”	FBXO32	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	33
Likely benign	1
Benign	17

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1188824	NM_058229.4(FBXO32):c.881AGA[1] (p.Lys295del)	Likely pathogenic

SpliceAI

1181 predictions. Top by Δscore:

Variant	Effect	Δscore
8:123504599:CATA:C	donor_loss	1.0000
8:123504600:ATACC:A	donor_loss	1.0000
8:123504601:TACCT:T	donor_loss	1.0000
8:123504748:C:CC	acceptor_gain	1.0000
8:123504748:CT:C	acceptor_loss	1.0000
8:123504749:T:G	acceptor_loss	1.0000
8:123504757:CAAA:C	acceptor_gain	1.0000
8:123506388:TGAC:T	donor_loss	1.0000
8:123506390:A:AG	donor_loss	1.0000
8:123506394:G:A	donor_gain	1.0000
8:123506412:A:AC	donor_gain	1.0000
8:123506413:C:CC	donor_gain	1.0000
8:123506427:T:TA	donor_gain	1.0000
8:123506570:GCAGG:G	acceptor_gain	1.0000
8:123506571:CAGG:C	acceptor_gain	1.0000
8:123506571:CAGGC:C	acceptor_gain	1.0000
8:123506573:GG:G	acceptor_gain	1.0000
8:123506574:GC:G	acceptor_loss	1.0000
8:123506575:C:CC	acceptor_gain	1.0000
8:123506576:T:C	acceptor_loss	1.0000
8:123513196:AC:A	donor_gain	1.0000
8:123513197:CC:C	donor_gain	1.0000
8:123513384:T:C	acceptor_gain	1.0000
8:123513384:T:TC	acceptor_gain	1.0000
8:123513388:G:GC	acceptor_gain	1.0000
8:123531891:GACTT:G	donor_loss	1.0000
8:123531892:ACTT:A	donor_loss	1.0000
8:123531893:CTTA:C	donor_loss	1.0000
8:123531894:TTA:T	donor_loss	1.0000
8:123531895:T:TG	donor_loss	1.0000

AlphaMissense

2353 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:123504609:A:G	W325R	1.000
8:123504609:A:T	W325R	1.000
8:123506430:A:G	W266R	1.000
8:123506430:A:T	W266R	1.000
8:123513263:A:G	W196R	1.000
8:123513263:A:T	W196R	1.000
8:123513277:C:T	G191E	1.000
8:123514284:G:T	A141D	1.000
8:123514290:C:T	G139D	1.000
8:123514291:C:G	G139R	1.000
8:123514292:A:C	S138R	1.000
8:123514292:A:T	S138R	1.000
8:123514294:T:G	S138R	1.000
8:123514296:A:G	L137P	1.000
8:123514332:A:G	L125P	1.000
8:123531950:A:G	L107P	1.000
8:123531968:C:T	G101E	1.000
8:123531969:C:A	G101W	1.000
8:123531969:C:G	G101R	1.000
8:123531969:C:T	G101R	1.000
8:123540951:A:G	W22R	1.000
8:123540951:A:T	W22R	1.000
8:123503383:A:G	F353S	0.999
8:123503404:G:T	P346H	0.999
8:123503445:G:C	C332W	0.999
8:123503447:A:G	C332R	0.999
8:123504607:C:A	W325C	0.999
8:123504607:C:G	W325C	0.999
8:123504622:A:C	C320W	0.999
8:123504623:C:T	C320Y	0.999

dbSNP variants (sampled 300 via entrez): RS1000002739 (8:123517744 A>G), RS1000073659 (8:123498130 A>C), RS1000268305 (8:123541458 C>A,G), RS1000309521 (8:123517514 T>A,G), RS1000349680 (8:123538139 A>G), RS1000402731 (8:123503869 A>G), RS1000489217 (8:123498505 G>A), RS1000501668 (8:123525669 C>T), RS1000546687 (8:123536721 T>A), RS1000605703 (8:123542902 G>C), RS1000613407 (8:123535053 G>T), RS1000617881 (8:123505590 G>C), RS1000656766 (8:123543204 G>A), RS1000724615 (8:123498071 A>G), RS1000725443 (8:123532718 G>A)

Disease associations

OMIM: gene MIM:606604 | disease phenotypes: MIM:192600

GenCC curated gene-disease

Disease	Classification	Inheritance
dilated cardiomyopathy	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
dilated cardiomyopathy	Limited	AR

Mondo (2): familial hypertrophic cardiomyopathy (MONDO:0024573), dilated cardiomyopathy (MONDO:0005021)

Orphanet (2): Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155)

HPO phenotypes

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

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST004678_2	Psychosis proneness (hypomanic personality scale)	3.000000e-07
GCST004679_2	Psychosis proneness (hypomanic personality scale and perceptual aberration scale)	1.000000e-06
GCST004681_5	Psychosis proneness (hypomanic personality scale and revised physical anhedonia scale)	2.000000e-06
GCST004682_3	Psychosis proneness (hypomanic personality scale and revised social anhedonia scale)	2.000000e-07
GCST005580_262	Intraocular pressure	3.000000e-10
GCST005580_79	Intraocular pressure	2.000000e-11
GCST006061_183	Atrial fibrillation	9.000000e-17
GCST006061_26	Atrial fibrillation	1.000000e-16
GCST006061_84	Atrial fibrillation	1.000000e-10
GCST006065_24	Glaucoma (primary open-angle)	8.000000e-09
GCST006394_22	Intraocular pressure	1.000000e-14
GCST006395_10	Glaucoma	5.000000e-06
GCST006412_104	Intraocular pressure	4.000000e-17
GCST006414_131	Atrial fibrillation	4.000000e-19
GCST006414_60	Atrial fibrillation	1.000000e-09
GCST009725_24	Intraocular pressure	7.000000e-15
GCST010796_4661	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_4662	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_4663	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST90011770_17	Glaucoma (primary open-angle)	4.000000e-22

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008337	psychosis predisposition measurement
EFO:0004695	intraocular pressure measurement
EFO:0004327	electrocardiography

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects cotreatment, increases methylation	4
Estradiol	decreases expression, decreases reaction, increases expression, affects cotreatment, increases reaction	4
sodium arsenite	decreases expression, increases expression	3
perfluorooctane sulfonic acid	decreases expression, increases expression	3
Arsenic	affects expression, affects methylation, increases abundance, increases expression	3
Sirolimus	affects cotreatment, affects expression, decreases reaction, increases expression	3
(+)-JQ1 compound	affects cotreatment, affects expression, decreases expression	2
Resveratrol	decreases expression, increases expression	2
Temozolomide	affects response to substance, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Benzo(a)pyrene	decreases expression, decreases methylation, increases methylation	2
Doxorubicin	affects expression, increases expression	2
Tetrachlorodibenzodioxin	increases expression, decreases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
Sodium Selenite	increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
afuresertib	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	increases abundance, increases expression	1
ascorbate-2-phosphate	affects cotreatment, increases expression, affects binding	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
sulforaphane	decreases expression	1
nickel chloride	increases expression	1
perfluorooctanoic acid	decreases expression	1
zinc chromate	increases abundance, increases expression	1
ochratoxin A	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00374465	PHASE4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	PHASE4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	PHASE4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	PHASE4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	PHASE4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	PHASE4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
NCT00333827	PHASE3	COMPLETED	Cell Therapy In Dilated Cardiomyopathy
NCT00505154	PHASE3	COMPLETED	Effect of Rosuvastatin on Left Ventricular Remodeling
NCT01223703	PHASE3	COMPLETED	PUFAs and Left Ventricular Function in Heart Failure
NCT01583114	PHASE3	TERMINATED	PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
NCT01914081	PHASE3	UNKNOWN	Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside
NCT02989181	PHASE3	UNKNOWN	Continues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea
NCT03439514	PHASE3	TERMINATED	A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT05849766	PHASE3	COMPLETED	Effect of Dapagliflozin on Cardiac Structure, Function and Secondary Mitral Regurgitation in Patients with Left Ventricle Dysfunction
NCT06250257	PHASE3	RECRUITING	Bromocriptine in Dilated Cardiomyopathy Among Women of Reproductive Age
NCT00629018	PHASE2	COMPLETED	Safety and Efficacy Study of Stem Cell Transplantation to Treat Dilated Cardiomyopathy
NCT00629096	PHASE2	COMPLETED	Intracoronary Infusion of Autologous Bone Marrow Cells for Treatment of Idiopathic Dilated Cardiomyopathy
NCT00765518	PHASE2	COMPLETED	Use of Ixmyelocel-T (Formerly Cardiac Repair Cell [CRC] Treatment) in Patients With Heart Failure Due to Dilated Cardiomyopathy (IMPACT-DCM)
NCT00847964	PHASE2	COMPLETED	Safety and Feasibility of Algisyl-LVR™ as a Method of Left Ventricular Restoration in Patients With DCM Undergoing Open-heart Surgery
NCT01020968	PHASE2	COMPLETED	Use of Ixmyelocel-T (Formerly Catheter-based Cardiac Repair Cell [CRC]) Treatment in Patients With Heart Failure Due to Dilated Cardiomyopathy
NCT01302171	PHASE2	COMPLETED	Bone Marrow Derived Adult Stem Cells for Dilated Cardiomyopathy
NCT01350310	PHASE2	COMPLETED	Safety and Efficacy Study of Intramyocardial Stem Cell Therapy in Patients With Dilated Cardiomyopathy
NCT02133911	PHASE2	COMPLETED	A Pilot Trial of Ranolazine to Treat Patients With Dilated Cardiomyopathy
NCT03071653	PHASE2	SUSPENDED	Left Cardiac Sympathetic Denervation for Cardiomyopathy Feasibility Pilot Study
NCT03572660	PHASE2	ACTIVE_NOT_RECRUITING	Use of Bone Marrow Derived Stem Cell and G-CSF With Circulatory Assistance in the Treatment of DCM
NCT03775070	PHASE2	COMPLETED	Simvastatin Therapy in Patients With Dilated Cardiomyopathy.
NCT04405804	PHASE2	UNKNOWN	Early Administration of Ivabradine in Children With Heart Failure
NCT05410873	PHASE2	COMPLETED	Examining the Effects of Mitochondrial Oxidative Stress in DCM
NCT06632834	PHASE2	RECRUITING	Outcome-targeted Therapy: Principle and Outcome Evaluation: Clinical Study and Phenotype-genotype Correlation
NCT00585546	PHASE1	TERMINATED	Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure
NCT02293603	PHASE1	UNKNOWN	Dilated cardiomYopathy iNtervention With Allogeneic MyocardIally-regenerative Cells (DYNAMIC)
NCT03062956	PHASE1	COMPLETED	A Single Ascending Dose Study Assessing the Safety, Tolerability, PK and PD of MYK-491
NCT03129568	PHASE1	COMPLETED	Transcoronary Infusion of Cardiac Progenitor Cells in Pediatric Dilated Cardiomyopathy
NCT04982081	PHASE1	UNKNOWN	Treating Congestive HF With hiPSC-CMs Through Endocardial Injection
NCT06381466	PHASE1	TERMINATED	A Study to Investigate Safety, Tolerability, and Pharmacokinetics of Oral AZD0233 Compared With Placebo in Healthy Adult Participants.
NCT06464588	PHASE1	RECRUITING	A Phase 1 Open-Label Study of the Safety of Intravenous Allogeneic Neonatal Mesenchymal Cells (nMSCs) in Young Adult (1A) and Pediatric (1B) Patients With Dilated Cardiomyopathy (DCM)
NCT06902896	PHASE1	COMPLETED	Safety and Efficacy of FAP iCDC in End-stage Dilated Cardiomyopathy
NCT07137338	PHASE1	RECRUITING	A Phase 1 AAV Gene Therapy Trial Evaluating Safety and Preliminary Efficacy of RP-A701 in Subjects With BAG3 Dilated Cardiomyopathy
NCT07241104	PHASE1	RECRUITING	A Study of AZD4063 in PLN R14del Dilated Cardiomyopathy