PPM1D

Summary

PPM1D (protein phosphatase, Mg2+/Mn2+ dependent 1D, HGNC:9277) is a protein-coding gene on chromosome 17q23.3, encoding Protein phosphatase 1D (O15297). Involved in the negative regulation of p53 expression. It is a selective cancer dependency (DepMap: 15.7% of cell lines).

The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. The expression of this gene is induced in a p53-dependent manner in response to various environmental stresses. While being induced by tumor suppressor protein TP53/p53, this phosphatase negatively regulates the activity of p38 MAP kinase, MAPK/p38, through which it reduces the phosphorylation of p53, and in turn suppresses p53-mediated transcription and apoptosis. This phosphatase thus mediates a feedback regulation of p38-p53 signaling that contributes to growth inhibition and the suppression of stress induced apoptosis. This gene is located in a chromosomal region known to be amplified in breast cancer. The amplification of this gene has been detected in both breast cancer cell line and primary breast tumors, which suggests a role of this gene in cancer development.

Source: NCBI Gene 8493 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic intellectual disability (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 392 total — 32 pathogenic, 33 likely-pathogenic
• Phenotypes (HPO): 37
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 5 cancer types
• Cancer dependency (DepMap): dependent in 15.7% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_003620

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9277
Approved symbol	PPM1D
Name	protein phosphatase, Mg2+/Mn2+ dependent 1D
Location	17q23.3
Locus type	gene with protein product
Status	Approved
Aliases	Wip1, PP2C-DELTA
Ensembl gene	ENSG00000170836
Ensembl biotype	protein_coding
OMIM	605100
Entrez	8493

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 7 nonsense_mediated_decay, 5 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000305921, ENST00000392995, ENST00000590418, ENST00000629650, ENST00000685212, ENST00000685582, ENST00000686064, ENST00000687355, ENST00000688505, ENST00000689445, ENST00000692386, ENST00000693102, ENST00000693196, ENST00000870218, ENST00000870219

RefSeq mRNA: 1 — MANE Select: NM_003620 NM_003620

CCDS: CCDS11625

Canonical transcript exons

ENST00000305921 — 6 exons

Exon	Start	End
ENSE00001132631	60656599	60656841
ENSE00001205615	60662995	60666280
ENSE00001261945	60647892	60648082
ENSE00001261954	60633853	60633977
ENSE00001261964	60623521	60623749
ENSE00003896583	60600193	60600886

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 93.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.9965 / max 347.9986, expressed in 1793 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162051	15.3500	1727
162052	6.6823	1472
162053	3.9642	1043

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	93.12	gold quality
amniotic fluid	UBERON:0000173	89.88	gold quality
endometrium epithelium	UBERON:0004811	89.25	gold quality
ventricular zone	UBERON:0003053	88.42	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.88	gold quality
placenta	UBERON:0001987	86.82	gold quality
ganglionic eminence	UBERON:0004023	86.21	gold quality
mucosa of sigmoid colon	UBERON:0004993	86.13	gold quality
embryo	UBERON:0000922	85.78	gold quality
jejunal mucosa	UBERON:0000399	85.47	gold quality
germinal epithelium of ovary	UBERON:0001304	85.33	gold quality
calcaneal tendon	UBERON:0003701	84.83	gold quality
colonic mucosa	UBERON:0000317	84.52	gold quality
cartilage tissue	UBERON:0002418	83.87	gold quality
esophagus squamous epithelium	UBERON:0006920	83.51	gold quality
adult organism	UBERON:0007023	83.43	gold quality
pigmented layer of retina	UBERON:0001782	83.25	gold quality
colonic epithelium	UBERON:0000397	82.91	gold quality
cortical plate	UBERON:0005343	82.81	gold quality
visceral pleura	UBERON:0002401	82.66	gold quality
sperm	CL:0000019	82.64	gold quality
pleura	UBERON:0000977	82.15	gold quality
parietal pleura	UBERON:0002400	82.00	gold quality
trabecular bone tissue	UBERON:0002483	81.93	gold quality
monocyte	CL:0000576	81.85	gold quality
leukocyte	CL:0000738	81.75	gold quality
tibia	UBERON:0000979	81.73	gold quality
cauda epididymis	UBERON:0004360	81.72	gold quality
ovary	UBERON:0000992	81.67	gold quality
mononuclear cell	CL:0000842	81.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.65

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, DDIT3, ESR1, JUN, NCOA1, NCOR2, NFKB, NR4A1, PARP1, TP53

miRNA regulators (miRDB)

145 targeting PPM1D, 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-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
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-4425	100.00	67.59	1049
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-10527-5P	99.91	72.28	3754

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 15.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Functional study of the mouse homolog (PMID:11809801)
• PPM1D, encoding a serine/threonine protein phosphatase, lies within an epicenter of the region at 17q23, is amplified in breast cancer (PMID:12021784)
• PPM1D amplification contributes to the development of human cancers by suppressing p53 activation (PMID:12021785)
• ablation of gene confers resistance to breast tumors induced by certain oncogenes (PMID:15054481)
• Data demonstrate that p53-induced phosphatase PPM1D interacts with the nuclear isoform of uracil DNA glycosylase, UNG2, and suppresses base excision repair. (PMID:15327777)
• suggest that substrate recognition by Wip1 is centered toward a very narrow region around the pTXpY sequence (PMID:15807522)
• Primary function of PPM1D is to reverse the p53 and Chk1-induced DNA damage and cell cycle checkpoint responses and return the cell to a homeostatic state following completion of DNA repair. (PMID:15870257)
• PPM1D is frequently activated through amplification in aggressive primary breast tumours (PMID:16254685)
• Wip1 acts as a negative regulator of Chk2 and inhibition of Wip1 expression by RNA interference results in abnormally sustained Thr68 phosphorylation of Chk2. (PMID:16311512)
• Increased protein-levels of PPM1D may link the TP53 and RB1 tumor suppressor pathways to medulloblastoma pathomechanisms. (PMID:16314645)
• Demonstrated the ability of protein phosphatase 1D magnesium-dependent, delta isoform (PPM1D) to positively modulate the activity of type I and II nuclear receptors. (PMID:16352595)
• PPM1D promotes breast tumor growth both by inhibiting p53 activity and by enhancing steroid hormone receptor action (PMID:16352595)
• an intrinsic kinase activity of Chk2, but not phosphatase activity of Wip1, is required for the association of fulllength Chk2 and Wip1 (PMID:16798742)
• Wip1 overexpression abrogates the homeostatic balance maintained through the p38-p53-Wip1 pathway, and contributes to malignant progression by inactivating wild-type p53 and p38 MAPK as well as decreasing p16 protein levels in human breast tissues. (PMID:16897432)
• E2F and Wip1 are modulators of E2F1-induced apoptosis involving p38 MAP kinase (PMID:16912047)
• These results indicate that Wip1 is one of the phosphatases regulating the activity of Chk2 in response to DNA damage. (PMID:16936775)
• Wip1 phosphatase is an integral component of an ATM-dependent signaling pathway. (PMID:16949371)
• Operates within the map kinase kinase 6/p38 map kinase signaling pathway to promote ErbB2-driven mammary gland tumorigenesis in transgenic mice. (PMID:17016428)
• WIP1 is expressed in non-neoplastic gastric mucosa and is frequently overexpressed in gastric cancers. (PMID:17685927)
• Wip1 acts as a gatekeeper in the Mdm2-p53 regulatory loop by stabilizing Mdm2 and promoting Mdm2-mediated proteolysis of p53. (PMID:17936559)
• The Wip1 phosphatase PPM1D dephosphorylates SQ/TQ motifs in checkpoint substrates phosphorylated by PI3K-like kinases. (PMID:17939684)
• PPM1D contributes to breast cancer associated phenotypic characteristics by directly or indirectly affecting several important cellular signaling pathways. (PMID:17977650)
• Our findings demonstrate that PPM1D is involved in the regulation of cell proliferation in breast cancer in a p53-dependent manner and that overexpression of PPM1D contributes to malignant phenotype by promoting sustained cell growth and cell survival. (PMID:18328948)
• ATO-induced activation of Chk2/p53 and p38 MAPK/p53 apoptotic pathways can be enhanced by siRNA-mediated suppression of Wip1 expression, further indicating that ATO inhibits Wip1 phosphatase in vivo (PMID:18482988)
• PPM1D430, a novel alternative splicing variant of the human PPM1D, can dephosphorylate p53 and exhibits specific tissue expression (PMID:18845566)
• identification of the active center and further elucidation of the substrate preference of PPM1D; findings showed that the putative active site residues of PPM1D are highly conserved among the PPM1 family members (PMID:18991770)
• Characterization of a conserved p53 response element located in the 5’ untranslated region of the PPM1D gene that is required for the p53-dependent induction of transcription from the human PPM1D promoter. (PMID:19015127)
• WIP1 is a direct phosphatase of Ser 536 of the p65 subunit of NF-kappaB and negatively regulates NF-kappaB signalling. (PMID:19377466)
• Results indicate that Wip1 up-regulation is important in the pathogenesis of p53(+) and ER(+) breast cancer through the inactivation of p53 by dephosphorylation and the amplification of subsequent estrogenic effects through the E(2)-ERalpha-Wip1 pathway. (PMID:19435816)
• Findings uncover Wip1 as a first in class recovery competence gene, and suggest that the principal function of Wip1 in cellular transformation is to retain proliferative capacity in the face of oncogene-induced stress. (PMID:19713933)
• Nuclear factor-kappaB (NF-kappaB) is a novel positive transcriptional regulator of the oncogenic Wip1 phosphatase (PMID:20007970)
• Wip1 (wild-type p53-induced phosphatase) expression is temporally induced by c-Jun and p53 in response to UV irradiation (PMID:20093361)
• Wip1 has an essential role in dephosphorylation of gamma-H2AX to silence the checkpoint and restore chromatin structure once DNA damage is repaired. (PMID:20101220)
• Wild-type p53-induced phosphatase 1 dephosphorylates histone variant gamma-H2AX and suppresses DNA double strand break repair. (PMID:20118229)
• The high expression of Wip1 mRNA and its protein in breast cancer tissue may promote the growth of breast cancer. (PMID:20367961)
• PPM1D is consistently overexpressed when amplified in breast cancer; however, PPM1D overexpression is more pervasive than gene amplification. (PMID:20543821)
• results suggest an important role of miR-16 in the regulation of Wip1 phosphatase in the DNA damage response and mammary tumorigenesis. (PMID:20668064)
• the increased expression of Wip1 in cancer epithelial cells has significant value for tumor progression and the clinical prognosis of patients with primary lung adenocarcinoma (PMID:21281403)
• the ability of LZAP to alter p38 phosphorylation depended, at least partially, on the p38 phosphatase, Wip1 (PMID:21283629)
• Down-regulation of PPM1D resulted in significantly increased cell apoptosis and reduced cell proliferation and invasion potential in U87-MG cells. (PMID:21336731)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppm1da	ENSDARG00000009273
danio_rerio	ppm1db	ENSDARG00000021380
mus_musculus	Ppm1d	ENSMUSG00000020525
rattus_norvegicus	Ppm1d	ENSRNOG00000003329
drosophila_melanogaster	Pp2C1	FBGN0022768
caenorhabditis_elegans		WBGENE00021856

Paralogs (16): PPM1F (ENSG00000100034), TAB1 (ENSG00000100324), PPM1A (ENSG00000100614), PPM1H (ENSG00000111110), PPM1G (ENSG00000115241), ILKAP (ENSG00000132323), PPM1B (ENSG00000138032), PPM1J (ENSG00000155367), PPM1L (ENSG00000163590), PPM1K (ENSG00000163644), PPM1M (ENSG00000164088), PDP1 (ENSG00000164951), PDP2 (ENSG00000172840), PPM1E (ENSG00000175175), PP2D1 (ENSG00000183977), PPM1N (ENSG00000213889)

Protein

Protein identifiers

Protein phosphatase 1D — O15297 (reviewed: O15297)

Alternative names: Protein phosphatase 2C isoform delta, Protein phosphatase magnesium-dependent 1 delta, p53-induced protein phosphatase 1

All UniProt accessions (10): O15297, A0A0S2Z4M2, A0A0S2Z4W0, A0A8I5KNX5, A0A8I5KT72, A0A8I5KUN6, A0A8I5KUX8, A0A8I5QJK9, A0A8I5QKP1, A0A8J9C7E3

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the negative regulation of p53 expression. Required for the relief of p53-dependent checkpoint mediated cell cycle arrest. Binds to and dephosphorylates ‘Ser-15’ of TP53 and ‘Ser-345’ of CHEK1 which contributes to the functional inactivation of these proteins. Mediates MAPK14 dephosphorylation and inactivation. Is also an important regulator of global heterochromatin silencing and critical in maintaining genome integrity.

Subunit / interactions. Interacts with CHEK1 and CHEK2; dephosphorylates them. Interacts with MAPK14.

Subcellular location. Nucleus. Cytoplasm. Cytosol.

Tissue specificity. Expressed in fetal and adult brain. Also detected in fetal liver and skeletal muscle, but not in their adult counterparts.

Disease relevance. Jansen-de Vries syndrome (JDVS) [MIM:617450] An autosomal dominant neurodevelopmental disorder characterized by mild to severe intellectual disability, psychomotor developmental delay, speech delay, and behavioral manifestations including attention deficit-hyperactivity disorder, autism and anxiety disorders. Most patients have variable additional features, including feeding and gastrointestinal difficulties, high pain threshold, hypersensitivity to sound, hypotonia, broad-based gait, and dysmorphic features, including mild facial abnormalities, strabismus, and small hands and feet. The disease is caused by variants affecting the gene represented in this entry. Breast cancer (BC) [MIM:114480] A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Ovarian cancer (OC) [MIM:167000] The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

Cofactor. Binds 2 magnesium or manganese ions per subunit.

Induction. By p53/TP53.

Similarity. Belongs to the PP2C family.

Isoforms (2)

UniProt ID	Names	Canonical?
O15297-1	1	yes
O15297-2	2

RefSeq proteins (1): NP_003611* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000222	PP2C_BS	Binding_site
IPR001932	PPM-type_phosphatase-like_dom	Domain
IPR015655	PP2C	Family
IPR036457	PPM-type-like_dom_sf	Homologous_superfamily

Pfam: PF00481

Catalyzed reactions (Rhea), 2 shown:

• O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate (RHEA:20629)
• O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate (RHEA:47004)

UniProt features (58 total): strand 14, sequence variant 11, helix 10, binding site 5, turn 5, region of interest 3, compositionally biased region 3, modified residue 2, splice variant 2, chain 1, domain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8T2J	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15297-F1	68.15	0.43

Functional residue map

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

Ligand- & substrate-binding residues (5): 106; 314; 366; 105; 105

Post-translational modifications (2): 40, 85

Mutagenesis-validated functional residues (1):

Position	Phenotype
314	abrogates phosphatase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8878166	Transcriptional regulation by RUNX2

MSigDB gene sets: 381 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, RNGTGGGC_UNKNOWN, E2F_Q4, E2F_Q4_01, FREAC2_01, E2F4DP1_01, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, TTTGTAG_MIR520D, GOBP_CELL_CYCLE_PHASE_TRANSITION, GCM_PPM1D, ATGCAGT_MIR217, CTATGCA_MIR153, GGGTGGRR_PAX4_03, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_DNA_METHYLATION_DEPENDENT_CONSTITUTIVE_HETEROCHROMATIN_FORMATION

GO Biological Process (12): G2/M transition of mitotic cell cycle (GO:0000086), DNA methylation-dependent constitutive heterochromatin formation (GO:0006346), protein dephosphorylation (GO:0006470), negative regulation of cell population proliferation (GO:0008285), cellular response to starvation (GO:0009267), response to radiation (GO:0009314), response to bacterium (GO:0009617), DNA damage response, signal transduction by p53 class mediator (GO:0030330), peptidyl-threonine dephosphorylation (GO:0035970), negative regulation of gene expression, epigenetic (GO:0045814), regulation of transcription initiation by RNA polymerase II (GO:0060260), regulation of intracellular signal transduction (GO:1902531)

GO Molecular Function (8): protein serine/threonine kinase activity (GO:0004674), protein serine/threonine phosphatase activity (GO:0004722), metal ion binding (GO:0046872), mitogen-activated protein kinase binding (GO:0051019), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787), cation binding (GO:0043169)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
nuclear lumen	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G2/M phase transition	1
constitutive heterochromatin formation	1
dephosphorylation	1
protein modification process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
response to abiotic stimulus	1
response to other organism	1
signal transduction in response to DNA damage	1
signal transduction by p53 class mediator	1
protein dephosphorylation	1
negative regulation of gene expression	1
epigenetic regulation of gene expression	1
regulation of transcription by RNA polymerase II	1
transcription initiation at RNA polymerase II promoter	1
regulation of DNA-templated transcription initiation	1
regulation of signal transduction	1
intracellular signal transduction	1
protein kinase activity	1
phosphoprotein phosphatase activity	1
cation binding	1
protein kinase binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
ion binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2407 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPM1D	ATM	Q13315	924
PPM1D	APPBP2	Q92624	842
PPM1D	CHEK2	O96017	822
PPM1D	MDM2	Q00987	790
PPM1D	CHEK1	O14757	761
PPM1D	MDM4	O15151	728
PPM1D	TP53	P04637	721
PPM1D	PTEN	P60484	601
PPM1D	ASXL1	Q8IXJ9	588
PPM1D	TET2	Q6N021	571
PPM1D	CCNG1	P51959	551
PPM1D	RAD51C	O43502	549
PPM1D	PPM1M	Q96MI6	527
PPM1D	DNMT3A	Q9Y6K1	507
PPM1D	WT1	P19544	496

IntAct

56 interactions, top by confidence:

A	B	Type	Score
PPM1D	RUNX2	psi-mi:“MI:0915”(physical association)	0.600
PPM1D	RUNX2	psi-mi:“MI:0203”(dephosphorylation reaction)	0.600
PPM1D	BRAF	psi-mi:“MI:0915”(physical association)	0.550
PPM1D	BRAF	psi-mi:“MI:2364”(proximity)	0.550
BRAF	PPM1D	psi-mi:“MI:0915”(physical association)	0.550
MDM2	PPM1D	psi-mi:“MI:0915”(physical association)	0.540
PPM1D	MDM2	psi-mi:“MI:0915”(physical association)	0.540
PPM1D	MDM2	psi-mi:“MI:0203”(dephosphorylation reaction)	0.540
PPM1D	H2AX	psi-mi:“MI:0203”(dephosphorylation reaction)	0.540
PPM1D	H2AX	psi-mi:“MI:0915”(physical association)	0.540
H2AX	PPM1D	psi-mi:“MI:0915”(physical association)	0.540
PPM1D		psi-mi:“MI:0203”(dephosphorylation reaction)	0.440
PPP4C	PPM1D	psi-mi:“MI:0915”(physical association)	0.400
PPM1D	BEX2	psi-mi:“MI:0915”(physical association)	0.370
CASZ1	PPM1D	psi-mi:“MI:0915”(physical association)	0.370
PPM1D	DIRAS3	psi-mi:“MI:0915”(physical association)	0.370
DKK3	PPM1D	psi-mi:“MI:0915”(physical association)	0.370
EPSTI1	PPM1D	psi-mi:“MI:0915”(physical association)	0.370
PPM1D	ERRFI1	psi-mi:“MI:0915”(physical association)	0.370
GLCE	PPM1D	psi-mi:“MI:0915”(physical association)	0.370
ITIH5	PPM1D	psi-mi:“MI:0915”(physical association)	0.370
LYPD3	PPM1D	psi-mi:“MI:0915”(physical association)	0.370
PPM1D	MRC2	psi-mi:“MI:0915”(physical association)	0.370
PPM1D	NAT2	psi-mi:“MI:0915”(physical association)	0.370
PPM1D	OSGIN1	psi-mi:“MI:0915”(physical association)	0.370
PPM1D	RHOBTB2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (89): KDM1A (Biochemical Activity), KDM1A (Affinity Capture-Western), PPM1D (Affinity Capture-Western), KDM1A (Reconstituted Complex), BEX2 (Two-hybrid), CASZ1 (Two-hybrid), DIRAS3 (Two-hybrid), DKK3 (Two-hybrid), EPSTI1 (Two-hybrid), ERRFI1 (Two-hybrid), GLCE (Two-hybrid), ITIH5 (Two-hybrid), LYPD3 (Two-hybrid), MRC2 (Two-hybrid), NAT2 (Two-hybrid)

ESM2 similar proteins: A3A8Q4, A3A8W6, A6QLI5, B0Y8Z0, B9F4I8, F4JFR7, F4JRP0, F4K5K6, F4KAV2, O15297, O81472, O82302, P48785, Q06003, Q0D598, Q0DZT4, Q10NB9, Q2PS26, Q4WWA0, Q5N712, Q5XUX6, Q651A1, Q6ITT4, Q6K1U0, Q6K1U4, Q6K5I0, Q6WLH4, Q6ZGY0, Q7L311, Q7TQI8, Q7XRV0, Q84T94, Q8GYY5, Q8L7S0, Q8RWN7, Q8W119, Q96JG8, Q9BE64, Q9ES73, Q9FNK5

Diamond homologs: A0A7U2MSD6, A0BLX0, A0BQL0, A0CUB5, A0DSB3, A0DTY1, A3A8W2, A3A8W6, A3CCP9, A5PJZ2, A6K136, B8NLZ3, G0RT93, O15297, O62829, O62830, O75688, O81716, P20650, P34221, P35182, P35813, P35814, P35815, P36982, P36993, P38089, P39966, P40371, P49443, P49444, P49596, P49597, P49598, P93006, Q09172, Q09173, Q0D629, Q0DBU3, Q0DZT4

SIGNOR signaling

41 interactions.

A	Effect	B	Mechanism
PPM1D	down-regulates	CHEK1	dephosphorylation
PPM1D	down-regulates	MAPK12	dephosphorylation
PPM1D	down-regulates	TP53	dephosphorylation
PPM1D	up-regulates	MDM2	dephosphorylation
PPM1D	down-regulates	H2AX	dephosphorylation
PPM1D	down-regulates	ATM	dephosphorylation
PPM1D	“down-regulates activity”	MAPK14	dephosphorylation
PPM1D	“down-regulates activity”	CHEK1	dephosphorylation
PPM1D	“down-regulates activity”	TP53	dephosphorylation
PPM1D	“down-regulates quantity by destabilization”	MDM2	dephosphorylation
PPM1D	“down-regulates activity”	ATM	dephosphorylation
PPM1D	“down-regulates activity”	KDM1A	dephosphorylation
PPM1D	“down-regulates quantity by destabilization”	TP53	dephosphorylation
PPM1D	“up-regulates quantity by stabilization”	MDM4	dephosphorylation
PPM1D	“down-regulates activity”	BAX	dephosphorylation
PPM1D	“up-regulates activity”	RBM38	dephosphorylation
PPM1D	“down-regulates activity”	TP53BP1	dephosphorylation
PPM1D	“down-regulates activity”	CDKN1B	dephosphorylation
PPM1D	“up-regulates activity”	RUNX2	dephosphorylation
PPM1D	“down-regulates activity”	GPI	dephosphorylation
PPM1D	“down-regulates activity”	UNG	dephosphorylation
HIPK2	“down-regulates quantity by destabilization”	PPM1D	phosphorylation
PPM1D	“down-regulates activity”	RPS6KA3	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 36 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.

GO biological processes:

GO term	Partners	Fold	FDR
epidermal growth factor receptor signaling pathway	5	35.4×	2e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 5 cancer types — BCC, BRCA, HGGNOS, LUAD, PAST.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	32
Likely pathogenic	33
Uncertain significance	148
Likely benign	111
Benign	26

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1031346	NM_003620.4(PPM1D):c.1278dup (p.Trp427fs)	Pathogenic
148363	GRCh38/hg38 17q23.1-25.1(chr17:36449220-75053130)x3	Pathogenic
1700115	NM_003620.4(PPM1D):c.1262dup (p.Leu422fs)	Pathogenic
1704248	NM_003620.4(PPM1D):c.1262C>A (p.Ser421Ter)	Pathogenic
1704910	NM_003620.4(PPM1D):c.1280G>A (p.Trp427Ter)	Pathogenic
2442251	NM_003620.4(PPM1D):c.1288del (p.Arg429_Val430insTer)	Pathogenic
3024290	NM_003620.4(PPM1D):c.1204_1208del (p.Asn402fs)	Pathogenic
3067690	NM_003620.4(PPM1D):c.1275del (p.Pro426fs)	Pathogenic
3238648	NM_003620.4(PPM1D):c.1216dup (p.Thr406fs)	Pathogenic
3248542	NM_003620.4(PPM1D):c.1305_1308dup (p.Pro437fs)	Pathogenic
3254874	NM_003620.4(PPM1D):c.1503_1507del (p.Ser503fs)	Pathogenic
3336919	NM_003620.4(PPM1D):c.1233_1234del (p.Ser412fs)	Pathogenic
3350239	NM_003620.4(PPM1D):c.1403C>A (p.Ser468Ter)	Pathogenic
3600723	NM_003620.4(PPM1D):c.1273del (p.Asp425fs)	Pathogenic
392920	NM_003620.4(PPM1D):c.1267G>T (p.Glu423Ter)	Pathogenic
424876	NM_003620.4(PPM1D):c.1216del (p.Thr406fs)	Pathogenic
424878	NM_003620.4(PPM1D):c.1281G>A (p.Trp427Ter)	Pathogenic
424879	NM_003620.4(PPM1D):c.1250dup (p.Pro418fs)	Pathogenic
449085	NM_003620.4(PPM1D):c.1210C>T (p.Gln404Ter)	Pathogenic
4531673	NM_003620.4(PPM1D):c.1280_1281insT (p.Trp427fs)	Pathogenic
4688060	NM_003620.4(PPM1D):c.1455del (p.Ile486fs)	Pathogenic
488841	NM_003620.4(PPM1D):c.1451T>G (p.Leu484Ter)	Pathogenic
503784	NM_003620.4(PPM1D):c.1212del (p.Glu405fs)	Pathogenic
524006	NM_003620.4(PPM1D):c.1246_1249dup (p.Pro417fs)	Pathogenic
625529	NM_003620.4(PPM1D):c.1248_1252del (p.Pro417fs)	Pathogenic
638685	NM_003620.4(PPM1D):c.1259dup (p.Ser421fs)	Pathogenic
817626	NM_003620.4(PPM1D):c.1535del (p.Asn512fs)	Pathogenic
871467	NM_003620.4(PPM1D):c.1270_1274dup (p.Asp425fs)	Pathogenic
871468	NM_003620.4(PPM1D):c.1275_1281del (p.Pro426fs)	Pathogenic
982378	NM_003620.4(PPM1D):c.1388_1389delinsA (p.Gly463fs)	Pathogenic

SpliceAI

1295 predictions. Top by Δscore:

Variant	Effect	Δscore
17:60623516:TACA:T	acceptor_loss	1.0000
17:60623517:ACAGC:A	acceptor_gain	1.0000
17:60623518:CA:C	acceptor_loss	1.0000
17:60623519:A:AG	acceptor_gain	1.0000
17:60623519:AGC:A	acceptor_gain	1.0000
17:60623519:AGCG:A	acceptor_gain	1.0000
17:60623520:G:GT	acceptor_gain	1.0000
17:60623520:GC:G	acceptor_gain	1.0000
17:60623520:GCG:G	acceptor_gain	1.0000
17:60623520:GCGG:G	acceptor_gain	1.0000
17:60623520:GCGGA:G	acceptor_gain	1.0000
17:60623719:A:T	donor_gain	1.0000
17:60623737:G:GT	donor_gain	1.0000
17:60623747:G:GT	donor_gain	1.0000
17:60623747:G:T	donor_gain	1.0000
17:60623748:AGGTA:A	donor_loss	1.0000
17:60623750:G:GA	donor_loss	1.0000
17:60623751:T:G	donor_loss	1.0000
17:60633849:TTAGT:T	acceptor_loss	1.0000
17:60633851:A:AG	acceptor_gain	1.0000
17:60633851:AGT:A	acceptor_gain	1.0000
17:60633852:G:GA	acceptor_gain	1.0000
17:60633852:GT:G	acceptor_gain	1.0000
17:60633852:GTG:G	acceptor_gain	1.0000
17:60633852:GTGT:G	acceptor_gain	1.0000
17:60633852:GTGTA:G	acceptor_gain	1.0000
17:60633973:ACTTG:A	donor_gain	1.0000
17:60633974:CTTG:C	donor_gain	1.0000
17:60633974:CTTGG:C	donor_loss	1.0000
17:60633975:TTG:T	donor_gain	1.0000

AlphaMissense

3949 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:60600460:G:C	G16R	1.000
17:60600467:G:C	R18T	1.000
17:60600467:G:T	R18M	1.000
17:60600468:G:C	R18S	1.000
17:60600468:G:T	R18S	1.000
17:60600477:G:A	M21I	1.000
17:60600477:G:C	M21I	1.000
17:60600477:G:T	M21I	1.000
17:60600481:G:C	D23H	1.000
17:60600482:A:C	D23A	1.000
17:60600482:A:G	D23G	1.000
17:60600482:A:T	D23V	1.000
17:60600727:G:C	D105H	1.000
17:60600728:A:C	D105A	1.000
17:60600728:A:G	D105G	1.000
17:60600728:A:T	D105V	1.000
17:60600729:C:A	D105E	1.000
17:60600729:C:G	D105E	1.000
17:60600730:G:A	G106R	1.000
17:60600730:G:C	G106R	1.000
17:60600730:G:T	G106W	1.000
17:60600731:G:A	G106E	1.000
17:60600731:G:C	G106A	1.000
17:60600731:G:T	G106V	1.000
17:60600733:C:G	H107D	1.000
17:60600735:C:A	H107Q	1.000
17:60600735:C:G	H107Q	1.000
17:60600736:G:A	G108S	1.000
17:60600736:G:C	G108R	1.000
17:60600736:G:T	G108C	1.000

dbSNP variants (sampled 300 via entrez): RS1000068951 (17:60644970 CAT>C), RS1000107362 (17:60632985 A>C), RS1000201530 (17:60616307 A>G), RS1000235917 (17:60639623 A>C), RS1000284408 (17:60644215 C>T), RS1000308482 (17:60610764 G>A,T), RS1000312626 (17:60650702 G>C), RS1000323954 (17:60650538 A>T), RS1000381333 (17:60604958 A>G), RS1000392422 (17:60599126 C>A), RS1000413924 (17:60604690 G>A), RS1000478466 (17:60643970 C>G,T), RS1000495810 (17:60645332 C>A), RS1000510185 (17:60628296 C>G,T), RS1000521574 (17:60632711 C>T)

Disease associations

OMIM: gene MIM:605100 | disease phenotypes: MIM:617450, MIM:114480, MIM:167000

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder with gastrointestinal difficulties and high pain threshold	Definitive	Autosomal dominant
hereditary breast carcinoma	Disputed Evidence	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
syndromic intellectual disability	Definitive	AD

Mondo (6): intellectual developmental disorder with gastrointestinal difficulties and high pain threshold (MONDO:0044318), hereditary neoplastic syndrome (MONDO:0015356), hereditary breast carcinoma (MONDO:0016419), ovarian cancer (MONDO:0008170), autosomal dominant non-syndromic intellectual disability (MONDO:0015802), lung carcinoma (MONDO:0005138)

Orphanet (5): Jansen-de Vries syndrome (Orphanet:653767), Inherited cancer-predisposing syndrome (Orphanet:140162), Hereditary breast cancer (Orphanet:227535), Rare ovarian cancer (Orphanet:213500), Autosomal dominant non-syndromic intellectual disability (Orphanet:178469)

HPO phenotypes

37 total (30 of 37 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000154	Wide mouth
HP:0000219	Thin upper lip vermilion
HP:0000337	Broad forehead
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000540	Hypermetropia
HP:0000722	Compulsive behaviors
HP:0000729	Autistic behavior
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0001156	Brachydactyly
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001442	Typified by somatic mosaicism
HP:0001601	Laryngomalacia
HP:0001629	Ventricular septal defect
HP:0001647	Bicuspid aortic valve
HP:0001773	Short foot
HP:0001792	Small nail
HP:0002013	Vomiting
HP:0002019	Constipation
HP:0002020	Gastroesophageal reflux
HP:0002136	Broad-based gait
HP:0002697	Parietal foramina
HP:0002719	Recurrent infections
HP:0003002	Breast carcinoma

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008062_38	Blood urea nitrogen levels	6.000000e-09

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
C562840	Breast Cancer, Familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1938224 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Metal-dependent protein phosphatase (PPM) family

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
GSK2830371	Inhibition	7.07	pIC50
SL-176	Inhibition	6.96	pIC50

ChEMBL bioactivities

14 potent at pChembl≥5 of 33 total, top 12 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.22	IC50	6	nM	CHEMBL3613749
7.89	IC50	13	nM	CHEMBL5418953
7.06	IC50	86.9	nM	CHEMBL1939361
7.06	IC50	86.3	nM	CHEMBL3613749
6.96	IC50	110	nM	CHEMBL3613748
6.82	Ki	150	nM	CHEMBL3109288
6.67	IC50	215	nM	CHEMBL3613747
6.64	Ki	228	nM	CHEMBL3613748
6.32	IC50	480	nM	CHEMBL1939361
5.42	IC50	3800	nM	CHEMBL5416471
5.14	IC50	7300	nM	CHEMBL5415785
5.14	IC50	7200	nM	CHEMBL5400889

PubChem BioAssay actives

8 with measured affinity, of 6100 total; 6 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
(1R,3R,4aS,4bR,6R,8R,8aS,10S,10aS)-10-[tert-butyl(dimethyl)silyl]oxy-1-(hydroxymethyl)-1,4a,6-trimethyl-8-triethylsilyloxy-2,3,4,4b,5,6,7,8,8a,9,10,10a-dodecahydrophenanthren-3-ol	1245781: Inhibition of His-tagged PPM1D (1 to 420 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) pLysS cells using Ac-VEPPLS(P)QETFSDLW-NH2 substrate	ic50	0.0869	uM
(1R,3S,4aS,5R,8aR)-3-[tert-butyl(dimethyl)silyl]oxy-1-methyl-5-triethylsilyloxy-3,4,4a,5,6,7,8,8a-octahydro-2H-naphthalene-1-carboxylic acid	1245781: Inhibition of His-tagged PPM1D (1 to 420 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) pLysS cells using Ac-VEPPLS(P)QETFSDLW-NH2 substrate	ic50	0.1100	uM
[(1R,3S,4aS,5R,8aR)-3-[tert-butyl(dimethyl)silyl]oxy-1-methyl-5-triethylsilyloxy-3,4,4a,5,6,7,8,8a-octahydro-2H-naphthalen-1-yl]methanol	1245781: Inhibition of His-tagged PPM1D (1 to 420 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) pLysS cells using Ac-VEPPLS(P)QETFSDLW-NH2 substrate	ic50	0.2150	uM
[3-[[4-[[3-[(3-chlorophenyl)carbamoyl]phenyl]methylamino]-3-(cyclohexylmethyl)benzoyl]amino]phenyl] dihydrogen phosphate	1986727: Inhibition of recombinant human Wip1 (1 to 420 residues) using human ATM phosphopeptide (AFEEG-pS-QSTTIGY) as substrate incubated for 7 mins by Bio-mol green assay	ic50	3.8000	uM
[3-[[4-[[3-[(3-chloroanilino)methyl]benzoyl]amino]-3-(cyclohexylmethyl)benzoyl]amino]phenyl] dihydrogen phosphate	1986727: Inhibition of recombinant human Wip1 (1 to 420 residues) using human ATM phosphopeptide (AFEEG-pS-QSTTIGY) as substrate incubated for 7 mins by Bio-mol green assay	ic50	7.2000	uM
[3-[[4-[[3-[(3-chlorophenyl)carbamoyl]benzoyl]amino]-3-(cyclohexylmethyl)benzoyl]amino]phenyl] dihydrogen phosphate	1986727: Inhibition of recombinant human Wip1 (1 to 420 residues) using human ATM phosphopeptide (AFEEG-pS-QSTTIGY) as substrate incubated for 7 mins by Bio-mol green assay	ic50	7.3000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects expression, affects cotreatment, increases expression	7
Aflatoxin B1	affects expression, increases expression, affects reaction	5
Cisplatin	increases expression	4
bisphenol A	decreases expression, affects cotreatment, increases expression	3
Fluorouracil	increases expression, affects reaction, increases reaction	3
Methyl Methanesulfonate	increases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	3
sodium arsenite	decreases expression, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
Arsenic Trioxide	affects activity, decreases expression, affects reaction, increases activity, increases phosphorylation (+1 more)	2
Acetaminophen	increases expression	2
Formaldehyde	increases expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Quercetin	increases expression	2
Valproic Acid	increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
chloroacetaldehyde	affects expression	1
naringenin	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
benzo(b)fluoranthene	increases expression, affects cotreatment	1
deoxynivalenol	increases expression	1
VX-agent	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
afimoxifene	decreases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	increases expression	1

ChEMBL screening assays

22 unique, capped per target: 22 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1941223	Binding	Inhibition of N-terminal histidine-tagged PPM1Dc at 4 uM after 10 mins by BIOMOL GREEN assay	A small molecule inhibitor of p53-inducible protein phosphatase PPM1D. — Bioorg Med Chem Lett

Cellosaurus cell lines

2,444 cell lines: 2,442 cancer cell line, 2 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0042	U2OS	Cancer cell line	Female
CVCL_0291	HCT 116	Cancer cell line	Male
CVCL_1Q94	H414	Cancer cell line	Male
CVCL_1Q95	H414-LIG4(+/-)	Cancer cell line	Male
CVCL_1Q96	H414-MDC1(+/-)	Cancer cell line	Male
CVCL_1Q97	H414-MDC1(-/-)	Cancer cell line	Male
CVCL_1Q98	H414-RAD18(+/-)	Cancer cell line	Male
CVCL_1Q99	H414-RAD18(-/-)	Cancer cell line	Male
CVCL_1R00	HCT116-53BPI(+/-)	Cancer cell line	Male
CVCL_1R01	HCT116-DNAPKcs(+/-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00727961	PHASE4	COMPLETED	A Study to Evaluate Efficacy and Tolerance of Caelyx in Patients With Epithelial Ovarian Cancer. (Study P04072)(COMPLETED)
NCT00740116	PHASE4	COMPLETED	Tranexamic Acid in Surgery of Advanced Ovarian Cancer
NCT00817479	PHASE4	COMPLETED	Tumor Gene Expression in Women With Ovarian Cancer
NCT01432015	PHASE4	COMPLETED	Fosaprepitant Versus Aprepitant in the Prevention of Chemotherapy Induced Nausea and Vomiting
NCT01706120	PHASE4	UNKNOWN	Study of Clinical and Biological Prognostic Factors in Patients With Ovarian Cancer Receiving Carboplatin +Paclitaxel With Bevacizumab
NCT01932125	PHASE4	COMPLETED	An Interventional Study of Avastin (Bevacizumab) in Patients With Advanced/Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer
NCT01953107	PHASE4	COMPLETED	Oral Iron vs. Placebo in Newly Diagnosed Gynecologic Oncology Patients Who Are Surgical Candidates.
NCT02035345	PHASE4	TERMINATED	Slowed Carboplatin Infusion for Ovarian Cancer Patients Receiving Carboplatin Re-Treatment
NCT02243059	PHASE4	WITHDRAWN	Magnetic Resonance Imaging for Lymph Node Staging in Ovarian Cancer
NCT03164980	PHASE4	TERMINATED	QoL-Comparison Between Trabectedin/PLD and Pt-based Therapy in Patients With Pt-sensitive Recurrent Ovarian Cancer
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03543462	PHASE4	COMPLETED	Diaphragmatic Resection And Gynecological Ovarian Neoplasm
NCT03752216	PHASE4	COMPLETED	NIraparib and Quality of LifE is a Longitudinal Study Evaluating in Real Life the Tolerability of Niraparib.
NCT03858166	PHASE4	TERMINATED	Efficacy and Safety of PEG-rhG-CSF Secondary Prophylaxis vs. Therapeutic Administration in Patients With Ovarian Cancer
NCT04024254	PHASE4	COMPLETED	A Study of Serum Folate Levels in Patients Treated With Olaparib
NCT04330040	PHASE4	COMPLETED	Prospective Multicentre Phase-IV Clinical Trial of Olaparib in Indian Patients With Ovarian and Metastatic Breast Cancer
NCT04352439	PHASE4	COMPLETED	Aspirin for Prevention of Venous Thromboembolism Among Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy
NCT05187208	PHASE4	UNKNOWN	PARP Inhibitor Oral Maintenance in Low-Risk Ovarian Cancer
NCT05606692	PHASE4	RECRUITING	Influences of Propofol and Sevoflurane Anesthesia in Ovarian Cancer (Anesthetics)
NCT05926336	PHASE4	RECRUITING	The Effects of Using Different Anesthetics on the Prognosis of Primary Tumors and Its Mechanism of Action
NCT06412120	PHASE4	RECRUITING	Study Evaluating Safety, Tolerability, and Metabolism of Niraparib
NCT06871787	PHASE4	NOT_YET_RECRUITING	Near-Infrared Fluorescence Imaging With Indocyanine Green to Evaluate Bowel Anastomoses in Gynecologic Oncology Surgery
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