CRELD2

Summary

CRELD2 (CRELD disulfide isomerase 2, HGNC:28150) is a protein-coding gene on chromosome 22q13.33, encoding Protein disulfide isomerase CRELD2 (Q6UXH1). Protein disulfide isomerase.

Predicted to enable calcium ion binding activity and protein disulfide isomerase activity. Predicted to be located in Golgi apparatus; endoplasmic reticulum; and extracellular space.

Source: NCBI Gene 79174 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 129 total
• MANE Select transcript: NM_024324

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28150
Approved symbol	CRELD2
Name	CRELD disulfide isomerase 2
Location	22q13.33
Locus type	gene with protein product
Status	Approved
Aliases	MGC11256
Ensembl gene	ENSG00000184164
Ensembl biotype	protein_coding
OMIM	607171
Entrez	79174

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 34 protein_coding, 3 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000328268, ENST00000403427, ENST00000404488, ENST00000407217, ENST00000444954, ENST00000450207, ENST00000462253, ENST00000482956, ENST00000483652, ENST00000487969, ENST00000498354, ENST00000905816, ENST00000905817, ENST00000905818, ENST00000905819, ENST00000905820, ENST00000905821, ENST00000905822, ENST00000905823, ENST00000905824, ENST00000905825, ENST00000905826, ENST00000905827, ENST00000905828, ENST00000905829, ENST00000905830, ENST00000905831, ENST00000915447, ENST00000915448, ENST00000915449, ENST00000915450, ENST00000915451, ENST00000915452, ENST00000967730, ENST00000967731, ENST00000967732, ENST00000967733, ENST00000967734, ENST00000967735, ENST00000967736

RefSeq mRNA: 4 — MANE Select: NM_024324 NM_001135101, NM_001284317, NM_001284318, NM_024324

CCDS: CCDS14082, CCDS46730, CCDS63515, CCDS63516

Canonical transcript exons

ENST00000328268 — 10 exons

Exon	Start	End
ENSE00001323718	49925417	49925557
ENSE00001897449	49918634	49918898
ENSE00003466698	49919230	49919312
ENSE00003474188	49919730	49919840
ENSE00003478333	49924360	49924455
ENSE00003543209	49921585	49921761
ENSE00003557714	49927255	49927537
ENSE00003607096	49923234	49923317
ENSE00003641038	49920156	49920247
ENSE00003787973	49922612	49922707

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 99.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.3191 / max 200.7850, expressed in 1808 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192933	9.3992	1729
192932	6.8500	1709
192934	0.9968	495
192936	0.0696	24
192935	0.0034	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.44	gold quality
oocyte	CL:0000023	98.20	gold quality
trachea	UBERON:0003126	97.18	gold quality
pituitary gland	UBERON:0000007	96.70	gold quality
adenohypophysis	UBERON:0002196	96.61	gold quality
tibia	UBERON:0000979	96.59	gold quality
body of pancreas	UBERON:0001150	96.28	gold quality
corpus epididymis	UBERON:0004359	96.03	gold quality
right lobe of thyroid gland	UBERON:0001119	95.86	gold quality
pericardium	UBERON:0002407	95.77	gold quality
pylorus	UBERON:0001166	95.64	gold quality
left lobe of thyroid gland	UBERON:0001120	95.52	gold quality
type B pancreatic cell	CL:0000169	95.42	silver quality
thyroid gland	UBERON:0002046	95.11	gold quality
right testis	UBERON:0004534	94.92	gold quality
right lobe of liver	UBERON:0001114	94.86	gold quality
periodontal ligament	UBERON:0008266	94.85	gold quality
cardia of stomach	UBERON:0001162	94.69	gold quality
left testis	UBERON:0004533	94.57	gold quality
parotid gland	UBERON:0001831	94.18	gold quality
ileal mucosa	UBERON:0000331	94.01	gold quality
mucosa of transverse colon	UBERON:0004991	93.99	gold quality
tendon of biceps brachii	UBERON:0008188	93.91	gold quality
stromal cell of endometrium	CL:0002255	93.73	gold quality
esophagus squamous epithelium	UBERON:0006920	93.66	gold quality
epithelium of nasopharynx	UBERON:0001951	93.42	gold quality
pancreas	UBERON:0001264	93.38	gold quality
body of stomach	UBERON:0001161	93.30	gold quality
olfactory bulb	UBERON:0002264	93.24	silver quality
epithelium of esophagus	UBERON:0001976	93.10	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-MTAB-9154	yes	3073.88
E-CURD-88	yes	99.14
E-HCAD-4	yes	50.50
E-CURD-122	yes	43.98
E-HCAD-1	yes	42.84
E-CURD-46	yes	40.94
E-MTAB-8410	yes	40.27
E-ANND-3	yes	28.56
E-HCAD-11	yes	20.06
E-HCAD-9	yes	17.25
E-MTAB-10553	yes	10.58
E-HCAD-38	no	428.39
E-CURD-112	no	3.63

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXC1, SMAD1

miRNA regulators (miRDB)

25 targeting CRELD2, 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-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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-1301-3P	98.64	68.27	1071
HSA-MIR-5047	98.64	68.62	1035
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-4475	97.36	66.95	761
HSA-MIR-5187-3P	97.28	67.10	1037
HSA-MIR-6892-5P	97.27	68.60	847
HSA-MIR-3918	96.13	64.65	1300

Literature-anchored findings (GeneRIF, showing 9)

• CRELD2 can act as a specific regulator of alpha4beta2 nAChR expression (PMID:16238698)
• Mapping of CRELD2 by FISH shows that it maps to 22q13 rather than the GenBank reported locus of 22p13. (PMID:16919896)
• We demonstrate that Armet and Creld2 are genotype-specific ER stress response proteins with substrate specificities, and that aggregation of mutant matrilin-3 is a key disease trigger in MED that could be exploited as a potential therapeutic target (PMID:23956175)
• results strongly suggest that Creld2 may be directly regulated by BMP9 and ER stress response may play an important role in regulating osteogenic differentiation (PMID:24019898)
• intravesicular acidification by V-ATPase regulates the secretion of CRELD2 without relying on the balance of intracellular calcium ions and the expression of endoplasmic reticulum chaperones such as GRP78 and protein disulfide isomerase. (PMID:24687431)
• ROCK-mediated selective activation of PERK signalling causes fibroblast reprogramming and tumour progression through a CRELD2-dependent mechanism. (PMID:32451439)
• Creld2 function during unfolded protein response is essential for liver metabolism homeostasis. (PMID:34549824)
• CRELD2, endoplasmic reticulum stress, and human diseases. (PMID:36936176)
• Molecular characterization of the ER stress-inducible factor CRELD2. (PMID:38753249)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	creld2	ENSDARG00000029071
mus_musculus	Creld2	ENSMUSG00000023272
rattus_norvegicus	Creld2	ENSRNOG00000004659
caenorhabditis_elegans		WBGENE00000168
caenorhabditis_elegans		WBGENE00012018
caenorhabditis_elegans		WBGENE00013480
caenorhabditis_elegans		WBGENE00013486
caenorhabditis_elegans		WBGENE00013487
caenorhabditis_elegans		WBGENE00018906
caenorhabditis_elegans		WBGENE00019901
caenorhabditis_elegans		WBGENE00022858

Paralogs (8): DLL3 (ENSG00000090932), CD93 (ENSG00000125810), FBLN7 (ENSG00000144152), WIF1 (ENSG00000156076), CRELD1 (ENSG00000163703), DLK2 (ENSG00000171462), CD248 (ENSG00000174807), CLEC14A (ENSG00000176435)

Protein

Protein identifiers

Protein disulfide isomerase CRELD2 — Q6UXH1 (reviewed: Q6UXH1)

Alternative names: Cysteine-rich with EGF-like domain protein 2

All UniProt accessions (2): A6PWM2, Q6UXH1

UniProt curated annotations — full annotation on UniProt →

Function. Protein disulfide isomerase. Might play a role in the unfolded protein response. May regulate transport of alpha4-beta2 neuronal acetylcholine receptor.

Subunit / interactions. Interacts with CHRNA4. Component of a complex containing at least CRELD2, MANF, MATN3 and PDIA4.

Subcellular location. Endoplasmic reticulum.

Tissue specificity. Ubiquitously expressed. Highly expressed in skeletal muscle, heart, liver, kidney and placenta.

Miscellaneous. Minor isoform.

Similarity. Belongs to the CRELD family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q6UXH1-1	1, Delta	yes
Q6UXH1-2	2, Alpha
Q6UXH1-3	3, Beta
Q6UXH1-4	4, Gamma
Q6UXH1-5	5, Epsilon
Q6UXH1-6	6, Zeta

RefSeq proteins (4): NP_001128573, NP_001271246, NP_001271247, NP_077300* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000742	EGF	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR002049	LE_dom	Domain
IPR006212	Furin_repeat	Repeat
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR049883	NOTCH1_EGF-like	Domain

Pfam: PF07645

UniProt features (28 total): disulfide bond 8, splice variant 6, sequence variant 3, domain 2, repeat 2, short sequence motif 2, signal peptide 1, chain 1, glycosylation site 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UXH1-F1	87.63	0.73

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (8): 31–34, 140–154, 148–166, 168–177, 263–266, 294–308, 301–317, 319–330

Glycosylation sites (1): 251

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 163 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GSE45365_NK_CELL_VS_CD8A_DC_UP, GSE45365_NK_CELL_VS_BCELL_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, YY1_Q6, NIKOLSKY_BREAST_CANCER_22Q13_AMPLICON, BILD_E2F3_ONCOGENIC_SIGNATURE, NADLER_HYPERGLYCEMIA_AT_OBESITY, MORI_PLASMA_CELL_UP, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, NICK_RESPONSE_TO_PROC_TREATMENT_UP, chr22q13, WANG_TUMOR_INVASIVENESS_UP, GOMF_INTRAMOLECULAR_OXIDOREDUCTASE_ACTIVITY, GOMF_ISOMERASE_ACTIVITY

GO Biological Process (0):

GO Molecular Function (4): protein disulfide isomerase activity (GO:0003756), calcium ion binding (GO:0005509), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
intramolecular oxidoreductase activity, transposing S-S bonds	1
catalytic activity, acting on a protein	1
metal ion binding	1
binding	1
catalytic activity	1

Protein interactions and networks

STRING

834 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRELD2	MANF	P55145	644
CRELD2	SDF2L1	Q9HCN8	619
CRELD2	CHRNA4	P43681	616
CRELD2	MATN3	O15232	564
CRELD2	DERL3	Q96Q80	530
CRELD2	HERPUD1	Q15011	528
CRELD2	PDIA4	P13667	478
CRELD2	PDIA6	Q15084	477
CRELD2	ALG12	Q9BV10	471
CRELD2	THBS1	P07996	459
CRELD2	ATF6	P18850	434
CRELD2	HSPA5	P11021	430
CRELD2	HYOU1	Q9Y4L1	426
CRELD2	XBP1	P17861	408
CRELD2	HSP90B1	P14625	408

IntAct

84 interactions, top by confidence:

A	B	Type	Score
CHCHD4	SSNA1	psi-mi:“MI:0914”(association)	0.640
MATN3	PDIA4	psi-mi:“MI:0914”(association)	0.560
ZFP41	LRP4	psi-mi:“MI:0914”(association)	0.530
WNT7A	LDLR	psi-mi:“MI:0914”(association)	0.530
GALNS	FBXO21	psi-mi:“MI:0914”(association)	0.530
CDKN2A	CRELD2	psi-mi:“MI:0915”(physical association)	0.510
HSP90B1	CRELD2	psi-mi:“MI:0915”(physical association)	0.400
CRELD2	LTB4R2	psi-mi:“MI:0915”(physical association)	0.370
CRELD2	HOXA1	psi-mi:“MI:0915”(physical association)	0.370
C8orf33	CRELD2	psi-mi:“MI:0915”(physical association)	0.370
CRELD2	CDK5	psi-mi:“MI:0915”(physical association)	0.370
CDKN1A	CRELD2	psi-mi:“MI:0915”(physical association)	0.370
CRELD2	CSNK2B	psi-mi:“MI:0915”(physical association)	0.370
CRELD2	CTSL	psi-mi:“MI:0915”(physical association)	0.370
CRELD2	DNAJB11	psi-mi:“MI:0915”(physical association)	0.370
FZD4	CRELD2	psi-mi:“MI:0915”(physical association)	0.370
GADD45A	CRELD2	psi-mi:“MI:0915”(physical association)	0.370
CRELD2	GSK3B	psi-mi:“MI:0915”(physical association)	0.370
IGF2	CRELD2	psi-mi:“MI:0915”(physical association)	0.370
MAPK6	CRELD2	psi-mi:“MI:0915”(physical association)	0.370
CRELD2	MEST	psi-mi:“MI:0915”(physical association)	0.370
CRELD2	NDUFB11	psi-mi:“MI:0915”(physical association)	0.370
CRELD2	NR1H2	psi-mi:“MI:0915”(physical association)	0.370
PIN1	CRELD2	psi-mi:“MI:0915”(physical association)	0.370
CRELD2	PLA2G2A	psi-mi:“MI:0915”(physical association)	0.370
PLK1	CRELD2	psi-mi:“MI:0915”(physical association)	0.370
RAC1	CRELD2	psi-mi:“MI:0915”(physical association)	0.370
CRELD2	RCC1	psi-mi:“MI:0915”(physical association)	0.370
CRELD2	REG1B	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (77): CRELD2 (Affinity Capture-MS), CRELD2 (Affinity Capture-MS), CRELD2 (Affinity Capture-MS), CRELD2 (Affinity Capture-MS), CRELD2 (Affinity Capture-MS), CRELD2 (Affinity Capture-MS), CRELD2 (Affinity Capture-MS), CRELD2 (Affinity Capture-MS), CRELD2 (Affinity Capture-MS), CRELD2 (Affinity Capture-MS), CRELD2 (Proximity Label-MS), CRELD2 (Proximity Label-MS), CRELD2 (Two-hybrid), CRELD2 (Two-hybrid), CRELD2 (Affinity Capture-MS)

ESM2 similar proteins: A0A6I8RMG7, A2A863, A2VCU8, A7E2Z9, P01130, P01131, P04412, P0CY46, P16144, P18563, P18564, P24043, P35555, P35950, P35952, P35953, P98133, P98155, P98156, P98165, P98166, Q1RPR6, Q28832, Q2KIT5, Q3UZV7, Q4G063, Q4V7M2, Q5XH36, Q60438, Q61220, Q61554, Q62918, Q64632, Q6AYF4, Q6DDW2, Q6UXH1, Q7SXF6, Q7ZXL5, Q863C4, Q8CFM6

Diamond homologs: A0A6I8RMG7, A2AJ76, B3EWY9, B5DFC9, O35568, O77469, O88322, P10493, P14543, P41413, P48960, P98095, Q04592, Q09165, Q14112, Q19267, Q2KIT5, Q2Q421, Q2Q426, Q4G063, Q4V7F2, Q4V7M2, Q5EA46, Q5RBP1, Q5XH36, Q60438, Q6UXH1, Q6UXI9, Q7SXF6, Q7ZXL5, Q86XX4, Q8BPB5, Q8K4G1, Q8R4U0, Q8R4Y4, Q91XD7, Q96HD1, Q96RW7, Q9CYA0, Q9JJS0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 112 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Neutrophil degranulation	14	4.0×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	89
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2120 predictions. Top by Δscore:

Variant	Effect	Δscore
22:49918882:TGGAC:T	donor_gain	1.0000
22:49919836:CAGCT:C	donor_gain	1.0000
22:49919838:GCT:G	donor_gain	1.0000
22:49919839:CT:C	donor_gain	1.0000
22:49919841:G:GG	donor_gain	1.0000
22:49921583:A:AG	acceptor_gain	1.0000
22:49921584:G:GG	acceptor_gain	1.0000
22:49923280:GTTCT:G	donor_gain	1.0000
22:49925410:A:AG	acceptor_gain	1.0000
22:49925413:TTAG:T	acceptor_loss	1.0000
22:49925414:TAGA:T	acceptor_loss	1.0000
22:49925415:A:AG	acceptor_gain	1.0000
22:49925415:AGAT:A	acceptor_gain	1.0000
22:49925415:AGATG:A	acceptor_loss	1.0000
22:49925416:G:GT	acceptor_gain	1.0000
22:49925416:GA:G	acceptor_gain	1.0000
22:49925416:GAT:G	acceptor_gain	1.0000
22:49925416:GATG:G	acceptor_gain	1.0000
22:49925416:GATGT:G	acceptor_gain	1.0000
22:49925553:GGCTG:G	donor_gain	1.0000
22:49925554:GCTG:G	donor_gain	1.0000
22:49925554:GCTGG:G	donor_gain	1.0000
22:49925555:CTGGT:C	donor_loss	1.0000
22:49925556:TGGT:T	donor_loss	1.0000
22:49925557:GGTGA:G	donor_loss	1.0000
22:49925558:G:C	donor_loss	1.0000
22:49925558:G:GG	donor_gain	1.0000
22:49925559:TGAGT:T	donor_loss	1.0000
22:49925560:GAGTG:G	donor_loss	1.0000
22:49918260:GA:G	donor_loss	0.9900

AlphaMissense

2318 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:49919280:G:C	W60C	0.998
22:49919280:G:T	W60C	0.998
22:49919303:A:G	Y68C	0.996
22:49925428:T:A	C294S	0.995
22:49925429:G:C	C294S	0.995
22:49922682:G:C	W221C	0.994
22:49922682:G:T	W221C	0.994
22:49925470:T:A	C308S	0.994
22:49925471:G:C	C308S	0.994
22:49919283:G:C	E61D	0.992
22:49919283:G:T	E61D	0.992
22:49920191:G:A	C120Y	0.992
22:49923284:T:A	C247S	0.992
22:49923285:G:C	C247S	0.992
22:49924407:T:A	C274S	0.992
22:49924408:G:C	C274S	0.992
22:49924449:T:A	C288S	0.992
22:49924450:G:C	C288S	0.992
22:49919257:T:C	F53L	0.991
22:49919259:T:A	F53L	0.991
22:49919259:T:G	F53L	0.991
22:49919829:G:C	W104C	0.991
22:49919829:G:T	W104C	0.991
22:49923245:T:A	C234S	0.991
22:49923246:G:C	C234S	0.991
22:49924383:T:A	C266S	0.991
22:49924384:G:C	C266S	0.991
22:49925478:T:A	N310K	0.991
22:49925478:T:G	N310K	0.991
22:49919312:G:T	S71I	0.990

dbSNP variants (sampled 300 via entrez): RS1000124441 (22:49927004 C>A,T), RS1000177265 (22:49927139 G>A,C), RS1000214560 (22:49927560 T>C), RS1000398676 (22:49923434 C>T), RS1000460944 (22:49927784 C>T), RS1000514577 (22:49927966 G>A,C), RS1000939120 (22:49918856 G>A,T), RS1001058264 (22:49923679 C>T), RS1001340837 (22:49924599 G>A), RS1001651023 (22:49927067 G>A), RS1001765080 (22:49922750 C>A,G,T), RS1001979530 (22:49927917 C>T), RS1002205147 (22:49923923 C>A,G), RS1002214600 (22:49917981 G>A), RS1002750217 (22:49921962 G>A,C)

Disease associations

OMIM: gene MIM:607171 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002481_12	Acne (severe)	4.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	6
Tunicamycin	increases expression	5
sodium arsenite	decreases expression, increases expression	3
Valproic Acid	increases methylation, increases expression	3
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases expression, decreases expression	2
Ozone	affects cotreatment, increases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cadmium Chloride	increases abundance, increases expression	2
Thapsigargin	increases expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
methyleugenol	decreases expression	1
alpha-pinene	increases abundance, affects cotreatment, increases expression	1
bisphenol A	increases expression	1
beta-lapachone	decreases expression	1
sodium bichromate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
K 7174	decreases expression	1
pinostrobin	decreases expression	1
fenpyroximate	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

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery