FBXL13

Summary

FBXL13 (F-box and leucine rich repeat protein 13, HGNC:21658) is a protein-coding gene on chromosome 7q22.1, encoding F-box and leucine-rich repeat protein 13 (Q8NEE6). 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 FBXL13, 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 222235 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 162 total
• MANE Select transcript: NM_001394494

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21658
Approved symbol	FBXL13
Name	F-box and leucine rich repeat protein 13
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC21636, Fbl13, DRC6, CFAP169
Ensembl gene	ENSG00000161040
Ensembl biotype	protein_coding
OMIM	609080
Entrez	222235

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 6 nonsense_mediated_decay, 5 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000313221, ENST00000379305, ENST00000436908, ENST00000440067, ENST00000448002, ENST00000455112, ENST00000456695, ENST00000468216, ENST00000471074, ENST00000477915, ENST00000480422, ENST00000694870, ENST00000694871, ENST00000965689

RefSeq mRNA: 4 — MANE Select: NM_001394494 NM_001111038, NM_001287150, NM_001394494, NM_145032

CCDS: CCDS5726, CCDS94164

Canonical transcript exons

ENST00000440067 — 21 exons

Exon	Start	End
ENSE00001132796	102877467	102877593
ENSE00001132800	102878331	102878450
ENSE00001480493	103055088	103055178
ENSE00001613129	102832840	102832974
ENSE00001623646	103028600	103028748
ENSE00001671783	103074696	103074796
ENSE00001759645	103025063	103025230
ENSE00002157469	102854777	102854860
ENSE00003541269	102931881	102931933
ENSE00003557605	102913086	102913215
ENSE00003558093	102884214	102884312
ENSE00003579136	103027449	103027558
ENSE00003581462	102822040	102822203
ENSE00003638684	102963533	102963665
ENSE00003660759	103055644	103055747
ENSE00003755257	103029351	103029418
ENSE00003961105	102811189	102813531
ENSE00003963346	102883568	102883685
ENSE00003963348	102883305	102883467
ENSE00003963365	102968022	102968117
ENSE00003963369	102926274	102926374

Expression profiles

Bgee: expression breadth ubiquitous, 170 present calls, max score 97.36.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2421 / max 105.6757, expressed in 365 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85360	0.4638	108
85362	0.3477	150
85361	0.2689	85
85363	0.1616	70

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	97.36	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.34	gold quality
right testis	UBERON:0004534	85.52	gold quality
left testis	UBERON:0004533	85.07	gold quality
testis	UBERON:0000473	83.52	gold quality
bronchial epithelial cell	CL:0002328	77.97	gold quality
secondary oocyte	CL:0000655	77.73	gold quality
right uterine tube	UBERON:0001302	77.33	gold quality
calcaneal tendon	UBERON:0003701	76.70	gold quality
bronchus	UBERON:0002185	76.29	gold quality
adrenal tissue	UBERON:0018303	74.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	73.92	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	72.55	gold quality
blood	UBERON:0000178	72.46	gold quality
stomach	UBERON:0000945	72.42	gold quality
body of stomach	UBERON:0001161	71.87	gold quality
right adrenal gland cortex	UBERON:0035827	70.06	gold quality
fallopian tube	UBERON:0003889	69.90	gold quality
fundus of stomach	UBERON:0001160	69.47	gold quality
cardia of stomach	UBERON:0001162	69.18	gold quality
right adrenal gland	UBERON:0001233	69.14	gold quality
oviduct epithelium	UBERON:0004804	69.03	gold quality
left ovary	UBERON:0002119	68.56	gold quality
left adrenal gland	UBERON:0001234	68.16	gold quality
adrenal gland	UBERON:0002369	67.28	gold quality
right ovary	UBERON:0002118	67.23	gold quality
left adrenal gland cortex	UBERON:0035825	66.66	gold quality
ventricular zone	UBERON:0003053	65.75	gold quality
corpus callosum	UBERON:0002336	65.70	gold quality
right coronary artery	UBERON:0001625	65.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.95

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting FBXL13, 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-4531	99.99	69.70	3181
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-4662B	98.33	66.37	1163
HSA-MIR-4647	98.30	66.41	1139
HSA-MIR-5691	98.23	67.02	1335
HSA-MIR-10395-3P	98.10	66.70	1726
HSA-MIR-3159	97.94	66.79	1098
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-4703-3P	96.68	68.61	545

Cross-species orthologs

30 orthologs

Organism	Symbol	Gene ID
danio_rerio	fbxl13	ENSDARG00000076191
mus_musculus	Fbxl13	ENSMUSG00000048520
rattus_norvegicus	Fbxl13	ENSRNOG00000043035
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), FBXL14 (ENSG00000171823), FBXL6 (ENSG00000182325), FBXL7 (ENSG00000183580), FBXL22 (ENSG00000197361)

Protein

Protein identifiers

F-box and leucine-rich repeat protein 13 — Q8NEE6 (reviewed: Q8NEE6)

Alternative names: Dynein regulatory complex subunit 6, F-box/LRR-repeat protein 13

All UniProt accessions (8): Q8NEE6, A0A8Q3WK56, A0A8Q3WK79, A0A8Q3WKA2, A0A8Q3WLA0, A0A8V8NC12, C9JI88, E7ERH8

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes. Specifically targets CEP192 isoform 3 for ubiquitin-mediated proteolysis and thereby acts as a regulator of microtubule nucleation activity.

Subunit / interactions. Component of the nexin-dynein regulatory complex (N-DRC). Directly interacts with SKP1 and CUL1. Interacts with DRC5.

Subcellular location. Cytoplasm. Cytoskeleton. Flagellum axoneme. Microtubule organizing center. Centrosome.

Similarity. Belongs to the DRC6 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8NEE6-1	1	yes
Q8NEE6-2	2
Q8NEE6-3	3
Q8NEE6-4	4

RefSeq proteins (4): NP_001104508, NP_001274079, NP_001381423, NP_659469 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001810	F-box_dom	Domain
IPR006553	Leu-rich_rpt_Cys-con_subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR036047	F-box-like_dom_sf	Homologous_superfamily
IPR057207	FBXL15_LRR	Domain

Pfam: PF12937, PF25372

UniProt features (33 total): repeat 17, sequence variant 5, sequence conflict 4, splice variant 3, chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NEE6-F1	88.67	0.73

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: 93 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_CILIUM_MOVEMENT, GOBP_REGULATION_OF_CELL_CYCLE, GOCC_CENTROSOME, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_REGULATION_OF_CENTROSOME_CYCLE, GOBP_SCF_DEPENDENT_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOBP_REGULATION_OF_CELL_CYCLE_PROCESS

GO Biological Process (1): SCF-dependent proteasomal ubiquitin-dependent protein catabolic process (GO:0031146)

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

GO Cellular Component (8): centrosome (GO:0005813), cytosol (GO:0005829), SCF ubiquitin ligase complex (GO:0019005), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), motile cilium (GO:0031514), cell projection (GO:0042995)

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
proteasome-mediated ubiquitin-dependent protein catabolic process	1
binding	1
centriole	1
microtubule organizing center	1
cytoplasm	1
cullin-RING ubiquitin ligase complex	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1

Protein interactions and networks

STRING

904 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FBXL13	CUL1	Q13616	800
FBXL13	SKP1	P34991	798
FBXL13	CETN2	P41208	766
FBXL13	DRC3	Q9H069	713
FBXL13	CEP152	O94986	701
FBXL13	CETN3	O15182	680
FBXL13	DRC5	Q5JU00	670
FBXL13	FBXL3	Q9UKT7	662
FBXL13	DRC7	Q8IY82	639
FBXL13	DRC4	O95995	611
FBXL13	DRC9	Q9H095	594
FBXL13	LRRC17	Q8N6Y2	572
FBXL13	AK5	Q9Y6K8	560
FBXL13	FAM185A	Q8N0U4	532
FBXL13	CATIP	Q7Z7H3	520

IntAct

6 interactions, top by confidence:

A	B	Type	Score
FBXL13	TOP2A	psi-mi:“MI:0915”(physical association)	0.400
FBXL13	CETN2	psi-mi:“MI:0915”(physical association)	0.400
FBXL13	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
M		psi-mi:“MI:0914”(association)	0.350
AGO1	PRMT5	psi-mi:“MI:0914”(association)	0.350

BioGRID (45): CETN2 (Affinity Capture-MS), CETN2 (Affinity Capture-MS), CETN3 (Affinity Capture-MS), SNX2 (Affinity Capture-MS), PPP6R1 (Affinity Capture-MS), AGTPBP1 (Affinity Capture-MS), CEP152 (Affinity Capture-MS), RAPGEF4 (Affinity Capture-MS), NACA (Affinity Capture-MS), BRCA2 (Affinity Capture-MS), CIART (Affinity Capture-MS), LONRF1 (Affinity Capture-MS), SACS (Affinity Capture-MS), UFSP1 (Affinity Capture-MS), IL16 (Affinity Capture-MS)

ESM2 similar proteins: A4IHG1, A5PK13, A6QLV3, A7SFP1, A8XWW4, B0W6M9, B3LWU3, B3P3E8, B4IBI9, B4JTV9, B4LXW1, B4N9T4, B4PU77, B4QVR7, B5DX45, B9F655, O35125, O88520, Q1L8Y7, Q22875, Q32NT4, Q498T9, Q4H4B6, Q4R3P6, Q4V8I7, Q5F4C4, Q5M8G4, Q5RAV5, Q5RFE9, Q5U308, Q6AYI5, Q6DHL5, Q6GPJ5, Q6INV3, Q7KRY7, Q7L1W4, Q7SXW3, Q80VQ1, Q80WG5, Q8AVI4

Diamond homologs: Q8CDU4, Q8NEE6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
FBXL13	“form complex”	“Nexin-dynein regulatory complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	131
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4786 predictions. Top by Δscore:

Variant	Effect	Δscore
7:102816230:T:A	donor_gain	1.0000
7:102822038:A:AC	donor_gain	1.0000
7:102822039:C:CC	donor_gain	1.0000
7:102877461:TTTTA:T	donor_loss	1.0000
7:102877462:TTTAC:T	donor_loss	1.0000
7:102877463:TTACC:T	donor_loss	1.0000
7:102877464:TACC:T	donor_loss	1.0000
7:102877465:A:G	donor_loss	1.0000
7:102877466:CCTCA:C	donor_loss	1.0000
7:102877591:CAG:C	acceptor_gain	1.0000
7:102878330:CCG:C	donor_gain	1.0000
7:102878364:AG:A	donor_gain	1.0000
7:102878365:G:C	donor_gain	1.0000
7:102878397:AT:A	donor_gain	1.0000
7:102878446:CAATT:C	acceptor_gain	1.0000
7:102878448:ATT:A	acceptor_gain	1.0000
7:102878448:ATTCT:A	acceptor_loss	1.0000
7:102878449:TT:T	acceptor_gain	1.0000
7:102878450:TCTGT:T	acceptor_loss	1.0000
7:102878451:C:CC	acceptor_gain	1.0000
7:102878451:CTGT:C	acceptor_loss	1.0000
7:102878452:T:A	acceptor_loss	1.0000
7:102884201:C:A	donor_gain	1.0000
7:102884212:A:AC	donor_gain	1.0000
7:102884213:C:CC	donor_gain	1.0000
7:102884327:G:GC	acceptor_gain	1.0000
7:102913213:TGC:T	acceptor_gain	1.0000
7:102913216:C:CC	acceptor_gain	1.0000
7:102926372:ATCC:A	acceptor_loss	1.0000
7:102926373:TC:T	acceptor_gain	1.0000

AlphaMissense

1394 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:103027496:A:G	W94R	0.963
7:103027496:A:T	W94R	0.963
7:103029394:C:G	A9P	0.956
7:103029383:A:C	F12L	0.949
7:103029383:A:T	F12L	0.949
7:103029385:A:G	F12L	0.949
7:103028744:A:G	W25R	0.944
7:103028744:A:T	W25R	0.944
7:103029393:G:T	A9D	0.931
7:103027494:C:A	W94C	0.926
7:103027494:C:G	W94C	0.926
7:103028639:A:G	W60R	0.915
7:103028639:A:T	W60R	0.915
7:103027492:C:G	R95P	0.914
7:103028687:C:G	A44P	0.899
7:103027495:C:G	W94S	0.896
7:103028742:C:A	W25C	0.885
7:103028742:C:G	W25C	0.885
7:103029353:A:C	F22L	0.879
7:103029353:A:T	F22L	0.879
7:103029355:A:G	F22L	0.879
7:103027484:C:G	A98P	0.869
7:103027504:A:G	L91P	0.862
7:103029395:T:A	K8N	0.859
7:103029395:T:G	K8N	0.859
7:103029401:C:A	M6I	0.832
7:103029401:C:G	M6I	0.832
7:103029401:C:T	M6I	0.832
7:103028637:C:A	W60C	0.825
7:103028637:C:G	W60C	0.825

dbSNP variants (sampled 300 via entrez): RS1000005866 (7:102879144 T>C,G), RS1000007686 (7:102922871 A>G), RS1000044793 (7:103016059 C>T), RS1000046218 (7:102903600 G>A), RS1000065122 (7:103032453 A>G,T), RS1000067206 (7:102816734 C>T), RS1000077325 (7:103015760 G>A), RS1000090733 (7:102970502 T>C), RS1000096810 (7:102903381 C>T), RS1000098600 (7:102878840 A>G), RS1000145710 (7:102837730 A>G), RS1000148890 (7:103053214 G>A), RS1000152977 (7:102948589 A>C), RS1000153446 (7:103022340 G>A,C,T), RS1000156138 (7:102967492 C>T)

Disease associations

OMIM: gene MIM:609080 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST002247_1	Blood pressure measurement (cold pressor test)	4.000000e-09
GCST002247_2	Blood pressure measurement (cold pressor test)	3.000000e-06
GCST002247_6	Blood pressure measurement (cold pressor test)	1.000000e-06
GCST003429_6	Morning vs. evening chronotype	6.000000e-09
GCST003453_10	Chronotype	5.000000e-10
GCST003454_8	Morning vs. evening chronotype	4.000000e-07
GCST007565_120	Morning person	1.000000e-13
GCST007565_192	Morning person	4.000000e-24
GCST007576_429	Chronotype	2.000000e-06
GCST007576_430	Chronotype	2.000000e-19
GCST007576_431	Chronotype	2.000000e-12
GCST007600_27	Alzheimer’s disease	2.000000e-06
GCST009379_71	Type 2 diabetes	2.000000e-06
GCST009379_72	Type 2 diabetes	1.000000e-08

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0005404	response to cold pressor test
EFO:0006340	mean arterial pressure
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
entinostat	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Panobinostat	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Caffeine	decreases phosphorylation	1
Estradiol	affects cotreatment, increases expression	1
Nickel	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
Valproic Acid	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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