PTEN

Summary

PTEN (phosphatase and tensin homolog, HGNC:9588) is a protein-coding gene on chromosome 10q23.31, encoding Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (P60484). Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins. In precision oncology, PIK3CA Mutation OR PTEN Mutation OR AKT1 Mutation confers sensitivity to Capivasertib + Fulvestrant in Breast Cancer (CIViC Level A); 59 further curated variant–drug associations are listed below. It is haploinsufficient (ClinGen: sufficient evidence).

This gene was identified as a tumor suppressor that is mutated in a large number of cancers at high frequency. The protein encoded by this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases. Unlike most of the protein tyrosine phosphatases, this protein preferentially dephosphorylates phosphoinositide substrates. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/PKB signaling pathway. The use of a non-canonical (CUG) upstream initiation site produces a longer isoform that initiates translation with a leucine, and is thought to be preferentially associated with the mitochondrial inner membrane. This longer isoform may help regulate energy metabolism in the mitochondria. A pseudogene of this gene is found on chromosome 9. Alternative splicing and the use of multiple translation start codons results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 5728 — RefSeq curated summary.

At a glance

• Gene–disease (curated): PTEN hamartoma tumor syndrome (Definitive, ClinGen) — +10 more curated relationships
• GWAS associations: 39
• Clinical variants (ClinVar): 3,617 total — 909 pathogenic, 277 likely-pathogenic
• Phenotypes (HPO): 238
• Druggable target: yes
• Precision-oncology evidence (CIViC): 60 curated variant–drug associations
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 38 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000314

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9588
Approved symbol	PTEN
Name	phosphatase and tensin homolog
Location	10q23.31
Locus type	gene with protein product
Status	Approved
Aliases	MMAC1, TEP1, PTEN1
Ensembl gene	ENSG00000171862
Ensembl biotype	protein_coding
OMIM	601728
Entrez	5728

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 8 retained_intron, 7 protein_coding, 6 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000371953, ENST00000416679, ENST00000462694, ENST00000472832, ENST00000487939, ENST00000498703, ENST00000686459, ENST00000688158, ENST00000688308, ENST00000688922, ENST00000693560, ENST00000700021, ENST00000700022, ENST00000700023, ENST00000700024, ENST00000700025, ENST00000700026, ENST00000700029, ENST00000706955, ENST00000710265, ENST00000713837, ENST00000713839

RefSeq mRNA: 3 — MANE Select: NM_000314 NM_000314, NM_001304717, NM_001304718

CCDS: CCDS31238

Canonical transcript exons

ENST00000371953 — 9 exons

Exon	Start	End
ENSE00001156315	87960894	87961118
ENSE00001156327	87952118	87952259
ENSE00001156330	87933013	87933251
ENSE00001156344	87925513	87925557
ENSE00001156351	87894025	87894109
ENSE00001456541	87965287	87971930
ENSE00003595610	87931046	87931089
ENSE00003725338	87957853	87958019
ENSE00004011725	87863625	87864548

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 99.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 113.2629 / max 2431.7639, expressed in 1824 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106035	109.7376	1824
106034	2.4679	1230
106032	0.4510	207
106036	0.3003	102
106033	0.1966	58
205933	0.0942	29
205932	0.0153	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.31	gold quality
endothelial cell	CL:0000115	99.21	gold quality
calcaneal tendon	UBERON:0003701	99.20	gold quality
upper arm skin	UBERON:0004263	99.15	gold quality
epithelial cell of pancreas	CL:0000083	99.00	gold quality
kidney epithelium	UBERON:0004819	98.91	gold quality
middle temporal gyrus	UBERON:0002771	98.68	gold quality
parietal pleura	UBERON:0002400	98.62	gold quality
ileal mucosa	UBERON:0000331	98.56	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.40	gold quality
visceral pleura	UBERON:0002401	98.29	gold quality
gingival epithelium	UBERON:0001949	98.06	gold quality
pancreatic ductal cell	CL:0002079	98.00	gold quality
gingiva	UBERON:0001828	98.00	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.00	gold quality
tibialis anterior	UBERON:0001385	97.93	gold quality
mammary duct	UBERON:0001765	97.87	gold quality
epithelium of mammary gland	UBERON:0003244	97.87	gold quality
blood	UBERON:0000178	97.86	gold quality
dorsal root ganglion	UBERON:0000044	97.84	gold quality
germinal epithelium of ovary	UBERON:0001304	97.84	gold quality
trigeminal ganglion	UBERON:0001675	97.76	gold quality
tibia	UBERON:0000979	97.71	gold quality
stromal cell of endometrium	CL:0002255	97.60	gold quality
esophagus squamous epithelium	UBERON:0006920	97.59	gold quality
mammalian vulva	UBERON:0000997	97.47	gold quality
superficial temporal artery	UBERON:0001614	97.45	gold quality
pericardium	UBERON:0002407	97.43	gold quality
trabecular bone tissue	UBERON:0002483	97.39	gold quality
thoracic mammary gland	UBERON:0005200	97.32	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	28978.26
E-GEOD-135922	yes	24.67
E-CURD-46	yes	14.91
E-HCAD-35	yes	8.27
E-MTAB-6678	yes	8.21
E-ANND-3	yes	7.00
E-CURD-122	yes	4.49
E-GEOD-124858	no	2590.46
E-MTAB-7051	no	1377.24
E-GEOD-70580	no	1150.04
E-GEOD-81608	no	18.78
E-ENAD-27	no	11.81

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

9 targets.

Target	Regulation
ABTB1	Activation
DUSP1	Activation
EGR2	Activation
HCLS1	Activation
NDRG1	Activation
NFIL3	Activation
PINK1	Activation
RAD51
SH2B2	Activation

Upstream regulators (CollecTRI, top): APEX1, APP, AR, ATF2, BMI1, CTNNB1, DNMT1, EGR1, EPAS1, ESR2, EZH2, FOXC1, GATA2, GATA4, GLI2, GRHL3, HES1, HIF1A, HNF4A, HOXA9, ID1, JUN, KAT7, KDM5A, KDM5C, MTA1, MXD1, MYC, MYT1, NFATC1, NFATC4, NFKB1, NFKB, NR2E1, NTS, PPARG, PSEN1, RBPJ, RELA, RUNX1

miRNA regulators (miRDB)

293 targeting PTEN, 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-5011-5P	100.00	83.46	5820
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-8485	100.00	77.57	4731
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-3064-3P	100.00	70.09	1254
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-6867-5P	100.00	82.21	3464
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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-32-5P	99.98	75.21	1964

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• PTEN mutations are uncommon in Proteus syndrome (PMID:11476065)
• PTEN protects p53 from survival signals, permitting p53 to function as a guardian of the genome. By virtue of its capacity to protect p53, PTEN can sensitize tumor cells to chemotherapy that relies on p53 activity (PMID:11729185)
• novel germline mutation of the PTEN gene in a patient with macrocephaly, ventricular dilatation, and features of VATER association (PMID:11748304)
• modulates vascular endothelial growth factor-mediated signaling and angiogenic effects (PMID:11784722)
• blockage of tumor necrosis factors-induced NF-kappa B-dependent transcription by inhibiting transactivation potential of the p65 subunit (PMID:11799112)
• Germline PTEN mutations have not been identified nor has linkage to 10p21 been demonstrated in 8 subjects with Birt-Hogg-Dube (BHD) syndrome, suggesting that PTEN should be excluded as a candidate gene for BHD. (PMID:11836379)
• PTEN mutations are associated with endometrial carcinomas and hyperplasia (PMID:11849740)
• Mutations in endometrial cancer are the consequence of mismatch repair deficiencies in HNPCC-related cases, but may precede them in sporadic cases. (PMID:11854177)
• expression reduced in pancreatic cancer may give tumor cells growth advantage and contribute to aggressive phenotype (PMID:11870516)
• Review: form and function in human syndromes (PMID:11875759)
• Abnormalities of the PTEN gene are associated with tumor progression, metastasis, and survival. (PMID:11896207)
• Promoter analysis of PTEN:identification of minimum promoter region (PMID:11906179)
• MMAC1 may not play an important role in carcinogenesis in primary brain lymphoma, as in the systemic counterpart. (PMID:11908870)
• reversible inactivation by hydrogen peroxide (PMID:11916965)
• The phosphatidylinositol phosphatase PTEN is under control of costimulation and regulates proliferation in human T cells. PTEN negatively controls costimulatory signals by antagonizing PI3 K activity in the absence of TCR engagement. (PMID:11932928)
• data suggest that PTEN expression is frequently reduced in advanced breast cancers (PMID:12055674)
• Results show that 9 out of 10 carcinomas exhibited some degree of staining for Akt or PTEN, while normal tissue showed no staining. Akt and PTEN may be diagnostic markers for lung carcinoma. (PMID:12067477)
• PTEN normally is subjected to a feedback mechanism of regulation aimed at maintaining homeostatic levels of D3-phosphoinositides, which are crucial for T cell survival and activation. (PMID:12077256)
• The tumor-suppressive function of Pten depends on its lipid phosphatase activity which disrupts PI-3K/Akt signaling. Loss/mutation of Pten is a marker for poor prognosis in gliomas. (PMID:12084351)
• An Arg234Gln missense PTEN mutation from a patient with multiple brain tumors can’t induce apoptosis and leads to high PKB/Akt activation & cell proliferation. (PMID:12085208)
• down regulation of PTEN is associated with HCV-positive cirrhotic hepatocarcinogenesis and increased expression of iNOS and COXII (PMID:12115563)
• role in the pathogenesis of epithelial thyroid neoplasias - review (PMID:12119278)
• PTEN potently inhibited the growth and reduced the size of Jurkat cells. The growth-suppressive effect of PTEN was associated with its ability to induce apoptotic cell death with little or no effect on cell cycle. (PMID:12133897)
• PTEN modulates angiogenesis in prostate cancer by regulating VEGF expression. (PMID:12168088)
• PTEN alterations are late genetic events in the progression of low to high-grade astrocytomas. (PMID:12168116)
• search for potential PTEN modulators through protein-protein interaction (PMID:12177006)
• PTEN may play a critical role in regulating cellular signaling in prostate cancer cells (PMID:12190124)
• PTEN mutations were detected in ILC (truncating mutations) in around 2% of the tumors (PMID:12203362)
• PTEN silencing in anaplastic thyroid cancer is a result of a wide variety of epigenetic and/or structural silencing mechanisms rather than a consequence of structural biallelic inactivation of the classical type. (PMID:12203792)
• PTEN expression in endometrial neoplasms (PMID:12209607)
• These results suggest that PTEN controls mammary gland development and, consequently, lactation. (PMID:12235113)
• used mass spectrometric methods to identify Ser(370) and Ser(385) as in vivo phosphorylation sites of PTEN (PMID:12297295)
• cell growth control by PTEN and it’s ability to regulate known cell size regulators involved in protein translation (review) (PMID:12367630)
• there are high frequencies of somatic mutations in PTEN (encoding phosphate and tensin homolog) in breast neoplastic epithelium and stroma (PMID:12379854)
• PTEN suppresses hyaluronic acid-induced matrix metalloproteinase-9 expression in U87MG glioblastoma cells through focal adhesion kinase dephosphorylation. (PMID:12414663)
• A patient with Cowden Disease and all family members exhibited the same 4-bp deletion in exon 8 of the PTEN gene. (PMID:12415190)
• induction of Skp2 may be causally linked with decreased levels of p27 in prostate cancer and implicate PTEN in the regulation of Skp2 expression (PMID:12429629)
• PTEN gene was deleted or weakly expressed in primary renal significant cell carcinoma, which is probably related to tumorigenesis and development of renal cell carcinoma. (PMID:12452054)
• PTEN inactivation may be important for the propagation of melanoma cells in culture, and that another chromosome 10 tumour suppressor gene may be important for melanoma pathogenesis. (PMID:12459646)
• REVIEW: the cellular mechanisms of PTEN and MTMR function and their role in the etiology of cancer and other human diseases (PMID:12495846)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptenb	ENSDARG00000056623
danio_rerio	ptena	ENSDARG00000071018
drosophila_melanogaster	Pten	FBGN0026379

Paralogs (6): TNS1 (ENSG00000079308), HVCN1 (ENSG00000122986), TPTE2 (ENSG00000132958), TNS3 (ENSG00000136205), TMEM266 (ENSG00000169758), TPTE (ENSG00000274391)

Protein

Protein identifiers

Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN — P60484 (reviewed: P60484)

Alternative names: Inositol polyphosphate 3-phosphatase, Mutated in multiple advanced cancers 1, Phosphatase and tensin homolog

All UniProt accessions (13): P60484, A0A087X033, A0A8I5KR36, A0A8I5KSF9, A0A8I5KVQ8, A0A8V8TP77, A0A8V8TPK6, A0A8V8TQX2, A0A9L9PYJ2, A0AA34QVZ8, A0AAQ5BGY7, A0AAQ5BH13, F6KD01

UniProt curated annotations — full annotation on UniProt →

Function. Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins. Also functions as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring of PtdIns(3,4,5)P3/phosphatidylinositol 3,4,5-trisphosphate, PtdIns(3,4)P2/phosphatidylinositol 3,4-diphosphate and PtdIns3P/phosphatidylinositol 3-phosphate with a preference for PtdIns(3,4,5)P3. Furthermore, this enzyme can also act as a cytosolic inositol 3-phosphatase acting on Ins(1,3,4,5,6)P5/inositol 1,3,4,5,6 pentakisphosphate and possibly Ins(1,3,4,5)P4/1D-myo-inositol 1,3,4,5-tetrakisphosphate. Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival. The unphosphorylated form cooperates with MAGI2 to suppress AKT1 activation. In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement. Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation. Required for growth factor-induced epithelial cell migration; growth factor stimulation induces PTEN phosphorylation which changes its binding preference from the p85 regulatory subunit of the PI3K kinase complex to DLC1 and results in translocation of the PTEN-DLC1 complex to the posterior of migrating cells to promote RHOA activation. Meanwhile, TNS3 switches binding preference from DLC1 to p85 and the TNS3-p85 complex translocates to the leading edge of migrating cells to activate RAC1 activation. Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Involved in the regulation of synaptic function in excitatory hippocampal synapses. Recruited to the postsynaptic membrane upon NMDA receptor activation, is required for the modulation of synaptic activity during plasticity. Enhancement of lipid phosphatase activity is able to drive depression of AMPA receptor-mediated synaptic responses, activity required for NMDA receptor-dependent long-term depression (LTD). May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue. The nuclear monoubiquitinated form possesses greater apoptotic potential, whereas the cytoplasmic nonubiquitinated form induces less tumor suppressive ability. Functional kinase, like isoform 1 it antagonizes the PI3K-AKT/PKB signaling pathway. Plays a role in mitochondrial energetic metabolism by promoting COX activity and ATP production, via collaboration with isoform 1 in increasing protein levels of PINK1.

Subunit / interactions. Monomer. The unphosphorylated form interacts with the second PDZ domain of MAGI2 and with DLG1 and MAST2 in vitro. Interacts with MAGI2, MAGI3, MAST1 and MAST3, but neither with MAST4 nor with DLG5; interaction with MAGI2 increases protein stability. Interacts with NEDD4. Interacts with NDFIP1 and NDFIP2; in the presence of NEDD4 or ITCH, this interaction promotes PTEN ubiquitination. Interacts (via C2 domain) with FRK. Interacts with USP7; the interaction is direct. Interacts with ROCK1. Interacts with XIAP/BIRC4. Interacts with STK11; the interaction phosphorylates PTEN. Interacts with PPP1R16B. Interacts with NOP53; regulates PTEN phosphorylation and increases its stability. Interacts (via PDZ domain-binding motif) with DLG4; the interaction is induced by NMDA and is required for PTEN location at postsynaptic density. Interacts with the regulatory p85 subunit of the PI3K kinase complex and with Rho GTPase-activating protein DLC1; in resting cells, interacts (via C2 tensin-type domain) with p85 but, following growth factor stimulation, PTEN is phosphorylated which leads to weakened interaction with p85 and enhanced interaction (via C2 tensin-type domain) with DLC1 while p85 interaction with TNS3 increases.

Subcellular location. Cytoplasm. Nucleus. PML body. Cell projection. Dendritic spine. Postsynaptic density Secreted.

Tissue specificity. Expressed at a relatively high level in all adult tissues, including heart, brain, placenta, lung, liver, muscle, kidney and pancreas.

Post-translational modifications. Constitutively phosphorylated by CK2 under normal conditions. Phosphorylated in vitro by MAST1, MAST2, MAST3 and STK11. Phosphorylation results in an inhibited activity towards PIP3. Phosphorylation can both inhibit or promote PDZ-binding. Phosphorylation at Tyr-336 by FRK/PTK5 protects this protein from ubiquitin-mediated degradation probably by inhibiting its binding to NEDD4. Phosphorylation by ROCK1 is essential for its stability and activity. Phosphorylation by PLK3 promotes its stability and prevents its degradation by the proteasome. Phosphorylated on Thr-319 and Thr-321 in the C2-type tensin domain following EGF stimulation which changes its binding preference from the p85 regulatory subunit of the PI3K kinase complex to DLC1. Monoubiquitinated; monoubiquitination is increased in presence of retinoic acid. Deubiquitinated by USP7; leading to its nuclear exclusion. Monoubiquitination of one of either Lys-13 and Lys-289 amino acid is sufficient to modulate PTEN compartmentalization. Ubiquitinated by XIAP/BIRC4. Ubiquitinated by the DCX(DCAF13) E3 ubiquitin ligase complex, leading to its degradation. ISGylated. ISGylation promotes PTEN degradation.

Disease relevance. Cowden syndrome 1 (CWS1) [MIM:158350] An autosomal dominant hamartomatous polyposis syndrome with age-related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but most commonly in the skin, gastrointestinal tract, breast and thyroid. The disease is caused by variants affecting the gene represented in this entry. Lhermitte-Duclos disease (LDD) [MIM:158350] A rare disease characterized by the occurrence of a slowly enlarging mass within the cerebellar cortex corresponding histologically to a cerebellar hamartoma. It manifests, most commonly in the third and fourth decades of life, with increased intracranial pressure, headache, nausea, cerebellar dysfunction, occlusive hydrocephalus, ataxia, visual disturbances and other cranial nerve palsies. Various associated abnormalities may be present such as megalencephaly, microgyria, hydromyelia, polydactyly, partial gigantism, macroglossia. LDD is part of the PTEN hamartoma tumor syndromes spectrum that also includes Cowden syndrome. The disease is caused by variants affecting the gene represented in this entry. Squamous cell carcinoma of the head and neck (HNSCC) [MIM:275355] A non-melanoma skin cancer affecting the head and neck. The hallmark of cutaneous SCC is malignant transformation of normal epidermal keratinocytes. The disease is caused by variants affecting the gene represented in this entry. Endometrial cancer (ENDMC) [MIM:608089] A malignancy of endometrium, the mucous lining of the uterus. Most endometrial cancers are adenocarcinomas, cancers that begin in cells that make and release mucus and other fluids. Disease susceptibility is associated with variants affecting the gene represented in this entry. PTEN mutations are found in a subset of patients with Proteus syndrome, a genetically heterogeneous condition. The molecular diagnosis of PTEN mutation positive cases classifies Proteus syndrome patients as part of the PTEN hamartoma syndrome spectrum. As such, patients surviving the early years of Proteus syndrome are likely at a greater risk of developing malignancies. Glioma 2 (GLM2) [MIM:613028] Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes. Disease susceptibility is associated with variants affecting the gene represented in this entry. Prostate cancer (PC) [MIM:176807] A malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. Disease susceptibility is associated with variants affecting the gene represented in this entry. Macrocephaly/autism syndrome (MCEPHAS) [MIM:605309] Patients have autism spectrum disorders and macrocephaly, with head circumferences ranging from +2.5 to +8 SD for age and sex (average head circumference +4.0 SD). The disease is caused by variants affecting the gene represented in this entry. A microdeletion of chromosome 10q23 involving BMPR1A and PTEN is a cause of chromosome 10q23 deletion syndrome, which shows overlapping features of the following three disorders: Bannayan-Zonana syndrome, Cowden disease and juvenile polyposis syndrome.

Activity regulation. Enzymatic activity is enhanced in the presence of phosphatidylserine.

Domain organisation. The C2 domain binds phospholipid membranes in vitro in a Ca(2+)-independent manner; this binding is important for its tumor suppressor function.

Induction. Down-regulated by TGFB1.

Miscellaneous. Produced by alternative initiation at an upstream CTG start codon. May contain a signal peptide at positions 1-21.

Similarity. Belongs to the PTEN phosphatase protein family.

Isoforms (3)

UniProt ID	Names	Canonical?
P60484-1	1, 55kDa	yes
P60484-2	alpha, 70kDa, PTEN-long
P60484-3	3

RefSeq proteins (3): NP_000305, NP_001291646, NP_001291647 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000387	Tyr_Pase_dom	Domain
IPR003595	Tyr_Pase_cat	Domain
IPR014020	Tensin_C2-dom	Domain
IPR016130	Tyr_Pase_AS	Active_site
IPR017361	Bifunc_PIno_P3_Pase/Pase_PTEN	Family
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR029023	Tensin_phosphatase	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR045101	PTP_PTEN	Domain
IPR051281	Dual-spec_lipid-protein_phosph	Family

Pfam: PF10409, PF22785

Enzyme classification (BRENDA):

• EC 3.1.3.16 — protein-serine/threonine phosphatase (BRENDA: 92 organisms, 641 substrates, 468 inhibitors, 127 Km, 67 kcat entries)
• EC 3.1.3.67 — phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase (BRENDA: 10 organisms, 75 substrates, 9 inhibitors, 3 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

62 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
6,8-DIFLUORO-4-METHYLUMBELLIFERYL PHOSPHATE	0.023–0.862	22
4-NITROPHENYL PHOSPHATE	0.0028–12.7	13
P-NITROPHENYL PHOSPHATE	3–200	11
RRAPTVA	0.058–1.954	4
PHOSPHOCASEIN	0.0001–0.002	3
PHOSPHOHISTONE	0.0023–0.0723	3
PHOSPHORYLATED MYOSIN LIGHT CHAIN PEPTIDE	0.01–0.11	3
PHOSPHOSERINE-MYELIN BASIC PROTEIN	0.0004–0.022	3
DLDVPIPGRFDRRVSVAAE	0.0006–0.0138	2
DLDVPIPGRFDRRVY(P)VAAE	0.0025–0.023	2
PHOSPHORYLASE A	0.004–0.021	2
RRA(PT)VA	0.0536–0.308	2
80S-RIBOSOME	0.0027	1
AAAPTVA	0.206	1
AGPALSPVPPV	0.357	1

Catalyzed reactions (Rhea), 8 shown:

• O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate (RHEA:10684)
• O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate (RHEA:20629)
• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + phosphate (RHEA:25017)
• 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + H2O = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + phosphate (RHEA:43552)
• 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + H2O = 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + phosphate (RHEA:43560)
• O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate (RHEA:47004)
• 1D-myo-inositol 1,3,4,5,6-pentakisphosphate + H2O = 1D-myo-inositol 1,4,5,6-tetrakisphosphate + phosphate (RHEA:77143)
• 1D-myo-inositol 1,3,4,5-tetrakisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + phosphate (RHEA:77155)

UniProt features (178 total): sequence variant 81, mutagenesis site 31, strand 25, modified residue 12, helix 11, splice variant 4, turn 2, domain 2, cross-link 2, region of interest 2, compositionally biased region 2, initiator methionine 1, chain 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
8X3S	X-RAY DIFFRACTION	1.87
4O1V	X-RAY DIFFRACTION	2
1D5R	X-RAY DIFFRACTION	2.1
7PC7	X-RAY DIFFRACTION	2.1
5BZZ	X-RAY DIFFRACTION	2.2
5BUG	X-RAY DIFFRACTION	2.4
5BZX	X-RAY DIFFRACTION	2.5
7JUL	X-RAY DIFFRACTION	2.53
7JUK	X-RAY DIFFRACTION	3.15
7JVX	X-RAY DIFFRACTION	3.2
7JTX	X-RAY DIFFRACTION	3.23
2KYL	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P60484-F1	83.76	0.70

Functional residue map

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

Catalytic / active sites (1): 124 (phosphocysteine intermediate)

Post-translational modifications (14): 2, 294, 319, 321, 336, 366, 370, 380, 382, 383, 385, 401, 13, 289

Mutagenesis-validated functional residues (31):

Position	Phenotype
1	prevents expression of isoform 1 and increased expression of isoform alpha.
13	nuclear. cytoplasmic; when associated with e-289. shows less tumor suppressive ability; when associated with e-289.
92	700-fold reduction in phosphatase activity towards ptdins(3,4,5)p3. loss of protein phosphatase activity. unable to inhi
93	75% reduction in phosphatase activity towards ptdins(3,4,5)p3. modest reduction in phosphatase activity towards ptdins(3
124	loss of protein phosphatase activity. unable to inhibit focal adhesion formation.
125	reduced phosphatase activity towards ptdins(3,4,5)p3, ptdins(3,4)p2 and ptdins(3)p.
126	does not reduce phosphatase activity towards ptdins(3,4,5)p3 and ptdins(3,4)p2.
128	85% reduction in phosphatase activity towards ptdins(3,4,5)p3.
128	does not reduce phosphatase activity towards ptdins(3,4,5)p3.
130	does not affect the ability to inhibit akt/pkb activation.
167	60% reduction in phosphatase activity towards ptdins(3,4,5)p3.
171	75% reduction in phosphatase activity towards ptdins(3,4,5)p3.
229	no effect on interaction with dlc1 or p85.
232	no effect on interaction with dlc1 or p85.
263–269	reduces the growth suppression activity and cells show anchorage-independent growth. reduces binding to phospholipid mem
289	cytoplasmic; when associated with e-13. shows less tumor suppressive ability; when associated with e-13.
319	reduces phosphorylation of the c2 tensin-like domain and abolishes interaction with dlc1 following egf stimulation. abol
319	constitutive interaction with dlc1.
319	constitutive interaction with dlc1 and interaction with p85 following egf stimulation.
321	reduces phosphorylation of the c2 tensin-like domain and abolishes interaction with dlc1 following egf stimulation. abol
321	constitutive interaction with dlc1.
327–335	reduces growth suppression activity and promotes anchorage-independent growth. reduces binding to phospholipid membranes
336	significantly lower phosphatase activity, reduced protein stability and decreased growth-inhibitory effect.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-1660499	Synthesis of PIPs at the plasma membrane
R-HSA-1855204	Synthesis of IP3 and IP4 in the cytosol
R-HSA-199418	Negative regulation of the PI3K/AKT network
R-HSA-202424	Downstream TCR signaling
R-HSA-5628897	TP53 Regulates Metabolic Genes
R-HSA-5674404	PTEN Loss of Function in Cancer
R-HSA-5689880	Ub-specific processing proteases
R-HSA-5689896	Ovarian tumor domain proteases
R-HSA-8943723	Regulation of PTEN mRNA translation
R-HSA-8948747	Regulation of PTEN localization
R-HSA-8948751	Regulation of PTEN stability and activity
R-HSA-8986944	Transcriptional Regulation by MECP2
R-HSA-8943724	Regulation of PTEN gene transcription

MSigDB gene sets: 1411 (showing top): PID_BCR_5PATHWAY, GOBP_CIRCADIAN_RHYTHM, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_DENDRITE_DEVELOPMENT, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_LIPID_MODIFICATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_SYNAPTIC_VESICLE_LOCALIZATION, GOBP_DENTATE_GYRUS_DEVELOPMENT, BIOCARTA_PTEN_PATHWAY, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT

GO Biological Process (73): protein dephosphorylation (GO:0006470), phosphatidylinositol biosynthetic process (GO:0006661), apoptotic process (GO:0006915), spindle assembly involved in female meiosis (GO:0007056), neuron-neuron synaptic transmission (GO:0007270), synapse assembly (GO:0007416), central nervous system development (GO:0007417), heart development (GO:0007507), learning or memory (GO:0007611), locomotory behavior (GO:0007626), positive regulation of cell population proliferation (GO:0008284), negative regulation of cell population proliferation (GO:0008285), negative regulation of epithelial to mesenchymal transition (GO:0010719), regulation of neuron projection development (GO:0010975), negative regulation of neuron projection development (GO:0010977), cell migration (GO:0016477), dentate gyrus development (GO:0021542), central nervous system neuron axonogenesis (GO:0021955), negative regulation of cell migration (GO:0030336), adult behavior (GO:0030534), regulation of protein stability (GO:0031647), central nervous system myelin maintenance (GO:0032286), negative regulation of peptidyl-serine phosphorylation (GO:0033137), multicellular organismal response to stress (GO:0033555), social behavior (GO:0035176), maternal behavior (GO:0042711), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), locomotor rhythm (GO:0045475), negative regulation of osteoblast differentiation (GO:0045668), negative regulation of cell size (GO:0045792), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of organ growth (GO:0046621), phosphatidylinositol dephosphorylation (GO:0046856), forebrain morphogenesis (GO:0048853), cell motility (GO:0048870), negative regulation of axonogenesis (GO:0050771), protein stabilization (GO:0050821), negative regulation of keratinocyte migration (GO:0051548), negative regulation of focal adhesion assembly (GO:0051895), regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051896)

GO Molecular Function (21): phosphatidylinositol-3-phosphate phosphatase activity (GO:0004438), phosphoprotein phosphatase activity (GO:0004721), protein serine/threonine phosphatase activity (GO:0004722), protein tyrosine phosphatase activity (GO:0004725), beta-catenin binding (GO:0008013), lipid binding (GO:0008289), anaphase-promoting complex binding (GO:0010997), phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity (GO:0016314), enzyme binding (GO:0019899), PDZ domain binding (GO:0030165), inositol-1,3,4,5,6-pentakisphosphate 3-phosphatase activity (GO:0030351), identical protein binding (GO:0042802), inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity (GO:0051717), phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity (GO:0051800), phosphatidylinositol phosphate phosphatase activity (GO:0052866), molecular function inhibitor activity (GO:0140678), ubiquitin-specific protease binding (GO:1990381), ubiquitin ligase activator activity (GO:1990757), protein binding (GO:0005515), hydrolase activity (GO:0016787), phosphatase activity (GO:0016791)

GO Cellular Component (18): extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasmic side of plasma membrane (GO:0009898), postsynaptic density (GO:0014069), apical plasma membrane (GO:0016324), PML body (GO:0016605), myelin sheath adaxonal region (GO:0035749), cell projection (GO:0042995), neuron projection (GO:0043005), dendritic spine (GO:0043197), Schmidt-Lanterman incisure (GO:0043220), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
PTEN Regulation	4
Deubiquitination	2
PI Metabolism	1
Inositol phosphate metabolism	1
PIP3 activates AKT signaling	1
TCR signaling	1
Transcriptional Regulation by TP53	1
PI3K/AKT Signaling in Cancer	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	9
behavior	3
protein binding	3
nervous system development	2
cell population proliferation	2
regulation of cell population proliferation	2
neuron projection development	2
phosphatase activity	2
phosphoprotein phosphatase activity	2
binding	2
sperm flagellum	2
dephosphorylation	1
protein modification process	1
biosynthetic process	1
phosphatidylinositol metabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
female meiotic nuclear division	1
meiotic spindle assembly	1
chemical synaptic transmission	1
cell junction assembly	1
synapse organization	1
system development	1
animal organ development	1
circulatory system development	1
cognition	1
positive regulation of cellular process	1
negative regulation of cellular process	1
epithelial to mesenchymal transition	1
regulation of epithelial to mesenchymal transition	1
negative regulation of cell differentiation	1
negative regulation of multicellular organismal process	1
regulation of plasma membrane bounded cell projection organization	1
regulation of neuron projection development	1
negative regulation of cell projection organization	1
cell motility	1
hippocampus development	1
anatomical structure development	1
axonogenesis	1

Protein interactions and networks

STRING

9614 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTEN	MAGI2	Q86UL8	974
PTEN	STK11	Q15831	971
PTEN	TP53	P04637	969
PTEN	PREX2	Q70Z35	969
PTEN	AKT1	P31749	968
PTEN	MAGI3	Q5TCQ9	962
PTEN	PIK3CA	P42336	949
PTEN	PIK3R1	P27986	944
PTEN	NOP53	Q9NZM5	937
PTEN	KRAS	P01116	930
PTEN	CDH1	P12830	930
PTEN	BRAF	P15056	928
PTEN	EGFR	P00533	926
PTEN	MTOR	P42345	923
PTEN	SMAD4	Q13485	909

IntAct

690 interactions, top by confidence:

A	B	Type	Score
PTEN	NHERF1	psi-mi:“MI:0915”(physical association)	0.830
PTEN	FRK	psi-mi:“MI:0915”(physical association)	0.640
FRK	PTEN	psi-mi:“MI:0915”(physical association)	0.640
PTEN	FRK	psi-mi:“MI:0217”(phosphorylation reaction)	0.640
FRK	PTEN	psi-mi:“MI:0217”(phosphorylation reaction)	0.640
PTEN	CDC27	psi-mi:“MI:0914”(association)	0.620
CDC27	PTEN	psi-mi:“MI:0914”(association)	0.620
CDC27	PTEN	psi-mi:“MI:0915”(physical association)	0.620
PTEN	CDC27	psi-mi:“MI:0403”(colocalization)	0.620
CDC27	PTEN	psi-mi:“MI:0403”(colocalization)	0.620
BMI1	PTEN	psi-mi:“MI:0915”(physical association)	0.610
PTEN	BMI1	psi-mi:“MI:0403”(colocalization)	0.610
NEDD4	PTEN	psi-mi:“MI:0915”(physical association)	0.590
PTEN	NEDD4	psi-mi:“MI:0915”(physical association)	0.590
PTEN	PPP1CA	psi-mi:“MI:0915”(physical association)	0.520
PTEN	ERBB3	psi-mi:“MI:0915”(physical association)	0.520
CXXC1	PTEN	psi-mi:“MI:0915”(physical association)	0.510
PICK1	PTEN	psi-mi:“MI:0915”(physical association)	0.510
PTEN	USP7	psi-mi:“MI:0915”(physical association)	0.500

BioGRID (1322): PTEN (Affinity Capture-Western), SHARPIN (Affinity Capture-Western), PTEN (Affinity Capture-Western), PTEN (Affinity Capture-Western), CTNNB1 (Affinity Capture-Western), PTEN (Affinity Capture-Western), NEDD4 (Affinity Capture-Western), WWP1 (Affinity Capture-Western), TNKS (Affinity Capture-Western), TNKS2 (Affinity Capture-Western), PTEN (Affinity Capture-Western), PTEN (Biochemical Activity), PTEN (Biochemical Activity), RNF146 (Affinity Capture-Western), PTEN (Affinity Capture-Western)

ESM2 similar proteins: A0JMK5, A6QLT2, A6QQZ7, O08586, O43242, O43795, O54857, O55236, O60733, O60942, P11029, P11497, P14685, P23727, P26450, P27986, P29074, P46735, P60483, P60484, P97570, P97819, Q05096, Q13085, Q13613, Q13614, Q15139, Q28559, Q2KJ46, Q52KU6, Q5BJZ6, Q5EB32, Q5F452, Q5R685, Q5R6F6, Q5R8Q7, Q5REB9, Q5SWU9, Q5T2T1, Q5U2Y3

Diamond homologs: E9Q0S6, G5EE01, H2L045, O08586, O14976, O54857, P60483, P60484, P97874, Q04205, Q32PJ7, Q4R6N0, Q4V8I3, Q54JL7, Q5SSZ5, Q63HR2, Q68CZ2, Q6NR09, Q8BZ33, Q8CGB6, Q8H106, Q8IZW8, Q8T9S7, Q99KY4, Q9FLZ5, Q9GLM4, Q9HBL0, Q9LT75, Q9PUT6, O94526, P56180, Q9P7H1, Q5B323, Q6XPS3, Q86IL4, O75061, Q27974, Q5T6R2, Q80TZ3, Q96D96

SIGNOR signaling

102 interactions.

A	Effect	B	Mechanism
SRC	down-regulates	PTEN	phosphorylation
LCK	up-regulates	PTEN	phosphorylation
ROCK1	up-regulates	PTEN	phosphorylation
MAST1	down-regulates	PTEN	phosphorylation
MAST2	up-regulates	PTEN	phosphorylation
MAST3	up-regulates	PTEN	binding
MAST3	unknown	PTEN	phosphorylation
PTEN	down-regulates	GLI1
CSNK2A1	“down-regulates activity”	PTEN	phosphorylation
STK11	“down-regulates activity”	PTEN	phosphorylation
PIK3C3	up-regulates	PTEN	binding
PTEN	“down-regulates activity”	AKT
PTEN	down-regulates	STAT5A	dephosphorylation
PLK3	“down-regulates activity”	PTEN	phosphorylation
PTEN	up-regulates	PPM1A	binding
BMI1	“down-regulates quantity by repression”	PTEN	“transcriptional regulation”
PTEN	“down-regulates activity”	AKT1
FGFR2	unknown	PTEN	phosphorylation
FGFR3	unknown	PTEN	phosphorylation
PTEN	“down-regulates activity”	PIK3CA
PTEN	“down-regulates quantity”	PIP3	“chemical modification”
GSK3B	“down-regulates activity”	PTEN	phosphorylation
PTEN	“down-regulates activity”	PIK3CB
STK11	unknown	PTEN	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 177 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
Signaling by ALK	6	23.0×	2e-05
PI3K events in ERBB2 signaling	5	22.5×	1e-04
Interleukin-2 family signaling	5	21.3×	1e-04
CD28 dependent PI3K/Akt signaling	8	21.1×	5e-07
PI-3K cascade:FGFR1	6	20.9×	2e-05
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	6	20.9×	2e-05
Regulation of signaling by CBL	6	20.0×	3e-05
Interleukin-3, Interleukin-5 and GM-CSF signaling	8	17.0×	3e-06

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of glycogen biosynthetic process	5	29.2×	7e-05
insulin-like growth factor receptor signaling pathway	6	17.5×	1e-04
intracellular glucose homeostasis	5	17.1×	6e-04
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	7	16.9×	2e-05
extrinsic apoptotic signaling pathway in absence of ligand	6	16.5×	1e-04
lipopolysaccharide-mediated signaling pathway	5	15.5×	9e-04
peptidyl-tyrosine phosphorylation	6	14.9×	2e-04
positive regulation of TOR signaling	5	14.6×	1e-03

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

PTEN is a multi-functional tumor suppressor that is very commonly lost in human cancer. Observed in prostate cancer, glioblastoma, endometrial, lung and breast cancer to varying degrees. Up to 70% of prostate cancer patients have been observed to have loss of expression of the gene. It is a part of the PI3K/AKT/mTOR pathway and mTOR inhibitors have been relatively ineffective in treating patients with PTEN loss. New appoaches using microRNAs are currently being investigated.

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 38 cancer types — ANGS, BLCA, BRCA, CCRCC, CEAD, CESC, CHOL, CHRCC, COADREAD, CSCC, ESCA, GB…(+26 more).

Clinical variants and AI predictions

ClinVar

3617 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	909
Likely pathogenic	277
Uncertain significance	1187
Likely benign	567
Benign	92

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1014805	NM_000314.8(PTEN):c.801G>C (p.Lys267Asn)	Pathogenic
1018969	NM_000314.8(PTEN):c.141_142inv (p.Arg47_Asn48delinsSerHis)	Pathogenic
1048543	NM_000314.8(PTEN):c.255_262delinsC (p.Ala86fs)	Pathogenic
1048544	NM_000314.8(PTEN):c.1110_1111dup (p.Asp371fs)	Pathogenic
1067089	NM_000314.8(PTEN):c.376G>C (p.Ala126Pro)	Pathogenic
1067224	NM_000314.8(PTEN):c.523G>A (p.Val175Met)	Pathogenic
1067457	NC_000010.10:g.(?89685260)(89685324_?)del	Pathogenic
1068214	NM_000314.8(PTEN):c.75G>C (p.Leu25Phe)	Pathogenic
1068748	NM_000314.8(PTEN):c.440del (p.Lys147fs)	Pathogenic
1069185	NC_000010.10:g.89711945_89711946insAlu	Pathogenic
1069313	NM_000314.8(PTEN):c.224_233del (p.His75fs)	Pathogenic
1069314	NM_000314.8(PTEN):c.502_503del (p.Ile168fs)	Pathogenic
1069418	NM_000314.8(PTEN):c.688_689dup (p.Pro231fs)	Pathogenic
1069915	NM_000314.8(PTEN):c.184A>T (p.Lys62Ter)	Pathogenic
1070574	NM_000314.8(PTEN):c.158_162dup (p.Arg55Ter)	Pathogenic
1070828	NM_000314.8(PTEN):c.49_61dup (p.Phe21fs)	Pathogenic
1070951	NM_000314.8(PTEN):c.301del (p.Ile101fs)	Pathogenic
1071470	NM_000314.8(PTEN):c.260_261dup (p.Tyr88fs)	Pathogenic
1072116	NM_000314.8(PTEN):c.641del (p.Gln214fs)	Pathogenic
1072117	NM_000314.8(PTEN):c.672dup (p.Tyr225fs)	Pathogenic
1073539	NM_000314.8(PTEN):c.628del (p.Thr210fs)	Pathogenic
1073577	NM_000314.8(PTEN):c.17_20dup (p.Ile8fs)	Pathogenic
1074078	NM_000314.8(PTEN):c.304A>T (p.Lys102Ter)	Pathogenic
1074735	NM_000314.8(PTEN):c.989_992del (p.Lys330fs)	Pathogenic
1075090	NM_000314.8(PTEN):c.785dup (p.Asn262fs)	Pathogenic
1075679	NM_000314.8(PTEN):c.536_539dup (p.Tyr180Ter)	Pathogenic
1075939	NM_000314.8(PTEN):c.250A>T (p.Arg84Ter)	Pathogenic
1076052	NM_000314.8(PTEN):c.562_563insGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCAGGAGATCGAGACCATCNAAAAAAAAAAAAAAAAAAAAAA (p.Tyr188fs)	Pathogenic
1076154	NM_000314.8(PTEN):c.547_548del (p.Lys183fs)	Pathogenic
1076438	NM_001304718.2(PTEN):c.-541-5533del	Pathogenic

SpliceAI

3139 predictions. Top by Δscore:

Variant	Effect	Δscore
10:87863244:G:C	donor_gain	1.0000
10:87925553:AATCT:A	donor_gain	1.0000
10:87925554:ATCT:A	donor_gain	1.0000
10:87925555:TCT:T	donor_gain	1.0000
10:87925556:CT:C	donor_gain	1.0000
10:87925557:TG:T	donor_loss	1.0000
10:87925558:G:A	donor_loss	1.0000
10:87925558:G:GG	donor_gain	1.0000
10:87925559:TAAG:T	donor_loss	1.0000
10:87928426:G:GT	donor_gain	1.0000
10:87931040:TTTTA:T	acceptor_loss	1.0000
10:87931041:TTTA:T	acceptor_loss	1.0000
10:87931042:TTA:T	acceptor_loss	1.0000
10:87931043:TAGTT:T	acceptor_loss	1.0000
10:87931044:A:AG	acceptor_gain	1.0000
10:87931044:A:AT	acceptor_loss	1.0000
10:87931045:G:GC	acceptor_gain	1.0000
10:87931045:GT:G	acceptor_gain	1.0000
10:87931045:GTT:G	acceptor_gain	1.0000
10:87931045:GTTGT:G	acceptor_gain	1.0000
10:87931087:GAG:G	donor_gain	1.0000
10:87933011:A:AG	acceptor_gain	1.0000
10:87933012:G:GA	acceptor_gain	1.0000
10:87933012:GTT:G	acceptor_gain	1.0000
10:87933252:G:GG	donor_gain	1.0000
10:87952117:GGGA:G	acceptor_gain	1.0000
10:87952257:GCA:G	donor_gain	1.0000
10:87952260:G:GG	donor_gain	1.0000
10:87958017:AAGGT:A	donor_loss	1.0000
10:87958018:AGGT:A	donor_loss	1.0000

AlphaMissense

2714 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:87864495:T:A	V9D	1.000
10:87864506:A:G	K13E	1.000
10:87864507:A:T	K13I	1.000
10:87864508:A:C	K13N	1.000
10:87864508:A:T	K13N	1.000
10:87864513:G:C	R15T	1.000
10:87864513:G:T	R15I	1.000
10:87864514:A:C	R15S	1.000
10:87864514:A:T	R15S	1.000
10:87864530:T:C	F21L	1.000
10:87864531:T:C	F21S	1.000
10:87864532:C:A	F21L	1.000
10:87864532:C:G	F21L	1.000
10:87864537:T:C	L23S	1.000
10:87864539:G:A	D24N	1.000
10:87864539:G:C	D24H	1.000
10:87864539:G:T	D24Y	1.000
10:87864540:A:C	D24A	1.000
10:87864540:A:G	D24G	1.000
10:87864540:A:T	D24V	1.000
10:87864541:C:A	D24E	1.000
10:87864541:C:G	D24E	1.000
10:87864543:T:C	L25S	1.000
10:87864543:T:G	L25W	1.000
10:87894028:T:A	I28N	1.000
10:87894028:T:G	I28S	1.000
10:87894040:T:A	I32N	1.000
10:87894043:T:A	I33N	1.000
10:87894043:T:G	I33S	1.000
10:87894045:G:C	A34P	1.000

dbSNP variants (sampled 300 via entrez): RS1000005146 (10:87875801 C>G), RS1000027151 (10:87913668 C>G), RS1000056744 (10:87913903 T>C), RS1000110099 (10:87922372 T>C), RS1000134376 (10:87881506 T>A), RS1000140492 (10:87895417 G>A,C), RS1000141743 (10:87967304 T>C), RS1000166908 (10:87881245 A>G,T), RS1000175170 (10:87947241 A>G), RS1000178397 (10:87899400 A>G), RS1000209515 (10:87964052 G>GAAAT), RS1000211398 (10:87864412 C>A,G,T), RS1000225723 (10:87946929 C>T), RS1000303263 (10:87864169 C>G,T), RS1000303586 (10:87904926 A>G)

Disease associations

OMIM: gene MIM:601728 | disease phenotypes: MIM:158350, MIM:605309, MIM:613028, MIM:153480, MIM:601518, MIM:607174, MIM:176807, MIM:155600, MIM:188470, MIM:275355, MIM:276950, MIM:114480, MIM:613659, MIM:181500, MIM:167000, MIM:604370, MIM:109800, MIM:309800, MIM:612555, MIM:209850, MIM:615107

GenCC curated gene-disease

Disease	Classification	Inheritance
Cowden syndrome 1	Definitive	Autosomal dominant
macrocephaly-autism syndrome	Strong	Autosomal dominant
leiomyosarcoma	Moderate	Autosomal recessive
renal cell carcinoma	Moderate	Autosomal dominant
Bannayan-Riley-Ruvalcaba syndrome	Supportive	Autosomal dominant
Cowden disease	Supportive	Autosomal dominant
Proteus-like syndrome	Supportive	Autosomal dominant
activated PI3K-delta syndrome	Supportive	Autosomal dominant
Lhermitte-Duclos disease	Supportive	Autosomal dominant
glioma susceptibility 2	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
PTEN hamartoma tumor syndrome	Definitive	AD

Mondo (63): PTEN hamartoma tumor syndrome (MONDO:0017623), hereditary neoplastic syndrome (MONDO:0015356), Cowden syndrome 1 (MONDO:0008021), macrocephaly-autism syndrome (MONDO:0011537), hemimegalencephaly (MONDO:0020492), breast cancer (MONDO:0007254), familial ovarian cancer (MONDO:0016248), glioma susceptibility 2 (MONDO:0013092), Bannayan-Riley-Ruvalcaba syndrome (MONDO:0007924), Cowden disease (MONDO:0016063), prostate cancer, hereditary, 1 (MONDO:0011098), familial meningioma (MONDO:0011789), prostate cancer, hereditary (MONDO:0700275), breast carcinoma (MONDO:0004989), gastrointestinal hamartoma (MONDO:0006231)

Orphanet (34): PTEN hamartoma tumor syndrome (Orphanet:306498), Inherited cancer-predisposing syndrome (Orphanet:140162), Macrocephaly-intellectual disability-autism syndrome (Orphanet:210548), Hemimegalencephaly (Orphanet:99802), Glial tumor (Orphanet:182067), Bannayan-Riley-Ruvalcaba syndrome (Orphanet:109), Cowden syndrome (Orphanet:201), Familial prostate cancer (Orphanet:1331), Familial multiple meningioma (Orphanet:263662), Hereditary breast cancer (Orphanet:227535), VACTERL with hydrocephalus (Orphanet:3412), Familial melanoma (Orphanet:618), Squamous cell carcinoma of head and neck (Orphanet:67037), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), Specific learning disability (Orphanet:211047)

HPO phenotypes

238 total (30 of 238 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000034	Hydrocele testis
HP:0000036	Abnormal penis morphology
HP:0000077	Abnormality of the kidney
HP:0000098	Tall stature
HP:0000130	Abnormality of the uterus
HP:0000138	Ovarian cyst
HP:0000147	Polycystic ovaries
HP:0000158	Macroglossia
HP:0000160	Narrow mouth
HP:0000189	Narrow palate
HP:0000218	High palate
HP:0000221	Furrowed tongue
HP:0000238	Hydrocephalus
HP:0000256	Macrocephaly
HP:0000268	Dolichocephaly
HP:0000286	Epicanthus
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000327	Hypoplasia of the maxilla
HP:0000331	Short chin
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000403	Recurrent otitis media
HP:0000445	Wide nose
HP:0000463	Anteverted nares

GWAS associations

39 associations (top):

Study	Trait	p-value
GCST002127_36	Periodontitis (Mean PAL)	3.000000e-06
GCST002352_33	Type 2 diabetes	9.000000e-06
GCST002927_18	Mercury levels	3.000000e-06
GCST004346_46	Psoriasis	3.000000e-08
GCST004600_92	Eosinophil percentage of white cells	2.000000e-14
GCST004606_193	Eosinophil count	2.000000e-15
GCST004617_183	Eosinophil percentage of granulocytes	7.000000e-12
GCST004623_49	Neutrophil percentage of granulocytes	5.000000e-09
GCST004624_178	Sum eosinophil basophil counts	1.000000e-13
GCST005976_7	White blood cell count (basophil)	2.000000e-10
GCST006899_4	Thyroid stimulating hormone levels	2.000000e-10
GCST007096_92	Pulse pressure	2.000000e-09
GCST008362_119	Birth weight	2.000000e-08
GCST008839_135	Height	1.000000e-06
GCST009380_2	Type 2 diabetes (adjusted for BMI)	5.000000e-08
GCST009597_149	Multiple sclerosis	1.000000e-07
GCST010118_111	Type 2 diabetes	4.000000e-10
GCST010653_44	Thyroid stimulating hormone levels	1.000000e-13
GCST012189_12	Systolic blood pressure and diastolic blood pressure (bivariate analysis)	8.000000e-06
GCST90002381_281	Eosinophil count	7.000000e-12
GCST90002381_282	Eosinophil count	2.000000e-30
GCST90002382_192	Eosinophil percentage of white cells	5.000000e-28
GCST90002389_448	Lymphocyte percentage of white cells	1.000000e-10
GCST90002390_493	Mean corpuscular hemoglobin	2.000000e-14
GCST90002392_617	Mean corpuscular volume	6.000000e-12
GCST90002392_618	Mean corpuscular volume	1.000000e-14
GCST90002396_489	Mean reticulocyte volume	9.000000e-28
GCST90002397_541	Mean spheric corpuscular volume	8.000000e-11
GCST90002398_178	Neutrophil count	7.000000e-21
GCST90002399_50	Neutrophil percentage of white cells	6.000000e-09

EFO canonical traits (19, from GWAS)

EFO ID	Trait name
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0005763	pulse pressure measurement
EFO:0004344	birth weight
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume
EFO:0004833	neutrophil count
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007985	platelet crit
EFO:0004309	platelet count
EFO:0004305	erythrocyte count
EFO:0009902	handedness
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (27)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D001943	Breast Neoplasms	C04.588.180; C17.800.090.500
D002292	Carcinoma, Renal Cell	C04.557.470.200.025.390; C04.588.945.947.535.160; C12.050.351.937.820.535.160; C12.050.351.968.419.473.160; C12.200.758.820.750.160; C12.200.777.419.473.160; C12.900.820.535.160; C12.950.419.473.160; C12.950.983.535.160
D002294	Carcinoma, Squamous Cell	C04.557.470.200.400; C04.557.470.700.400
D005910	Glioma	C04.557.465.625.600.380; C04.557.470.670.380; C04.557.580.625.600.380
D006223	Hamartoma Syndrome, Multiple	C04.445.435; C04.651.435; C04.700.435; C16.320.700.435
D006391	Hemangioma	C04.557.645.375
D065705	Hemimegalencephaly	C05.660.207.536.500; C10.500.507.400.249.500; C16.131.621.207.532.500; C16.131.666.507.400.249.500
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D007890	Leiomyosarcoma	C04.557.450.590.455; C04.557.450.795.455
D007947	Leukemia, Megakaryoblastic, Acute	C04.557.337.539.275.450; C15.378.508.539.275.450
D016403	Lymphoma, Large B-Cell, Diffuse	C04.557.386.480.150.585; C15.604.515.569.480.150.585; C20.683.515.761.480.150.585
D008545	Melanoma	C04.557.465.625.650.510; C04.557.580.625.650.510; C04.557.665.510; C04.588.805.377; C17.800.882.445
D008579	Meningioma	C04.557.580.520; C04.557.645.520; C04.588.614.250.580.500; C10.551.240.500.500
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D065886	Neurodevelopmental Disorders	F03.625
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
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
D012208	Rhabdomyosarcoma	C04.557.450.590.550.660; C04.557.450.795.550.660
D000067559	Specific Learning Disorder	C10.597.606.150.550.700; C23.888.592.604.150.550.700; F03.625.374.188.700; F03.625.562.700
C585640	Activated PI3K-delta Syndrome (supp.)
C562840	Breast Cancer, Familial (supp.)
C565342	Macrocephaly Autism Syndrome (supp.)
C537443	Meningioma, familial (supp.)
C537243	Prostate cancer, familial (supp.)
C572845	Thyroid cancer, follicular (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2052032 (SINGLE PROTEIN), CHEMBL4523606 (PROTEIN-PROTEIN INTERACTION)

Clinical evidence (CIViC)

Drug × variant × indication: 60 predictive associations from 66 curated evidence items; also 3 prognostic, 3 predisposing, 2 oncogenic, 2 diagnostic, 1 functional.

Variant	Therapy	Indication	Effect	Level	CIViC
PIK3CA Mutation OR PTEN Mutation OR AKT1 Mutation	Capivasertib + Fulvestrant	Breast Cancer	Sensitivity/Response	CIViC A	EID12020
PTEN Loss	Ipatasertib	Prostate Cancer	Sensitivity/Response	CIViC B	EID10876 +1
MTOR Mutation OR PIK3CA Mutation OR PTEN Mutation OR AKT1 Mutation OR AKT2 Mutation	Sapanisertib	Solid Tumor	Sensitivity/Response	CIViC B	EID12075
PIK3CA Mutation OR PTEN Mutation OR PIK3R1 Mutation	Aspirin	Colorectal Cancer	Sensitivity/Response	CIViC B	EID12602
PTEN Deletion	Everolimus	Prostate Cancer	Sensitivity/Response	CIViC B	EID1231
PTEN Expression	Erlotinib + Gefitinib	Glioblastoma	Sensitivity/Response	CIViC B	EID1129
PTEN Expression	Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor	Glioblastoma	Sensitivity/Response	CIViC B	EID774
PTEN Expression	Trastuzumab	Breast Cancer	Sensitivity/Response	CIViC B	EID955
PTEN Loss	Everolimus	Her2-receptor Positive Breast Cancer	Sensitivity/Response	CIViC B	EID1297
PTEN Loss	Everolimus	Cancer	Sensitivity/Response	CIViC B	EID5840
PTEN Loss	Buparlisib + Carboplatin + Paclitaxel	Solid Tumor	Sensitivity/Response	CIViC B	EID5957
PTEN Mutation	Everolimus	Endometrial Carcinoma	Sensitivity/Response	CIViC B	EID1232
PTEN Mutation	Buparlisib	Glioblastoma	Sensitivity/Response	CIViC B	EID7074
PTEN Loss	Trastuzumab	Her2-receptor Positive Breast Cancer	Resistance	CIViC B	EID1385 +4
PTEN Loss	Trastuzumab	Breast Cancer	Resistance	CIViC B	EID2043 +1
PTEN Loss	Chemotherapy	Stomach Carcinoma	Resistance	CIViC B	EID1493
PTEN Loss	Cetuximab	Colorectal Cancer	Resistance	CIViC B	EID506
PTEN Loss	Panitumumab + Cetuximab	Colorectal Cancer	Resistance	CIViC B	EID6315
PTEN Loss	Cetuximab + Panitumumab	Colorectal Cancer	Resistance	CIViC B	EID6361
PTEN Loss	Everolimus	Bladder Carcinoma	Resistance	CIViC B	EID644
PTEN Loss	Trastuzumab + Lapatinib	Gastric Adenocarcinoma	Resistance	CIViC B	EID864
PTEN Loss	Trastuzumab Emtansine	Her2-receptor Positive Breast Cancer	Resistance	CIViC B	EID8706
PTEN Loss	Temsirolimus + Ridaforolimus	Endometrial Cancer	Resistance	CIViC B	EID893
PTEN Mutation	Nivolumab + Pembrolizumab	Glioblastoma	Resistance	CIViC B	EID8176
PTEN Loss	Carboplatin + Buparlisib + Paclitaxel	Cancer	Sensitivity/Response	CIViC C	EID714
PTEN Loss	Akt Inhibitor MK2206	Pancreatic Carcinoma	Sensitivity/Response	CIViC C	EID938
PTEN Expression	Everolimus + Fulvestrant	Her2-receptor Positive Breast Cancer	Resistance	CIViC C	EID1624
PTEN Loss	Pembrolizumab	Uterus Leiomyosarcoma	Resistance	CIViC C	EID12145
PTEN Expression	Dacomitinib	Glioblastoma	Sensitivity/Response	CIViC D	EID775
PTEN Loss	PI3K/BET Inhibitor LY294002 + Trastuzumab	Her2-receptor Positive Breast Cancer	Sensitivity/Response	CIViC D	EID1455

+30 more predictive associations (showing top 30 by evidence level).

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs17431184	Efficacy	3	capecitabine;fluorouracil	Metastatic neoplasm
rs2299939	Toxicity	3	carboplatin;cisplatin	Non-Small Cell Lung Carcinoma

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2299939	PTEN	3	2.50	1	carboplatin;cisplatin
rs17431184	PTEN	3	0.00	1	capecitabine;fluorouracil

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Lipid phosphate phosphatases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
P6949	Inhibition	5.05	pIC50

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.05	IC50	8870	nM	CHEMBL2057662
5.00	IC50	1e+04	nM	CHEMBL2000194

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases phosphorylation, affects activity, affects response to substance, increases reaction, decreases expression (+8 more)	12
Resveratrol	decreases reaction, decreases activity, increases activity, affects cotreatment, decreases methylation (+5 more)	12
Cadmium Chloride	decreases expression, decreases reaction, increases phosphorylation, increases reaction, decreases response to substance	9
bisphenol A	increases phosphorylation, decreases reaction, affects reaction, affects expression, affects cotreatment (+2 more)	8
Doxorubicin	increases response to substance, affects expression, increases activity, decreases reaction, increases phosphorylation (+6 more)	8
Arsenic Trioxide	increases phosphorylation, increases response to substance, increases reaction, decreases expression, increases expression (+3 more)	7
Estradiol	affects reaction, increases expression, decreases reaction, increases response to substance, affects cotreatment (+3 more)	6
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases reaction, increases response to substance, affects cotreatment, decreases phosphorylation, increases cleavage (+1 more)	5
Rosiglitazone	affects reaction, decreases phosphorylation, affects response to substance, decreases reaction, increases expression	5
Cisplatin	increases expression, affects reaction, increases phosphorylation, affects cotreatment, increases activity (+4 more)	5
trichostatin A	affects cotreatment, increases expression, affects response to substance, increases reaction, affects binding	4
ochratoxin A	decreases phosphorylation, increases expression, decreases expression	4
Decitabine	increases expression, decreases expression, decreases reaction, decreases methylation, increases reaction (+1 more)	4
Quercetin	increases expression, increases response to substance, decreases reaction, decreases expression	4
Tretinoin	affects cotreatment, increases expression, decreases methylation, increases reaction	4
Valproic Acid	affects cotreatment, increases expression, decreases expression, decreases methylation	4
Sirolimus	increases expression, decreases response to substance, decreases expression, decreases reaction, affects cotreatment	4
cobaltous chloride	increases activity, increases reaction, increases expression, decreases reaction	3
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects response to substance, decreases reaction, increases reaction, affects cotreatment, increases expression	3
2-chloro-5-nitrobenzanilide	increases expression, decreases reaction	3
Fulvestrant	decreases reaction, increases expression, increases methylation, increases response to substance	3
Acetylcysteine	decreases activity, increases methylation, decreases reaction, increases expression, decreases expression (+2 more)	3
Tobacco Smoke Pollution	decreases expression, decreases reaction, increases reaction	3
Genistein	decreases reaction, increases expression, affects expression, increases response to substance	3
Particulate Matter	increases expression, increases phosphorylation	3
methylmercuric chloride	decreases expression, increases expression	2
bis(tri-n-butyltin)oxide	increases expression	2
bisphenol A diglycidyl ether	decreases reaction, increases expression	2
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression, increases ubiquitination	2
1-(methylimino-N-oxy)-6-(2-morpholinoethoxy)-3-phenyl-1H-indene-2-carboxylic acid ethyl ester	decreases reaction, increases expression	2

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2061290	Binding	Inhibition of human PTEN using 3-O-Methylfluorescein phosphate as substrate incubated for 10 mins prior to substrate addition by fluorometry	Arylstibonic acids are potent and isoform-selective inhibitors of Cdc25a and Cdc25b phosphatases. — Bioorg Med Chem

Cellosaurus cell lines

1,214 cell lines: 1,199 cancer cell line, 9 spontaneously immortalized cell line, 5 telomerase immortalized cell line, 1 hybrid cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0007	U-937	Cancer cell line	Male
CVCL_0011	KM-3	Cancer cell line	Female
CVCL_0013	MOLT-4	Cancer cell line	Male
CVCL_0020	U-138MG	Cancer cell line	Male
CVCL_0021	U-251MG	Cancer cell line	Male
CVCL_0022	U-87MG ATCC	Cancer cell line	Male
CVCL_0028	AN3-CA	Cancer cell line	Female
CVCL_0040	WM115	Cancer cell line	Female
CVCL_0107	BCP-1	Cancer cell line	Male
CVCL_0110	1321N1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00414765	PHASE4	COMPLETED	Aldesleukin in Participants With Metastatic Renal Cell Carcinoma or Metastatic Melanoma
NCT00777504	PHASE4	UNKNOWN	Study to the Optimal Duration of Therapy With Oral Angiogenesis Inhibitors
NCT00930345	PHASE4	TERMINATED	Biological, Pathological and Imagery Markers in the First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma
NCT01206764	PHASE4	COMPLETED	A Trial of Everolimis in Patients With Advanced Renal Cell Carcinoma.
NCT01266837	PHASE4	COMPLETED	Open Label, Single Arm Trial to Characterize Patients With Metastatic RCC Treated With Everolimus After Failure of the First VEGF-targeted Therapy (MARC-2)
NCT02056587	PHASE4	COMPLETED	Everolimus in Patients With Metastatic Renal Cell Carcinoma Following Progression on Prior Bevacizumab Treatment
NCT02338570	PHASE4	TERMINATED	Outcome-related Factors in Patients With Metastatic Renal Cell Carcinoma Treated With Everolimus (ORCHIDEE)
NCT02596035	PHASE4	COMPLETED	An Investigational Immuno-therapy Safety Trial of Nivolumab in Patients With Advanced or Metastatic Renal Cell Carcinoma
NCT02982954	PHASE4	COMPLETED	A Study to Evaluate the Safety of Nivolumab and Ipilimumab in Subjects With Previously Untreated Advanced or Metastatic Renal Cell Cancer
NCT05949424	PHASE4	UNKNOWN	OPTI - DOSE: Optimal Dosing of Oral Anticancer Drugs in Older Adults
NCT07028125	PHASE4	RECRUITING	Digital Monitoring of Self-reported Symptoms by Patients Treated With Cabozantinib Plus Nivolumab for Advanced Clear-cell Renal Carcinoma
NCT07405086	PHASE4	RECRUITING	Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study
NCT00014638	PHASE4	COMPLETED	Letrozole in Treating Postmenopausal Women With Metastatic Breast Cancer
NCT00022386	PHASE4	COMPLETED	Epoetin Alfa in Treating Chemotherapy-Related Anemia in Women With Stage I, Stage II, or Stage III Breast Cancer
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00030758	PHASE4	UNKNOWN	Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer
NCT00082277	PHASE4	COMPLETED	Anastrozole Biphosphonate Study in Postmenopausal Women With Hormone-Receptor-Positive Early Breast Cancer
NCT00087620	PHASE4	TERMINATED	A Study of Capecitabine In Combination With Docetaxel vs Capecitabine Followed by Docetaxel As First-Line Treatment For Metastatic Breast Cancer
NCT00121836	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) in Women With HER2-Negative Metastatic Breast Cancer
NCT00126360	PHASE4	UNKNOWN	STARS Breast Trial (Study of Anastrozole and Radiotherapy Sequencing Pilot)
NCT00127933	PHASE4	COMPLETED	XeNA Study - A Study of Xeloda (Capecitabine) in Patients With Invasive Breast Cancer
NCT00128297	PHASE4	COMPLETED	Pamidronate Administration in Breast Cancer Patients With Bone Metastases
NCT00129597	PHASE4	UNKNOWN	Effect of Ketalar to Prevent Postoperative Chronic Pain After Mastectomy
NCT00131170	PHASE4	COMPLETED	Paravertebral Block for Breast Surgery
NCT00156039	PHASE4	COMPLETED	Randomized Trial of Follow-up Strategies in Breast Cancer
NCT00160901	PHASE4	COMPLETED	Complementary Therapies for the Reduction of Side Effects During Chemotherapy for Breast Cancer
NCT00171847	PHASE4	TERMINATED	Study of the Efficacy and Safety of Letrozole Combined With Trastuzumab in Patients With Metastatic Breast Cancer
NCT00176046	PHASE4	COMPLETED	Mistletoe Extract in Early or Advanced Breast Cancer, A Feasibility Study
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00234195	PHASE4	COMPLETED	Wellbutrin XL, Major Depressive Disorder and Breast Cancer
NCT00237133	PHASE4	COMPLETED	Treatment of Locally Advanced Breast Cancer With Letrozole in Postmenopausal Women
NCT00237224	PHASE4	COMPLETED	Open Label Study of Postmenopausal Women With ER and /or PgR Positive Breast Cancer Treated With Letrozole
NCT00241046	PHASE4	TERMINATED	Letrozole in the Treatment of 1st and 2nd Line Hormone Receptor Positive Breast Cancer: Pre-therapeutic Risk Assessment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00323479	PHASE4	COMPLETED	Arthralgia During Anastrozole Therapy for Breast Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00356148	PHASE4	COMPLETED	The Efficacy of Prophylactic Antibiotic Administration During Breast Cancer Surgery in Overweight Patients.
NCT00372476	PHASE4	COMPLETED	Efficacy and Safety of Imatinib and Vinorelbine in Patients With Advanced Breast Cancer
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