FBXO36

Summary

FBXO36 (F-box protein 36, HGNC:27020) is a protein-coding gene on chromosome 2q36.3, encoding F-box only protein 36 (Q8NEA4). 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 FBXO36, 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 130888 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 52 total — 5 pathogenic
• MANE Select transcript: NM_174899

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27020
Approved symbol	FBXO36
Name	F-box protein 36
Location	2q36.3
Locus type	gene with protein product
Status	Approved
Aliases	Fbx36, FLJ37592
Ensembl gene	ENSG00000153832
Ensembl biotype	protein_coding
OMIM	609105
Entrez	130888

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000283946, ENST00000373652, ENST00000409992, ENST00000465090, ENST00000943498

RefSeq mRNA: 1 — MANE Select: NM_174899 NM_174899

CCDS: CCDS2472

Canonical transcript exons

ENST00000283946 — 4 exons

Exon	Start	End
ENSE00001012617	229996751	229996923
ENSE00001183403	229976241	229976349
ENSE00001929778	229922503	229922609
ENSE00003844308	230010696	230013119

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 83.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.0107 / max 73.4486, expressed in 1602 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
25804	4.4850	1516
25803	1.5257	945

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	83.93	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	83.88	gold quality
bronchial epithelial cell	CL:0002328	83.10	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.16	gold quality
bronchus	UBERON:0002185	81.19	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.80	gold quality
right uterine tube	UBERON:0001302	79.72	gold quality
ventricular zone	UBERON:0003053	78.09	gold quality
mucosa of paranasal sinus	UBERON:0005030	74.61	silver quality
stromal cell of endometrium	CL:0002255	74.52	gold quality
islet of Langerhans	UBERON:0000006	73.45	gold quality
right adrenal gland cortex	UBERON:0035827	72.70	gold quality
right adrenal gland	UBERON:0001233	72.31	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	72.21	gold quality
left adrenal gland	UBERON:0001234	71.97	gold quality
cortical plate	UBERON:0005343	71.94	gold quality
left adrenal gland cortex	UBERON:0035825	71.73	gold quality
prefrontal cortex	UBERON:0000451	71.69	gold quality
adrenal tissue	UBERON:0018303	71.19	gold quality
ganglionic eminence	UBERON:0004023	71.09	gold quality
testis	UBERON:0000473	70.58	gold quality
caput epididymis	UBERON:0004358	70.49	gold quality
fallopian tube	UBERON:0003889	70.35	gold quality
adrenal gland	UBERON:0002369	70.27	gold quality
adult organism	UBERON:0007023	70.14	gold quality
left testis	UBERON:0004533	69.93	gold quality
adrenal cortex	UBERON:0001235	69.73	gold quality
Brodmann (1909) area 9	UBERON:0013540	69.42	gold quality
caudate nucleus	UBERON:0001873	69.39	gold quality
hypothalamus	UBERON:0001898	69.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.17

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

78 targeting FBXO36, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-2681-5P	99.75	67.64	1655

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	fbxo36a	ENSDARG00000010662
danio_rerio	fbxo36b	ENSDARG00000039152
mus_musculus	Fbxo36	ENSMUSG00000073633
rattus_norvegicus	Fbxo36	ENSRNOG00000017053

Paralogs (14): WDR54 (ENSG00000005448), FBXW11 (ENSG00000072803), FBXW7 (ENSG00000109670), TRAF7 (ENSG00000131653), FBXW9 (ENSG00000132004), WDR64 (ENSG00000162843), FBXW12 (ENSG00000164049), BTRC (ENSG00000166167), WDR49 (ENSG00000174776), FBXW8 (ENSG00000174989), PAAF1 (ENSG00000175575), WDR86 (ENSG00000187260), FBXO16 (ENSG00000214050), EFCAB8 (ENSG00000215529)

Protein

Protein identifiers

F-box only protein 36 — Q8NEA4 (reviewed: Q8NEA4)

All UniProt accessions (2): Q8NEA4, B8ZZQ1

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.

Subunit / interactions. Directly interacts with SKP1 and CUL1.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NEA4-1	1	yes
Q8NEA4-3	2

RefSeq proteins (1): NP_777559* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001810	F-box_dom	Domain
IPR036047	F-box-like_dom_sf	Homologous_superfamily
IPR052301	SCF_F-box/WD-repeat	Family

Pfam: PF12937

UniProt features (4 total): chain 1, domain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NEA4-F1	89.64	0.63

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 113 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, RNGTGGGC_UNKNOWN, PAX4_01, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, TCF11_01, HFH4_01, TGACATY_UNKNOWN, TATA_C, GOBP_SCF_DEPENDENT_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, VDR_Q3, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, NERF_Q2, GOBP_PROTEIN_CATABOLIC_PROCESS

GO Biological Process (0):

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

464 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FBXO36	SKP1	P34991	607
FBXO36	CUL1	Q13616	605
FBXO36	TEX44	Q53QW1	568
FBXO36	TRIP12	Q14669	541
FBXO36	SPATS1	Q496A3	493
FBXO36	BBOF1	Q8ND07	485
FBXO36	MROH2A	A6NES4	477
FBXO36	FBXO34	Q9NWN3	475
FBXO36	MOSPD1	Q9UJG1	434
FBXO36	PIH1D2	Q8WWB5	429
FBXO36	DNAJC25	Q9H1X3	428
FBXO36	TSPYL6	Q8N831	380
FBXO36	NBL1	P41271	377
FBXO36	SPATA3	Q8NHX4	376
FBXO36	PSMG4	Q5JS54	369

IntAct

3 interactions, top by confidence:

A	B	Type	Score
SKP1	MYCBP2	psi-mi:“MI:0914”(association)	0.640
SKP1	BHLHE40	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): FBXO36 (Synthetic Lethality), SKP1 (Affinity Capture-Western), FBXO36 (Affinity Capture-MS), FBXO36 (Co-fractionation), FBXO36 (Affinity Capture-MS)

ESM2 similar proteins: A1A5Q7, A4D126, A4II32, A6NCI4, A8K8P3, A8MTL0, A8MYZ5, A9CB34, E0CYC6, F1QWK4, O14772, O15554, O89109, P0C7M6, P0C8N6, Q05AA6, Q08CB3, Q13474, Q1HAQ0, Q1LWG4, Q2M2U5, Q32KU4, Q3SYS7, Q3TFD2, Q3UVV9, Q4AC99, Q5I0I4, Q5R796, Q5RFS1, Q8BHD4, Q8BP00, Q8BPW0, Q8CB65, Q8CHT6, Q8IXL9, Q8K2I9, Q8N0W5, Q8N6M8, Q8NEA4, Q8NF37

Diamond homologs: Q5R796, Q8NEA4, Q9CQ24

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	35
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1340890	GRCh37/hg19 2q36.3(chr2:230689315-230810845)x1	Pathogenic
59174	GRCh38/hg38 2q36.3(chr2:229308268-229952405)x3	Pathogenic
686021	GRCh37/hg19 2q36.3(chr2:230622100-230870340)x1	Pathogenic
688541	GRCh37/hg19 2q36.3(chr2:230769636-230792670)x1	Pathogenic
816580	GRCh37/hg19 2q36.3(chr2:230626876-230887430)x1	Pathogenic

SpliceAI

1388 predictions. Top by Δscore:

Variant	Effect	Δscore
2:229976233:A:AG	acceptor_gain	1.0000
2:229976234:A:G	acceptor_gain	1.0000
2:229976239:A:AG	acceptor_gain	1.0000
2:229976239:AG:A	acceptor_gain	1.0000
2:229976240:G:GC	acceptor_gain	1.0000
2:229976240:GG:G	acceptor_gain	1.0000
2:229976240:GGT:G	acceptor_gain	1.0000
2:229976240:GGTA:G	acceptor_gain	1.0000
2:229976240:GGTAA:G	acceptor_gain	1.0000
2:229976346:CAAGG:C	donor_loss	1.0000
2:229976348:AG:A	donor_gain	1.0000
2:229976348:AGGTA:A	donor_loss	1.0000
2:229976349:GG:G	donor_gain	1.0000
2:229976350:G:GG	donor_gain	1.0000
2:229976350:GT:G	donor_loss	1.0000
2:229996745:TTACA:T	acceptor_loss	1.0000
2:229996746:TACAG:T	acceptor_loss	1.0000
2:229996747:ACAG:A	acceptor_loss	1.0000
2:229996748:CAGGT:C	acceptor_loss	1.0000
2:229996749:A:AG	acceptor_gain	1.0000
2:229996749:A:T	acceptor_loss	1.0000
2:229996750:G:GA	acceptor_gain	1.0000
2:229996919:CAAAG:C	donor_loss	1.0000
2:229996920:AAAG:A	donor_loss	1.0000
2:229996922:AGGTA:A	donor_loss	1.0000
2:229996925:T:G	donor_loss	1.0000
2:230010695:GCT:G	acceptor_gain	1.0000
2:230010695:GCTGT:G	acceptor_gain	1.0000
2:229976230:T:G	acceptor_gain	0.9900
2:229976237:A:AG	acceptor_gain	0.9900

AlphaMissense

1215 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:229976256:T:A	W38R	0.992
2:229976256:T:C	W38R	0.992
2:230010789:T:A	W158R	0.989
2:230010789:T:C	W158R	0.989
2:230010717:T:A	W134R	0.987
2:230010717:T:C	W134R	0.987
2:229976258:G:C	W38C	0.983
2:229976258:G:T	W38C	0.983
2:230010719:G:C	W134C	0.983
2:230010719:G:T	W134C	0.983
2:230010791:G:C	W158C	0.981
2:230010791:G:T	W158C	0.981
2:229922596:T:A	V28D	0.977
2:229976257:G:C	W38S	0.976
2:229976263:T:G	I40S	0.971
2:229922576:A:C	K21N	0.970
2:229922576:A:T	K21N	0.970
2:229922590:T:C	L26S	0.969
2:229976263:T:C	I40T	0.968
2:229922577:G:C	D22H	0.965
2:229996895:T:C	L117P	0.963
2:230010718:G:C	W134S	0.963
2:229922575:A:T	K21I	0.962
2:229922579:C:A	D22E	0.962
2:229922579:C:G	D22E	0.962
2:229976273:G:C	R43S	0.961
2:229976273:G:T	R43S	0.961
2:229976257:G:T	W38L	0.959
2:229922559:G:C	G16R	0.957
2:229922583:T:G	Y24D	0.957

dbSNP variants (sampled 300 via entrez): RS1000003438 (2:229962896 C>G), RS1000017238 (2:229922449 C>T), RS1000018466 (2:229930884 T>A), RS1000053425 (2:229971179 C>G), RS1000082030 (2:230007270 C>T), RS1000117022 (2:229973357 A>G), RS1000129906 (2:229922248 T>A,C), RS1000188954 (2:229989553 G>A), RS1000201375 (2:229946265 C>T), RS1000256106 (2:229946878 G>A), RS1000267584 (2:229940355 A>G), RS1000284466 (2:229977131 A>G,T), RS1000297900 (2:229991475 C>A), RS1000309613 (2:230004511 C>G), RS1000324022 (2:229982932 C>T)

Disease associations

OMIM: gene MIM:609105 | 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
GCST005860_3	Cholangiocarcinoma in primary sclerosing cholangitis (time to event)	1.000000e-06
GCST010988_129	Adult body size	7.000000e-13

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects expression, affects cotreatment, decreases expression, increases abundance	3
Acetaminophen	decreases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, increases expression	2
sotorasib	affects cotreatment, decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
resorcinol	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
bisphenol S	decreases methylation	1
jinfukang	increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Vorinostat	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	decreases expression	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Silicon Dioxide	decreases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases expression	1
Aflatoxin B1	decreases expression	1

Clinical trials (associated diseases)

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