PDCD4

Summary

PDCD4 (programmed cell death 4, HGNC:8763) is a protein-coding gene on chromosome 10q25.2, encoding Programmed cell death protein 4 (Q53EL6). Inhibits translation initiation and cap-dependent translation. In precision oncology, PDCD4 EXPRESSION confers sensitivity to Paclitaxel in Lung Cancer (CIViC Level B).

This gene is a tumor suppressor and encodes a protein that binds to the eukaryotic translation initiation factor 4A1 and inhibits its function by preventing RNA binding. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 27250 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 74 total
• GTEx eGene: eQTL in 18 tissues, sQTL in 5 (q < 0.05)
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.67 (unconstrained)
• MANE Select transcript: NM_014456
• Interaction hub: 1,936 STRING partners (top 8% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8763
Approved symbol	PDCD4
Name	programmed cell death 4
Location	10q25.2
Locus type	gene with protein product
Status	Approved
Aliases	H731
Ensembl gene	ENSG00000150593
Ensembl biotype	protein_coding
OMIM	608610
Entrez	27250

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 26 protein_coding, 8 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

MANE Select: ENST00000280154

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 2, TSL 3: 4, TSL 5: 3

ENST00000280154, ENST00000393104, ENST00000444997, ENST00000462577, ENST00000467574, ENST00000481353, ENST00000483595, ENST00000483670, ENST00000489049, ENST00000492932, ENST00000498367, ENST00000888006, ENST00000888007, ENST00000888008, ENST00000888009, ENST00000888010, ENST00000888011, ENST00000888012, ENST00000888013, ENST00000888014, ENST00000888015, ENST00000888016, ENST00000919434, ENST00000919435, ENST00000963371, ENST00000963372, ENST00000963373, ENST00000963374, ENST00000963375, ENST00000963376, ENST00000963377, ENST00001010320, ENST00001099279, ENST00001121314, ENST00001123900, ENST00001136580

RefSeq mRNA: 3 — MANE Select: NM_014456 NM_001199492, NM_014456, NM_145341

CCDS: CCDS44478, CCDS7567

Canonical transcript exons

ENST00000280154 — 12 exons

Exon	Start	End
ENSE00001840051	110898028	110900006
ENSE00001922986	110871928	110872018
ENSE00003465513	110890556	110890670
ENSE00003467056	110887665	110887886
ENSE00003498310	110894412	110894522
ENSE00003541455	110895948	110896087
ENSE00003544242	110894091	110894198
ENSE00003548022	110889533	110889630
ENSE00003566915	110875966	110876070
ENSE00003591656	110885253	110885366
ENSE00003591665	110883003	110883097
ENSE00003615472	110881233	110881535

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 99.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 94.8829 / max 2013.3210, expressed in 1812 samples.

Highest expression (Bgee): body of pancreas, skin of abdomen, skin of leg, rectum, lobe of thyroid gland.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PDCD4 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 18 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 23 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Esophagus Mucosa	eqtl	9.2e-18	+0.18	10:110817418:C:T
Cells Cultured fibroblasts	eqtl	1.0e-09	-0.18	10:110908623:A:G
Cells EBV-transformed lymphocytes	eqtl	4.4e-09	-0.62	10:110843187:C:T
Esophagus Muscularis	eqtl	2.8e-07	+0.25	10:110790755:G:T
Adipose Subcutaneous	eqtl	3.0e-07	-0.19	10:110784305:A:C
Brain Putamen basal ganglia	eqtl	9.2e-05	+0.38	10:110766111:T:TA
Nerve Tibial	eqtl	9.4e-05	+0.20	10:110793712:T:C
Thyroid	eqtl	3.9e-04	+0.52	10:111742407:C:T
Brain Hippocampus	eqtl	1.0e-03	+0.24	10:110783950:C:T
Pituitary	sqtl	1.8e-03	+1.31	10:110734358:G:C
Adipose Visceral Omentum	eqtl	2.0e-03	-0.17	10:110784305:A:C
Muscle Skeletal	eqtl	3.6e-03	-0.19	10:110890297:T:C
Skin Sun Exposed Lower leg	eqtl	4.0e-03	-0.34	10:111847304:G:C
Adipose Subcutaneous	sqtl	5.5e-03	-0.54	10:110918728:G:GA
Whole Blood	eqtl	1.1e-02	-0.33	10:110615386:T:C
Cells Cultured fibroblasts	sqtl	1.5e-02	-1.36	10:111356424:G:A
Artery Tibial	eqtl	2.5e-02	-0.14	10:110011407:G:A
Pancreas	sqtl	2.6e-02	+0.67	10:110918333:C:A
Brain Cerebellum	eqtl	3.2e-02	-0.30	10:111032550:G:T
Brain Substantia nigra	eqtl	4.0e-02	-0.44	10:110769146:A:G

FANTOM5 promoters

showing 10 of 12 alternative TSS:

Promoter ID	TPM avg	Samples expressed
107008	78.8805	1811
107017	8.1449	1606
107007	2.8709	1201
107009	2.3967	1078
107006	0.8215	362
107018	0.5878	314
107011	0.4881	178
107010	0.3505	165
107012	0.1484	52
205987	0.0942	34

Top tissues by expression

showing 100 of 299 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.70	gold quality
skin of abdomen	UBERON:0001416	99.43	gold quality
skin of leg	UBERON:0001511	99.31	gold quality
rectum	UBERON:0001052	99.30	gold quality
right lobe of thyroid gland	UBERON:0001119	99.16	gold quality
left lobe of thyroid gland	UBERON:0001120	99.11	gold quality
minor salivary gland	UBERON:0001830	99.05	gold quality
left ovary	UBERON:0002119	98.99	gold quality
ventricular zone	UBERON:0003053	98.97	gold quality
right ovary	UBERON:0002118	98.96	gold quality
thyroid gland	UBERON:0002046	98.94	gold quality
transverse colon	UBERON:0001157	98.88	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.88	gold quality
mucosa of transverse colon	UBERON:0004991	98.87	gold quality
colonic epithelium	UBERON:0000397	98.86	gold quality
right uterine tube	UBERON:0001302	98.85	gold quality
esophagus mucosa	UBERON:0002469	98.82	gold quality
saliva-secreting gland	UBERON:0001044	98.80	gold quality
adrenal tissue	UBERON:0018303	98.77	gold quality
zone of skin	UBERON:0000014	98.74	gold quality
pancreas	UBERON:0001264	98.66	gold quality
lower esophagus mucosa	UBERON:0035834	98.64	gold quality
mouth mucosa	UBERON:0003729	98.57	gold quality
body of uterus	UBERON:0009853	98.56	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.51	gold quality
adenohypophysis	UBERON:0002196	98.49	gold quality
calcaneal tendon	UBERON:0003701	98.36	gold quality
body of stomach	UBERON:0001161	98.29	gold quality
tonsil	UBERON:0002372	98.26	gold quality
islet of Langerhans	UBERON:0000006	98.11	gold quality
small intestine	UBERON:0002108	98.01	gold quality
colon	UBERON:0001155	98.00	gold quality
gall bladder	UBERON:0002110	98.00	gold quality
vagina	UBERON:0000996	97.98	gold quality
intestine	UBERON:0000160	97.93	gold quality
large intestine	UBERON:0000059	97.87	gold quality
mucosa of stomach	UBERON:0001199	97.83	gold quality
esophagus	UBERON:0001043	97.81	gold quality
stomach	UBERON:0000945	97.80	gold quality
upper leg skin	UBERON:0004262	97.63	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.62	gold quality
pituitary gland	UBERON:0000007	97.58	gold quality
ovary	UBERON:0000992	97.52	gold quality
sigmoid colon	UBERON:0001159	97.51	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.42	gold quality
spleen	UBERON:0002106	97.39	gold quality
upper arm skin	UBERON:0004263	97.28	gold quality
ectocervix	UBERON:0012249	97.27	gold quality
endocervix	UBERON:0000458	97.26	gold quality
parotid gland	UBERON:0001831	97.26	gold quality
granulocyte	CL:0000094	97.23	gold quality
omental fat pad	UBERON:0010414	97.21	gold quality
peritoneum	UBERON:0002358	97.19	gold quality
left uterine tube	UBERON:0001303	97.08	gold quality
tibial nerve	UBERON:0001323	97.08	gold quality
right lung	UBERON:0002167	97.07	gold quality
colonic mucosa	UBERON:0000317	97.04	gold quality
lymph node	UBERON:0000029	96.99	gold quality
stromal cell of endometrium	CL:0002255	96.84	gold quality
descending thoracic aorta	UBERON:0002345	96.79	gold quality
leukocyte	CL:0000738	96.63	gold quality
lower esophagus	UBERON:0013473	96.63	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.61	gold quality
monocyte	CL:0000576	96.60	gold quality
fundus of stomach	UBERON:0001160	96.59	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.58	gold quality
vermiform appendix	UBERON:0001154	96.55	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.49	gold quality
mononuclear cell	CL:0000842	96.48	gold quality
caecum	UBERON:0001153	96.15	gold quality
subcutaneous adipose tissue	UBERON:0002190	96.07	gold quality
skin of hip	UBERON:0001554	96.05	gold quality
right testis	UBERON:0004534	95.91	gold quality
thoracic aorta	UBERON:0001515	95.86	gold quality
ascending aorta	UBERON:0001496	95.81	gold quality
female reproductive system	UBERON:0000474	95.76	gold quality
right coronary artery	UBERON:0001625	95.69	gold quality
left testis	UBERON:0004533	95.57	gold quality
left coronary artery	UBERON:0001626	95.55	gold quality
uterine cervix	UBERON:0000002	95.51	gold quality
upper lobe of left lung	UBERON:0008952	95.46	gold quality
bone marrow cell	CL:0002092	95.39	gold quality
tongue squamous epithelium	UBERON:0006919	95.35	gold quality
ganglionic eminence	UBERON:0004023	95.33	gold quality
prostate gland	UBERON:0002367	95.26	gold quality
aorta	UBERON:0000947	95.08	gold quality
right atrium auricular region	UBERON:0006631	95.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.02	gold quality
esophagus squamous epithelium	UBERON:0006920	95.01	gold quality
coronary artery	UBERON:0001621	94.98	gold quality
sural nerve	UBERON:0015488	94.93	gold quality
testis	UBERON:0000473	94.87	gold quality
uterus	UBERON:0000995	94.73	gold quality
epithelium of esophagus	UBERON:0001976	94.63	gold quality
penis	UBERON:0000989	94.62	gold quality
endometrium	UBERON:0001295	94.60	gold quality
tibial artery	UBERON:0007610	94.60	gold quality
artery	UBERON:0001637	94.59	gold quality
popliteal artery	UBERON:0002250	94.58	gold quality
right adrenal gland cortex	UBERON:0035827	94.58	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-9841	yes	1564.77
E-MTAB-10855	yes	1242.21
E-MTAB-3929	yes	762.86
E-HCAD-6	yes	56.35
E-MTAB-6701	yes	37.58
E-MTAB-6678	yes	24.17
E-CURD-122	yes	23.48
E-MTAB-9388	yes	12.42
E-MTAB-10137	yes	4.60
E-CURD-97	no	2669.12
E-MTAB-7606	no	428.08
E-MTAB-7303	no	230.41
E-CURD-112	no	3.10
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Pancreas	tissue	476.5	high
Parathyroid gland	tissue	266.7	high
Salivary gland	tissue	240.2	high
Colon	tissue	147.7	high
Thyroid gland	tissue	144.7	high
Esophagus	tissue	142.1	high
Breast	tissue	136.9	high
Rectum	tissue	122.5	high
Cerebellum	tissue	106.3	low
Ovary	tissue	102.2	high
Stomach 1	tissue	96.5	high
Small intestine	tissue	94.4	high
Skin 1	tissue	94.0	high
Placenta	tissue	91.1	high
Olfactory bulb	tissue	90.6
Tonsil	tissue	89.4	high
Hypothalamus	tissue	88.0
Duodenum	tissue	85.3	high
Spinal cord	tissue	84.8
Pons	tissue	82.3
Septum	tissue	82.3
Superior colliculi	tissue	79.5
Thalamus	tissue	77.9
Amygdala	tissue	72.5
Midbrain	tissue	70.8
Hippocampal formation	tissue	70.8
Ventral forebrain	tissue	70.7
Periaqueductal gray	tissue	70.6
Putamen	tissue	70.3
Bone marrow	tissue	69.7	high
Substantia nigra	tissue	69.2
Thymus	tissue	68.9
Medulla oblongata	tissue	64.7
Spleen	tissue	63.7	high
Basal ganglia	tissue	63.5	low
Endometrium 1	tissue	62.7	high
Frontal cortex	tissue	60.9
Vagina	tissue	60.5	high
Entorhinal cortex	tissue	58.6
Cerebral cortex	tissue	57.4	medium
Temporal cortex	tissue	57.4
Seminal vesicle	tissue	56.9	high
Lymph node	tissue	56.8	high
Prefrontal cortex	tissue	56.6
Motor cortex	tissue	56.1
Occipital cortex	tissue	56.0
Fallopian tube	tissue	54.3	high
Retrosplenial and cingulate cortex	tissue	53.8
Somatosensory cortex	tissue	53.7
Prostate	tissue	51.9	high
Appendix	tissue	50.2	high
Retrosplenial cortex	tissue	49.4
Insular cortex	tissue	48.5
Smooth muscle	tissue	48.0	medium
Retina	tissue	46.6
Cervix	tissue	46.3	high
Caudate putamen	tissue	44.3
Adipose tissue	tissue	42.8	medium
Gallbladder	tissue	40.7	high
Choroid plexus	tissue	40.6

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Dorsal spinal cord (84.8), Subiculum (70.8), Ventral hippocampus (67.9), Ventral spinal cord (62.6), Dorsal hippocampus (59.6).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): JUN, MYB, MYC, NFKB1, NFKB, NKX6-3, RELA, SP1, SP3, TP53

miRNA regulators (miRDB)

Targeting PDCD4 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 120 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-613	99.91	71.50	1710

Functional genomics

gnomAD constraint: pLI 0.00127, LOEUF 1.67, missense Z 0.85 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000280154 — one region, missense o/e 1.04.

Literature-anchored findings (GeneRIF, showing 40)

• up-regulated in senescent diploid fibroblasts (PMID:12054647)
• Results indicate that not only binding to eIF4A but also prevention of eIF4A binding to the MA-3 domain of eIF4Gc contributes to the mechanism by which Pdcd4 inhibits translation. (PMID:15082783)
• overexpression of PDCD4 in carcinoid cells results in inhibition of cell proliferation. (PMID:15153438)
• expression of pdcd4 as an indirect suppressor of CDK1/cdc2 is lost in progressed carcinomas of lung, breast, colon, and prostate (PMID:15317660)
• Pdcd4 suppresses tumor progression in colon carcinoma cells by the novel mechanism of down-regulating MAP4K1 transcription, with consequent inhibition of c-Jun activation and AP-1-dependent transcription. (PMID:16449643)
• data suggest that PDCD4 is a proapoptotic molecule involved in TGF-beta1-induced apoptosis in human HCC cells, and a possible tumor suppressor in hepatocarcinogenesis (PMID:16682950)
• in response to mitogens, PDCD4 was rapidly phosphorylated by protein kinase S6K1 & then degraded by ubiquitin ligase SCF(betaTRCP); it is proposed that regulated degradation of PDCD4 in response to mitogens allows efficient protein synthesis & cell growth (PMID:17053147)
• These data suggest Pdcd4 as a new negative regulator of intravasation, and qas the invasion-related gene u-PAR. It is the first study to implicate Pdcd4 regulation of gene expression via Sp1/Sp3. (PMID:17297470)
• Downregulation of tumor suppressor Pdcd4 promotes colonic neoplastic transformation and tumor invasion (PMID:17828298)
• Loss of programmed cell death 4 expression is associated with colorectal cancer (PMID:17849461)
• we conclude that the function of Pdcd4 might be cell type specific. A role for Pdcd4 in apoptosis or as a tumor suppressor might be limited to certain cell types. (PMID:17955371)
• Altered cellular localization of PDCD4 when comparing normal breast to neoplastic breast tissue. (PMID:17982621)
• Programmed Cell Death 4 (PDCD4) is regulated by microrna miR-21 and demonstrate that PDCD4 is a functionally important target for miR-21 in breast cancer cells. (PMID:17991735)
• the PDCD4 MA3 domains compete with the eIF4G MA3 domain and RNA for eIF4A binding. PDCD4 inhibits translation initiation by displacing eIF4G and RNA from eIF4A. (PMID:18296639)
• Pdcd4 is a translation inhibitor targeted for degradation during tumor promotion (PMID:18296647)
• mir-21 functions as an oncogene by a mechanism that involves translational repression of the tumor suppressor Pdcd4 (PMID:18372920)
• Suppression of PDCD4 expression is associated with breast cancer cell invasion. (PMID:18386173)
• results provide the first evidence that Pdcd4 is important role in the DNA-damage response and suggest that low levels of Pdcd4 expression observed in certain tumor cells contribute to tumorigenesis by affecting the fate of DNA-damaged cells (PMID:18427550)
• in squamous cell carcinoma lung cancer lines, alterations in Pdcd4 mRNA and protein levels are not directly linked. (PMID:18457901)
• the pathogenesis, development and prognosis of laryngeal carcinoma maybe closely related to the high expression of PD4 and CD44v6, CD44v9 proteins. (PMID:18476625)
• Suppression of Pdcd4 resulted in an increased release of CgA and Sg II and was accompanied by an up-regulation of intracellular PC1. (PMID:18549351)
• PDCD4 5’CpG island methylation blocks PDCD4 expression at mRNA levels in gliomas. (PMID:18793349)
• Inhibition of miR-21 increases endogenous levels of PDCD4 in cell line T98G and over-expression miR-21 inhibits PDCD4-dependent apoptosis (PMID:19013014)
• Lost or reduced PDCD4 expression is associated with the progression of ovarian serous cystadenocarcinomas and may serve as an important prognostic marker. (PMID:19031945)
• Structural and mutational analyses reveal that Pdcd4 inhibits translation initiation by trapping eIF4A in an inactive conformation, and blocking its incorporation into the eIF4F complex. (PMID:19153607)
• reveals insights into the inhibition mechanism of eIF4A by PDCD4 and provides a framework for designing chemicals that target eIF4A (PMID:19204291)
• Inhibitors of miR-21 increased levels of PDCD4 in cholangiocarcinoma. (PMID:19296468)
• PDCD4 inhibits the malignant phenotype of ovarian cancer cells. (PMID:19493270)
• Results indicate that HA binding to CD44 promotes PKCepsilon activation, increases the phosphorylation of the stem cell marker, Nanog, leads to microRNA-21 (miR-21) production and PDCD4 reduction. (PMID:19633292)
• Reducing expression of miR-21 or miR-155 led to up-regulation of phosphatase and tensin homologue (PTEN), programmed cell death 4 (PDCD4), or Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP1). (PMID:19641183)
• Identified up-regulation of microRNA-21 (hsa-miR-21) concurrent with down-regulation of potent tumor suppressor proteins PTEN and programmed cell death 4 in cholesteatoma as compared with normal skin. (PMID:19672202)
• miR-21 in HeLa cervical cancer cells caused profound suppression of cell proliferation, and up-regulated the expression of the tumor suppressor gene PDCD4. (PMID:19682430)
• Study demonstrated that the loss of Pdcd4 was a common abnormality at molecular level in ovarian cancer and it might be a potential prognostic factor in ovarian cancer patients. (PMID:19728867)
• Data show that elevated Snail expression by Pdcd4 knockdown leads to downregulation of E-cadherin resulting in activating beta-catenin/Tcf-dependent transcription. (PMID:19784072)
• Recent findings indicate that the microRNA miR-21 posttranscriptionally regulates Pdcd4, as well as invasion, intravasation, and metastasis of colon cancer. (PMID:19836969)
• miR-21 regulates PDCD4 expression after LPS stimulation. (PMID:19946272)
• found that PDCD4 inhibits c-Jun amino-terminal kinase activity resulting in inhibition of the phosphorylation of c-Jun, one isoform of AP-1 (PMID:20359850)
• PDCD4 and microRNA-21 have a role in human gastric cancer (PMID:20372781)
• Two isoforms of PKCs are involved in the regulation of the PDCD4 protein expression related to the proteasomal degradation pathway. (PMID:20471435)
• The loss of Pdcd4 early in cancer progression may have an important role in the increased sensitivity of cancer cells to hypoxia through increased LOX activity and concomitant enhanced invasiveness. (PMID:20498644)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pdcd4b	ENSDARG00000041022
mus_musculus	Pdcd4	ENSMUSG00000024975
rattus_norvegicus	Pdcd4	ENSRNOG00000014779
drosophila_melanogaster	Pdcd4	FBGN0030520

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:107490) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 10 distinct phenotype terms.

Mouse phenotype (MP)	Records
preneoplasia	1
increased papilloma incidence	1
ovary cyst	1
increased B cell derived lymphoma incidence	1
premature death	1
abnormal cytokine secretion	1
kidney cyst	1
decreased susceptibility to experimental autoimmune encephalomyelitis	1
decreased susceptibility to autoimmune diabetes	1
prostate gland cyst	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R8S3	98.7%	Diamond
Gallus gallus	Q98TX3	84.9%	Diamond
Arabidopsis thaliana	Q94BR1	79.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ADRA2A	protein-coding	150
SHOC2	protein-coding	8036
BBIP1	protein-coding	92482
PDCD4-AS1	ncRNA	282997
MIR4680	ncRNA	100616113
RBM20	protein-coding	282996
MIR548E	ncRNA	100313921

Protein

Protein identifiers

Programmed cell death protein 4 — Q53EL6 (reviewed: Q53EL6)

Alternative names: Neoplastic transformation inhibitor protein, Nuclear antigen H731-like, Protein 197/15a

All UniProt accessions (2): Q53EL6, Q5VZS7

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits translation initiation and cap-dependent translation. May excert its function by hindering the interaction between EIF4A1 and EIF4G. Inhibits the helicase activity of EIF4A. Modulates the activation of JUN kinase. Down-regulates the expression of MAP4K1, thus inhibiting events important in driving invasion, namely, MAPK85 activation and consequent JUN-dependent transcription. May play a role in apoptosis. Tumor suppressor. Inhibits tumor promoter-induced neoplastic transformation. Binds RNA.

Subunit / interactions. Interacts (via MI domains) with EIF4A2. Interacts (via MI domains) with EIF4A1 (via N-terminal domain). Heterotrimer with EIF4A1; one molecule of PDCD4 binds two molecules of EIF4A1. Interacts with EIF4G1. May form a complex with EIF4A1 and EIF4G1. The interaction between PDCD4 and EIF4A1 interferes with the interaction between EIF4A1 and EIF4G. When phosphorylated, interacts with BTRC and FBXW11.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Up-regulated in proliferative cells. Highly expressed in epithelial cells of the mammary gland. Reduced expression in lung cancer and colon carcinoma.

Post-translational modifications. Polyubiquitinated, leading to its proteasomal degradation. Rapidly degraded in response to mitogens. Phosphorylation of the phosphodegron promotes interaction with BTRC and proteasomal degradation. Phosphorylated at Ser-67 by RPS6KB1 in response to mitogens; phosphorylation promotes proteasomal degradation of PDCD4.

Domain organisation. Binds EIF4A1 via both MI domains.

Induction. IL2/interleukin-2 stimulation inhibits expression, while IL12/interleukin-12 increases expression.

Similarity. Belongs to the PDCD4 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q53EL6-1	1	yes
Q53EL6-2	2

RefSeq proteins (3): NP_001186421, NP_055271, NP_663314 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003891	Initiation_fac_eIF4g_MI	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR039778	PDCD4	Family

Pfam: PF02847

UniProt features (78 total): mutagenesis site 19, helix 19, modified residue 13, sequence conflict 8, sequence variant 3, short sequence motif 3, strand 3, domain 2, region of interest 2, turn 2, compositionally biased region 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

11 structures by resolution:

PDB	Title	Method	Resolution (Å)
9TES	Crystal structure of beta-TrCP bound by diphosphorylated PDCD4 degron peptide	X-RAY DIFFRACTION	1.22
2RG8	Crystal Structure of Programmed for Cell Death 4 Middle MA3 domain	X-RAY DIFFRACTION	1.8
9BKD	The structure of human Pdcd4 bound to the 40S small ribosomal subunit	ELECTRON MICROSCOPY	2.6
2ZU6	crystal structure of the eIF4A-PDCD4 complex	X-RAY DIFFRACTION	2.8
3EIJ	Crystal structure of Pdcd4	X-RAY DIFFRACTION	2.8
8XXL	Cryo-EM structure of the human 40S ribosome with PDCD4	ELECTRON MICROSCOPY	2.9
8XXM	Cryo-EM structure of the human 40S ribosome with PDCD4 and eIF3G	ELECTRON MICROSCOPY	3.2
8XXN	Cryo-EM structure of the human 43S ribosome with PDCD4	ELECTRON MICROSCOPY	3.6
9BLN	The structure of human Pdcd4 bound to the 40S-eIF4A-eIF3-eIF1 complex	ELECTRON MICROSCOPY	3.9
2GGF	Solution structure of the MA3 domain of human Programmed cell death 4	SOLUTION NMR
2KZT	Structure of the Tandem MA-3 Region of Pdcd4	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q53EL6-F1	77.03	0.55

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH enhanced · IF approved

Functional residue map

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

Post-translational modifications (13)

Type	Positions
N-acetylmethionine	1
Phosphoserine	25, 67, 68, 71, 76, 78, 80, 94, 313, 317, 457
Phosphotyrosine	152

Mutagenesis-validated functional residues (19)

Position	Phenotype
67	loss of phosphorylation site. reduces interaction with btrc. abolishes phosphorylation by pkb; when associated with a-457.
71	strongly reduced interaction with btrc. strongly reduced ubiquitination.
76	strongly reduced interaction with btrc. strongly reduced ubiquitination.
174	reduced inhibition of eif4a1 helicase activity.
210	reduced inhibition of eif4a1 helicase activity. strongly reduced inhibition of translation.
249	reduced interaction with eif4a1.
252	strongly reduced interaction with eif4a1. reduced inhibition of eif4a1 helicase activity. strongly reduced inhibition of translation.
253	strongly reduced interaction with eif4a1. strongly reduced inhibition of translation. reduced inhibition of eif4a1 helicase activity.
255	reduced inhibition of eif4a1 helicase activity. strongly reduced inhibition of translation.
333	no effect on inhibition of eif4a1 and on inhibition of translation; when associated with a-340.
337	no effect on inhibition of eif4a1 and on inhibition of translation.
340	no effect on inhibition of eif4a1 and on inhibition of translation; when associated with a-333.
358	strongly reduced interaction with eif4a1.
359	strongly reduced inhibition of eif4a1. strongly reduced inhibition of translation.
361	strongly reduced inhibition of eif4a1. strongly reduced inhibition of translation.
414	strongly reduced interaction with eif4a1. strongly reduced inhibition of translation.
418	reduced interaction with eif4a1. strongly reduced inhibition of translation.
420	strongly reduced interaction with eif4a1. strongly reduced inhibition of translation.
457	loss of phosphorylation site, and loss of nuclear accumulation. abolishes phosphorylation by pkb; when associated with a-67.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 6; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

6 pathways:

ID	Pathway	Evidence
R-HSA-8950505	Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	curated
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-168256	Immune System	—
R-HSA-447115	Interleukin-12 family signaling	—
R-HSA-9020591	Interleukin-12 signaling	—
R-HSA-449147	Signaling by Interleukins	—

MSigDB gene sets: 457 (showing top): GOBP_NEGATIVE_REGULATION_OF_MAP_KINASE_ACTIVITY, KOBAYASHI_EGFR_SIGNALING_24HR_UP, JI_RESPONSE_TO_FSH_UP, HNF3ALPHA_Q6, GOBP_NEGATIVE_REGULATION_OF_SMOOTH_MUSCLE_CELL_PROLIFERATION, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_SMOOTH_MUSCLE_CELL_DIFFERENTIATION, GOBP_SMOOTH_MUSCLE_CELL_DIFFERENTIATION, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS

GO Biological Process (14): apoptotic process (GO:0006915), BMP signaling pathway (GO:0030509), negative regulation of JUN kinase activity (GO:0043508), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of inflammatory response (GO:0050729), epithelial to mesenchymal transition involved in cardiac fibroblast development (GO:0060940), cellular response to lipopolysaccharide (GO:0071222), negative regulation of cytokine production involved in inflammatory response (GO:1900016), positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224), negative regulation of vascular associated smooth muscle cell proliferation (GO:1904706), negative regulation of myofibroblast differentiation (GO:1904761), negative regulation of vascular associated smooth muscle cell differentiation (GO:1905064), positive regulation of vascular associated smooth muscle cell apoptotic process (GO:1905461), positive regulation of endothelial cell apoptotic process (GO:2000353)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

5 top-level categories:

Category	Pathways
Interleukin-12 signaling	1
Immune System	1
Signaling by Interleukins	1
Cytokine Signaling in Immune system	1
Interleukin-12 family signaling	1

GO top-level categories

49 GO namespaces:

Category	Terms
cellular anatomical structure	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular response to BMP stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
JUN kinase activity	1
negative regulation of MAP kinase activity	1
regulation of JUN kinase activity	1
negative regulation of JNK cascade	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
inflammatory response	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
regulation of inflammatory response	1
cardiac epithelial to mesenchymal transition	1
epicardium-derived cardiac fibroblast cell development	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
negative regulation of cytokine production	1
cytokine production involved in inflammatory response	1
regulation of cytokine production involved in inflammatory response	1
non-canonical NF-kappaB signal transduction	1
regulation of non-canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
negative regulation of smooth muscle cell proliferation	1
regulation of vascular associated smooth muscle cell proliferation	1
vascular associated smooth muscle cell proliferation	1
myofibroblast differentiation	1
negative regulation of cell differentiation	1
regulation of myofibroblast differentiation	1
vascular associated smooth muscle cell differentiation	1
negative regulation of smooth muscle cell differentiation	1
regulation of vascular associated smooth muscle cell differentiation	1
positive regulation of smooth muscle cell apoptotic process	1
vascular associated smooth muscle cell apoptotic process	1
regulation of vascular associated smooth muscle cell apoptotic process	1
positive regulation of apoptotic process	1
endothelial cell apoptotic process	1
regulation of endothelial cell apoptotic process	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 11 of 19 annotations. The rest are phylogenetic / computational / electronic (IEA).

11 experimentally-supported GO terms:

GO term	NS	Evidence
BMP signaling pathway	BP	direct assay
negative regulation of DNA-templated transcription	BP	direct assay
negative regulation of myofibroblast differentiation	BP	mutant phenotype
negative regulation of vascular associated smooth muscle cell differentiation	BP	direct assay
negative regulation of vascular associated smooth muscle cell proliferation	BP	mutant phenotype
positive regulation of endothelial cell apoptotic process	BP	mutant phenotype
positive regulation of non-canonical NF-kappaB signal transduction	BP	mutant phenotype
positive regulation of vascular associated smooth muscle cell apoptotic process	BP	mutant phenotype
cytoplasm	CC	mutant phenotype
cytosol	CC	direct assay
nucleus	CC	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 1,936 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDCD4	EIF4A1	P04765	837
PDCD4	EIF4A2	Q14240	836
PDCD4	DROSHA	Q9NRR4	826
PDCD4	RECK	O95980	787
PDCD4	PTEN	P60484	773
PDCD4	SMAD5	Q99717	766
PDCD4	DDX5	P17844	738
PDCD4	SMAD4	Q13485	733
PDCD4	TGFB1	P01137	730
PDCD4	SMAD2	Q15796	705
PDCD4	SMAD7	O15105	700
PDCD4	EIF4B	P23588	682
PDCD4	RPS6KB1	P23443	674
PDCD4	SMAD3	P84022	674
PDCD4	TPM1	P09493	664

IntAct

Human interaction partners of PDCD4 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

22 partners by confidence:

Partner	Interaction type	MIscore	Records
EIF4A1	direct interaction	0.950	10
EIF4A3	physical association	0.780	6
EIF4A2	physical association	0.680	9
RELA	physical association	0.600	5
RPL5	physical association	0.550	1
RPS13	physical association	0.530	2
APOE	association	0.480	3
PSEN2	association	0.480	3
CSNK2A1	phosphorylation reaction	0.440	1
LRRK1	direct interaction	0.440	1
LRRK2	direct interaction	0.440	1
EIF4G1	physical association	0.400	1
H2BC12L	physical association	0.400	1
H2BC14	physical association	0.400	1
H2BC21	physical association	0.400	1
H2BC5	physical association	0.400	1
H2BC9	physical association	0.400	1
HMGN2	physical association	0.400	1
LMNA	physical association	0.400	1
RPLP1	physical association	0.370	1
BRAF	proximity	0.270	1
PTPN11	proximity	0.270	1

BioGRID (255 interactions; top human partners by supporting records): BTRC (Biochemical Activity; 11 records), FBXW11 (Affinity Capture-MS; 8 records), EIF4A1 (Affinity Capture-MS; 6 records), EIF4A2 (Two-hybrid; 5 records), SKP2 (Affinity Capture-MS; 5 records), DTL (Affinity Capture-MS; 4 records), EIF4G1 (Affinity Capture-Western; 4 records), COMTD1 (Affinity Capture-MS; 3 records), EIF4A3 (Two-hybrid; 3 records), HIST1H2BD (Cross-Linking-MS (XL-MS); 3 records), RPL5 (Two-hybrid; 3 records), TMEM51 (Affinity Capture-MS; 3 records), WWP2 (Affinity Capture-MS; 3 records), AGO2 (Affinity Capture-RNA; 2 records), APOE (Two-hybrid; 2 records)

SIGNOR signaling

showing 5 of 10 signaling interactions:

A	Effect	B	Mechanism
AKT	down-regulates	PDCD4	phosphorylation
RPS6KB1	down-regulates	PDCD4	phosphorylation
BTRC	down-regulates	PDCD4	ubiquitination
RPS6KB2	down-regulates	PDCD4	phosphorylation
AKT1	down-regulates	PDCD4	phosphorylation

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
★ Emerin complex 52	23	DDX39A, ILF3, LEMD3, RBL2, H1-1, HNRNPK, HNRNPU, IQGAP1, NMI, PDCD4, SNRPD1, THRA, API5, CKB, EMD, HDGF, LSM8, YWHAQ, ACTB, C1QBP, HNRNPL, LMNB1, YWHAE
PDCD4-RICTOR complex	2	PDCD4, RICTOR

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 22 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
Replacement of protamines by nucleosomes in the male pronucleus	5	68.0×	9e-07
Packaging Of Telomere Ends	5	54.9×	1e-06
Recognition and association of DNA glycosylase with site containing an affected purine	5	51.0×	1e-06
Cleavage of the damaged purine	5	51.0×	1e-06
Recognition and association of DNA glycosylase with site containing an affected pyrimidine	5	46.0×	1e-06
Cleavage of the damaged pyrimidine	5	46.0×	1e-06
RNA Polymerase I Promoter Opening	5	46.0×	1e-06
ChAHP complex assembly	5	46.0×	1e-06

Disease & clinical

Genetic variants

Variant evidence for PDCD4: 74 ClinVar records (0 pathogenic / likely pathogenic); 1 CIViC cancer variant; 2 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	0
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 23 predictions of 1,223):

Position(s)	Effect	Δscore	Sites
10:110872052	donor_gain	1.0000
10:110881231	acceptor_gain	1.0000
10:110881231–110881232	acceptor_loss	1.0000	4
10:110881264–110881265	acceptor_gain	1.0000	2
10:110882986–110882987	acceptor_gain	1.0000	2
10:110882992	acceptor_gain	1.0000
10:110883002	acceptor_loss	1.0000
10:110883098–110883099	donor_loss	1.0000	3
10:110885250–110885251	acceptor_gain	1.0000	2
10:110885367–110885368	donor_loss	1.0000	6

AlphaMissense

1,190 missense substitutions predicted likely pathogenic (of 3,074 scored), across 295 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D140	8	0.992	0.998
H361	8	0.990	0.996
D253	8	0.988	0.994
D418	8	0.984	0.993
S457	8	0.983	0.999
D460	8	0.982	0.995
F264	8	0.955	0.998
F240	8	0.947	0.993
N142	8	0.921	0.997
H358	8	0.919	0.988
H178	8	0.905	0.994
D137	8	0.900	0.963
D271	8	0.882	0.965
D70	8	0.872	0.954
D399	8	0.729	0.898
W124	7	0.998	1.000
F359	7	0.996	0.999
W315	7	0.990	0.999
E458	7	0.988	0.993
E174	7	0.981	0.990

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	5.47e-09

Disease associations

OMIM: gene MIM:608610 | disease phenotypes:

GWAS associations

2 associations:

Study	Trait	p-value
GCST010142_18	Fish- and plant-related diet	3e-10
GCST010142_94	Fish- and plant-related diet	4e-8

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1781868 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 174,652 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL413	SIROLIMUS	4	174,652

Clinical evidence (CIViC)

Drug × variant × indication, from 1 curated evidence items. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

1 predictive associations by evidence level:

Variant	Therapy	Indication	Effect	Level	CIViC
PDCD4 EXPRESSION	Paclitaxel	Lung Cancer	Sensitivity/Response	CIViC B	EID821

CIViC curated variants (1)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

EXPRESSION.

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

12 measured of 12 human assays (12 total across all organisms); most potent 12 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Rapamycin C-7, analog 4	IC50	1250 nM
Cryptocaryol G	EC50	1300 nM
CHEMBL5653589	KD	1440 nM
Cryptocaryol D	EC50	1500 nM
Cryptocaryol C	EC50	1600 nM
Cryptocaryol E	EC50	1800 nM
Cryptocaryol H	EC50	1800 nM
CHEMBL5170759	EC50	2250 nM
Cryptocaryol B	EC50	3000 nM
Cryptocaryol F	EC50	3500 nM
Cryptocaryol A	EC50	4900 nM
‘2-(4-AMINO-PYRROLO[2,3-D]PYRIMIDIN-7-YL)-5-HYDROXYMETHYL-TETRAHYDRO-FURAN-3,4-DIOL	IC50	10000 nM

ChEMBL bioactivities

13 potent at pChembl≥5 of 13 total, top 13 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.30	EC50	50	nM	SIROLIMUS
6.90	Kd	126.9	nM	CHEMBL5653589
6.90	ED50	126.9	nM	CHEMBL5653589
6.06	IC50	880	nM	TUBERCIDIN
5.89	EC50	1300	nM	CRYPTOCARYOL G
5.82	EC50	1500	nM	CRYPTOCARYOL D
5.80	EC50	1600	nM	CRYPTOCARYOL C
5.75	EC50	1800	nM	CRYPTOCARYOL E
5.75	EC50	1800	nM	CRYPTOCARYOL H
5.65	EC50	2251	nM	CHEMBL5170759
5.52	EC50	3000	nM	CRYPTOCARYOL B
5.46	EC50	3500	nM	CRYPTOCARYOL F
5.31	EC50	4900	nM	CRYPTOCARYOL A

PubChem BioAssay actives

12 with measured affinity, of 62 total; 12 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
Sirolimus	601333: Inhibition of TPA-induced degradation of Pdcd4 (amino acid 39-91) expressed in human HEK293 cells assessed as minimum compound concentration required for 50% recovery of Pdcd4-luciferase signal incubated for 8 hrs by luciferase reporter gene assay	ec50	0.0500	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148953: Binding affinity to human PDCD4 incubated for 45 mins by Kinobead based pull down assay	kd	0.1269	uM
(2R,3R,4S,5R)-2-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)oxolane-3,4-diol	626968: Stabilization of Pdcd4 expressed in human HEK293 cells assessed as inhibition of TPA-induced degradation by luciferase reporter assay	ic50	0.8800	uM
(2S,3S)-3-hydroxy-2-[(Z,2S,4S,6S,8R)-2,4,6,8-tetrahydroxytetratriacont-21-enyl]-2,3-dihydropyran-6-one	601333: Inhibition of TPA-induced degradation of Pdcd4 (amino acid 39-91) expressed in human HEK293 cells assessed as minimum compound concentration required for 50% recovery of Pdcd4-luciferase signal incubated for 8 hrs by luciferase reporter gene assay	ec50	1.3000	uM
[(2S,4S,6R,8R,10R)-2,4,6,8-tetrahydroxy-1-[(2S,3S)-3-hydroxy-6-oxo-2,3-dihydropyran-2-yl]pentacosan-10-yl] acetate	601333: Inhibition of TPA-induced degradation of Pdcd4 (amino acid 39-91) expressed in human HEK293 cells assessed as minimum compound concentration required for 50% recovery of Pdcd4-luciferase signal incubated for 8 hrs by luciferase reporter gene assay	ec50	1.5000	uM
(2S,3S)-3-hydroxy-2-[(2S,4S,6S,8S,10R)-2,4,6,8,10-pentahydroxypentacosyl]-2,3-dihydropyran-6-one	601333: Inhibition of TPA-induced degradation of Pdcd4 (amino acid 39-91) expressed in human HEK293 cells assessed as minimum compound concentration required for 50% recovery of Pdcd4-luciferase signal incubated for 8 hrs by luciferase reporter gene assay	ec50	1.6000	uM
(2S,3S)-3-hydroxy-2-[(Z,2S,4S,6R)-2,4,6-trihydroxydotriacont-19-enyl]-2,3-dihydropyran-6-one	601333: Inhibition of TPA-induced degradation of Pdcd4 (amino acid 39-91) expressed in human HEK293 cells assessed as minimum compound concentration required for 50% recovery of Pdcd4-luciferase signal incubated for 8 hrs by luciferase reporter gene assay	ec50	1.8000	uM
(2S,3S)-3-hydroxy-2-[(2S,4S,6S,8R)-2,4,6,8-tetrahydroxytricosyl]-2,3-dihydropyran-6-one	601333: Inhibition of TPA-induced degradation of Pdcd4 (amino acid 39-91) expressed in human HEK293 cells assessed as minimum compound concentration required for 50% recovery of Pdcd4-luciferase signal incubated for 8 hrs by luciferase reporter gene assay	ec50	1.8000	uM
ethyl 2-(4-methoxyphenyl)-5-methyl-1,3-oxazole-4-carboxylate	1884647: Inhibition of PDCD4 in human HeLa cells tranfected with pCI-neo-luciferase-PDCD4 3’-UTR plasmid assessed as increase in luciferase activity by luciferase reporter assay	ec50	2.2510	uM
[(2S,4S,6R,8R,10R)-2,4,6,8-tetrahydroxy-1-[(2R)-6-oxo-2,3-dihydropyran-2-yl]pentacosan-10-yl] acetate	601333: Inhibition of TPA-induced degradation of Pdcd4 (amino acid 39-91) expressed in human HEK293 cells assessed as minimum compound concentration required for 50% recovery of Pdcd4-luciferase signal incubated for 8 hrs by luciferase reporter gene assay	ec50	3.0000	uM
(2S,3S)-3-hydroxy-2-[(Z,2S,4S,6S,8S,10R)-2,4,6,8,10-pentahydroxyhexatriacont-23-enyl]-2,3-dihydropyran-6-one	601333: Inhibition of TPA-induced degradation of Pdcd4 (amino acid 39-91) expressed in human HEK293 cells assessed as minimum compound concentration required for 50% recovery of Pdcd4-luciferase signal incubated for 8 hrs by luciferase reporter gene assay	ec50	3.5000	uM
(2R)-2-[(2S,4S,6S,8S,10R)-2,4,6,8,10-pentahydroxypentacosyl]-2,3-dihydropyran-6-one	601333: Inhibition of TPA-induced degradation of Pdcd4 (amino acid 39-91) expressed in human HEK293 cells assessed as minimum compound concentration required for 50% recovery of Pdcd4-luciferase signal incubated for 8 hrs by luciferase reporter gene assay	ec50	4.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation	9
Resveratrol	affects response to substance, affects cotreatment, increases expression, increases stability	5
Arsenic Trioxide	increases expression	5
Estradiol	decreases expression, increases reaction, affects reaction, increases expression, decreases reaction	5
chromium hexavalent ion	decreases expression, decreases reaction, affects reaction	3
Benzo(a)pyrene	decreases expression, increases expression	3
Quercetin	affects cotreatment, decreases reaction, increases expression, decreases expression	3
Cadmium Chloride	decreases expression, increases expression	3
Sirolimus	affects cotreatment, increases stability, increases expression, increases reaction	3
bisphenol A	affects cotreatment, increases methylation, decreases methylation, increases expression	2
arsenite	decreases reaction, decreases expression, affects binding	2
cobaltous chloride	increases expression, decreases expression	2
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	increases expression, increases reaction	2
entinostat	decreases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment, increases expression	2
Air Pollutants	increases abundance, decreases expression	2
Dimethyl Sulfoxide	increases expression	2
Dust	decreases expression, increases expression	2
Hydrogen Peroxide	affects expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tretinoin	increases expression, increases reaction, decreases expression, increases response to substance, affects localization	2
Cyclosporine	decreases expression, increases expression	2
Aflatoxin B1	decreases expression	2
Genistein	affects expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, affects expression	2
aristolochic acid I	decreases expression	1
afuresertib	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1787264	Binding	Inhibition of TPA-induced degradation of Pdcd4 (amino acid 39-91) expressed in human HEK293 cells assessed as minimum compound concentration required for 50% recovery of Pdcd4-luciferase signal incubated for 8 hrs by luciferase reporter gen	Cryptocaryols A-H, α-pyrone-containing 1,3-polyols from Cryptocarya sp. implicated in stabilizing the tumor suppressor Pdcd4. — *J Nat Prod*

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2A6	Abcam HeLa PDCD4 KO	Cancer cell line	Female
CVCL_TC60	HAP1 PDCD4 (-) 1	Cancer cell line	Male
CVCL_TC61	HAP1 PDCD4 (-) 2	Cancer cell line	Male
CVCL_ZJ06	LanthaScreen PDCD4 HEK 293E	Transformed cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PDCD4 across ~30M SureChEMBL compounds — explore on Sugi Predict.