FBXO27

Summary

FBXO27 (F-box protein 27, HGNC:18753) is a protein-coding gene on chromosome 19q13.2, encoding F-box only protein 27 (Q8NI29). 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 FBXO27, 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 126433 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_178820

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18753
Approved symbol	FBXO27
Name	F-box protein 27
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	Fbg5, Fbx27
Ensembl gene	ENSG00000161243
Ensembl biotype	protein_coding
OMIM	609099
Entrez	126433

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 retained_intron

ENST00000292853, ENST00000593847, ENST00000594770, ENST00000595166, ENST00000598394, ENST00000600828, ENST00000881775, ENST00000881776, ENST00000917173, ENST00000917174

RefSeq mRNA: 1 — MANE Select: NM_178820 NM_178820

CCDS: CCDS12527

Canonical transcript exons

ENST00000292853 — 6 exons

Exon	Start	End
ENSE00001057108	39031864	39032253
ENSE00001057109	39031209	39031320
ENSE00001199294	39024021	39025554
ENSE00001369471	39032503	39032549
ENSE00003486032	39031029	39031124
ENSE00003531316	39026870	39027005

Expression profiles

Bgee: expression breadth ubiquitous, 165 present calls, max score 88.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.8287 / max 113.4571, expressed in 1168 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180839	1.8923	700
180838	1.7808	918
180837	0.1556	67

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	88.19	gold quality
skin of abdomen	UBERON:0001416	85.77	gold quality
skin of leg	UBERON:0001511	85.26	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.23	gold quality
cerebellar cortex	UBERON:0002129	85.04	gold quality
cerebellar hemisphere	UBERON:0002245	85.03	gold quality
cerebellum	UBERON:0002037	83.66	gold quality
right frontal lobe	UBERON:0002810	83.56	gold quality
anterior cingulate cortex	UBERON:0009835	82.74	gold quality
prefrontal cortex	UBERON:0000451	82.49	gold quality
islet of Langerhans	UBERON:0000006	82.46	gold quality
zone of skin	UBERON:0000014	82.32	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.10	gold quality
oocyte	CL:0000023	80.65	gold quality
esophagus mucosa	UBERON:0002469	80.59	gold quality
amygdala	UBERON:0001876	79.34	gold quality
frontal cortex	UBERON:0001870	78.56	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	78.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.45	gold quality
neocortex	UBERON:0001950	78.45	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	77.68	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.29	gold quality
hypothalamus	UBERON:0001898	77.01	gold quality
apex of heart	UBERON:0002098	76.65	gold quality
right atrium auricular region	UBERON:0006631	76.50	gold quality
cardiac atrium	UBERON:0002081	75.92	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	75.82	gold quality
right lobe of liver	UBERON:0001114	75.74	gold quality
heart left ventricle	UBERON:0002084	75.59	gold quality
spinal cord	UBERON:0002240	75.57	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.56
E-HCAD-8	no	314.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting FBXO27, 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-4283	100.00	66.42	2097
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-3136-3P	99.57	66.59	781

Literature-anchored findings (GeneRIF, showing 1)

• SCF(FBXO27) ubiquitinates glycoproteins exposed upon lysosomal damage to induce lysophagy. (PMID:28743755)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fbxo27	ENSMUSG00000037463
rattus_norvegicus	AABR07002848.1	ENSRNOG00000050453

Paralogs (5): FBXO2 (ENSG00000116661), FBXO6 (ENSG00000116663), FBXO44 (ENSG00000132879), NCCRP1 (ENSG00000188505), FBXO17 (ENSG00000269190)

Protein

Protein identifiers

F-box only protein 27 — Q8NI29 (reviewed: Q8NI29)

Alternative names: F-box/G-domain protein 5

All UniProt accessions (5): A0A384MR61, Q8NI29, M0QYQ6, M0R0I8, M0R1C3

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Able to recognize and bind denatured glycoproteins, which are modified with complex-type oligosaccharides.

Subunit / interactions. Part of a SCF (SKP1-cullin-F-box) protein ligase complex. Interacts with SKP1 and CUL1.

Tissue specificity. Predominantly expressed in brain, heart and kidney. Expressed at lower levels in liver and lung.

RefSeq proteins (1): NP_849142* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001810	F-box_dom	Domain
IPR007397	F-box-assoc_dom	Domain
IPR008979	Galactose-bd-like_sf	Homologous_superfamily
IPR036047	F-box-like_dom_sf	Homologous_superfamily
IPR039752	F-box_only	Family

Pfam: PF00646, PF04300

UniProt features (6 total): domain 2, chain 1, region of interest 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NI29-F1	91.66	0.84

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
262–263	reduces interaction with glycosylated concanavalin-a in vitro.

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: 95 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GTGCCTT_MIR506, KOYAMA_SEMA3B_TARGETS_UP, GOBP_SCF_DEPENDENT_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOBP_ERAD_PATHWAY, GOBP_PROTEIN_CATABOLIC_PROCESS, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS

GO Biological Process (3): glycoprotein catabolic process (GO:0006516), SCF-dependent proteasomal ubiquitin-dependent protein catabolic process (GO:0031146), ERAD pathway (GO:0036503)

GO Molecular Function (2): protein binding (GO:0005515), ubiquitin protein ligase activity (GO:0061630)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), SCF ubiquitin ligase complex (GO:0019005)

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
glycoprotein metabolic process	1
protein catabolic process	1
carbohydrate derivative catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
response to endoplasmic reticulum stress	1
response to chemical	1
binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
intracellular anatomical structure	1
cytoplasm	1
cullin-RING ubiquitin ligase complex	1

Protein interactions and networks

STRING

332 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FBXO27	SKP1	P34991	820
FBXO27	CUL1	Q13616	805
FBXO27	B7Z1P2	B7Z1P2	587
FBXO27	UBE2QL1	A1L167	549
FBXO27	TRIM16	O95361	505
FBXO27	TMEM192	Q8IY95	452
FBXO27	FBXO17	Q96EF6	402
FBXO27	LGALS8	O00214	374
FBXO27	FBXW5	Q969U6	352
FBXO27	YOD1	Q5VVQ6	332
FBXO27	FBXO4	Q9UKT5	331
FBXO27	ASB1	Q9Y576	323
FBXO27	FBXO6	Q9NRD1	309
FBXO27	FBXL3	Q9UKT7	306
FBXO27	UBXN6	Q9BZV1	305

IntAct

15 interactions, top by confidence:

A	B	Type	Score
SKP1	FBXO27	psi-mi:“MI:0915”(physical association)	0.560
SMPD1	CLGN	psi-mi:“MI:0914”(association)	0.530
FBXO27	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
NELL1	MATN2	psi-mi:“MI:0914”(association)	0.350
CLU	TOR1A	psi-mi:“MI:0914”(association)	0.350
CD79A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
OIT3	WNT10B	psi-mi:“MI:0914”(association)	0.350
TMEM25	CRLF1	psi-mi:“MI:0914”(association)	0.350
BOC	ALDH1A2	psi-mi:“MI:0914”(association)	0.350
TOR1B	HSPA5	psi-mi:“MI:0914”(association)	0.350
SKP1	FBXO27	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (25): FBXO27 (Affinity Capture-MS), FBXO27 (Affinity Capture-MS), TFRC (Affinity Capture-Western), LAMP1 (Affinity Capture-Western), LAMP2 (Affinity Capture-Western), FBXO27 (Two-hybrid), FBXO27 (Affinity Capture-MS), FBXO27 (Affinity Capture-MS), FBXO27 (Affinity Capture-MS), FBXO27 (Affinity Capture-MS), FBXO27 (Affinity Capture-MS), FBXO27 (Affinity Capture-MS), FBXO27 (Affinity Capture-MS), FBXO27 (Affinity Capture-MS), STUB1 (Reconstituted Complex)

ESM2 similar proteins: A0A1D5PJB7, A1A4Q9, A5YM72, A6NLP5, D3KCC4, I3L5V6, O43292, P10938, Q00973, Q05B52, Q09200, Q10468, Q14623, Q148G5, Q16586, Q2V8X7, Q3SZV0, Q561R2, Q5E9M9, Q5M868, Q5ZL13, Q66H45, Q69ZF3, Q6P3D0, Q6P7A1, Q6P9Z4, Q6SZW1, Q6TEC1, Q6ZPS2, Q7TMC8, Q864R5, Q86TX2, Q8IXI1, Q8N0W3, Q8N3Y3, Q8N6R0, Q8NF37, Q8NI29, Q8TCD5, Q8VBW8

Diamond homologs: G3X9C2, Q17QK6, Q3SX24, Q568V3, Q6AY27, Q6DIA9, Q6ZVX7, Q80UW2, Q8NI29, Q923V4, Q96EF6, Q9H4M3, Q9N0C8, Q9NRD1, Q9QZM8, Q9UK22, Q8BK26, Q9QZN4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
FBXO27	“down-regulates quantity by destabilization”	LAMP2	binding
FBXO27	“up-regulates activity”	“Cullin 1-RBX1-Skp1”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

827 predictions. Top by Δscore:

Variant	Effect	Δscore
19:39026864:ACTC:A	donor_loss	1.0000
19:39026866:TCACG:T	donor_loss	1.0000
19:39026867:CAC:C	donor_loss	1.0000
19:39026868:A:AC	donor_gain	1.0000
19:39026868:A:T	donor_loss	1.0000
19:39026869:C:CC	donor_gain	1.0000
19:39026869:CGTG:C	donor_gain	1.0000
19:39026869:CGTGA:C	donor_gain	1.0000
19:39027001:CCCAC:C	acceptor_gain	1.0000
19:39027002:CCACC:C	acceptor_gain	1.0000
19:39031121:CCAG:C	acceptor_gain	1.0000
19:39031122:CAGC:C	acceptor_gain	1.0000
19:39031836:T:TA	donor_gain	1.0000
19:39031845:T:TA	donor_gain	1.0000
19:39031851:T:TA	donor_gain	1.0000
19:39026863:GACT:G	donor_loss	0.9900
19:39026869:CG:C	donor_gain	0.9900
19:39026869:CGT:C	donor_gain	0.9900
19:39027002:CCAC:C	acceptor_gain	0.9900
19:39027003:CAC:C	acceptor_gain	0.9900
19:39027003:CACC:C	acceptor_gain	0.9900
19:39027003:CACCT:C	acceptor_loss	0.9900
19:39027004:ACC:A	acceptor_loss	0.9900
19:39027005:CCTGT:C	acceptor_loss	0.9900
19:39027006:CTGTG:C	acceptor_loss	0.9900
19:39027007:T:A	acceptor_loss	0.9900
19:39031318:CTT:C	acceptor_gain	0.9900
19:39031832:AGCAT:A	donor_gain	0.9900
19:39032393:T:TA	donor_gain	0.9900
19:39025551:TGACC:T	acceptor_loss	0.9800

AlphaMissense

1819 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:39031223:G:C	F154L	0.989
19:39031223:G:T	F154L	0.989
19:39031225:A:G	F154L	0.989
19:39031211:G:C	F158L	0.988
19:39031211:G:T	F158L	0.988
19:39031213:A:G	F158L	0.988
19:39031112:C:A	K163N	0.986
19:39031112:C:G	K163N	0.986
19:39025540:G:C	F241L	0.980
19:39025540:G:T	F241L	0.980
19:39025542:A:G	F241L	0.980
19:39031279:A:G	W136R	0.976
19:39031279:A:T	W136R	0.976
19:39031306:A:G	W127R	0.976
19:39031306:A:T	W127R	0.976
19:39026921:G:C	F219L	0.972
19:39026921:G:T	F219L	0.972
19:39026923:A:G	F219L	0.972
19:39031304:C:A	W127C	0.966
19:39031304:C:G	W127C	0.966
19:39031044:A:G	I186T	0.964
19:39032057:C:A	W57C	0.962
19:39032057:C:G	W57C	0.962
19:39025488:C:G	D259H	0.959
19:39031877:G:C	N117K	0.959
19:39031877:G:T	N117K	0.959
19:39025511:A:T	V251E	0.958
19:39025513:A:C	F250L	0.958
19:39025513:A:T	F250L	0.958
19:39025515:A:G	F250L	0.958

dbSNP variants (sampled 300 via entrez): RS1000031369 (19:39021937 A>G), RS1000050828 (19:39021684 A>G), RS1000057116 (19:39020968 C>T), RS1000065194 (19:39033061 CTG>C), RS1000111855 (19:39027346 C>T), RS1000119320 (19:39020432 C>T), RS1000666117 (19:39031761 C>T), RS1000756402 (19:39008630 G>A), RS1000825312 (19:39026159 T>C), RS1000922507 (19:39020158 G>C), RS1001120811 (19:39032000 G>A,T), RS1001126983 (19:39013639 TA>T,TAA), RS1001438501 (19:39020481 G>A), RS1001539400 (19:39021428 G>A), RS1001547886 (19:39014470 T>A,C)

Disease associations

OMIM: gene MIM:609099 | 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

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	2
afuresertib	increases expression	1
aminomethylphosphonic acid (AMPA)	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
zinc chromate	decreases expression, increases abundance	1
chromium hexavalent ion	decreases expression, increases abundance	1
ICG 001	increases expression	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
jinfukang	increases expression	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Air Pollutants	affects methylation, increases abundance	1
Atrazine	decreases expression	1
Catechin	increases expression, affects cotreatment	1
Lead	affects expression	1
Ozone	affects methylation, increases abundance	1
Rotenone	increases expression	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
2,4-Dichlorophenoxyacetic Acid	decreases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Acrylamide	decreases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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