FBXL17

Summary

FBXL17 (F-box and leucine rich repeat protein 17, HGNC:13615) is a protein-coding gene on chromosome 5q21.3, encoding F-box/LRR-repeat protein 17 (Q9UF56). Substrate-recognition component of the SCF(FBXL17) E3 ubiquitin ligase complex, a key component of a quality control pathway required to ensure functional dimerization of BTB domain-containing proteins (dimerization quality control, DQC).

Members of the F-box protein family, such as FBXL17, 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 64839 — RefSeq curated summary.

At a glance

• GWAS associations: 38
• Clinical variants (ClinVar): 130 total
• MANE Select transcript: NM_001163315

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13615
Approved symbol	FBXL17
Name	F-box and leucine rich repeat protein 17
Location	5q21.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP434C1715, Fbx13, Fbl17
Ensembl gene	ENSG00000145743
Ensembl biotype	protein_coding
OMIM	609083
Entrez	64839

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 retained_intron, 2 protein_coding

ENST00000481160, ENST00000496714, ENST00000518486, ENST00000542267

RefSeq mRNA: 1 — MANE Select: NM_001163315 NM_001163315

CCDS: CCDS54886

Canonical transcript exons

ENST00000542267 — 9 exons

Exon	Start	End
ENSE00001181727	108020925	108021001
ENSE00001407858	107881037	107881179
ENSE00001432663	107859035	107861860
ENSE00002311033	108380699	108382098
ENSE00003554603	108186117	108186247
ENSE00003580133	108224121	108224228
ENSE00003624727	108364738	108364995
ENSE00003652527	108367831	108367953
ENSE00003673019	108348399	108348530

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 97.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.5883 / max 342.1206, expressed in 1801 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
62866	11.2121	1751
62872	2.1854	1011
62868	1.3740	842
62871	1.0912	610
62869	0.8948	510
62875	0.8356	540
62870	0.6739	406
62863	0.4685	227
62867	0.4631	227
62874	0.4235	188

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	97.21	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.69	gold quality
endothelial cell	CL:0000115	96.44	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.18	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.50	gold quality
lateral globus pallidus	UBERON:0002476	95.33	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.24	gold quality
buccal mucosa cell	CL:0002336	95.22	gold quality
vastus lateralis	UBERON:0001379	94.83	gold quality
ventral tegmental area	UBERON:0002691	94.10	gold quality
occipital lobe	UBERON:0002021	93.41	gold quality
biceps brachii	UBERON:0001507	93.37	gold quality
dorsal plus ventral thalamus	UBERON:0001897	93.27	gold quality
quadriceps femoris	UBERON:0001377	93.25	gold quality
medulla oblongata	UBERON:0001896	93.20	gold quality
skeletal muscle tissue	UBERON:0001134	93.13	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.06	gold quality
primary visual cortex	UBERON:0002436	93.00	gold quality
tongue	UBERON:0001723	92.97	gold quality
parietal lobe	UBERON:0001872	92.88	gold quality
superior frontal gyrus	UBERON:0002661	92.81	gold quality
superior surface of tongue	UBERON:0007371	92.79	gold quality
substantia nigra pars reticulata	UBERON:0001966	92.74	gold quality
superior vestibular nucleus	UBERON:0007227	92.74	gold quality
body of tongue	UBERON:0011876	92.73	gold quality
pons	UBERON:0000988	92.71	gold quality
substantia nigra pars compacta	UBERON:0001965	92.68	gold quality
muscle tissue	UBERON:0002385	92.60	gold quality
myocardium	UBERON:0002349	92.50	gold quality
postcentral gyrus	UBERON:0002581	92.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.97

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

195 targeting FBXL17, 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-3613-3P	100.00	76.36	7965
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753

Literature-anchored findings (GeneRIF, showing 5)

• F-box protein 17 (FBXL17) can serve as a therapeutic target and surrogate marker for breast cancer therapy. (PMID:18820369)
• Identify a role for SCF(FBXL17) in controlling the threshold for NRF2-dependent gene activation via BACH1 repressor turnover. (PMID:24035498)
• In summary, these findings reveal Fbxl17 as a novel regulator of the Hedgehog signaling pathway and highlight the perturbation of the Fbxl17-Sufu axis in the pathogenesis of medulloblastoma. (PMID:27234298)
• Rearrangements of Fbxl17 in breast cancer affect its ability to bind substrates and to assemble as part of a functional SCF ubiquitin ligase complex. (PMID:31560077)
• Structural basis for dimerization quality control. (PMID:32814905)

Cross-species orthologs

30 orthologs

Organism	Symbol	Gene ID
danio_rerio	fbxl17	ENSDARG00000042072
mus_musculus	Fbxl17	ENSMUSG00000023965
rattus_norvegicus	Fbxl17	ENSRNOG00000081964
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), FBXL2 (ENSG00000153558), FBXL18 (ENSG00000155034), FBXL13 (ENSG00000161040), FBXL14 (ENSG00000171823), FBXL6 (ENSG00000182325), FBXL7 (ENSG00000183580), FBXL22 (ENSG00000197361)

Protein

Protein identifiers

F-box/LRR-repeat protein 17 — Q9UF56 (reviewed: Q9UF56)

Alternative names: F-box and leucine-rich repeat protein 17, F-box only protein 13

All UniProt accessions (2): A0A6E1XD66, Q9UF56

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-recognition component of the SCF(FBXL17) E3 ubiquitin ligase complex, a key component of a quality control pathway required to ensure functional dimerization of BTB domain-containing proteins (dimerization quality control, DQC). FBXL17 specifically recognizes and binds a conserved degron of non-consecutive residues present at the interface of BTB dimers of aberrant composition: aberrant BTB dimer are then ubiquitinated by the SCF(FBXL17) complex and degraded by the proteasome. The ability of the SCF(FBXL17) complex to eliminate compromised BTB dimers is required for the differentiation and survival of neural crest and neuronal cells. The SCF(FBXL17) complex mediates ubiquitination and degradation of BACH1. The SCF(FBXL17) complex is also involved in the regulation of the hedgehog/smoothened (Hh) signaling pathway by mediating the ubiquitination and degradation of SUFU, allowing the release of GLI1 from SUFU for proper Hh signal transduction. The SCF(FBXL17) complex mediates ubiquitination and degradation of PRMT1.

Subunit / interactions. Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL17) composed of CUL1, SKP1, RBX1 and FBXL17. Interacts with BTB domain-containing proteins such as KLHL12, BCL6 and BACH1; specifically recognizes and binds a conserved degron of non-consecutive residues present at the interface of BTB dimers of aberrant composition. Interacts with SUFU. Interacts with PRMT1.

Subcellular location. Cytoplasm. Nucleus.

Similarity. Belongs to the FBXL17 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UF56-1	1	yes
Q9UF56-3	2
Q9UF56-2	3

RefSeq proteins (1): NP_001156787* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
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
IPR050648	F-box_LRR-repeat	Family
IPR057207	FBXL15_LRR	Domain

Pfam: PF12937, PF13516, PF25372

UniProt features (48 total): helix 19, strand 13, turn 5, region of interest 3, compositionally biased region 3, splice variant 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
8UBT	ELECTRON MICROSCOPY	3.1
6W66	X-RAY DIFFRACTION	3.21
8UAH	ELECTRON MICROSCOPY	3.3
8UBV	ELECTRON MICROSCOPY	4.1
8UBU	ELECTRON MICROSCOPY	4.6
6WCQ	ELECTRON MICROSCOPY	8.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UF56-F1	70.03	0.50

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9708530	Regulation of BACH1 activity

MSigDB gene sets: 173 (showing top): GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_MESENCHYMAL_CELL_DIFFERENTIATION, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_POLYUBIQUITINATION, GOBP_REGULATION_OF_SMOOTHENED_SIGNALING_PATHWAY, GOBP_SCF_DEPENDENT_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, GOBP_SMOOTHENED_SIGNALING_PATHWAY, GOBP_MESENCHYME_DEVELOPMENT, GOBP_STEM_CELL_DIFFERENTIATION, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, chr5q21, GOBP_PROTEIN_CATABOLIC_PROCESS, GOBP_NEURAL_CREST_CELL_DIFFERENTIATION, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN

GO Biological Process (8): protein polyubiquitination (GO:0000209), protein quality control for misfolded or incompletely synthesized proteins (GO:0006515), nervous system development (GO:0007399), regulation of smoothened signaling pathway (GO:0008589), neural crest cell differentiation (GO:0014033), protein ubiquitination (GO:0016567), SCF-dependent proteasomal ubiquitin-dependent protein catabolic process (GO:0031146), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161)

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

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), SCF ubiquitin ligase complex (GO:0019005), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
KEAP1-NFE2L2 pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein ubiquitination	1
protein catabolic process	1
system development	1
smoothened signaling pathway	1
regulation of signal transduction	1
mesenchymal cell differentiation	1
stem cell differentiation	1
protein modification by small protein conjugation	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cullin-RING ubiquitin ligase complex	1

Protein interactions and networks

STRING

1064 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FBXL17	CUL1	Q13616	850
FBXL17	SKP1	P34991	753
FBXL17	RABGGTB	P53611	524
FBXL17	KLHL21	Q9UJP4	508
FBXL17	ZNF584	Q8IVC4	501
FBXL17	RLF	Q13129	495
FBXL17	UAP1	Q16222	469
FBXL17	TVP23A	A6NH52	456
FBXL17	PRAME	P78395	450
FBXL17	PRXL2C	Q7RTV5	446
FBXL17	SUFU	Q9UMX1	445
FBXL17	LGI2	Q8N0V4	443
FBXL17	NRXN1	Q9ULB1	443
FBXL17	SGCZ	Q96LD1	433
FBXL17	PCCB	P05166	423

IntAct

80 interactions, top by confidence:

A	B	Type	Score
BACH1	MAFG	psi-mi:“MI:0914”(association)	0.870
KLHL9	CUL3	psi-mi:“MI:0914”(association)	0.860
KLHL12	KLHL2	psi-mi:“MI:0914”(association)	0.850
FBXL17	SKP1	psi-mi:“MI:0914”(association)	0.790
FBXL17	SKP1	psi-mi:“MI:0915”(physical association)	0.790
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
KLHL24	CUL3	psi-mi:“MI:0914”(association)	0.730
FBXL17	BACH1	psi-mi:“MI:0914”(association)	0.730
KLHL21	CUL3	psi-mi:“MI:0914”(association)	0.640
KLHL25	ENC1	psi-mi:“MI:0914”(association)	0.640
ZBTB18	HSPA8	psi-mi:“MI:0914”(association)	0.640
SKP1	MYCBP2	psi-mi:“MI:0914”(association)	0.640
KLHL9	ENC1	psi-mi:“MI:0914”(association)	0.640
FBXL17	SPAST	psi-mi:“MI:0915”(physical association)	0.600
SPAST	FBXL17	psi-mi:“MI:0407”(direct interaction)	0.600
SPAST	FBXL17	psi-mi:“MI:0915”(physical association)	0.600
FBXL17	SPAST	psi-mi:“MI:0407”(direct interaction)	0.590

BioGRID (151): FBXL17 (Affinity Capture-MS), FBXL17 (Affinity Capture-MS), FBXL17 (Affinity Capture-MS), SKP1 (Affinity Capture-MS), CUL1 (Affinity Capture-MS), SUFU (Affinity Capture-MS), ZBTB10 (Affinity Capture-MS), KIAA1671 (Affinity Capture-MS), ZBTB33 (Affinity Capture-MS), BACH1 (Affinity Capture-MS), MAP3K7 (Affinity Capture-MS), PJA2 (Affinity Capture-MS), NOTCH2 (Affinity Capture-MS), STK31 (Affinity Capture-MS), DVL2 (Affinity Capture-MS)

ESM2 similar proteins: A2VE78, B1H1X1, B4F7C5, E1C3P4, O94898, O95170, P55265, P97432, Q14596, Q1L994, Q2HJ90, Q2TBA3, Q3UGM2, Q496Y0, Q4KM95, Q52KR2, Q5F3F2, Q5KSL6, Q5Q9Z2, Q5R6E1, Q641K1, Q69ZK0, Q6NTL4, Q7TPQ3, Q80TL0, Q80XG9, Q80Z30, Q86VH4, Q8C2S5, Q8IUZ0, Q8K2I9, Q8N4P6, Q8NA31, Q8NEE8, Q8NFZ0, Q8R2U7, Q8WY54, Q91YK0, Q95LZ5, Q96EK7

Diamond homologs: B1H1X1, Q9QZN1, Q9UF56

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
FBXL17	“down-regulates quantity by destabilization”	SUFU	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 58 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
Class I MHC mediated antigen processing & presentation	11	20.8×	4e-10
Neddylation	13	16.6×	1e-10
KEAP1-NFE2L2 pathway	5	16.2×	5e-04
Antigen processing: Ubiquitination & Proteasome degradation	13	13.1×	6e-10
Adaptive Immune System	14	11.3×	6e-10

GO biological processes:

GO term	Partners	Fold	FDR
protein monoubiquitination	5	32.5×	6e-05
protein K48-linked ubiquitination	6	19.1×	7e-05
proteasome-mediated ubiquitin-dependent protein catabolic process	15	14.8×	8e-12
protein ubiquitination	17	13.3×	1e-12

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	113
Likely benign	8
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

5952 predictions. Top by Δscore:

Variant	Effect	Δscore
5:107861857:TGAC:T	acceptor_gain	1.0000
5:107861858:GAC:G	acceptor_gain	1.0000
5:107861858:GACCT:G	acceptor_loss	1.0000
5:107861859:ACCTG:A	acceptor_loss	1.0000
5:107861860:CCTGC:C	acceptor_loss	1.0000
5:107861861:C:CC	acceptor_gain	1.0000
5:107861861:CTG:C	acceptor_loss	1.0000
5:107861862:T:C	acceptor_loss	1.0000
5:107861868:C:CT	acceptor_gain	1.0000
5:107881035:A:AC	donor_gain	1.0000
5:107881036:C:CC	donor_gain	1.0000
5:107881038:TTATC:T	donor_gain	1.0000
5:107881175:CAGTG:C	acceptor_gain	1.0000
5:107881180:C:CC	acceptor_gain	1.0000
5:107881574:TAAAC:T	donor_gain	1.0000
5:107881575:AAACA:A	donor_gain	1.0000
5:108186112:GTTA:G	donor_loss	1.0000
5:108186113:TTA:T	donor_loss	1.0000
5:108186114:TACCT:T	donor_loss	1.0000
5:108186115:A:C	donor_loss	1.0000
5:108186116:C:G	donor_loss	1.0000
5:108186243:CTTAG:C	acceptor_gain	1.0000
5:108186248:C:CC	acceptor_gain	1.0000
5:108223377:CTCAG:C	acceptor_gain	1.0000
5:108223379:CAG:C	acceptor_gain	1.0000
5:108223382:C:CC	acceptor_gain	1.0000
5:108224116:CCTA:C	donor_loss	1.0000
5:108224118:TA:T	donor_loss	1.0000
5:108224119:A:AT	donor_loss	1.0000
5:108224120:C:T	donor_loss	1.0000

AlphaMissense

4530 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:107861766:G:T	A687D	1.000
5:107861790:T:A	D679V	1.000
5:107861790:T:G	D679A	1.000
5:107861791:C:G	D679H	1.000
5:107861804:G:C	S674R	1.000
5:107861804:G:T	S674R	1.000
5:107861806:T:G	S674R	1.000
5:107861808:A:G	F673S	1.000
5:107861835:A:G	L664P	1.000
5:107881043:A:C	C653W	1.000
5:107881044:C:A	C653F	1.000
5:107881044:C:T	C653Y	1.000
5:107881045:A:G	C653R	1.000
5:107881046:T:A	R652S	1.000
5:107881046:T:G	R652S	1.000
5:107881047:C:A	R652I	1.000
5:107881047:C:G	R652T	1.000
5:107881053:A:G	L650P	1.000
5:107881053:A:T	L650Q	1.000
5:107881056:C:A	G649V	1.000
5:107881056:C:T	G649E	1.000
5:107881057:C:A	G649W	1.000
5:107881057:C:G	G649R	1.000
5:107881057:C:T	G649R	1.000
5:107881059:A:G	L648S	1.000
5:107881089:A:T	I638N	1.000
5:107881098:G:T	A635D	1.000
5:107881101:C:T	G634E	1.000
5:107881102:C:G	G634R	1.000
5:107881102:C:T	G634R	1.000

dbSNP variants (sampled 300 via entrez): RS1000003831 (5:107935304 A>G), RS1000011838 (5:108291366 A>G,T), RS1000015600 (5:108306842 G>A), RS1000015632 (5:108370898 T>C), RS1000026682 (5:108245817 A>G), RS1000027787 (5:107867067 T>C,G), RS1000029983 (5:108089371 C>A,T), RS1000040425 (5:108368374 C>G,T), RS1000041261 (5:108228683 G>A,T), RS1000047137 (5:107953073 G>A,C,T), RS1000048227 (5:108106156 G>C), RS1000051664 (5:108261863 A>G), RS1000053972 (5:108066677 A>G), RS1000068590 (5:108088473 G>A), RS1000077025 (5:108267640 G>A)

Disease associations

OMIM: gene MIM:609083 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

38 associations (top):

Study	Trait	p-value
GCST001651_35	Response to amphetamines	1.000000e-06
GCST001723_2	Eye color	1.000000e-06
GCST002306_49	Bipolar disorder (body mass index interaction)	4.000000e-06
GCST002783_188	Body mass index	4.000000e-06
GCST002783_342	Body mass index	3.000000e-06
GCST004557_216	Body mass index	6.000000e-06
GCST004557_218	Body mass index	1.000000e-08
GCST004557_52	Body mass index	1.000000e-08
GCST004557_91	Body mass index	5.000000e-06
GCST004558_236	Body mass index (joint analysis main effects and physical activity interaction)	2.000000e-07
GCST004558_88	Body mass index (joint analysis main effects and physical activity interaction)	3.000000e-08
GCST004559_165	Body mass index in physically active individuals	1.000000e-06
GCST004559_82	Body mass index in physically active individuals	1.000000e-06
GCST005170_53	Intraocular pressure	1.000000e-13
GCST005316_595	Intelligence (MTAG)	5.000000e-09
GCST005830_135	Hand grip strength	2.000000e-09
GCST006046_1	Number of children ever born	1.000000e-08
GCST006629_99	Pulse pressure	1.000000e-09
GCST006940_66	Neurociticism	2.000000e-08
GCST006940_7	Neurociticism	5.000000e-09
GCST006940_8	Neurociticism	3.000000e-10
GCST006941_21	Irritable mood	1.000000e-08
GCST006941_22	Irritable mood	2.000000e-08
GCST006941_67	Irritable mood	2.000000e-09
GCST006944_38	Experiencing mood swings	5.000000e-08
GCST007327_41	Smoking status (ever vs never smokers)	1.000000e-08
GCST007709_23	General factor of neuroticism	5.000000e-09
GCST007709_24	General factor of neuroticism	5.000000e-09
GCST007876_28	Estimated glomerular filtration rate	4.000000e-08
GCST008152_88	Weight	3.000000e-06

EFO canonical traits (19, from GWAS)

EFO ID	Trait name
EFO:0003949	eye color
EFO:0004340	body mass index
EFO:0008002	physical activity measurement
EFO:0004695	intraocular pressure measurement
EFO:0004337	intelligence
EFO:0006941	grip strength measurement
EFO:0009102	number of children ever born measurement
EFO:0005763	pulse pressure measurement
EFO:0007660	neuroticism measurement
EFO:0009594	irritability measurement
EFO:0008475	mood instability measurement
EFO:0004318	smoking behavior
EFO:0004338	body weight
EFO:0006917	spontaneous preterm birth
EFO:0004784	self reported educational attainment
EFO:0010505	isocitrate measurement
EFO:0010396	sphingomyelin 22:1 measurement
EFO:0006527	smoking status measurement
EFO:0005670	smoking initiation

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs4431329	Efficacy	3	hydrochlorothiazide	Essential hypertension
rs7706429	Efficacy	3	hydrochlorothiazide	Essential hypertension

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4431329	FBXL17	3	0.00	1	hydrochlorothiazide
rs7706429	FBXL17	3	0.00	1	hydrochlorothiazide

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation	5
entinostat	decreases expression, affects cotreatment	2
Acetaminophen	decreases expression	2
Benzo(a)pyrene	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Aflatoxin B1	affects expression, decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
sodium arsenite	affects expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, affects expression	1
Caffeine	increases phosphorylation	1
Carbamazepine	affects expression	1
Cisplatin	affects cotreatment, decreases expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	increases expression	1
Ozone	increases abundance, affects expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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