FBXL22

Summary

FBXL22 (F-box and leucine rich repeat protein 22, HGNC:27537) is a protein-coding gene on chromosome 15q22.31, encoding F-box and leucine-rich protein 22 (Q6P050). 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. This F-box protein interacts with S-phase kinase-associated protein 1A and cullin in order to form SCF complexes which function as ubiquitin ligases.

Source: NCBI Gene 283807 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 50 total
• MANE Select transcript: NM_001367807

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27537
Approved symbol	FBXL22
Name	F-box and leucine rich repeat protein 22
Location	15q22.31
Locus type	gene with protein product
Status	Approved
Aliases	Fbl22, FLJ39626
Ensembl gene	ENSG00000197361
Ensembl biotype	protein_coding
OMIM	609088
Entrez	283807

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000360587, ENST00000534939, ENST00000560325, ENST00000638704

RefSeq mRNA: 4 — MANE Select: NM_001367807 NM_001367807, NM_001367808, NM_001367809, NM_203373

CCDS: CCDS10187, CCDS92015, CCDS92016

Canonical transcript exons

ENST00000638704 — 2 exons

Exon	Start	End
ENSE00003803070	63597387	63597745
ENSE00003803500	63600697	63601241

Expression profiles

Bgee: expression breadth ubiquitous, 158 present calls, max score 91.10.

FANTOM5 (CAGE): breadth broad, TPM avg 1.7718 / max 241.6096, expressed in 282 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
147151	1.2057	207
147152	0.3189	109
147150	0.1117	46
147153	0.0848	42
147154	0.0387	22
147155	0.0119	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
muscle layer of sigmoid colon	UBERON:0035805	91.10	gold quality
smooth muscle tissue	UBERON:0001135	90.65	gold quality
body of uterus	UBERON:0009853	90.24	gold quality
right coronary artery	UBERON:0001625	90.18	gold quality
apex of heart	UBERON:0002098	88.46	gold quality
popliteal artery	UBERON:0002250	87.94	gold quality
tibial artery	UBERON:0007610	87.92	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.81	gold quality
left uterine tube	UBERON:0001303	87.02	gold quality
aorta	UBERON:0000947	86.82	gold quality
myometrium	UBERON:0001296	86.33	gold quality
thoracic aorta	UBERON:0001515	85.69	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.59	gold quality
ascending aorta	UBERON:0001496	85.58	gold quality
lower esophagus	UBERON:0013473	85.57	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	85.25	gold quality
descending thoracic aorta	UBERON:0002345	84.44	gold quality
seminal vesicle	UBERON:0000998	83.77	silver quality
left coronary artery	UBERON:0001626	83.63	gold quality
right atrium auricular region	UBERON:0006631	83.35	gold quality
cardiac atrium	UBERON:0002081	82.91	gold quality
coronary artery	UBERON:0001621	82.80	gold quality
heart left ventricle	UBERON:0002084	80.76	gold quality
heart	UBERON:0000948	80.00	gold quality
cardiac ventricle	UBERON:0002082	79.97	gold quality
gall bladder	UBERON:0002110	78.99	gold quality
ectocervix	UBERON:0012249	77.71	gold quality
urinary bladder	UBERON:0001255	77.08	gold quality
endocervix	UBERON:0000458	75.69	gold quality
fundus of stomach	UBERON:0001160	75.52	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.58

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting FBXL22, 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-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-6878-3P	99.24	64.23	920
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-1304-5P	98.90	68.58	1054
HSA-MIR-936	98.87	70.51	1124
HSA-MIR-589-5P	98.72	66.96	927
HSA-MIR-218-1-3P	98.63	67.97	832
HSA-MIR-3188	98.58	65.60	878
HSA-MIR-4773	98.35	67.30	1710

Literature-anchored findings (GeneRIF, showing 1)

• Fbxl22 promotes the proteasome-dependent degradation of sarcomeric proteins and is essential for maintenance of normal contractile function. (PMID:22972877)

Cross-species orthologs

30 orthologs

Organism	Symbol	Gene ID
danio_rerio	fbxl22	ENSDARG00000096995
mus_musculus	Fbxl22	ENSMUSG00000050503
rattus_norvegicus	Fbxl22	ENSRNOG00000017684
drosophila_melanogaster	CG15056	FBGN0030918
drosophila_melanogaster	CG8272	FBGN0033337
drosophila_melanogaster	CG9003	FBGN0033639
drosophila_melanogaster	Skp2	FBGN0037236
drosophila_melanogaster	CG14891	FBGN0038445
drosophila_melanogaster	CG5003	FBGN0039554
drosophila_melanogaster	FipoQ	FBGN0039667
caenorhabditis_elegans		WBGENE00007206
caenorhabditis_elegans		WBGENE00007208
caenorhabditis_elegans		WBGENE00007887
caenorhabditis_elegans		WBGENE00008177
caenorhabditis_elegans		WBGENE00009689
caenorhabditis_elegans	gadr-6	WBGENE00009823
caenorhabditis_elegans		WBGENE00010365
caenorhabditis_elegans	K05C4.9	WBGENE00010585
caenorhabditis_elegans		WBGENE00012655
caenorhabditis_elegans		WBGENE00015350
caenorhabditis_elegans		WBGENE00018561
caenorhabditis_elegans		WBGENE00018613
caenorhabditis_elegans		WBGENE00018766
caenorhabditis_elegans		WBGENE00019239
caenorhabditis_elegans		WBGENE00020884
caenorhabditis_elegans		WBGENE00021053
caenorhabditis_elegans		WBGENE00021180
caenorhabditis_elegans	zeel-1	WBGENE00021463
caenorhabditis_elegans		WBGENE00044459
caenorhabditis_elegans	gadr-5	WBGENE00045058

Paralogs (15): FBXL3 (ENSG00000005812), FBXL19 (ENSG00000099364), FBXL15 (ENSG00000107872), FBXL20 (ENSG00000108306), FBXL4 (ENSG00000112234), FBXL5 (ENSG00000118564), FBXL16 (ENSG00000127585), SKP2 (ENSG00000145604), FBXL17 (ENSG00000145743), FBXL2 (ENSG00000153558), FBXL18 (ENSG00000155034), FBXL13 (ENSG00000161040), FBXL14 (ENSG00000171823), FBXL6 (ENSG00000182325), FBXL7 (ENSG00000183580)

Protein

Protein identifiers

F-box and leucine-rich protein 22 — Q6P050 (reviewed: Q6P050)

All UniProt accessions (4): A0A1W2PQW8, H0YMQ4, Q6P050, R4GNI3

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Promotes ubiquitination of sarcomeric proteins alpha-actinin-2 (ACTN2) and filamin-C (FLNC).

Subunit / interactions. Directly interacts with SKP1 and CUL1.

Subcellular location. Cytoplasm. Myofibril. Sarcomere. Z line.

Tissue specificity. Enriched in cardiac muscle.

Pathway. Protein modification; protein ubiquitination.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6P050-1	1	yes
Q6P050-2	2

RefSeq proteins (4): NP_001354736, NP_001354737, NP_001354738, NP_976307 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001810	F-box_dom	Domain
IPR036047	F-box-like_dom_sf	Homologous_superfamily

Pfam: PF12937

UniProt features (12 total): repeat 6, chain 1, domain 1, splice variant 1, sequence variant 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P050-F1	60.74	0.02

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: 77 (showing top): FREAC2_01, HNF3ALPHA_Q6, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, RORA1_01, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, TGACCTY_ERR1_Q2, MEF2_02, SRF_C, FOXJ2_01, HFH3_01, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, TATA_C, GOBP_SCF_DEPENDENT_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS

GO Biological Process (2): protein ubiquitination (GO:0016567), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161)

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

GO Cellular Component (5): nucleolus (GO:0005730), cytosol (GO:0005829), Z disc (GO:0030018), cytoplasm (GO:0005737), 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	3
protein modification by small protein conjugation	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
nuclear lumen	1
intracellular membraneless organelle	1
cytoplasm	1
I band	1
intracellular anatomical structure	1
cullin-RING ubiquitin ligase complex	1

Protein interactions and networks

STRING

606 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FBXL22	SKP1	P34991	813
FBXL22	CUL1	Q13616	808
FBXL22	FBXL8	Q96CD0	547
FBXL22	Q8WV35	Q8WV35	541
FBXL22	FBXL13	Q8NEE6	507
FBXL22	FBXO2	Q9UK22	488
FBXL22	FBXL7	Q9UJT9	460
FBXL22	FBXO32	Q969P5	459
FBXL22	FBXL15	Q9H469	454
FBXL22	KLHL25	Q9H0H3	438
FBXL22	FBXO48	Q5FWF7	438
FBXL22	FBXW10	Q5XX13	431
FBXL22	FBXL14	Q8N1E6	430
FBXL22	CCNF	P41002	425
FBXL22	FBXO11	Q86XK2	422
FBXL22	KLHL21	Q9UJP4	422

IntAct

14 interactions, top by confidence:

A	B	Type	Score
SKP1	FBXL22	psi-mi:“MI:0915”(physical association)	0.770
FBXL22	SKP1	psi-mi:“MI:0915”(physical association)	0.770
FBXL22	SKP1	psi-mi:“MI:0914”(association)	0.770
FBXL22	ACTN2	psi-mi:“MI:0915”(physical association)	0.510
FBXL22	FLNC	psi-mi:“MI:0915”(physical association)	0.510
FBXL22	GNAO1	psi-mi:“MI:0914”(association)	0.350

BioGRID (18): FBXL22 (Two-hybrid), SKP1 (Affinity Capture-MS), BLK (Affinity Capture-MS), SRC (Affinity Capture-MS), CTDSP1 (Affinity Capture-MS), GNAO1 (Affinity Capture-MS), USP22 (Affinity Capture-MS), NCS1 (Affinity Capture-MS), EEF1A2 (Affinity Capture-MS), CLTCL1 (Affinity Capture-MS), SKP1 (Two-hybrid), ACTN2 (Two-hybrid), FLNC (Two-hybrid), SKP1 (Affinity Capture-Western), CUL1 (Affinity Capture-Western)

ESM2 similar proteins: A0A5N6H279, A4D2B8, D3ZML2, O76081, O91531, P03327, P0C678, P0C733, P79348, Q00731, Q09PK2, Q13670, Q1HVB5, Q1ZZU3, Q4KL35, Q4R1S1, Q52993, Q5JLA7, Q5JN07, Q5MFW3, Q63553, Q64902, Q6DN03, Q6NUI1, Q6P050, Q6SW81, Q86UQ5, Q8AZJ3, Q8BG31, Q8BVZ5, Q8CE90, Q8CEZ0, Q8K3M5, Q8LN49, Q8N5Z5, Q8TE04, Q8VDU5, Q8WTX9, Q8WXT5, Q9BTV7

Diamond homologs: Q2HJF2, Q6P050, Q8C7B6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

503 predictions. Top by Δscore:

Variant	Effect	Δscore
15:63597743:CAG:C	donor_loss	1.0000
15:63597744:AG:A	donor_loss	1.0000
15:63597745:GGTAG:G	donor_loss	1.0000
15:63597746:G:GA	donor_loss	1.0000
15:63597747:T:A	donor_loss	1.0000
15:63597715:TC:T	donor_gain	0.9800
15:63597746:G:GG	donor_gain	0.9700
15:63597741:GACAG:G	donor_gain	0.9600
15:63600691:TCACA:T	acceptor_loss	0.9600
15:63600692:CACA:C	acceptor_loss	0.9600
15:63600694:CAG:C	acceptor_loss	0.9600
15:63597716:C:A	donor_gain	0.9500
15:63600261:C:G	acceptor_gain	0.9500
15:63600269:C:A	acceptor_gain	0.9300
15:63600695:A:AG	acceptor_gain	0.9300
15:63600696:G:GG	acceptor_gain	0.9300
15:63600696:GGT:G	acceptor_gain	0.8700
15:63600695:AG:A	acceptor_gain	0.8600
15:63600696:GG:G	acceptor_gain	0.8600
15:63600895:C:G	donor_gain	0.8600
15:63600261:C:CA	acceptor_gain	0.8500
15:63597718:A:G	donor_gain	0.8300
15:63599246:TCGG:T	donor_gain	0.8100
15:63597647:GTGC:G	donor_gain	0.8000
15:63599247:C:A	donor_gain	0.8000
15:63600270:G:A	acceptor_gain	0.8000
15:63600696:GGTGC:G	acceptor_gain	0.8000
15:63597738:T:A	donor_gain	0.7800
15:63599519:T:G	donor_gain	0.7800
15:63600260:A:AG	acceptor_gain	0.7700

AlphaMissense

1499 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:63597459:T:C	F23L	0.998
15:63597461:C:A	F23L	0.998
15:63597461:C:G	F23L	0.998
15:63597552:T:C	F54L	0.998
15:63597554:C:A	F54L	0.998
15:63597554:C:G	F54L	0.998
15:63597553:T:C	F54S	0.997
15:63597585:T:C	F65L	0.997
15:63597587:C:A	F65L	0.997
15:63597587:C:G	F65L	0.997
15:63597453:T:C	F21L	0.996
15:63597455:C:A	F21L	0.996
15:63597455:C:G	F21L	0.996
15:63597479:G:C	R29S	0.996
15:63597479:G:T	R29S	0.996
15:63597586:T:C	F65S	0.996
15:63597619:T:A	I76N	0.996
15:63597624:T:A	W78R	0.996
15:63597624:T:C	W78R	0.996
15:63597626:G:C	W78C	0.996
15:63597626:G:T	W78C	0.996
15:63597519:T:C	F43L	0.995
15:63597521:T:A	F43L	0.995
15:63597521:T:G	F43L	0.995
15:63597537:T:A	W49R	0.995
15:63597537:T:C	W49R	0.995
15:63597671:G:C	K93N	0.995
15:63597671:G:T	K93N	0.995
15:63597442:T:C	L17P	0.994
15:63597451:T:C	L20P	0.994

dbSNP variants (sampled 300 via entrez): RS1000069419 (15:63602675 G>C), RS1000312275 (15:63597993 G>C), RS1000695375 (15:63608160 A>G), RS1000861474 (15:63604224 G>C,T), RS1001126449 (15:63596444 C>T), RS1001200341 (15:63598626 A>T), RS1001212302 (15:63607947 C>T), RS1001355836 (15:63603572 G>A), RS1001584674 (15:63600304 G>A), RS1001823717 (15:63606711 G>C), RS1002362059 (15:63605041 G>A,C), RS1002373984 (15:63599672 C>G,T), RS1002587627 (15:63598828 A>G), RS1002641998 (15:63599197 G>A), RS1002660447 (15:63605577 C>T)

Disease associations

OMIM: gene MIM:609088 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007656_8	Chronic obstructive pulmonary disease or resting heart rate (pleiotropy)	1.000000e-12
GCST010146_33	Serum immune biomarker levels	4.000000e-15

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004869	YKL40 measurement
EFO:0004872	inflammatory biomarker measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	increases methylation	2
triphenyl phosphate	decreases expression	1
butyraldehyde	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Sunitinib	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Doxorubicin	affects expression	1
Ozone	affects expression, increases abundance	1
Dronabinol	increases expression	1
Triclosan	decreases expression	1

Clinical trials (associated diseases)

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