FBH1

Summary

FBH1 (F-box DNA helicase 1, HGNC:13620) is a protein-coding gene on chromosome 10p15.1, encoding F-box DNA helicase 1 (Q8NFZ0). 3’-5’ DNA helicase and substrate-recognition component of the SCF(FBH1) E3 ubiquitin ligase complex that plays a key role in response to stalled/damaged replication forks.

This gene encodes a member of the F-box protein family, members of which are characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into three 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 Fbx class. It contains an F-box motif and seven conserved helicase motifs, and has both DNA-dependent ATPase and DNA unwinding activities. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene.

Source: NCBI Gene 84893 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 192 total
• MANE Select transcript: NM_178150

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13620
Approved symbol	FBH1
Name	F-box DNA helicase 1
Location	10p15.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14590, Fbx18
Ensembl gene	ENSG00000134452
Ensembl biotype	protein_coding
OMIM	607222
Entrez	84893

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 15 protein_coding, 13 protein_coding_CDS_not_defined

ENST00000362091, ENST00000379999, ENST00000397269, ENST00000460453, ENST00000461504, ENST00000462507, ENST00000469009, ENST00000470089, ENST00000470353, ENST00000475867, ENST00000479433, ENST00000481029, ENST00000485290, ENST00000489042, ENST00000494526, ENST00000496013, ENST00000908864, ENST00000908865, ENST00000908866, ENST00000908867, ENST00000908868, ENST00000914586, ENST00000951953, ENST00000951954, ENST00000951955, ENST00000951956, ENST00000951957, ENST00000951958

RefSeq mRNA: 4 — MANE Select: NM_178150 NM_001258452, NM_001258453, NM_032807, NM_178150

CCDS: CCDS7072, CCDS7073, CCDS73064

Canonical transcript exons

ENST00000362091 — 21 exons

Exon	Start	End
ENSE00000915038	5916234	5916456
ENSE00000915040	5917590	5917676
ENSE00001870782	5937110	5937593
ENSE00002725711	5890243	5890346
ENSE00003281305	5921258	5921357
ENSE00003399913	5918342	5918478
ENSE00003414604	5917420	5917507
ENSE00003464302	5914178	5914269
ENSE00003474855	5925367	5925492
ENSE00003488981	5924311	5924508
ENSE00003512461	5923621	5923696
ENSE00003521972	5908925	5909055
ENSE00003559835	5903020	5903175
ENSE00003566621	5921448	5921569
ENSE00003598707	5927435	5927541
ENSE00003647443	5909159	5909294
ENSE00003661667	5906037	5906632
ENSE00003693231	5936456	5936587
ENSE00003720792	5913747	5913839
ENSE00003732893	5910938	5911128
ENSE00003748119	5915403	5915571

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 97.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.1208 / max 71.6892, expressed in 1810 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103658	16.1208	1810

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	97.99	gold quality
adrenal tissue	UBERON:0018303	96.70	gold quality
mucosa of transverse colon	UBERON:0004991	96.69	gold quality
skin of abdomen	UBERON:0001416	96.45	gold quality
right uterine tube	UBERON:0001302	96.40	gold quality
left uterine tube	UBERON:0001303	96.36	gold quality
body of uterus	UBERON:0009853	96.36	gold quality
lower esophagus mucosa	UBERON:0035834	96.33	gold quality
skin of leg	UBERON:0001511	96.31	gold quality
colonic epithelium	UBERON:0000397	96.21	gold quality
ascending aorta	UBERON:0001496	96.01	gold quality
adenohypophysis	UBERON:0002196	95.98	gold quality
thoracic aorta	UBERON:0001515	95.95	gold quality
spleen	UBERON:0002106	95.92	gold quality
endocervix	UBERON:0000458	95.90	gold quality
right atrium auricular region	UBERON:0006631	95.87	gold quality
right adrenal gland cortex	UBERON:0035827	95.86	gold quality
left adrenal gland cortex	UBERON:0035825	95.81	gold quality
right ovary	UBERON:0002118	95.80	gold quality
ectocervix	UBERON:0012249	95.78	gold quality
heart left ventricle	UBERON:0002084	95.76	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.76	gold quality
left ovary	UBERON:0002119	95.71	gold quality
bone marrow cell	CL:0002092	95.70	gold quality
right coronary artery	UBERON:0001625	95.69	gold quality
right adrenal gland	UBERON:0001233	95.66	gold quality
right lung	UBERON:0002167	95.64	gold quality
descending thoracic aorta	UBERON:0002345	95.64	gold quality
right lobe of thyroid gland	UBERON:0001119	95.58	gold quality
transverse colon	UBERON:0001157	95.58	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting FBH1, 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-548N	99.98	71.94	4170
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-374A-3P	98.87	67.82	1531
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-12115	94.19	66.37	738

Literature-anchored findings (GeneRIF, showing 14)

• hFBH1 exhibited DNA-dependent ATPase and DNA unwinding activities that displace duplex DNA in the 3’ to 5’ direction. (PMID:11956208)
• These findings suggest that the hFBH1 helicase is a functional human orthologue of budding yeast Srs2 that also possesses self-regulation properties necessary to execute its recombination functions. (PMID:17724085)
• Data show that the human Fbh1 (hFbh1) helicase accumulates at sites of DNA damage or replication stress in a manner dependent fully on its helicase activity and partially on its conserved F box. (PMID:19736316)
• FBH1 helicase activity is required for the efficient induction of DSBs and apoptosis specifically in response to DNA replication stress. (PMID:23319600)
• FBH1 helicase activity is required to eliminate cells with excessive replication stress through the generation of MUS81-induced DNA double-strand breaks. (PMID:23361013)
• Ubiquitylation affects FBH1 interaction with the RAD51 nucleoprotein filament, but not its translocase and helicase activities. (PMID:23393192)
• FBH1 inactivation appears to contribute to oncogenic transformation by allowing survival of cells undergoing replicative stress due to external factors such as UV irradiation. (PMID:23466708)
• The study reports a mechanism that controls the degradation of FBH1 after DNA damage. (PMID:23677613)
• FBH1 restraining RAD51 DNA binding under unperturbed growth conditions to prevent unwanted or unscheduled DNA recombination. (PMID:24108124)
• FBH1 acts as a negative regulator of RAD51 function in human cells (PMID:25585578)
• study does not provide evidence for the contribution of rare non-synonymous FBXO18 variations to the genetic etiol - ogy of schizophrenia in the Japanese population. (PMID:28317220)
• Report a requirement for PARP2 in stabilizing replication forks that encounter base excision repair (BER) intermediates through Fbh1-dependent regulation of Rad51. Whereas PARP2 is dispensable for tolerance of cells to single stranded breaks or homologous recombination dysfunction, it is redundant with PARP1 in BER. (PMID:29467415)
• Molecular insight into the PCNA-binding mode of FBH1. (PMID:36990095)
• FBH1 deficiency sensitizes cells to WEE1 inhibition by promoting mitotic catastrophe. (PMID:38103522)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fbxo18	ENSDARG00000062983
mus_musculus	Fbh1	ENSMUSG00000058594
rattus_norvegicus	Fbh1	ENSRNOG00000018549

Protein

Protein identifiers

F-box DNA helicase 1 — Q8NFZ0 (reviewed: Q8NFZ0)

Alternative names: DNA 3’-5’ helicase 1, F-box only protein 18

All UniProt accessions (2): Q8NFZ0, F6UZG9

UniProt curated annotations — full annotation on UniProt →

Function. 3’-5’ DNA helicase and substrate-recognition component of the SCF(FBH1) E3 ubiquitin ligase complex that plays a key role in response to stalled/damaged replication forks. Involved in genome maintenance by acting as an anti-recombinogenic helicase and preventing extensive strand exchange during homologous recombination: promotes RAD51 filament dissolution from stalled forks, thereby inhibiting homologous recombination and preventing excessive recombination. Also promotes cell death and DNA double-strand breakage in response to replication stress: together with MUS81, promotes the endonucleolytic DNA cleavage following prolonged replication stress via its helicase activity, possibly to eliminate cells with excessive replication stress. Plays a major role in remodeling of stalled DNA forks by catalyzing fork regression, in which the fork reverses and the two nascent DNA strands anneal. In addition to the helicase activity, also acts as the substrate-recognition component of the SCF(FBH1) E3 ubiquitin ligase complex, a complex that mediates ubiquitination of RAD51, leading to regulate RAD51 subcellular location.

Subunit / interactions. Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBH1) composed of CUL1, SKP1, RBX1 and FBH1. Interacts with RAD51. Interacts with RPA2. Interacts (via PIP-box and RanBP2-type zinc finger) with PCNA.

Subcellular location. Nucleus. Chromosome.

Post-translational modifications. Ubiquitinated. Ubiquitination by the DCX(DTL) complex, also named CRL4(CDT2), leading to its degradation: ubiquitination takes place after its localization to DNA damage sites, possibly to facilitate the translesion synthesis (TLS) pathway.

Disease relevance. Defects in FBH1 are frequently observed in melanomas, resulting in increased survival in response to replicative stress. Its inactivation may play a role in oncogenic transformation.

Domain organisation. The PIP-box mediates the interaction with PCNA.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the helicase family. UvrD subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NFZ0-1	1	yes
Q8NFZ0-2	2

RefSeq proteins (4): NP_001245381, NP_001245382, NP_116196, NP_835363* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000212	UvrD-like	Family
IPR001810	F-box_dom	Domain
IPR014016	UvrD-like_ATP-bd	Domain
IPR014017	UvrD-like_C	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036047	F-box-like_dom_sf	Homologous_superfamily

Pfam: PF00580, PF12937, PF13361

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (24 total): mutagenesis site 7, sequence conflict 5, domain 2, region of interest 2, short sequence motif 2, chain 1, splice variant 1, helix 1, compositionally biased region 1, binding site 1, modified residue 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8F5Q	X-RAY DIFFRACTION	1.9
9XZL	ELECTRON MICROSCOPY	3
9XZJ	ELECTRON MICROSCOPY	3.13
9XZM	ELECTRON MICROSCOPY	10.27

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NFZ0-F1	76.84	0.48

Functional residue map

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

Ligand- & substrate-binding residues (1): 463–470

Post-translational modifications (1): 124

Mutagenesis-validated functional residues (7):

Position	Phenotype
56	no effect; when associated with a-583.
60–64	in pipdeg3a; reduced ubiquitination.
63–64	impaired localization to dna damage sites in response to uv irradiation.
227–228	impairs formation of the scf(fbh1) complex and impairs accumulation on single-stranded dna.
583	no effect; when associated with a-56.
647	abolishes helicase activity and prevents accumulation on single-stranded dna.
807–809	impaired localization to dna damage sites in response to uv irradiation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 161 (showing top): GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_REGULATION_OF_PHOSPHORYLATION, WHITEHURST_PACLITAXEL_SENSITIVITY, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_DNA_REPAIR, GOBP_NEGATIVE_REGULATION_OF_DNA_RECOMBINATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, TGACCTY_ERR1_Q2, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR_VIA_HOMOLOGOUS_RECOMBINATION, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_DNA_CATABOLIC_PROCESS, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS

GO Biological Process (10): double-strand break repair via homologous recombination (GO:0000724), positive regulation of protein phosphorylation (GO:0001934), DNA repair (GO:0006281), DNA catabolic process (GO:0006308), DNA damage response (GO:0006974), protein ubiquitination (GO:0016567), replication fork processing (GO:0031297), response to intra-S DNA damage checkpoint signaling (GO:0072429), positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage (GO:1902231), negative regulation of double-strand break repair via homologous recombination (GO:2000042)

GO Molecular Function (13): DNA helicase activity (GO:0003678), double-stranded DNA binding (GO:0003690), single-stranded DNA binding (GO:0003697), ATP binding (GO:0005524), DNA translocase activity (GO:0015616), ATP hydrolysis activity (GO:0016887), 3’-5’ DNA helicase activity (GO:0043138), nucleotide binding (GO:0000166), DNA binding (GO:0003677), helicase activity (GO:0004386), protein binding (GO:0005515), hydrolase activity (GO:0016787), isomerase activity (GO:0016853)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), SCF ubiquitin ligase complex (GO:0019005), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA binding	3
DNA metabolic process	2
ATP-dependent activity, acting on DNA	2
ATP-dependent activity	2
catalytic activity	2
recombinational repair	1
double-strand break repair	1
regulation of protein phosphorylation	1
protein phosphorylation	1
positive regulation of protein modification process	1
positive regulation of phosphorylation	1
DNA damage response	1
DNA nuclease activity	1
nucleic acid catabolic process	1
cellular response to stress	1
protein modification by small protein conjugation	1
DNA-templated DNA replication maintenance of fidelity	1
response to DNA damage checkpoint signaling	1
intrinsic apoptotic signaling pathway in response to DNA damage	1
regulation of intrinsic apoptotic signaling pathway in response to DNA damage	1
positive regulation of intrinsic apoptotic signaling pathway	1
double-strand break repair via homologous recombination	1
regulation of double-strand break repair via homologous recombination	1
negative regulation of DNA recombination	1
negative regulation of double-strand break repair	1
helicase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
DNA helicase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
nucleic acid binding	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1
cullin-RING ubiquitin ligase complex	1

Protein interactions and networks

STRING

2120 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FBH1	CUL1	Q13616	869
FBH1	RECQL5	O94762	823
FBH1	SKP1	P34991	818
FBH1	RAD51	Q06609	735
FBH1	ZRANB3	Q5FWF4	731
FBH1	FANCM	Q8IYD8	730
FBH1	MUS81	Q96NY9	724
FBH1	RBX1	P62877	719
FBH1	DNA2	P51530	712
FBH1	SMARCAL1	Q9NZC9	707
FBH1	RTEL1	Q9NZ71	701
FBH1	RAD52	P43351	671
FBH1	WRN	Q14191	667
FBH1	RADX	Q6NSI4	664
FBH1	BRIP1	Q9BX63	656

IntAct

43 interactions, top by confidence:

A	B	Type	Score
SKP1	MYCBP2	psi-mi:“MI:0914”(association)	0.640
CUL1	FBXO21	psi-mi:“MI:0914”(association)	0.600
FBH1	APBB1	psi-mi:“MI:0915”(physical association)	0.560
FBH1	GRN	psi-mi:“MI:0915”(physical association)	0.560
FBH1	WFS1	psi-mi:“MI:0915”(physical association)	0.560
HTT	FBH1	psi-mi:“MI:0915”(physical association)	0.560
FBH1	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
SRC	FBH1	psi-mi:“MI:0915”(physical association)	0.400
FBH1	SRC	psi-mi:“MI:0915”(physical association)	0.400
FBH1	ZDHHC17	psi-mi:“MI:0915”(physical association)	0.370
Nedd1		psi-mi:“MI:0914”(association)	0.350
Rock1		psi-mi:“MI:0914”(association)	0.350
FBH1	PRR3	psi-mi:“MI:0914”(association)	0.350
SYNCRIP	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
RALA	AKR7A2	psi-mi:“MI:0914”(association)	0.350

BioGRID (69): FBXO18 (Two-hybrid), FBXO18 (Reconstituted Complex), PRR3 (Affinity Capture-MS), ILKAP (Affinity Capture-MS), FBXO18 (Affinity Capture-MS), FBXO18 (Affinity Capture-MS), MRRF (Affinity Capture-MS), FBXO18 (Affinity Capture-MS), FBXO18 (Affinity Capture-MS), RAD51 (Biochemical Activity), UBC (Biochemical Activity), FBXO18 (Affinity Capture-MS), FBXO18 (Affinity Capture-MS), FBXO18 (Affinity Capture-MS), SKP1 (Affinity Capture-Western)

ESM2 similar proteins: A0A1L1SUL6, F1LQY6, O35465, O43379, O75293, O88910, O88954, P0C0T1, P21964, P22339, P41214, P50747, Q13368, Q13572, Q14318, Q16342, Q1HAQ0, Q28955, Q2T9Z1, Q3B7U9, Q3TFD2, Q3TMX7, Q496Y0, Q4AC99, Q5BIM1, Q5E9A5, Q5R812, Q5RA63, Q5SZD4, Q64311, Q6DC64, Q6P5G6, Q6PFY8, Q80YV4, Q8BNV1, Q8BYN3, Q8NFZ0, Q8R1C6, Q8R1T1, Q8TCU6

Diamond homologs: F1ND48, Q8K2I9, Q8NFZ0, Q6NZ03

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
FBH1	“up-regulates activity”	RAD51	binding
FBH1	“up-regulates activity”	“Cullin 1-RBX1-Skp1”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 33 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Neddylation	5	11.3×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein stabilization	5	11.9×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	145
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4621 predictions. Top by Δscore:

Variant	Effect	Δscore
10:5890347:G:GG	donor_gain	1.0000
10:5890372:G:GT	donor_gain	1.0000
10:5895188:G:GG	donor_gain	1.0000
10:5903001:A:AG	acceptor_gain	1.0000
10:5903001:ACCT:A	acceptor_gain	1.0000
10:5903002:C:G	acceptor_gain	1.0000
10:5903004:T:TA	acceptor_gain	1.0000
10:5903008:G:A	acceptor_gain	1.0000
10:5903167:G:GT	donor_gain	1.0000
10:5903173:GGG:G	donor_gain	1.0000
10:5903174:GGG:G	donor_gain	1.0000
10:5908915:A:AG	acceptor_gain	1.0000
10:5908915:AACT:A	acceptor_gain	1.0000
10:5908916:A:AG	acceptor_gain	1.0000
10:5908918:T:A	acceptor_gain	1.0000
10:5908920:CATAG:C	acceptor_loss	1.0000
10:5908921:A:AG	acceptor_gain	1.0000
10:5908922:T:G	acceptor_gain	1.0000
10:5908922:TA:T	acceptor_loss	1.0000
10:5908923:A:AG	acceptor_gain	1.0000
10:5908924:G:GG	acceptor_gain	1.0000
10:5908924:GT:G	acceptor_gain	1.0000
10:5908924:GTT:G	acceptor_gain	1.0000
10:5908924:GTTC:G	acceptor_gain	1.0000
10:5908924:GTTCA:G	acceptor_gain	1.0000
10:5909053:ACGGT:A	donor_loss	1.0000
10:5909055:GGTG:G	donor_loss	1.0000
10:5909056:G:C	donor_loss	1.0000
10:5909056:G:GG	donor_gain	1.0000
10:5909057:TGAGC:T	donor_loss	1.0000

AlphaMissense

6896 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:5914267:C:A	A465D	1.000
10:5915409:G:A	G468E	1.000
10:5915411:A:C	K469Q	1.000
10:5915424:T:C	L473P	1.000
10:5915474:T:C	F490L	1.000
10:5915476:C:A	F490L	1.000
10:5915476:C:G	F490L	1.000
10:5917656:A:T	E648V	1.000
10:5917663:G:C	Q650H	1.000
10:5917663:G:T	Q650H	1.000
10:5917664:G:C	D651H	1.000
10:5917665:A:C	D651A	1.000
10:5917665:A:G	D651G	1.000
10:5917665:A:T	D651V	1.000
10:5917666:C:A	D651E	1.000
10:5917666:C:G	D651E	1.000
10:5918389:G:A	G671R	1.000
10:5918389:G:C	G671R	1.000
10:5918389:G:T	G671W	1.000
10:5918390:G:A	G671E	1.000
10:5918390:G:T	G671V	1.000
10:5918393:A:G	D672G	1.000
10:5918403:G:C	Q675H	1.000
10:5918403:G:T	Q675H	1.000
10:5918405:A:C	Q676P	1.000
10:5918406:G:C	Q676H	1.000
10:5918406:G:T	Q676H	1.000
10:5918416:T:C	F680L	1.000
10:5918418:C:A	F680L	1.000
10:5918418:C:G	F680L	1.000

dbSNP variants (sampled 300 via entrez): RS1000065942 (10:5912524 C>T), RS1000116251 (10:5912854 A>G), RS1000172864 (10:5919635 C>T), RS1000232610 (10:5934366 T>G), RS1000373699 (10:5901627 C>G,T), RS1000427714 (10:5901980 T>C), RS1000464899 (10:5897679 A>G), RS1000534557 (10:5927699 A>G), RS1000587384 (10:5896799 C>T), RS1000635675 (10:5890912 C>T), RS1000675193 (10:5906848 T>C), RS1000786278 (10:5929979 A>G), RS1000814084 (10:5891900 C>T), RS1000817763 (10:5912690 A>G), RS1000878324 (10:5892188 T>C)

Disease associations

OMIM: gene MIM:607222 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000678_12	Breast cancer	5.000000e-07
GCST005312_49	Menopause (age at onset)	4.000000e-08
GCST008916_1	Asthma	6.000000e-17

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004704	age at menopause

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
bisphenol A	affects expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	increases phosphorylation	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
CPG-oligonucleotide	decreases expression	1
pinostrobin	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Caffeine	affects phosphorylation	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Plant Extracts	increases expression, affects cotreatment	1
Valproic Acid	increases methylation	1
Zinc	increases expression	1
Asbestos, Crocidolite	decreases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SN23	HAP1 FBXO18 (-) 1	Cancer cell line	Male
CVCL_XN71	HAP1 FBXO18 (-) 2	Cancer cell line	Male
CVCL_XN72	HAP1 FBXO18 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer