FOXL1

Summary

FOXL1 (forkhead box L1, HGNC:3817) is a protein-coding gene on chromosome 16q24.1, encoding Forkhead box protein L1 (Q12952). Transcription factor required for proper proliferation and differentiation in the gastrointestinal epithelium.

This gene encodes a member of the forkhead/winged helix-box (FOX) family of transcription factors. FOX transcription factors are characterized by a distinct DNA-binding forkhead domain and play critical roles in the regulation of multiple processes including metabolism, cell proliferation and gene expression during ontogenesis.

Source: NCBI Gene 2300 — RefSeq curated summary.

At a glance

• Gene–disease (curated): otosclerosis 11 (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 32
• Clinical variants (ClinVar): 73 total
• Phenotypes (HPO): 7
• MANE Select transcript: NM_005250

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3817
Approved symbol	FOXL1
Name	forkhead box L1
Location	16q24.1
Locus type	gene with protein product
Status	Approved
Aliases	FREAC7, FKH6
Ensembl gene	ENSG00000176678
Ensembl biotype	protein_coding
OMIM	603252
Entrez	2300

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000320241, ENST00000593625, ENST00000954000

RefSeq mRNA: 1 — MANE Select: NM_005250 NM_005250

CCDS: CCDS10959

Canonical transcript exons

ENST00000320241 — 1 exons

Exon	Start	End
ENSE00001280396	86578549	86583478

Expression profiles

Bgee: expression breadth ubiquitous, 145 present calls, max score 89.12.

FANTOM5 (CAGE): breadth broad, TPM avg 2.6942 / max 102.4527, expressed in 725 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155462	1.1065	445
155456	0.6868	357
155464	0.3479	175
155457	0.1562	50
155460	0.1469	51
155463	0.1055	45
155461	0.0835	36
155459	0.0413	15
155458	0.0198	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	89.12	silver quality
tibial artery	UBERON:0007610	81.98	gold quality
popliteal artery	UBERON:0002250	81.97	gold quality
aorta	UBERON:0000947	81.32	gold quality
ascending aorta	UBERON:0001496	80.79	gold quality
thoracic aorta	UBERON:0001515	80.65	gold quality
descending thoracic aorta	UBERON:0002345	80.06	gold quality
epithelial cell of pancreas	CL:0000083	79.60	gold quality
right coronary artery	UBERON:0001625	79.36	gold quality
stromal cell of endometrium	CL:0002255	78.61	gold quality
left coronary artery	UBERON:0001626	77.49	gold quality
coronary artery	UBERON:0001621	76.61	gold quality
gall bladder	UBERON:0002110	73.09	gold quality
palpebral conjunctiva	UBERON:0001812	70.09	gold quality
jejunal mucosa	UBERON:0000399	68.97	gold quality
myocardium	UBERON:0002349	68.95	gold quality
mucosa of transverse colon	UBERON:0004991	68.41	gold quality
cardiac muscle of right atrium	UBERON:0003379	67.21	gold quality
duodenum	UBERON:0002114	66.82	gold quality
tibia	UBERON:0000979	66.78	silver quality
rectum	UBERON:0001052	66.70	gold quality
left ventricle myocardium	UBERON:0006566	66.70	gold quality
calcaneal tendon	UBERON:0003701	66.50	gold quality
metanephros	UBERON:0000081	66.47	gold quality
mucosa of sigmoid colon	UBERON:0004993	65.52	silver quality
gastrocnemius	UBERON:0001388	65.45	gold quality
urinary bladder	UBERON:0001255	65.44	gold quality
upper arm skin	UBERON:0004263	65.41	gold quality
vena cava	UBERON:0004087	65.08	silver quality
tendon	UBERON:0000043	65.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.12

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
BMP2
BMP4	Activation

JASPAR motifs

Motif	Name	Family
MA0033.1	FOXL1	FOX
MA0033.2	FOXL1	FOX

JASPAR matrix evidence (PMIDs): PMID:7957066, PMID:23836653

Upstream regulators (CollecTRI, top): GLI2, GLI3

miRNA regulators (miRDB)

49 targeting FOXL1, 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-6740-5P	100.00	65.64	932
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-153-5P	99.89	73.86	6317
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-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-569	99.42	66.32	1009
HSA-MIR-2116-5P	99.32	69.34	1273
HSA-MIR-1912-3P	99.32	67.40	936
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-1295B-5P	99.03	67.50	810
HSA-MIR-3164	99.02	68.39	1071
HSA-MIR-6820-3P	99.02	68.50	1035

Literature-anchored findings (GeneRIF, showing 15)

• two novel de novo mutations in rare patients inherited gene variants in FOXL1. (PMID:21457232)
• FUS-CREB3L2/L1-positive sarcomas show a specific gene expression profile with upregulation of CD24 and FOXL1. (PMID:21536545)
• Lower FOXL1 expression is correlated with metastasis and advanced pathologic stage of pancreatic cancer. (PMID:23801748)
• results suggest that Foxl1 plays an inhibitory role in renal tumor progression. (PMID:24427331)
• dysregulated FOXL1 is involved in tumorigenesis and progression of gallbladder cancer. (PMID:25010679)
• the downregulation of FOXL1 expression was associated with osteosarcoma cell growth. Restoration of FOXL1 gene expression by gene therapy may have a therapeutic potential for patients with osteosarcoma (PMID:26062977)
• our findings provide evidence that FOXL1 might serve as a candidate tumor suppressor and a potential prognostic biomarker for gastric cancer (PMID:26960689)
• FOXL1 inhibited the proliferation, invasion, and migration of breast cancer.FOXL1 expression was reduced in breast cancer. (PMID:27938507)
• FOXL1 and miR-301a-5p show opposite biological effects in cell proliferation and migration. miR-301a-5p overexpression rescued the EPB41L4A-AS2 upregulation induced depression in proliferation, migration and invasion of HCC cells, as well as promotion effect on FOXL1 expression. In vivo experiments proved that EPB41L4A-AS2 suppress tumor growth and extrahepatic metastasis (lung) via the miR-301a-5p-FOXL1 axis. (PMID:30971290)
• Low expression of FOSL1 is associated with favorable prognosis and sensitivity to radiation/pharmaceutical therapy in lower grade glioma. (PMID:32245342)
• Prognostic Significances of NEDD-9 and FOXL-1 Expression in Intestinal Type Gastric Carcinoma: an Immunohistochemical Study. (PMID:32794109)
• FOXL1 Regulates Lung Fibroblast Function via Multiple Mechanisms. (PMID:32946266)
• MiR-1471 protects the aggravation of non-small-cell lung carcinoma by targeting FOXL1. (PMID:33045131)
• NTF4 stimulates the progression of gastric cancer via regulating FOXL1. (PMID:34076998)
• A pathogenic deletion in Forkhead Box L1 (FOXL1) identifies the first otosclerosis (OTSC) gene. (PMID:34633540)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	foxl1	ENSDARG00000008133
mus_musculus	Foxl1	ENSMUSG00000097084
drosophila_melanogaster	FoxL1	FBGN0004895

Paralogs (41): FOXP3 (ENSG00000049768), FOXC1 (ENSG00000054598), FOXJ2 (ENSG00000065970), FOXF1 (ENSG00000103241), FOXN1 (ENSG00000109101), FOXM1 (ENSG00000111206), FOXP1 (ENSG00000114861), FOXO3 (ENSG00000118689), FOXA2 (ENSG00000125798), FOXA1 (ENSG00000129514), FOXJ1 (ENSG00000129654), FOXK2 (ENSG00000141568), FOXO1 (ENSG00000150907), FOXH1 (ENSG00000160973), FOXQ1 (ENSG00000164379), FOXK1 (ENSG00000164916), FOXD4 (ENSG00000170122), FOXA3 (ENSG00000170608), FOXB1 (ENSG00000171956), FOXR1 (ENSG00000176302), FOXC2 (ENSG00000176692), FOXE1 (ENSG00000178919), FOXS1 (ENSG00000179772), FOXL2 (ENSG00000183770), FOXO4 (ENSG00000184481), FOXD4L1 (ENSG00000184492), FOXD4L4 (ENSG00000184659), FOXD2 (ENSG00000186564), FOXI2 (ENSG00000186766), FOXE3 (ENSG00000186790), FOXD3 (ENSG00000187140), FOXD4L3 (ENSG00000187559), FOXR2 (ENSG00000189299), FOXJ3 (ENSG00000198815), FOXO6 (ENSG00000204060), FOXB2 (ENSG00000204612), FOXD4L5 (ENSG00000204779), FOXI3 (ENSG00000214336), FOXL3 (ENSG00000248767), FOXD1 (ENSG00000251493)

Protein

Protein identifiers

Forkhead box protein L1 — Q12952 (reviewed: Q12952)

Alternative names: Forkhead-related protein FKHL11, Forkhead-related transcription factor 7

All UniProt accessions (2): Q12952, M0R279

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor required for proper proliferation and differentiation in the gastrointestinal epithelium. Target gene of the hedgehog (Hh) signaling pathway via GLI2 and GLI3 transcription factors.

