NFE2L3

Summary

NFE2L3 (NFE2 like bZIP transcription factor 3, HGNC:7783) is a protein-coding gene on chromosome 7p15.2, encoding Nuclear factor erythroid 2-related factor 3 (Q9Y4A8). Activates erythroid-specific, globin gene expression. It is a selective cancer dependency (DepMap: 22.4% of cell lines).

This gene encodes a member of the cap ’n’ collar basic-region leucine zipper family of transcription factors. The encoded protein heterodimerizes with small musculoaponeurotic fibrosarcoma factors to bind antioxidant response elements in target genes. This protein is a membrane bound glycoprotein that is targeted to the endoplasmic reticulum and the nuclear envelope. Pseudogenes of this gene are found on chromosomes 16, 17, and 18.

Source: NCBI Gene 9603 — RefSeq curated summary.

At a glance

• GWAS associations: 78
• Clinical variants (ClinVar): 146 total
• Phenotypes (HPO): 1
• Cancer dependency (DepMap): dependent in 22.4% of screened cell lines
• MANE Select transcript: NM_004289

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7783
Approved symbol	NFE2L3
Name	NFE2 like bZIP transcription factor 3
Location	7p15.2
Locus type	gene with protein product
Status	Approved
Aliases	Nrf3
Ensembl gene	ENSG00000050344
Ensembl biotype	protein_coding
OMIM	604135
Entrez	9603

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 retained_intron

ENST00000056233, ENST00000606261, ENST00000607375, ENST00000927666, ENST00000927667, ENST00000927668, ENST00000927669

RefSeq mRNA: 1 — MANE Select: NM_004289 NM_004289

CCDS: CCDS5396

Canonical transcript exons

ENST00000056233 — 4 exons

Exon	Start	End
ENSE00000435637	26177943	26178122
ENSE00000674098	26152198	26153068
ENSE00000674110	26183701	26183784
ENSE00001420641	26184533	26187137

Expression profiles

Bgee: expression breadth ubiquitous, 214 present calls, max score 91.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.0834 / max 176.8566, expressed in 1465 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
77735	10.0834	1465

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.72	gold quality
placenta	UBERON:0001987	89.17	gold quality
body of pancreas	UBERON:0001150	88.96	gold quality
cerebellar hemisphere	UBERON:0002245	88.16	gold quality
cerebellar cortex	UBERON:0002129	87.94	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.84	gold quality
colonic epithelium	UBERON:0000397	87.34	gold quality
calcaneal tendon	UBERON:0003701	86.78	gold quality
adrenal tissue	UBERON:0018303	86.53	gold quality
metanephros cortex	UBERON:0010533	85.99	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.74	gold quality
vermiform appendix	UBERON:0001154	84.71	gold quality
rectum	UBERON:0001052	84.13	gold quality
mucosa of stomach	UBERON:0001199	83.89	gold quality
right lung	UBERON:0002167	83.83	gold quality
skin of leg	UBERON:0001511	83.81	gold quality
mucosa of transverse colon	UBERON:0004991	83.79	gold quality
cerebellum	UBERON:0002037	83.59	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.43	gold quality
skin of abdomen	UBERON:0001416	83.42	gold quality
body of stomach	UBERON:0001161	83.41	gold quality
spleen	UBERON:0002106	83.17	gold quality
right lobe of liver	UBERON:0001114	83.04	gold quality
cortical plate	UBERON:0005343	82.71	gold quality
monocyte	CL:0000576	82.39	gold quality
pancreas	UBERON:0001264	82.35	gold quality
lower esophagus mucosa	UBERON:0035834	81.93	gold quality
leukocyte	CL:0000738	81.82	gold quality
mononuclear cell	CL:0000842	81.80	gold quality
zone of skin	UBERON:0000014	81.79	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-24	yes	398.52
E-MTAB-6701	yes	126.24
E-ANND-3	yes	4.28
E-MTAB-3929	no	217.44

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
ACTA2	Activation
HBB	Repression
NQO1	Repression
PLA2G7	Activation
PRDX6	Repression
TAGLN	Activation
TBXAS1	Activation

miRNA regulators (miRDB)

90 targeting NFE2L3, 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-3646	100.00	73.56	5283
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-374C-5P	99.80	72.06	2910

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 22.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 23)

• Nrf3 is a negative regulator of ARE-mediated gene expression of NQO1 (PMID:15385560)
• NRF3 is highly expressed in primary placental cytotrophoblasts (PMID:15388789)
• Nrf3 is an N-glycosylated protein associated with the endoplasmic reticulum (PMID:17976382)
• 17beta-Estradiol treatment significantly increased but VC or Res decreased Nrf3 mRNA and protein expression levels. (PMID:25130429)
• findings reveal FBW7 and GSK3 as novel regulators of the NFE2L3 transcription factor and a potential mechanism by which FBW7 might regulate detoxification and the cellular response to stress (PMID:26306035)
• SNPs associated with type 2 diabetes and obesity may also increase the risk of developing gestational diabetes mellitus (GDM) in the Chinese population. Among these SNPs, we report for the first time that rs945508 in ARHGEF11, rs10804591 in PLXND1 and rs10245353 in NFE2L3 were associated with GDM. (PMID:28554271)
• Multiple regulatory mechanisms of the biological function of NFE2L3 control proliferation of cancer cells. (PMID:28970512)
• confirmed the regulatory role of NFE2L3 on VEGFA, an important player involved in tumor angiogenesis (PMID:30196752)
• Study identified that NFE2L3 was closely associated with the grade and stage of hepatocellular carcinoma (HCC) patients based on the TCGA database. Furthermore, study showed that shRNA-mediated knockdown of NFE2L3 exhibited tumor-suppressing effects in HCC cells. (PMID:30886504)
• Downregulation of NFE2L3 induces G0/G1 phase arrest in colorectal cancer cells through downregulation of CCND1 and pRb1-ser807/811. (PMID:31191746)
• we observed that the beta-catenin/TCF4 complex mediates NRF3 expression by binding directly to the WRE site. (PMID:31288376)
• analysis provides a comprehensive description of differential and overlapping gene regulation by the transcriptional regulators NFE2L1(NRF1), NFE2L2 (NRF2), and NFE2L3 (NRF3). (PMID:31628195)
• NFE2L3 Controls Colon Cancer Cell Growth through Regulation of DUX4, a CDK1 Inhibitor. (PMID:31693889)
• NRF3-POMP-20S Proteasome Assembly Axis Promotes Cancer Development via Ubiquitin-Independent Proteolysis of p53 and Retinoblastoma Protein. (PMID:32123008)
• NFE2L1 and NFE2L3 Complementarily Maintain Basal Proteasome Activity in Cancer Cells through CPEB3-Mediated Translational Repression. (PMID:32366381)
• Elevated expression of NFE2L3 promotes the development of gastric cancer through epithelial-mesenchymal transformation. (PMID:34783304)
• NFE2L3 promotes tumor progression and predicts a poor prognosis of bladder cancer. (PMID:35022660)
• Transcription factor NFE2L3 promotes the proliferation of esophageal squamous cell carcinoma cells and causes radiotherapy resistance by regulating IL-6. (PMID:36108571)
• NFE2L3 as a Potential Functional Gene Regulating Immune Microenvironment in Human Kidney Cancer. (PMID:36337840)
• Hypomethylation-Mediated Upregulation of NFE2L3 Promotes Malignant Phenotypes of Clear Cell Renal Cell Carcinoma Cells. (PMID:37071304)
• NRF3 suppresses squamous carcinogenesis, involving the unfolded protein response regulator HSPA5. (PMID:37807968)
• Identification roles of NFE2L3 in digestive system cancers. (PMID:38514488)
• NRF3 suppresses the malignant progression of TNBC by promoting M1 polarization of macrophages via ROS/HMGB1 axis. (PMID:39443820)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nfe2l3	ENSDARG00000019810
mus_musculus	Nfe2l3	ENSMUSG00000029832
rattus_norvegicus	Nfe2l3	ENSRNOG00000010886

Paralogs (3): NFE2L1 (ENSG00000082641), NFE2L2 (ENSG00000116044), NFE2 (ENSG00000123405)

Protein

Protein identifiers

Nuclear factor erythroid 2-related factor 3 — Q9Y4A8 (reviewed: Q9Y4A8)

Alternative names: Nuclear factor, erythroid derived 2, like 3

All UniProt accessions (2): Q9Y4A8, U3KQ19

UniProt curated annotations — full annotation on UniProt →

Function. Activates erythroid-specific, globin gene expression.

Subunit / interactions. Heterodimer with MAFG, MAFK and other small MAF proteins that binds to the MAF recognition elements (MARE).

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in human placenta and also in B-cell and monocyte cell lines. Low expression in heart, brain, lung, skeletal muscle, kidney and pancreas.

Similarity. Belongs to the bZIP family. CNC subfamily.

RefSeq proteins (1): NP_004280* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004826	bZIP_Maf	Domain
IPR004827	bZIP	Domain
IPR008917	TF_DNA-bd_sf	Homologous_superfamily
IPR046347	bZIP_sf	Homologous_superfamily
IPR047167	NFE2-like	Family

Pfam: PF03131

UniProt features (12 total): region of interest 4, compositionally biased region 4, chain 1, domain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y4A8-F1	54.20	0.16

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 188 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, BROWNE_HCMV_INFECTION_16HR_UP, GGGTGGRR_PAX4_03, MARTINEZ_RB1_TARGETS_DN, ROZANOV_MMP14_TARGETS_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, MODULE_206, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, MCBRYAN_PUBERTAL_BREAST_5_6WK_UP, TGANTCA_AP1_C, BENPORATH_ES_CORE_NINE_CORRELATED, MAGRANGEAS_MULTIPLE_MYELOMA_IGLL_VS_IGLK_UP, DODD_NASOPHARYNGEAL_CARCINOMA_UP, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_UP

GO Biological Process (5): regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), integrated stress response signaling (GO:0140467), negative regulation of transcription by RNA polymerase II (GO:0000122), 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 transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription factor activity (GO:0003700), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), RNA polymerase II transcription regulator complex (GO:0090575)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
DNA-templated transcription	2
regulation of transcription by RNA polymerase II	2
cellular response to stress	1
intracellular signaling cassette	1
negative regulation of 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
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
nucleic acid binding	1
binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1
transcription regulator complex	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

1110 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NFE2L3	MAF	O75444	888
NFE2L3	MAFK	O60675	873
NFE2L3	FOS	P01100	757
NFE2L3	JUN	P05412	727
NFE2L3	JUND	P17535	717
NFE2L3	MAFG	O15525	613
NFE2L3	NKRF	O15226	586
NFE2L3	KEAP1	Q14145	552
NFE2L3	GATA1	P15976	547
NFE2L3	NEIL2	Q969S2	533
NFE2L3	MAFF	Q9ULX9	513
NFE2L3	HOXA11	P31270	507
NFE2L3	GCLC	P48506	485
NFE2L3	CUL3	Q13618	484
NFE2L3	DDI2	Q5TDH0	480

IntAct

25 interactions, top by confidence:

A	B	Type	Score
NFE2L3	MAFG	psi-mi:“MI:0407”(direct interaction)	0.780
NFE2L3	MAFG	psi-mi:“MI:0914”(association)	0.780
MAFG	NFE2L3	psi-mi:“MI:0407”(direct interaction)	0.780
NFE2L3	MAFF	psi-mi:“MI:0407”(direct interaction)	0.690
MAFF	NFE2L3	psi-mi:“MI:0407”(direct interaction)	0.690
NFE2	NFE2L3	psi-mi:“MI:0407”(direct interaction)	0.620
NFE2L3	NFE2	psi-mi:“MI:0407”(direct interaction)	0.620
MAFF	NFE2L1	psi-mi:“MI:0914”(association)	0.590
MAFF	GAPDHS	psi-mi:“MI:0914”(association)	0.530
NFE2L3	ATF4	psi-mi:“MI:0407”(direct interaction)	0.440
NFE2L3	CREB3	psi-mi:“MI:0407”(direct interaction)	0.440
NFE2L3	NFE2L1	psi-mi:“MI:0407”(direct interaction)	0.440
NFE2L3	NFE2L2	psi-mi:“MI:0407”(direct interaction)	0.440
NFE2L3	NFE2L3	psi-mi:“MI:0407”(direct interaction)	0.440
NFE2L3	BACH2	psi-mi:“MI:0407”(direct interaction)	0.440
PSCA	METTL15	psi-mi:“MI:0914”(association)	0.350
NFE2L3	C4A	psi-mi:“MI:0914”(association)	0.350
FMR1	NFE2L3	psi-mi:“MI:0915”(physical association)	0.000
DSCR9	NFE2L3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (32): NFE2L3 (Protein-peptide), NFE2L3 (Affinity Capture-MS), FBXW7 (Affinity Capture-Western), GSK3B (Affinity Capture-Western), NFE2L3 (Biochemical Activity), NFE2L3 (Affinity Capture-MS), MAFK (Affinity Capture-MS), MAFG (Affinity Capture-MS), HCFC2 (Affinity Capture-MS), HCFC1 (Affinity Capture-MS), MAFK (Two-hybrid), MAFG (Affinity Capture-MS), HCFC1 (Affinity Capture-MS), NFE2L3 (Affinity Capture-MS), MAFK (Affinity Capture-MS)

ESM2 similar proteins: A1L3I3, A2AWH2, A2BDP1, A4IFM1, A4IHZ3, A5A6P7, A7E2V4, B1AL88, F1N4E5, O14525, O35181, O75949, O94901, O94983, P13265, P51654, P56975, P78333, Q07105, Q0VCT2, Q29016, Q2F7Z7, Q3T0Q2, Q3V140, Q4FZU8, Q4R8C8, Q5HZE8, Q5PQX1, Q5R7A3, Q5R800, Q60485, Q61137, Q68FE6, Q6H9L7, Q6P7B4, Q6V9Y8, Q6ZS17, Q7TNI2, Q80Y50, Q8BHP7

Diamond homologs: A5D7E9, O14867, O54968, P20482, P34707, P97302, P97303, Q07279, Q14494, Q16236, Q16621, Q5EAD3, Q5NUA6, Q5RA25, Q5ZL67, Q60795, Q61985, Q6AYT2, Q9BYV9, Q9Y4A8, Q9WTM4, A0JN76, A1L2U9, A1YPR0, B1WAZ8, B1WBU4, D4A2K4, E0CZ16, E1B932, F1LZ52, F1LZF0, F1MBP6, O15062, O43167, O43298, O88282, O88939, O93567, O95198, O95365

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
NFE2L3	“down-regulates quantity by repression”	NQO1	“transcriptional regulation”
NFE2L3	“up-regulates quantity by expression”	PLA2G7	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	130
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

666 predictions. Top by Δscore:

Variant	Effect	Δscore
7:26177940:TAG:T	acceptor_loss	1.0000
7:26177941:A:AG	acceptor_gain	1.0000
7:26177941:A:AT	acceptor_loss	1.0000
7:26177941:AG:A	acceptor_gain	1.0000
7:26177942:G:A	acceptor_loss	1.0000
7:26177942:G:GT	acceptor_gain	1.0000
7:26177942:GG:G	acceptor_gain	1.0000
7:26177942:GGA:G	acceptor_gain	1.0000
7:26177942:GGAGA:G	acceptor_gain	1.0000
7:26178118:ATGAG:A	donor_gain	1.0000
7:26178119:TGAGG:T	donor_loss	1.0000
7:26178120:GAG:G	donor_gain	1.0000
7:26178121:AGG:A	donor_loss	1.0000
7:26178123:G:GG	donor_gain	1.0000
7:26178123:GTA:G	donor_loss	1.0000
7:26178124:T:G	donor_loss	1.0000
7:26183695:CTACA:C	acceptor_loss	1.0000
7:26183696:TACA:T	acceptor_loss	1.0000
7:26183697:ACAG:A	acceptor_loss	1.0000
7:26183698:CAGAG:C	acceptor_loss	1.0000
7:26183699:A:AG	acceptor_gain	1.0000
7:26183699:A:C	acceptor_loss	1.0000
7:26183700:G:GC	acceptor_loss	1.0000
7:26183700:G:GG	acceptor_gain	1.0000
7:26183700:GA:G	acceptor_gain	1.0000
7:26183700:GAGAC:G	acceptor_gain	1.0000
7:26183780:TGGAG:T	donor_loss	1.0000
7:26183782:G:GT	donor_gain	1.0000
7:26183783:AGGT:A	donor_loss	1.0000
7:26183784:GGTA:G	donor_loss	1.0000

AlphaMissense

4574 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:26185447:A:C	R583S	0.994
7:26185447:A:T	R583S	0.994
7:26185458:A:T	K587I	0.994
7:26185446:G:C	R583T	0.993
7:26185449:G:C	R584P	0.993
7:26185459:A:C	K587N	0.992
7:26185459:A:T	K587N	0.992
7:26185382:T:C	F562L	0.991
7:26185383:T:C	F562S	0.991
7:26185384:C:A	F562L	0.991
7:26185384:C:G	F562L	0.991
7:26185453:A:C	R585S	0.991
7:26185453:A:T	R585S	0.991
7:26185484:C:A	R596S	0.989
7:26185465:A:C	K589N	0.988
7:26185465:A:T	K589N	0.988
7:26185470:C:A	A591D	0.988
7:26185462:T:A	N588K	0.986
7:26185462:T:G	N588K	0.986
7:26185437:G:C	R580P	0.985
7:26185460:A:G	N588D	0.985
7:26185491:G:C	R598P	0.985
7:26185485:G:C	R596P	0.984
7:26185490:C:A	R598S	0.983
7:26185323:C:A	A542D	0.982
7:26185338:T:C	I547T	0.982
7:26185458:A:C	K587T	0.982
7:26185446:G:T	R583I	0.981
7:26185455:G:A	G586E	0.981
7:26185461:A:C	N588T	0.981

dbSNP variants (sampled 300 via entrez): RS1000014363 (7:26187415 G>T), RS1000028102 (7:26172226 T>C), RS1000159250 (7:26185838 T>A,C), RS1000185130 (7:26175225 T>G), RS1000427915 (7:26150439 A>G), RS1000481388 (7:26159284 C>T), RS1000485848 (7:26172037 T>A), RS1000507880 (7:26185084 A>C,T), RS1000647604 (7:26153545 C>A,G), RS1000658549 (7:26154549 TTTTTGTTTG>T), RS1000679024 (7:26181257 G>A), RS1000778681 (7:26185269 G>A), RS1000806822 (7:26157743 G>A), RS1000842371 (7:26163691 T>A,C), RS1000939591 (7:26154324 A>G)

Disease associations

OMIM: gene MIM:604135 | disease phenotypes: MIM:148300

GenCC curated gene-disease

Mondo (2): keratoconus (MONDO:0015486), neurodevelopmental disorder (MONDO:0700092)

Orphanet (2): OBSOLETE: Keratoconus (Orphanet:156071), NON RARE IN EUROPE: Isolated keratoconus (Orphanet:2335)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000563	Keratoconus

GWAS associations

78 associations (top):

Study	Trait	p-value
GCST000829_6	Waist-hip ratio	1.000000e-24
GCST001762_736	Obesity-related traits	3.000000e-07
GCST001967_7	Body mass index	1.000000e-10
GCST002365_7	Response to anti-retroviral therapy (ddI/d4T) in HIV-1 infection (Grade 2 peripheral neuropathy)	5.000000e-06
GCST002366_5	Response to anti-retroviral therapy (ddI/d4T) in HIV-1 infection (Grade 1 peripheral neuropathy)	5.000000e-06
GCST002663_2	Superior frontal gyrus grey matter volume	8.000000e-07
GCST002782_20	Waist-to-hip ratio adjusted for body mass index	1.000000e-13
GCST002782_21	Waist-to-hip ratio adjusted for body mass index	6.000000e-14
GCST002782_22	Waist-to-hip ratio adjusted for body mass index	1.000000e-12
GCST002782_23	Waist-to-hip ratio adjusted for body mass index	2.000000e-13
GCST002782_37	Waist-to-hip ratio adjusted for body mass index	1.000000e-13
GCST002782_38	Waist-to-hip ratio adjusted for body mass index	2.000000e-16
GCST002782_85	Waist-to-hip ratio adjusted for body mass index	8.000000e-13
GCST002782_86	Waist-to-hip ratio adjusted for body mass index	8.000000e-16
GCST004063_137	Waist circumference adjusted for body mass index	5.000000e-11
GCST004063_141	Waist circumference adjusted for body mass index	3.000000e-15
GCST004063_97	Waist circumference adjusted for body mass index	2.000000e-07
GCST004064_5	Waist-hip ratio	1.000000e-09
GCST004064_50	Waist-hip ratio	2.000000e-10
GCST004368_2	Endometriosis	6.000000e-07
GCST004370_1	Deep ovarian and/or rectovaginal disease with dense adhesions	2.000000e-09
GCST004500_7	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	1.000000e-12
GCST004500_88	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	4.000000e-11
GCST004501_116	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	3.000000e-14
GCST004501_117	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	2.000000e-11
GCST004504_86	Waist circumference adjusted for BMI in non-smokers	1.000000e-10
GCST004504_87	Waist circumference adjusted for BMI in non-smokers	2.000000e-12
GCST004505_86	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	1.000000e-10
GCST004505_87	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	4.000000e-10
GCST004567_131	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	7.000000e-06

EFO canonical traits (20, from GWAS)

EFO ID	Trait name
EFO:0004343	waist-hip ratio
EFO:0003939	energy intake
EFO:0004340	body mass index
EFO:0000180	HIV-1 infection
EFO:0006516	superior frontal gyrus grey matter volume measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007789	BMI-adjusted waist circumference
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0004574	total cholesterol measurement
EFO:0005301	reading and spelling ability
EFO:0004530	triglyceride measurement
EFO:0004329	alcohol drinking
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004615	apolipoprotein B measurement
EFO:0006925	lipoprotein A measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D007640	Keratoconus	C11.204.627
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, increases methylation	10
Benzo(a)pyrene	increases expression, increases methylation, affects methylation, decreases expression	4
Resveratrol	affects cotreatment, increases expression, decreases expression	3
Estradiol	increases expression	3
Tretinoin	decreases expression	3
Smoke	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
4-(E)-((p-tolylimino)-methylbenzene-1,2-diol)	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
sodium arsenate	increases abundance, decreases expression	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
ochratoxin A	decreases expression	1
cupric oxide	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
4-((4-hydroxyphenylimino)methyl)benzene-1,2-diol	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01485211	PHASE4	COMPLETED	Corneal Thickness Changes During Corneal Collagen Cross-linking With Ultraviolet-A Irradiation and Riboflavin
NCT02119039	PHASE4	COMPLETED	Effect of CACICOL20 on Corneal Epithelial Healing After Cross-linking in Patients With Keratoconus
NCT03245853	PHASE4	COMPLETED	Epi-On Corneal Crosslinking for Keratoconus
NCT03429569	PHASE4	UNKNOWN	Cross-Linking ACcéléré Iontophorèse Confocal kératocONE
NCT04427956	PHASE4	COMPLETED	Corneal Crosslinking Treatment Study
NCT07474870	PHASE4	NOT_YET_RECRUITING	Outcomes of CTAK Surgery
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00371202	PHASE3	UNKNOWN	Comparison of Penetrating Keratoplasty and Deep Lamellar Keratoplasty With the Big Bubble Technique for Keratoconus
NCT00647699	PHASE3	COMPLETED	Corneal Collagen Cross-linking for Progressive Keratoconus
NCT00815256	PHASE3	UNKNOWN	Safety and Effectiveness of Collagen Cross Linking in Progressive Mild and Moderate Keratoconus
NCT00887900	PHASE3	COMPLETED	Deep Anterior Lamellar Keratoplasty (DALK)
NCT01112072	PHASE3	UNKNOWN	Corneal Collagen Crosslinking and Intacs for Keratoconus and Ectasia
NCT01152541	PHASE3	UNKNOWN	Corneal Collagen Crosslinking for Progressive Keratoconus and Ectasia Using Riboflavin/Dextran and Hypotonic Riboflavin
NCT01190306	PHASE3	TERMINATED	Safety Study of the VEGA UV-A System to Treat Keratoconus
NCT01344187	PHASE3	COMPLETED	Safety and Efficacy Study of Corneal Collagen Cross-Linking in Eyes With Keratoconus
NCT01459679	PHASE3	TERMINATED	Safety & Efficacy of Corneal Collagen Cross-Linking in Eyes With Keratoconus or Corneal Ectasia After Refractive Surgery
NCT01464268	PHASE3	UNKNOWN	Transepithelial Corneal Collagen Crosslinking for Keratoconus and Corneal Ectasia
NCT01604135	PHASE3	ACTIVE_NOT_RECRUITING	Collagen Crosslinking for Keratoconus - a Randomized Controlled Clinical Trial
NCT01643226	PHASE3	COMPLETED	Safety and Efficacy Study of Corneal Collagen Cross-Linking in Eyes With Keratoconus
NCT01672814	PHASE3	COMPLETED	Microwave Treatment and Corneal Collagen Crosslinking for Keratoconus
NCT01682993	PHASE3	TERMINATED	Corneal Cross Linking and Topography Guided Excimer Laser Treatment
NCT01972854	PHASE3	TERMINATED	Safety and Efficacy of Corneal Collagen Cross-Linking in Eyes With Keratoconus
NCT02613780	PHASE3	UNKNOWN	Refractive Treatment of Early Keratoconus
NCT02638376	PHASE3	UNKNOWN	Evaluating the Safety and Efficacy of the KXL System for Corneal Collagen Cross-Linking in Eyes Having Keratoconus
NCT03080077	PHASE3	UNKNOWN	Safety and Effectiveness of Corneal Crosslinking (CXL): Keratoconus and Post-Refractive Ectasia
NCT03187912	PHASE3	COMPLETED	Accelerated Corneal Cross-linking With Different Riboflavin Solutions
NCT03442751	PHASE3	COMPLETED	Study to Evaluate the Safety and Efficacy of Epi-on Corneal Cross-linking in Eyes With Progressive Keratoconus
NCT03858036	PHASE3	UNKNOWN	Corneal Collagen Cross-Linking (CXL) Performed With Epi-ON Versus Epi-OFF in Eyes With Keratoconus and Other Corneal Ectatic Disorders
NCT04897503	PHASE3	UNKNOWN	Corneal Collagen Crosslinking for Keratoconus and Ectasia Using Riboflavin/Dextran or Riboflavin/Methylcellulose
NCT04905108	PHASE3	UNKNOWN	Transepithelial (Epi-on) Corneal Collagen Crosslinking to Treat Keratoconus and Corneal Ectasia
NCT05027295	PHASE3	UNKNOWN	Accelerated Corneal Collagen Crosslinking for Keratoconus and Ectasia Using Pulse or Continuous UV-A Light
NCT06100939	PHASE3	ACTIVE_NOT_RECRUITING	Epithelium-On Corneal Cross-linking in Subjects 8 to 45 Years of Age With Keratoconus
NCT06100952	PHASE3	ACTIVE_NOT_RECRUITING	Epithelium-On Corneal Cross-linking in Subjects 8 to 45 Years of Age with Keratoconus
NCT06450470	PHASE3	RECRUITING	Use of a Freeze-dried Amniotic Membrane Post Crosslinking in Subjects With Progressive Keratoconus
NCT06601101	PHASE3	RECRUITING	Effects of Topical Insulin on Corneal Epithelium Healing After Corneal Crosslinking in Patients With Keratoconus
NCT07124910	PHASE3	RECRUITING	Comparison of Epi-ON Corneal Collagen Crosslinking Performed Using an 18-Minute UVA Exposure vs. a 24-Minute UVA Exposure on Eyes With Ectatic Corneal Diseases
NCT07135167	PHASE3	RECRUITING	Compassionate Use Study of Epi-ON Corneal Collagen Crosslinking Performed Using UVA Exposure on Eyes With Ectatic Corneal Diseases for Subjects With Down Syndrome
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders