FBXL7

Summary

FBXL7 (F-box and leucine rich repeat protein 7, HGNC:13604) is a protein-coding gene on chromosome 5p15.1, encoding F-box/LRR-repeat protein 7 (Q9UJT9). Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex.

This gene encodes a member of the F-box protein family which is characterized by a 42-48 amino acid motif, the F-box, which binds to the S-phase kinase-associated protein 1 (Skp1) protein. The F-box proteins constitute one of the four subunits of E3 ubiquitin protein ligases called SCFs (SKP1-Cul1-F-box), which play a role in phosphorylation-dependent ubiquitination of proteins. The F-box proteins are divided into 3 subfamilies based on the other domain in the protein: F-box proteins that also have a WD-40 domain (Fbws subfamily), F-box proteins that also have leucine-rich repeats (Fbls subfamily) and F-box proteins that contain other motifs or lack known protein-interaction domains (Fbxs subfamily). The protein encoded by this gene belongs to the Fbls subfamily. Alternative splicing results in multiple transcript variants of this gene.

Source: NCBI Gene 23194 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Hennekam syndrome (Limited, GenCC)
• GWAS associations: 21
• Clinical variants (ClinVar): 74 total
• MANE Select transcript: NM_012304

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13604
Approved symbol	FBXL7
Name	F-box and leucine rich repeat protein 7
Location	5p15.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0840, FBL7, FBL6
Ensembl gene	ENSG00000183580
Ensembl biotype	protein_coding
OMIM	605656
Entrez	23194

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000329673, ENST00000504595, ENST00000510662

RefSeq mRNA: 2 — MANE Select: NM_012304 NM_001278317, NM_012304

CCDS: CCDS54833, CCDS64129

Canonical transcript exons

ENST00000504595 — 4 exons

Exon	Start	End
ENSE00001561290	15936450	15939793
ENSE00002074672	15500180	15500713
ENSE00003539700	15927890	15928501
ENSE00003680069	15615983	15616072

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 97.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.7511 / max 205.3600, expressed in 1206 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
55838	9.1012	1201
55837	0.6499	454

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.42	gold quality
oocyte	CL:0000023	97.07	gold quality
ventricular zone	UBERON:0003053	96.59	gold quality
saphenous vein	UBERON:0007318	92.24	gold quality
urethra	UBERON:0000057	91.19	gold quality
tibia	UBERON:0000979	90.72	gold quality
vena cava	UBERON:0004087	90.66	gold quality
left ventricle myocardium	UBERON:0006566	90.40	gold quality
embryo	UBERON:0000922	89.73	gold quality
myometrium	UBERON:0001296	89.37	gold quality
trigeminal ganglion	UBERON:0001675	89.06	gold quality
right adrenal gland cortex	UBERON:0035827	88.89	gold quality
ganglionic eminence	UBERON:0004023	88.87	gold quality
olfactory bulb	UBERON:0002264	88.73	gold quality
smooth muscle tissue	UBERON:0001135	88.56	gold quality
left ovary	UBERON:0002119	88.24	gold quality
dorsal root ganglion	UBERON:0000044	88.21	gold quality
cardiac muscle of right atrium	UBERON:0003379	88.20	gold quality
cauda epididymis	UBERON:0004360	88.16	gold quality
cartilage tissue	UBERON:0002418	88.03	gold quality
body of uterus	UBERON:0009853	88.03	gold quality
myocardium	UBERON:0002349	88.01	gold quality
adrenal cortex	UBERON:0001235	87.96	gold quality
right ovary	UBERON:0002118	87.79	gold quality
right adrenal gland	UBERON:0001233	87.77	gold quality
popliteal artery	UBERON:0002250	87.59	gold quality
tibial artery	UBERON:0007610	87.58	gold quality
ovary	UBERON:0000992	87.44	gold quality
inferior vagus X ganglion	UBERON:0005363	87.44	gold quality
synovial joint	UBERON:0002217	87.35	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	74.82
E-CURD-119	yes	29.95
E-HCAD-25	yes	20.56
E-ANND-3	yes	10.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

106 targeting FBXL7, 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-4455	100.00	65.48	1587
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699

Literature-anchored findings (GeneRIF, showing 8)

• FBXL7 specifically interacts with Aurora A during mitosis but not in interphase, suggesting a regulatory role for FBXL7 in controlling Aurora A abundance during mitosis. (PMID:22306998)
• Fbxl18 regulates apoptosis by mediating ubiquitin-dependent proteasomal degradation of the pro-apoptotic protein Fbxl7 that may impact cellular processes involved in cell cycle progression. (PMID:25654763)
• the Skp1.Cul1.F-box protein complex subunit Fbxl7 modulates mitochondrial function by controlling the cellular abundance of survivin (PMID:25778398)
• Biallelic mutation of FBXL7 suggests a novel form of Hennekam syndrome. (PMID:31633297)
• miR-152-5p suppresses glioma progression and tumorigenesis and potentiates temozolomide sensitivity by targeting FBXL7. (PMID:32150671)
• Epigenetic silencing of the ubiquitin ligase subunit FBXL7 impairs c-SRC degradation and promotes epithelial-to-mesenchymal transition and metastasis. (PMID:32839549)
• 7-Ethoxyrosmanol alleviates hyperglycemia-induced vascular endothelial dysfunction by regulating FBXL7 expression. (PMID:34427826)
• FBXL7 Body Hypomethylation Is Frequent in Tumors from the Digestive and Respiratory Tracts and Is Associated with Risk-Factor Exposure. (PMID:35887149)

Cross-species orthologs

30 orthologs

Organism	Symbol	Gene ID
danio_rerio	fbxl7	ENSDARG00000062251
mus_musculus	Fbxl7	ENSMUSG00000043556
rattus_norvegicus	Fbxl7	ENSRNOG00000024433
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), FBXL22 (ENSG00000197361)

Protein

Protein identifiers

F-box/LRR-repeat protein 7 — Q9UJT9 (reviewed: Q9UJT9)

Alternative names: F-box and leucine-rich repeat protein 7, F-box protein FBL6/FBL7

All UniProt accessions (2): Q9UJT9, J3KNM9

UniProt curated annotations — full annotation on UniProt →

Function. Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex. During mitosis, it mediates the ubiquitination and subsequent proteasomal degradation of AURKA, causing mitotic arrest. It also regulates mitochondrial function by mediating the ubiquitination and proteasomal degradation of the apoptosis inhibitor BIRC5.

Subunit / interactions. Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL7) composed of CUL1, SKP1, RBX1 and FBXL7. Interacts with AURKA; interaction takes place during mitosis but not in interphase. Interacts with BIRC5; this interaction allows BIRC5 to be polyubiquitinated by the SCF(FBXL7) E3 ubiquitin-protein ligase complex.

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

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the FBXL7 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UJT9-1	1	yes
Q9UJT9-2	2

RefSeq proteins (2): NP_001265246, NP_036436* (*=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 (17 total): repeat 11, compositionally biased region 2, chain 1, domain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UJT9-F1	82.67	0.70

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8854050	FBXL7 down-regulates AURKA during mitotic entry and in early mitosis
R-HSA-8951664	Neddylation
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation

MSigDB gene sets: 143 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, AAGCAAT_MIR137, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOCC_MICROTUBULE_ORGANIZING_CENTER, MODULE_66, ONKEN_UVEAL_MELANOMA_UP, DOANE_RESPONSE_TO_ANDROGEN_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, GOCC_CENTROSOME, MODULE_99, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN

GO Biological Process (7): G2/M transition of mitotic cell cycle (GO:0000086), protein polyubiquitination (GO:0000209), mitotic cell cycle (GO:0000278), ubiquitin-dependent protein catabolic process (GO:0006511), protein ubiquitination (GO:0016567), SCF-dependent proteasomal ubiquitin-dependent protein catabolic process (GO:0031146), cell division (GO:0051301)

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

GO Cellular Component (6): ubiquitin ligase complex (GO:0000151), centrosome (GO:0005813), cytosol (GO:0005829), SCF ubiquitin ligase complex (GO:0019005), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
G2/M Transition	1
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
protein ubiquitination	2
cellular anatomical structure	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G2/M phase transition	1
cell cycle	1
mitotic nuclear division	1
modification-dependent protein catabolic process	1
protein modification by small protein conjugation	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
cellular process	1
binding	1
intracellular protein-containing complex	1
transferase complex	1
centriole	1
microtubule organizing center	1
cytoplasm	1
cullin-RING ubiquitin ligase complex	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1344 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FBXL7	SKP1	P34991	808
FBXL7	CCNF	P41002	730
FBXL7	CUL1	Q13616	626
FBXL7	DMWD	Q09019	584
FBXL7	BTRC	Q9Y297	574
FBXL7	FAT4	Q6V0I7	535
FBXL7	TRAF6	Q9Y4K3	505
FBXL7	FBXO2	Q9UK22	499
FBXL7	FBXO16	Q8IX29	496
FBXL7	FBXL18	Q96ME1	495
FBXL7	FBXO25	Q8TCJ0	491
FBXL7	FBXW7	Q969H0	487
FBXL7	FBXO45	P0C2W1	476
FBXL7	MARCHF11	A6NNE9	465
FBXL7	FBXL22	Q6P050	460

IntAct

12 interactions, top by confidence:

A	B	Type	Score
TBC1D5	FBXL7	psi-mi:“MI:0915”(physical association)	0.560
FCHO1	FBXL7	psi-mi:“MI:0915”(physical association)	0.560
SKP1	FBXL7	psi-mi:“MI:0915”(physical association)	0.400
	FBXL7	psi-mi:“MI:0915”(physical association)	0.400
FBXL7	NUDCD2	psi-mi:“MI:0915”(physical association)	0.400
FBXL7	NUDC	psi-mi:“MI:0915”(physical association)	0.400
FBXL7	TBC1D5	psi-mi:“MI:0915”(physical association)	0.000
FBXL7	FCHO1	psi-mi:“MI:0915”(physical association)	0.000
ggt	FBXL7	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (59): FBXL18 (Affinity Capture-Western), FBXL7 (Affinity Capture-Western), FBXL7 (Biochemical Activity), FBXL7 (Reconstituted Complex), CUL1 (Affinity Capture-Western), SKP1 (Affinity Capture-Western), BIRC5 (Biochemical Activity), BIRC5 (Affinity Capture-Western), BIRC5 (Reconstituted Complex), BIRC5 (Affinity Capture-Western), FBXL7 (Affinity Capture-Western), BIRC5 (Biochemical Activity), SKP1 (Affinity Capture-Western), FBXL7 (Affinity Capture-MS), FBXL7 (Two-hybrid)

ESM2 similar proteins: A1A5X2, A2RT62, A6H639, A8Y3R9, B3FL73, D3Z902, D3ZXS4, G5EDB9, O49286, P34284, P87053, Q09299, Q0P4D1, Q0VD31, Q17R01, Q19857, Q32PG9, Q4R642, Q570C0, Q5BJ29, Q5JU00, Q5MJ12, Q65XV2, Q8BFZ4, Q8BH70, Q8BID8, Q8BVU0, Q8C4V4, Q8CDU4, Q8CFJ9, Q8J2J3, Q8LB33, Q8N1E6, Q8N461, Q8W104, Q96S15, Q9EPX5, Q9LPL4, Q9LW29, Q9NXK8

Diamond homologs: A1A5X2, Q13309, Q5BJ29, Q6PB97, Q6PCT2, Q9EPX5, Q9NXK8, Q9QZN1, Q9UJT9, Q9Z0Z3, A6H779, B6Q4Z5, B8M7Q5, P34284, P39014, Q0WRC9, Q58DG6, Q5R3Z8, Q8BH16, Q8C2S5, Q96IG2, Q9CZV8, Q9QZH7, Q9SY03, Q9UKC9, Q32PG9, Q5XGI3, Q6INS1, Q7TPD1, Q7TSL3, Q86XK2, Q8N531, A2VE78, C0HAC0, Q2YDQ5, Q5R6E1, Q8CHQ0, Q9UKA1, B9G2A8, Q09855

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
FBXL7	“down-regulates quantity by destabilization”	BIRC5	binding
FBXL7	“up-regulates activity”	“Cullin 1-RBX1-Skp1”	binding
FBXL18	“down-regulates quantity by destabilization”	FBXL7	binding
“Cullin 1-RBX1-Skp1”	“down-regulates quantity by destabilization”	FBXL7	polyubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3671 predictions. Top by Δscore:

Variant	Effect	Δscore
5:15500712:GG:G	donor_gain	1.0000
5:15500713:GG:G	donor_gain	1.0000
5:15616068:CGAAG:C	donor_loss	1.0000
5:15616070:AAG:A	donor_loss	1.0000
5:15616071:AGGTA:A	donor_loss	1.0000
5:15616072:GG:G	donor_loss	1.0000
5:15616074:T:A	donor_loss	1.0000
5:15927888:A:AG	acceptor_gain	1.0000
5:15927889:G:GG	acceptor_gain	1.0000
5:15934767:G:GT	donor_gain	1.0000
5:15564894:T:G	donor_gain	0.9900
5:15672278:G:GG	donor_gain	0.9900
5:15792308:T:TA	acceptor_gain	0.9900
5:15792318:T:G	acceptor_gain	0.9900
5:15834854:G:GG	donor_gain	0.9900
5:15927884:TGCCA:T	acceptor_loss	0.9900
5:15927885:GCCAG:G	acceptor_loss	0.9900
5:15927887:CA:C	acceptor_loss	0.9900
5:15927888:A:AC	acceptor_loss	0.9900
5:15927889:G:GT	acceptor_loss	0.9900
5:15927889:GA:G	acceptor_gain	0.9900
5:15927889:GAC:G	acceptor_gain	0.9900
5:15928498:TCAGG:T	donor_loss	0.9900
5:15928499:CAG:C	donor_loss	0.9900
5:15928500:AGGT:A	donor_loss	0.9900
5:15928501:GGTA:G	donor_loss	0.9900
5:15928503:T:G	donor_loss	0.9900
5:15934823:C:G	donor_gain	0.9900
5:15936448:A:AG	acceptor_gain	0.9900
5:15936449:G:GG	acceptor_gain	0.9900

AlphaMissense

3187 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:15928207:T:A	W149R	1.000
5:15928207:T:C	W149R	1.000
5:15928222:T:A	W154R	1.000
5:15928222:T:C	W154R	1.000
5:15928490:T:C	L243P	1.000
5:15936776:A:C	S356R	1.000
5:15936778:C:A	S356R	1.000
5:15936778:C:G	S356R	1.000
5:15936809:G:C	G367R	1.000
5:15937131:T:A	V474D	1.000
5:15928192:T:A	W144R	0.999
5:15928192:T:C	W144R	0.999
5:15928209:G:C	W149C	0.999
5:15928209:G:T	W149C	0.999
5:15928223:G:C	W154S	0.999
5:15928224:G:C	W154C	0.999
5:15928224:G:T	W154C	0.999
5:15928369:G:A	G203R	0.999
5:15928369:G:C	G203R	0.999
5:15928403:T:C	L214P	0.999
5:15928412:T:C	L217P	0.999
5:15928481:T:C	L240P	0.999
5:15936452:T:C	C248R	0.999
5:15936540:T:C	L277P	0.999
5:15936554:T:C	C282R	0.999
5:15936556:C:G	C282W	0.999
5:15936609:T:A	L300H	0.999
5:15936618:T:C	L303P	0.999
5:15936630:G:C	R307P	0.999
5:15936632:T:C	C308R	0.999

dbSNP variants (sampled 300 via entrez): RS1000007770 (5:15918588 A>C), RS1000008388 (5:15817322 A>G), RS1000025863 (5:15678740 C>T), RS1000026724 (5:15649845 C>T), RS1000033765 (5:15731516 T>C), RS1000040226 (5:15710479 G>A), RS1000044557 (5:15696859 C>A,G), RS1000056687 (5:15564523 A>G), RS1000057736 (5:15838392 A>G), RS1000066651 (5:15844260 G>A), RS1000072159 (5:15691033 G>A), RS1000090225 (5:15586931 A>G), RS1000090807 (5:15628083 G>A), RS1000099124 (5:15736723 C>T), RS1000101123 (5:15542428 G>C,T)

Disease associations

OMIM: gene MIM:605656 | disease phenotypes: MIM:188400

GenCC curated gene-disease

Disease	Classification	Inheritance
Hennekam syndrome	Limited	Autosomal recessive

Mondo (2): DiGeorge syndrome (MONDO:0008564), Hennekam syndrome (MONDO:0016256)

Orphanet (1): 22q11.2 deletion syndrome (Orphanet:567)

HPO phenotypes

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

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST001514_7	Economic and political preferences (feminism/equality)	5.000000e-06
GCST001525_11	Visceral fat	7.000000e-06
GCST001762_288	Obesity-related traits	9.000000e-07
GCST002342_2	Asthma (corticosteroid response)	9.000000e-08
GCST002875_47	Diisocyanate-induced asthma	7.000000e-06
GCST002983_1	Alzheimer’s disease (late onset)	5.000000e-08
GCST003265_442	Post bronchodilator FEV1/FVC ratio in COPD	1.000000e-06
GCST003265_443	Post bronchodilator FEV1/FVC ratio in COPD	4.000000e-06
GCST003265_444	Post bronchodilator FEV1/FVC ratio in COPD	4.000000e-06
GCST003487_10	Response to fenofibrate (total cholesterol levels)	4.000000e-06
GCST003487_2	Response to fenofibrate (total cholesterol levels)	2.000000e-06
GCST004068_80	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	1.000000e-06
GCST004765_2	Total cholesterol change in response to fenofibrate in statin-treated type 2 diabetes	5.000000e-07
GCST007095_106	Systolic blood pressure	4.000000e-06
GCST007096_234	Pulse pressure	2.000000e-06
GCST007099_170	Systolic blood pressure	4.000000e-09
GCST009028_49	Adverse response to drug	3.000000e-07
GCST010701_79	Cortical surface area (MOSTest)	4.000000e-09
GCST010702_149	Subcortical volume (MOSTest)	1.000000e-12
GCST010703_10	Brain morphology (MOSTest)	9.000000e-10
GCST90014033_37	Haemorrhoidal disease	8.000000e-09

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004827	economic and social preference
EFO:0004730	hormone measurement
EFO:0006995	response to diisocyanate
EFO:0004713	FEV/FVC ratio
EFO:0007806	total cholesterol change measurement
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0009658	adverse effect
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D004062	DiGeorge Syndrome	C05.660.207.103.500; C14.240.400.021.500; C14.280.400.044.500; C15.604.451.249.500; C16.131.077.019.500; C16.131.240.400.021.500; C16.131.260.019.500; C16.131.482.249.500; C16.131.621.207.103.500; C16.320.180.019.500; C19.642.482.500.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, decreases expression, increases expression	3
bisphenol A	increases expression, affects cotreatment, increases methylation, decreases methylation	2
sodium arsenite	decreases expression, increases abundance, increases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	2
Valproic Acid	increases expression, increases methylation	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
benzo(e)pyrene	affects methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	decreases methylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	increases expression	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cadmium	increases abundance, decreases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Indomethacin	affects cotreatment, increases expression	1
Methapyrilene	affects methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Progesterone	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Vitamin E	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00395538	PHASE3	TERMINATED	Effects of PTH Replacement on Bone in Hypoparathyroidism
NCT00576407	PHASE2	COMPLETED	Thymus Transplantation in DiGeorge Syndrome #668
NCT00576836	PHASE2	COMPLETED	Thymus Transplantation Dose in DiGeorge #932
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT05149898	PHASE2	COMPLETED	Open-Label Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents With 22q11.2 Deletion Syndrome (INSPIRE)
NCT07284641	PHASE2	RECRUITING	Hematopoietic Stem Cell Transplantation (HSCT) for Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD)
NCT00566488	PHASE1	COMPLETED	Parathyroid and Thymus Transplantation in DiGeorge #931
NCT00579709	PHASE1	COMPLETED	Thymus Transplantation With Immunosuppression
NCT00849888	PHASE1	TERMINATED	Serum-Free Thymus Transplantation in DiGeorge Anomaly
NCT02895906	PHASE1	COMPLETED	Safety and Efficacy Study of NFC-1 in Subjects Aged 12-17 Years With 22q11.2DS & Associated Neuropsychiatric Conditions
NCT00579527	PHASE1/PHASE2	COMPLETED	Phase I/II Thymus Transplantation With Immunosuppression #950
NCT00004351	Not specified	COMPLETED	Study of Phenotype and Genotype Correlations in Patients With Contiguous Gene Deletion Syndromes
NCT00005102	Not specified	UNKNOWN	Immunologic Evaluation in Patients With DiGeorge Syndrome or Velocardiofacial Syndrome
NCT00105274	Not specified	COMPLETED	Velocardiofacial (VCFS; 22q11.2; DiGeorge) Syndrome Study
NCT00278005	Not specified	TERMINATED	Infection in DiGeorge Following CHD Surgery
NCT00556530	Not specified	RECRUITING	Examining Genetic Factors That Affect the Severity of 22q11.2 Deletion Syndrome
NCT00916955	Not specified	COMPLETED	Genetic Modifiers for 22q11.2 Syndrome
NCT01220531	Not specified	COMPLETED	Thymus Transplantation Safety-Efficacy
NCT01781923	Not specified	COMPLETED	Cognitive Remediation in 22q11DS
NCT02381457	Not specified	COMPLETED	SNP-based Microdeletion and Aneuploidy RegisTry (SMART)
NCT02430584	Not specified	UNKNOWN	Whole Blood Specimen Collection From Pregnant Subjects
NCT02460328	Not specified	COMPLETED	Resolution of Primary Immune Defect in 22q11.2 Deletion Syndrome
NCT02787486	Not specified	COMPLETED	Expanded Noninvasive Genomic Medical Assessment: The Enigma Study
NCT03284060	Not specified	TERMINATED	Social Cognition Training and Cognitive Remediation
NCT04141540	Not specified	COMPLETED	Molecular Variants Associated With Schizophrenia: Differential Analysis of Monozygotic Twins With Variable Phenotypic 22q11
NCT04373226	Not specified	TERMINATED	Arithmetic Abilities in Children With 22q11.2DS
NCT04639388	Not specified	RECRUITING	Understanding of Psychotic Disorders in Children With 22q11.2DS
NCT04639960	Not specified	TERMINATED	Neuroprotective Effects of Risperdal on Brain and Cognition in 22q11 Deletion Syndrome
NCT04647500	Not specified	COMPLETED	Effects of Methylphenidate on Brain and Cognition in 22q11 Deletion Syndrome
NCT05924347	Not specified	RECRUITING	Early Scoliotic Changes in Children at Increased Risk for Scoliosis Development
NCT07493096	Not specified	RECRUITING	Intensive Multimodal Neurorehabilitation Targeting Neuroplasticity in Pediatric Neurodevelopmental and Chromosomal Disorders