Subcellular location. Nucleus.

Disease relevance. Otosclerosis 11 (OTSC11) [MIM:620576] A form of otosclerosis, a pathological condition of the ear characterized by formation of spongy bone in the labyrinth capsule, especially in front of and posterior to the footplate of the stapes, resulting in conductive hearing impairment. Cochlear otosclerosis may also develop, resulting in sensorineural hearing loss. OTSC11 is an autosomal dominant form characterized by onset of progressive deafness in the second to third decade of life. Deafness ranges from moderate to severe, and may be conductive, sensorineural, or mixed. The disease may be caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_005241* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001766	Fork_head_dom	Domain
IPR018122	TF_fork_head_CS_1	Conserved_site
IPR030456	TF_fork_head_CS_2	Conserved_site
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR047514	FH_FOXL1	Domain
IPR050211	FOX_domain-containing	Family

Pfam: PF00250

UniProt features (8 total): compositionally biased region 4, chain 1, DNA-binding region 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12952-F1	64.30	0.24

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 113 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_CELL_CELL_SIGNALING, GOBP_DIGESTIVE_SYSTEM_DEVELOPMENT, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_HEMATOPOIETIC_OR_LYMPHOID_ORGAN_DEVELOPMENT, GOBP_TISSUE_MORPHOGENESIS, GOBP_MIDGUT_DEVELOPMENT, GOBP_CIRCULATORY_SYSTEM_DEVELOPMENT, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS, GOMF_DNA_BINDING_BENDING, GSE13522_WT_VS_IFNG_KO_SKIN_DN, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, MEISSNER_NPC_HCP_WITH_H3K27ME3

GO Biological Process (9): regulation of transcription by RNA polymerase II (GO:0006357), visceral mesoderm-endoderm interaction involved in midgut development (GO:0007495), heart development (GO:0007507), anatomical structure morphogenesis (GO:0009653), regulation of Wnt signaling pathway (GO:0030111), cell differentiation (GO:0030154), proteoglycan biosynthetic process (GO:0030166), Peyer’s patch morphogenesis (GO:0061146), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (6): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), DNA binding, bending (GO:0008301), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
DNA binding	2
transcription by RNA polymerase II	1
cell-cell signaling	1
midgut development	1
animal organ development	1
circulatory system development	1
developmental process	1
anatomical structure development	1
regulation of signal transduction	1
Wnt signaling pathway	1
cellular developmental process	1
proteoglycan metabolic process	1
glycoprotein biosynthetic process	1
Peyer’s patch development	1
tissue morphogenesis	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1668 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FOXL1	GLI1	P08151	725
FOXL1	CPS1	P31327	720
FOXL1	GLI2	P10070	663
FOXL1	GLI3	P10071	644
FOXL1	MTHFSD	Q2M296	633
FOXL1	SHH	Q15465	579
FOXL1	SLC5A1	P13866	567
FOXL1	AIMP1	Q12904	543
FOXL1	CTNNB1	P35222	534
FOXL1	WNT2B	Q93097	521
FOXL1	DMRTA2	Q96SC8	507
FOXL1	ZBTB40	Q9NUA8	507
FOXL1	LGR5	O75473	504
FOXL1	RSPO3	Q9BXY4	490
FOXL1	MYC	P01106	476

IntAct

5 interactions, top by confidence:

A	B	Type	Score
NFIB	FOXL1	psi-mi:“MI:0915”(physical association)	0.470
FOXL1	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXL1	IFRD1	psi-mi:“MI:0914”(association)	0.350
FOXL1	PGRMC1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (202): SCRIB (Affinity Capture-MS), PDS5A (Affinity Capture-MS), SYMPK (Affinity Capture-MS), BTAF1 (Affinity Capture-MS), DDX39A (Affinity Capture-MS), HEATR1 (Affinity Capture-MS), YARS (Affinity Capture-MS), MDN1 (Affinity Capture-MS), VARS (Affinity Capture-MS), NUP205 (Affinity Capture-MS), SMC2 (Affinity Capture-MS), SMPD4 (Affinity Capture-MS), RANGAP1 (Affinity Capture-MS), ORC3 (Affinity Capture-MS), HELLS (Affinity Capture-MS)

ESM2 similar proteins: A0A1W2PRP0, A6NCS4, A7Y7W2, O14512, O43638, O57601, O70220, O96004, P07812, P09023, P10085, P10284, P17483, P22091, P24899, P50548, P52954, P52955, P55318, P57100, P63156, P63157, P70447, P79772, P97832, Q02346, Q05917, Q0VCE2, Q12952, Q1XID0, Q28555, Q3I5G5, Q3Y598, Q60688, Q61660, Q63244, Q63250, Q64279, Q64305, Q64731

Diamond homologs: A0A078BQN7, A0A1W2PRP0, A0A8V0YY16, A1L1S5, A3KNJ3, A8MTJ6, A8XJN7, B5RHS5, D3Z120, F1R8Z9, O00358, O17617, O43638, O54743, O60129, O88470, P32027, P32028, P32030, P32315, P42128, P55316, P56260, P58012, P79772, P85037, P91278, Q00939, Q01167, Q02360, Q12946, Q12947, Q12948, Q12950, Q12951, Q12952, Q13461, Q19802, Q1A1A1, Q1A1A2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

50 predictions. Top by Δscore:

Variant	Effect	Δscore
16:86579152:G:GT	donor_gain	0.7100
16:86579530:A:T	donor_gain	0.6300
16:86579697:TCGG:T	acceptor_gain	0.5300
16:86579698:CGGG:C	acceptor_gain	0.5200
16:86579558:G:T	donor_gain	0.5100
16:86579575:TGCC:T	donor_gain	0.5100
16:86579571:G:GT	donor_gain	0.4900
16:86579700:G:GT	acceptor_gain	0.4400
16:86579558:G:GT	donor_gain	0.4200
16:86579146:G:GT	donor_gain	0.4100
16:86579557:G:T	donor_gain	0.3900
16:86579704:C:CA	acceptor_gain	0.3900
16:86579537:G:GT	donor_gain	0.3800
16:86579705:C:A	acceptor_gain	0.3800
16:86579234:G:GT	donor_gain	0.3700
16:86579709:T:TA	acceptor_gain	0.3700
16:86579495:TCC:T	donor_gain	0.3600
16:86579542:G:GT	donor_gain	0.3300
16:86579740:C:CG	acceptor_gain	0.3300
16:86579222:G:GT	donor_gain	0.3200
16:86579529:G:GT	donor_gain	0.3200
16:86579576:GCCA:G	donor_gain	0.3100
16:86580155:GC:G	donor_gain	0.3100
16:86579699:GGGA:G	acceptor_gain	0.2900
16:86579706:C:CA	acceptor_gain	0.2800
16:86579744:GT:G	acceptor_gain	0.2800
16:86579435:G:T	donor_gain	0.2700
16:86579696:CTCGG:C	acceptor_gain	0.2700
16:86579710:C:A	acceptor_gain	0.2600
16:86579726:CTGCA:C	acceptor_loss	0.2600

AlphaMissense

2221 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:86578893:T:C	L57P	1.000
16:86578938:T:A	L72H	1.000
16:86578955:T:C	F78L	1.000
16:86578957:C:A	F78L	1.000
16:86578957:C:G	F78L	1.000
16:86578970:T:C	F83L	1.000
16:86578972:C:A	F83L	1.000
16:86578972:C:G	F83L	1.000
16:86579000:T:A	W93R	1.000
16:86579000:T:C	W93R	1.000
16:86579002:G:C	W93C	1.000
16:86579002:G:T	W93C	1.000
16:86579006:A:G	N95D	1.000
16:86579007:A:T	N95I	1.000
16:86579008:C:A	N95K	1.000
16:86579008:C:G	N95K	1.000
16:86579013:T:A	I97N	1.000
16:86579013:T:C	I97T	1.000
16:86579013:T:G	I97S	1.000
16:86579015:C:A	R98S	1.000
16:86579015:C:G	R98G	1.000
16:86579016:G:C	R98P	1.000
16:86579018:C:A	H99N	1.000
16:86579018:C:G	H99D	1.000
16:86579019:A:C	H99P	1.000
16:86579019:A:G	H99R	1.000
16:86579019:A:T	H99L	1.000
16:86579020:C:A	H99Q	1.000
16:86579020:C:G	H99Q	1.000
16:86579023:C:A	N100K	1.000

dbSNP variants (sampled 300 via entrez): RS1000471177 (16:86580677 C>T), RS1000574648 (16:86577249 T>G), RS1000683970 (16:86581662 C>T), RS1001362928 (16:86577925 C>A,T), RS1001437465 (16:86581077 G>A,C), RS1001885922 (16:86579897 C>A,T), RS1001947272 (16:86580886 C>T), RS1002359172 (16:86577075 C>G), RS1002843258 (16:86580312 C>G,T), RS1003751590 (16:86577217 T>C), RS1003888085 (16:86582498 T>C), RS1004592562 (16:86577888 T>A,C), RS1004704226 (16:86577690 T>C), RS1005215571 (16:86582148 T>A), RS1005508406 (16:86577786 C>G)

Disease associations

OMIM: gene MIM:603252 | disease phenotypes: MIM:620576

GenCC curated gene-disease

Disease	Classification	Inheritance
otosclerosis 11	Limited	Autosomal dominant
congenital heart disease	Disputed Evidence	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
congenital heart disease	Disputed	AD

Mondo (2): otosclerosis 11 (MONDO:0957928), congenital heart disease (MONDO:0005453)

Orphanet (0):

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000362	Otosclerosis
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0003621	Juvenile onset
HP:0008529	Absence of acoustic reflex
HP:0011462	Young adult onset

GWAS associations

32 associations (top):

Study	Trait	p-value
GCST000494_4	Bone mineral density (spine)	2.000000e-08
GCST000495_7	Bone mineral density (hip)	2.000000e-07
GCST001762_888	Obesity-related traits	3.000000e-06
GCST002276_10	Bone mineral density	2.000000e-10
GCST002276_12	Bone mineral density	2.000000e-06
GCST002333_9	Bone properties (heel)	8.000000e-06
GCST002919_5	Colorectal cancer	5.000000e-08
GCST003430_4	Incident myocardial infarction	7.000000e-06
GCST003784_16	Multiple system atrophy	8.000000e-06
GCST003963_4	Possible neuropathic pain in post total joint replacement surgery for osteoarthritis	4.000000e-06
GCST003999_21	Nose size	2.000000e-07
GCST004025_25	Systemic juvenile idiopathic arthritis	5.000000e-06
GCST004230_1	Sepsis in extremely premature infants	1.000000e-07
GCST005795_5	Femoral neck bone mineral density	2.000000e-11
GCST005796_29	Lumbar spine bone mineral density	1.000000e-09
GCST006479_95	Diverticular disease	2.000000e-06
GCST007147_2	Lateral ventricular volume in normal aging	4.000000e-15
GCST007691_15	Femoral neck bone mineral density	1.000000e-14
GCST007856_21	Colorectal cancer or advanced adenoma	5.000000e-09
GCST007856_34	Colorectal cancer or advanced adenoma	5.000000e-06
GCST008295_41	Number of decayed, missing and filled tooth surfaces or use of dentures	5.000000e-14
GCST008306_10	Dentures	4.000000e-13
GCST008394_9	Mild to moderate chronic kidney disease	5.000000e-07
GCST009356_15	Nonsyndromic cleft palate	9.000000e-11
GCST010736_10	Urinary albumin-to-creatinine ratio	4.000000e-07
GCST010866_72	Coronary artery disease	4.000000e-09
GCST011946_5	White matter hyperintensity volume	2.000000e-06
GCST011947_56	White matter hyperintensity volume	2.000000e-07
GCST011949_23	White matter hyperintensity volume (adjusted for hypertension)	3.000000e-06
GCST011950_18	White matter hyperintensity volume (adjusted for hypertension)	3.000000e-07

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0005115	metabolic rate measurement
EFO:0005654	velocity of sound measurement
EFO:0005762	neuropathic pain
EFO:0007785	femoral neck bone mineral density
EFO:0007701	spine bone mineral density
EFO:0009959	diverticular disease
EFO:0008487	lateral ventricle volume measurement
EFO:0010078	dentures
EFO:0007778	urinary albumin to creatinine ratio
EFO:0005665	white matter hyperintensity measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression	2
2-methyl-4-isothiazolin-3-one	increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
abrine	increases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases reaction, increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Leflunomide	decreases expression	1
Bleomycin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
N-Nitrosopyrrolidine	increases expression	1
Niclosamide	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Asbestos, Crocidolite	decreases methylation	1
Asbestos, Amosite	decreases methylation	1
Cadmium Chloride	decreases expression	1
Palmitic Acid	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A2B2	SEES3-1V human FOXL1, clone1	Embryonic stem cell	Male
CVCL_A2B3	SEES3-1V human FOXL1, clone2	Embryonic stem cell	Male
CVCL_A2B4	SEES3-1V human FOXL1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	PHASE2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	PHASE2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE