TSC22D2

Summary

TSC22D2 (TSC22 domain family member 2, HGNC:29095) is a protein-coding gene on chromosome 3q25.1, encoding TSC22 domain family protein 2 (O75157). Reduces the level of nuclear PKM isoform M2 which results in repression of cyclin CCND1 transcription and reduced cell growth. It is a selective cancer dependency (DepMap: 36.1% of cell lines).

Involved in negative regulation of cell cycle.

Source: NCBI Gene 9819 — RefSeq curated summary.

At a glance

• GWAS associations: 53
• Clinical variants (ClinVar): 117 total
• Phenotypes (HPO): 1
• Cancer dependency (DepMap): dependent in 36.1% of screened cell lines
• MANE Select transcript: NM_001303264

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29095
Approved symbol	TSC22D2
Name	TSC22 domain family member 2
Location	3q25.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0669, TILZ4a, TILZ4b, TILZ4c
Ensembl gene	ENSG00000196428
Ensembl biotype	protein_coding
OMIM	617724
Entrez	9819

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000361875, ENST00000460316, ENST00000466814, ENST00000480589, ENST00000485421, ENST00000492828, ENST00000688009, ENST00000942129, ENST00000942130

RefSeq mRNA: 2 — MANE Select: NM_001303264 NM_001303264, NM_014779

CCDS: CCDS3149, CCDS93406

Canonical transcript exons

ENST00000688009 — 3 exons

Exon	Start	End
ENSE00001076872	150408298	150411308
ENSE00002611483	150458376	150466422
ENSE00003639179	150457076	150457127

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 99.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.1436 / max 348.2055, expressed in 1822 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
39186	11.7291	1781
39194	5.7372	1497
39188	3.5496	1477
39191	3.4226	1508
39193	2.6956	1307
39187	2.0442	690
39195	1.5005	664
39192	0.8598	409
39189	0.4895	266
39190	0.1154	51

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	99.43	gold quality
secondary oocyte	CL:0000655	97.76	gold quality
oocyte	CL:0000023	97.66	gold quality
vena cava	UBERON:0004087	97.57	gold quality
amniotic fluid	UBERON:0000173	96.82	gold quality
saphenous vein	UBERON:0007318	96.65	gold quality
cauda epididymis	UBERON:0004360	96.49	gold quality
cervix squamous epithelium	UBERON:0006922	95.63	silver quality
lower esophagus mucosa	UBERON:0035834	94.62	gold quality
ventricular zone	UBERON:0003053	94.34	gold quality
adult organism	UBERON:0007023	94.10	gold quality
endothelial cell	CL:0000115	94.08	gold quality
synovial joint	UBERON:0002217	94.02	gold quality
lower lobe of lung	UBERON:0008949	94.01	gold quality
seminal vesicle	UBERON:0000998	93.80	gold quality
pharyngeal mucosa	UBERON:0000355	93.53	gold quality
renal medulla	UBERON:0000362	93.42	gold quality
trigeminal ganglion	UBERON:0001675	93.17	gold quality
adrenal tissue	UBERON:0018303	93.11	gold quality
oviduct epithelium	UBERON:0004804	92.94	gold quality
superficial temporal artery	UBERON:0001614	92.91	gold quality
blood vessel layer	UBERON:0004797	92.76	gold quality
mammary duct	UBERON:0001765	92.73	gold quality
corpus callosum	UBERON:0002336	92.51	gold quality
dorsal root ganglion	UBERON:0000044	92.48	gold quality
urethra	UBERON:0000057	92.43	gold quality
caput epididymis	UBERON:0004358	92.43	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.21	gold quality
postcentral gyrus	UBERON:0002581	92.18	gold quality
oral cavity	UBERON:0000167	92.11	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	58.69
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

238 targeting TSC22D2, 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-3646	100.00	73.56	5283
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4768-5P	100.00	69.49	2861
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-3163	100.00	77.23	8605
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 36.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• Long form of TSC22DF is evolutionarily conserved and has growth-regulating potential. (PMID:20149264)
• TSC22D2 protein might be a member of the PRMT5 complex via direct binding of WDR77. (PMID:27337956)
• Results found TSC22D2 significantly downregulated in colorectal cancer (CRC). Its overexpression can inhibit CRC cell growth. Also, TSC22D2 physically associates with PKM2, and demonstrated that TSC22D2 overexpression reduces nuclear PKM2 levels and represses the expression of cyclin D1. (PMID:27573352)
• Genome-wide linkage analysis and whole-exome sequencing in a rare, large multi-cancer pedigree recently found in China identified a novel mutant of transforming growth factor beta stimulated clone 22 domain family, member 2 (TSC22D2, c.-91T-C) cosegregated with the cancer phenotype. Study found that histone H4 transcription factor (HINFP) binds to the promoter region of TSC22D2 and may regulate its transcription. (PMID:31125406)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tsc22d2	ENSMUSG00000027806
rattus_norvegicus	Tsc22d2	ENSRNOG00000038044
drosophila_melanogaster	bun	FBGN0259176
caenorhabditis_elegans		WBGENE00011824
caenorhabditis_elegans		WBGENE00012994

Paralogs (3): TSC22D1 (ENSG00000102804), TSC22D3 (ENSG00000157514), TSC22D4 (ENSG00000166925)

Protein

Protein identifiers

TSC22 domain family protein 2 — O75157 (reviewed: O75157)

Alternative names: TSC22-related-inducible leucine zipper protein 4

All UniProt accessions (4): O75157, H0Y865, H0Y8E9, H7C4U3

UniProt curated annotations — full annotation on UniProt →

Function. Reduces the level of nuclear PKM isoform M2 which results in repression of cyclin CCND1 transcription and reduced cell growth.

Subunit / interactions. Interacts with NRBP1. Interacts with PKM isoform M2; the interaction results in reduced nuclear levels of PKM isoform M2, leading to repression of cyclin CCND1 transcription and reduced cell growth. Interacts with WDR77.

Miscellaneous. May be involved in the loss of cell cycle regulation in colorectal tumors, expression is shown to be decreased in the majority of tumors.

Similarity. Belongs to the TSC-22/Dip/Bun family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75157-1	1, TILZ4a, TILZ4c	yes
O75157-2	2, TILZ4b

RefSeq proteins (2): NP_001290193, NP_055594 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000580	TSC22/Bun	Family
IPR047862	TSC22/BUN_CS	Conserved_site
IPR053049	TSC22_domain_protein_2	Family

Pfam: PF01166

UniProt features (18 total): compositionally biased region 10, region of interest 5, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75157-F1	48.04	0.07

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 284 (showing top): ATF_B, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, AAGCAAT_MIR137, BROWNE_HCMV_INFECTION_6HR_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, CREBP1_Q2, TGACCTY_ERR1_Q2, GTACAGG_MIR486, AATGGAG_MIR136, CREB_Q4, DOANE_RESPONSE_TO_ANDROGEN_DN, ATF1_Q6, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, DACOSTA_UV_RESPONSE_VIA_ERCC3_TTD_DN, GOBP_REGULATION_OF_CELL_CYCLE

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), response to osmotic stress (GO:0006970), negative regulation of cell cycle (GO:0045786)

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
response to stress	1
response to abiotic stimulus	1
cell cycle	1
negative regulation of cellular process	1
regulation of cell cycle	1
binding	1

Protein interactions and networks

STRING

748 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TSC22D2	LHX4	Q969G2	670
TSC22D2	LHX3	Q9UBR4	637
TSC22D2	NRBP1	Q9UHY1	549
TSC22D2	WDR77	Q9BQA1	517
TSC22D2	STAC2	Q6ZMT1	458
TSC22D2	GKN2	Q86XP6	438
TSC22D2	CCDC197	Q8NCU1	431
TSC22D2	TBL2	Q9Y4P3	421
TSC22D2	GKN1	Q9NS71	411
TSC22D2	ZC3H4	Q9UPT8	405
TSC22D2	UBE4A	Q14139	405
TSC22D2	ZNF579	Q8NAF0	398
TSC22D2	MCC	P23508	390
TSC22D2	NWD2	Q9ULI1	389
TSC22D2	CEP20	Q96NB1	380

IntAct

27 interactions, top by confidence:

A	B	Type	Score
NRBP1	TSC22D2	psi-mi:“MI:0914”(association)	0.730
TSC22D4	TSC22D2	psi-mi:“MI:0914”(association)	0.640
FAM117B	GAPDHS	psi-mi:“MI:0914”(association)	0.530
NRBP1	TBC1D4	psi-mi:“MI:0914”(association)	0.530
USP7	TSC22D2	psi-mi:“MI:0407”(direct interaction)	0.440
NRG2	TSC22D2	psi-mi:“MI:0915”(physical association)	0.400
TSC22D4	TBL1X	psi-mi:“MI:0914”(association)	0.350
TSC22D3	TSC22D2	psi-mi:“MI:0914”(association)	0.350
NRBP2	HAX1	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
SPANXN2	ZNF320	psi-mi:“MI:0914”(association)	0.350
MGARP	RTL8C	psi-mi:“MI:0914”(association)	0.350
TSC22D4	PSMA7	psi-mi:“MI:0914”(association)	0.350
ADAM19	TSC22D2	psi-mi:“MI:0914”(association)	0.350
C1QL3	TSC22D2	psi-mi:“MI:0914”(association)	0.350
TSC22D3	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
NRBP1	PDPK1	psi-mi:“MI:0914”(association)	0.350
TSC22D4	LANCL1	psi-mi:“MI:0914”(association)	0.350
DNM3	TSC22D2	psi-mi:“MI:0914”(association)	0.350
hrpA	TSC22D2	psi-mi:“MI:0915”(physical association)	0.000
TSC22D2	malQ	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (78): TSC22D2 (Affinity Capture-MS), RNF2 (Two-hybrid), WNK3 (Two-hybrid), OSBPL1A (Two-hybrid), PSMA7 (Two-hybrid), ZNF143 (Two-hybrid), NRBP1 (Two-hybrid), FLNB (Two-hybrid), LRRC6 (Two-hybrid), MPDZ (Two-hybrid), REV1 (Two-hybrid), TTN (Two-hybrid), WDR77 (Two-hybrid), CCDC141 (Two-hybrid), CCDC144A (Two-hybrid)

ESM2 similar proteins: A2AJK6, A2ICN5, A5D7F6, B2C6R6, B2RWS6, E9Q7M2, O00512, O75157, P34545, P45481, P46936, P62500, P62501, P81877, Q06A37, Q09472, Q14686, Q15714, Q17BA4, Q21955, Q29A33, Q2MJT0, Q4R4H5, Q4V3C1, Q5R4H1, Q61L47, Q63627, Q67FY2, Q67FY3, Q6DDH6, Q6JHU9, Q6SR68, Q6SR69, Q6SZ65, Q7TSH6, Q7ZUK7, Q86UU0, Q8CHI8, Q8SWR8, Q91012

Diamond homologs: E9Q7M2, O75157, P62500, P62501, P80220, Q22544, Q24522, Q24523, Q27I66, Q3B8N7, Q3MHL6, Q5R4H1, Q5RED5, Q99576, Q9EQN3, Q9EQZ1, Q9Y3Q8, Q9Z2S7, Q15714, Q4R4H5, Q91012

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	107
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1352 predictions. Top by Δscore:

Variant	Effect	Δscore
3:150457070:TTCCA:T	acceptor_loss	1.0000
3:150457074:A:AG	acceptor_gain	1.0000
3:150457074:AGT:A	acceptor_gain	1.0000
3:150457074:AGTGC:A	acceptor_loss	1.0000
3:150457075:G:GT	acceptor_gain	1.0000
3:150457075:GT:G	acceptor_gain	1.0000
3:150457075:GTG:G	acceptor_gain	1.0000
3:150457075:GTGC:G	acceptor_gain	1.0000
3:150457124:AATGG:A	acceptor_loss	1.0000
3:150457125:ATG:A	donor_gain	1.0000
3:150457125:ATGG:A	acceptor_loss	1.0000
3:150457126:TGGTA:T	acceptor_loss	1.0000
3:150457127:GGTA:G	donor_loss	1.0000
3:150457128:G:GG	donor_gain	1.0000
3:150457128:G:T	donor_loss	1.0000
3:150457129:T:A	donor_loss	1.0000
3:150423037:C:CA	acceptor_gain	0.9900
3:150423038:G:A	acceptor_gain	0.9900
3:150436461:A:AG	donor_gain	0.9900
3:150436461:A:G	donor_gain	0.9900
3:150436474:G:GT	donor_gain	0.9900
3:150457075:GTGCA:G	acceptor_gain	0.9900
3:150457126:TG:T	donor_gain	0.9900
3:150457127:GG:G	donor_gain	0.9900
3:150457130:AA:A	donor_loss	0.9900
3:150458370:TCACA:T	acceptor_loss	0.9900
3:150458371:CACAG:C	acceptor_loss	0.9900
3:150458372:ACAG:A	acceptor_gain	0.9900
3:150458372:ACAGG:A	acceptor_loss	0.9900
3:150458373:CA:C	acceptor_loss	0.9900

AlphaMissense

4837 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:150409384:T:C	F12L	1.000
3:150409385:T:C	F12S	1.000
3:150409385:T:G	F12C	1.000
3:150409386:C:A	F12L	1.000
3:150409386:C:G	F12L	1.000
3:150409391:T:A	I14N	1.000
3:150409391:T:C	I14T	1.000
3:150409391:T:G	I14S	1.000
3:150409400:T:A	V17D	1.000
3:150409834:T:C	F162L	1.000
3:150409834:T:G	F162V	1.000
3:150409835:T:C	F162S	1.000
3:150409835:T:G	F162C	1.000
3:150409836:T:A	F162L	1.000
3:150409836:T:G	F162L	1.000
3:150409844:T:A	I165N	1.000
3:150409882:G:C	G178R	1.000
3:150409888:T:A	W180R	1.000
3:150409888:T:C	W180R	1.000
3:150409889:G:C	W180S	1.000
3:150409890:G:C	W180C	1.000
3:150409890:G:T	W180C	1.000
3:150409894:T:C	C182R	1.000
3:150409895:G:A	C182Y	1.000
3:150409896:T:G	C182W	1.000
3:150457114:T:A	I690K	1.000
3:150457122:G:C	A693P	1.000
3:150458380:T:C	L696P	1.000
3:150458385:A:G	K698E	1.000
3:150458386:A:T	K698I	1.000

dbSNP variants (sampled 300 via entrez): RS1000042083 (3:150427769 C>A,G), RS1000080349 (3:150433408 C>T), RS1000089321 (3:150463886 G>C), RS1000234927 (3:150439882 A>G), RS1000285537 (3:150439611 G>T), RS1000322215 (3:150426568 G>A,C), RS1000332549 (3:150446358 T>G), RS1000354658 (3:150425983 C>T), RS1000406083 (3:150446081 G>A), RS1000439006 (3:150433038 T>G), RS1000517043 (3:150438655 G>A), RS1000669588 (3:150445006 C>T), RS1000690168 (3:150439625 A>C), RS1000741324 (3:150431836 C>G,T), RS1000741440 (3:150444683 T>C)

Disease associations

OMIM: gene MIM:617724 | disease phenotypes: MIM:148300

GenCC curated gene-disease

Mondo (1): keratoconus (MONDO:0015486)

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

53 associations (top):

Study	Trait	p-value
GCST001465_5	Adiponectin levels	6.000000e-07
GCST003075_112	Cognitive decline rate in late mild cognitive impairment	4.000000e-07
GCST003075_96	Cognitive decline rate in late mild cognitive impairment	4.000000e-07
GCST003335_2	Waist circumference	1.000000e-08
GCST003335_7	Waist circumference	2.000000e-06
GCST005170_17	Intraocular pressure	7.000000e-09
GCST005575_35	Moyamoya disease	2.000000e-09
GCST006065_20	Glaucoma (primary open-angle)	2.000000e-08
GCST006867_25	Type 2 diabetes	1.000000e-10
GCST006976_126	Macular thickness	2.000000e-08
GCST007096_31	Pulse pressure	7.000000e-09
GCST007099_58	Systolic blood pressure	9.000000e-09
GCST007930_16	Medication use (agents acting on the renin-angiotensin system)	8.000000e-09
GCST007931_71	Medication use (HMG CoA reductase inhibitors)	1.000000e-08
GCST009017_4	T wave morphology restitution during recovery from exercise (MTAG)	7.000000e-09
GCST009069_4	T wave morphology restitution during recovery from exercise	9.000000e-09
GCST009375_4	Mosaic loss of chromosome Y (Y chromosome dosage)	4.000000e-28
GCST009379_136	Type 2 diabetes	1.000000e-09
GCST009726_17	Glaucoma	2.000000e-07
GCST010002_443	Refractive error	1.000000e-10
GCST010173_66	Triglyceride levels	4.000000e-15
GCST010241_398	Apolipoprotein A1 levels	1.000000e-10
GCST010242_416	HDL cholesterol levels	2.000000e-23
GCST010242_58	HDL cholesterol levels	4.000000e-09
GCST010244_253	Triglyceride levels	6.000000e-23
GCST010320_39	PR interval	1.000000e-08
GCST010321_204	PR interval	2.000000e-09
GCST010699_112	Brain morphology (min-P)	4.000000e-08
GCST010701_67	Cortical surface area (MOSTest)	2.000000e-09
GCST010702_117	Subcortical volume (MOSTest)	2.000000e-09

EFO canonical traits (18, from GWAS)

EFO ID	Trait name
EFO:0004502	adiponectin measurement
EFO:0007710	cognitive decline measurement
EFO:0004695	intraocular pressure measurement
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0009932	HMG CoA reductase inhibitor use measurement
EFO:0008398	T wave morphology measurement
EFO:0007783	mosaic loss of chromosome Y measurement
EFO:0004530	triglyceride measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004462	PR interval
EFO:0004346	neuroimaging measurement
EFO:0004327	electrocardiography
EFO:0008039	BMI-adjusted hip circumference
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D007640	Keratoconus	C11.204.627

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, increases expression	3
Valproic Acid	affects expression, increases expression, increases methylation	3
Acetaminophen	increases expression	2
Estradiol	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Cyclosporine	increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol A	increases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, affects cotreatment	1
2-methyl-4-isothiazolin-3-one	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
coumarin	increases phosphorylation	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1

Clinical trials (associated diseases)

279 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
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
NCT00409955	PHASE2	COMPLETED	Lamellar Transplant With Lyophilized Corneas
NCT00925327	PHASE2	UNKNOWN	Safety and Effectiveness of the UV-X System for Corneal Collagen Cross-Linking for Compassionate Treatment in Pediatric Patients With Progressive Keratoconus
NCT01143389	PHASE2	COMPLETED	Corneal Crosslinking in Patients With Keratoconus and Post-Refractive Ectasia
NCT01181219	PHASE2	COMPLETED	Transepithelial Corneal Collagen Cross-linking (CXL) in Treatment of Keratoconus