PPP2CB

Summary

PPP2CB (protein phosphatase 2 catalytic subunit beta, HGNC:9300) is a protein-coding gene on chromosome 8p12, encoding Serine/threonine-protein phosphatase 2A catalytic subunit beta isoform (P62714). Catalytic subunit of protein phosphatase 2A (PP2A), a serine/threonine phosphatase involved in the regulation of a wide variety of enzymes, signal transduction pathways, and cellular events.

This gene encodes the phosphatase 2A catalytic subunit. Protein phosphatase 2A is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. This gene encodes a beta isoform of the catalytic subunit.

Source: NCBI Gene 5516 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 35 total
• Druggable target: yes
• MANE Select transcript: NM_001009552

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9300
Approved symbol	PPP2CB
Name	protein phosphatase 2 catalytic subunit beta
Location	8p12
Locus type	gene with protein product
Status	Approved
Aliases	PP2Abeta
Ensembl gene	ENSG00000104695
Ensembl biotype	protein_coding
OMIM	176916
Entrez	5516

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000221138, ENST00000518243, ENST00000518532, ENST00000518564, ENST00000520056, ENST00000520334, ENST00000520500, ENST00000522113, ENST00000523023, ENST00000523804, ENST00000906070, ENST00000906071, ENST00000966961, ENST00000966962, ENST00000966963

RefSeq mRNA: 1 — MANE Select: NM_001009552 NM_001009552

CCDS: CCDS6079

Canonical transcript exons

ENST00000221138 — 7 exons

Exon	Start	End
ENSE00000688018	30797581	30797754
ENSE00001483887	30812320	30812818
ENSE00001593515	30794192	30794281
ENSE00001625658	30791197	30791315
ENSE00001729232	30793917	30794078
ENSE00002094460	30785616	30786307
ENSE00003618118	30799546	30799755

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.1335 / max 271.3708, expressed in 1798 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92637	17.8412	1785
92638	1.1885	726
92636	0.7682	348
92639	0.3357	155

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pons	UBERON:0000988	99.65	gold quality
superior vestibular nucleus	UBERON:0007227	99.60	gold quality
subthalamic nucleus	UBERON:0001906	99.57	gold quality
cranial nerve II	UBERON:0000941	99.55	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.55	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.55	gold quality
postcentral gyrus	UBERON:0002581	99.54	gold quality
lateral globus pallidus	UBERON:0002476	99.52	gold quality
medulla oblongata	UBERON:0001896	99.51	gold quality
adult organism	UBERON:0007023	99.45	gold quality
bronchial epithelial cell	CL:0002328	99.44	gold quality
jejunal mucosa	UBERON:0000399	99.43	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.43	gold quality
parietal lobe	UBERON:0001872	99.41	gold quality
CA1 field of hippocampus	UBERON:0003881	99.41	gold quality
substantia nigra pars compacta	UBERON:0001965	99.40	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.40	gold quality
inferior vagus X ganglion	UBERON:0005363	99.35	gold quality
lower lobe of lung	UBERON:0008949	99.34	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.31	gold quality
orbitofrontal cortex	UBERON:0004167	99.27	gold quality
cerebellar vermis	UBERON:0004720	99.26	gold quality
entorhinal cortex	UBERON:0002728	99.23	gold quality
colonic mucosa	UBERON:0000317	99.22	gold quality
corpus epididymis	UBERON:0004359	99.22	gold quality
trigeminal ganglion	UBERON:0001675	99.21	gold quality
palpebral conjunctiva	UBERON:0001812	99.20	gold quality
cauda epididymis	UBERON:0004360	99.20	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.20	gold quality
superior frontal gyrus	UBERON:0002661	99.19	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-100618	no	232.24
E-CURD-89	no	67.00
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
CCL2	Repression
CCL5	Repression
IL6	Repression
RELA	Repression

miRNA regulators (miRDB)

63 targeting PPP2CB, 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-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-513A-3P	99.39	70.63	3620

Literature-anchored findings (GeneRIF, showing 7)

• Results describe the cell cycle expression, subcellular distribution, and metabolic stability of protein phosphatase 2Abeta in comparison with 2Aalpha. (PMID:12370081)
• Claspin may be one of the phosphoproteins through which PP2A(Aalpha/Cbeta) affects Chk1 phosphorylation when ATR is activated by human immunodeficiency virus-1 Vpr. (PMID:17210576)
• These data strongly support a recent proposal that a segment at 8p21.3 contains crucial prostate cancer tumor suppressors. (PMID:18460741)
• PP2B and PP1alpha cooperatively disrupt 7SK snRNP to release P-TEFb for transcription in response to Ca2+ signaling. (PMID:18483222)
• The GAS41-PP2Cbeta complex dephosphorylates p53 at serine 366 and regulates its stability (PMID:21317290)
• Protein phosphatase 2A in the healthy and failing heart: New insights and therapeutic opportunities. (PMID:34902541)
• Protein phosphatase 2A and complement component 4 are linked to the protective effect of APOE varepsilon2 for Alzheimer’s disease. (PMID:35142023)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppp2cb	ENSDARG00000099241
mus_musculus	Ppp2cb	ENSMUSG00000009630
rattus_norvegicus	Ppp2cb	ENSRNOG00000015182
drosophila_melanogaster	mts	FBGN0004177
caenorhabditis_elegans		WBGENE00002363

Paralogs (12): PPP5C (ENSG00000011485), PPEF1 (ENSG00000086717), PPP3CB (ENSG00000107758), PPP2CA (ENSG00000113575), PPP6C (ENSG00000119414), PPP3CC (ENSG00000120910), PPP3CA (ENSG00000138814), PPP4C (ENSG00000149923), PPEF2 (ENSG00000156194), PPP1CA (ENSG00000172531), PPP1CC (ENSG00000186298), PPP1CB (ENSG00000213639)

Protein

Protein identifiers

Serine/threonine-protein phosphatase 2A catalytic subunit beta isoform — P62714 (reviewed: P62714)

All UniProt accessions (7): A0A140VJS0, E5RFI3, E5RHC1, E5RJX4, H0YBN9, H0YC23, P62714

UniProt curated annotations — full annotation on UniProt →

Function. Catalytic subunit of protein phosphatase 2A (PP2A), a serine/threonine phosphatase involved in the regulation of a wide variety of enzymes, signal transduction pathways, and cellular events. PP2A can modulate the activity of phosphorylase B kinase, casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase. Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation.

Subunit / interactions. PP2A consists of a common heterodimeric core enzyme (composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65) (subunit A)) that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B’’/PR72/PR130/PR59 and R5/B’/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Binds PPME1. May indirectly interact with SGO1, most probably through regulatory B56 subunits. Interacts with CTTNBP2NL. Interacts with PTPA. Found in a complex with at least ARL2, PPP2CB, PPP2R1A, PPP2R2A, PPP2R5E and TBCD. Interacts with TBCD. Part of the core of STRIPAK complexes composed of PP2A catalytic and scaffolding subunits, the striatins (PP2A regulatory subunits), the striatin-associated proteins MOB4, STRIP1 and STRIP2, PDCD10 and members of the STE20 kinases, such as STK24 and STK26.

Subcellular location. Cytoplasm. Nucleus. Chromosome. Centromere. Cytoskeleton. Spindle pole.

Post-translational modifications. Reversibly methyl esterified on Leu-309 by leucine carboxyl methyltransferase 1 (LCMT1) and protein phosphatase methylesterase 1 (PPME1). Carboxyl methylation influences the affinity of the catalytic subunit for the different regulatory subunits, thereby modulating the PP2A holoenzyme’s substrate specificity, enzyme activity and cellular localization. Phosphorylation of either threonine (by autophosphorylation-activated protein kinase) or tyrosine results in inactivation of the phosphatase. Auto-dephosphorylation has been suggested as a mechanism for reactivation. May be monoubiquitinated by NOSIP.

Cofactor. Binds 2 manganese ions per subunit.

Similarity. Belongs to the PPP phosphatase family. PP-1 subfamily.

RefSeq proteins (1): NP_001009552* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004843	Calcineurin-like_PHP	Domain
IPR006186	Ser/Thr-sp_prot-phosphatase	Domain
IPR029052	Metallo-depent_PP-like	Homologous_superfamily
IPR047129	PPA2-like	Family

Pfam: PF00149

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 (14 total): binding site 7, modified residue 2, mutagenesis site 2, chain 1, active site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62714-F1	95.08	0.93

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): 118 (proton donor)

Ligand- & substrate-binding residues (7): 57; 59; 85; 85; 117; 167; 241

Post-translational modifications (2): 309, 307

Mutagenesis-validated functional residues (2):

Position	Phenotype
59	catalytically inactive. no effect on interaction with ppme1.
118	catalytically inactive. no effect on interaction with ppme1.

Function

Pathways and Gene Ontology

Reactome pathways

35 pathways

ID	Pathway
R-HSA-113501	Inhibition of replication initiation of damaged DNA by RB1/E2F1
R-HSA-1295596	Spry regulation of FGF signaling
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-163767	PP2A-mediated dephosphorylation of key metabolic factors
R-HSA-180024	DARPP-32 events
R-HSA-195253	Degradation of beta-catenin by the destruction complex
R-HSA-196299	Beta-catenin phosphorylation cascade
R-HSA-198753	ERK/MAPK targets
R-HSA-202670	ERKs are inactivated
R-HSA-2465910	MASTL Facilitates Mitotic Progression
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-389356	Co-stimulation by CD28
R-HSA-389513	Co-inhibition by CTLA4
R-HSA-432142	Platelet sensitization by LDL
R-HSA-4641262	Disassembly of the destruction complex and recruitment of AXIN to the membrane
R-HSA-5339716	Signaling by GSK3beta mutants
R-HSA-5358747	CTNNB1 S33 mutants aren’t phosphorylated
R-HSA-5358749	CTNNB1 S37 mutants aren’t phosphorylated
R-HSA-5358751	CTNNB1 S45 mutants aren’t phosphorylated
R-HSA-5358752	CTNNB1 T41 mutants aren’t phosphorylated
R-HSA-5467337	APC truncation mutants have impaired AXIN binding
R-HSA-5467340	AXIN missense mutants destabilize the destruction complex
R-HSA-5467348	Truncations of AMER1 destabilize the destruction complex
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-5673000	RAF activation
R-HSA-5675221	Negative regulation of MAPK pathway
R-HSA-6804757	Regulation of TP53 Degradation
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-68877	Mitotic Prometaphase

MSigDB gene sets: 329 (showing top): REACTOME_INHIBITION_OF_REPLICATION_INITIATION_OF_DAMAGED_DNA_BY_RB1_E2F1, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, REACTOME_SIGNALING_BY_FGFR, CHUANG_OXIDATIVE_STRESS_RESPONSE_UP, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, KEGG_TIGHT_JUNCTION

GO Biological Process (15): mitotic cell cycle (GO:0000278), protein dephosphorylation (GO:0006470), apoptotic mitochondrial changes (GO:0008637), response to lead ion (GO:0010288), negative regulation of gene expression (GO:0010629), negative regulation of tumor necrosis factor-mediated signaling pathway (GO:0010804), regulation of microtubule polymerization (GO:0031113), response to endoplasmic reticulum stress (GO:0034976), response to hydrogen peroxide (GO:0042542), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), negative regulation of Ras protein signal transduction (GO:0046580), response to antibiotic (GO:0046677), regulation of neurofibrillary tangle assembly (GO:1902996), regulation of gene expression (GO:0010468)

GO Molecular Function (7): protein serine/threonine phosphatase activity (GO:0004722), transmembrane transporter binding (GO:0044325), metal ion binding (GO:0046872), tau protein binding (GO:0048156), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (9): protein phosphatase type 2A complex (GO:0000159), chromosome, centromeric region (GO:0000775), spindle pole (GO:0000922), nucleus (GO:0005634), cytosol (GO:0005829), FAR/SIN/STRIPAK complex (GO:0090443), chromosome (GO:0005694), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-21 pathways:

Category	Pathways
Signaling by CTNNB1 phospho-site mutants	3
Regulation of T cell activation by CD28 family	2
E2F mediated regulation of DNA replication	1
Negative regulation of FGFR1 signaling	1
Negative regulation of FGFR2 signaling	1
Negative regulation of FGFR3 signaling	1
Negative regulation of FGFR4 signaling	1
Amplification of signal from the kinetochores	1
Integration of energy metabolism	1
Opioid Signalling	1
Signaling by WNT	1
Degradation of beta-catenin by the destruction complex	1
Nuclear Events (kinase and transcription factor activation)	1
MAPK targets/ Nuclear events mediated by MAP kinases	1
ERK/MAPK targets	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
gene expression	2
intracellular membraneless organelle	2
cell cycle	1
mitotic nuclear division	1
dephosphorylation	1
protein modification process	1
apoptotic process	1
mitochondrion organization	1
response to metal ion	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
negative regulation of cytokine-mediated signaling pathway	1
regulation of tumor necrosis factor-mediated signaling pathway	1
tumor necrosis factor-mediated signaling pathway	1
regulation of microtubule polymerization or depolymerization	1
regulation of protein polymerization	1
microtubule polymerization	1
regulation of supramolecular fiber organization	1
cellular response to stress	1
response to reactive oxygen species	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
Ras protein signal transduction	1
regulation of Ras protein signal transduction	1
negative regulation of small GTPase mediated signal transduction	1
response to chemical	1
regulation of inclusion body assembly	1
neurofibrillary tangle assembly	1
regulation of macromolecule biosynthetic process	1
phosphoprotein phosphatase activity	1
protein binding	1
cation binding	1
cytoskeletal protein binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

210 interactions, top by confidence:

A	B	Type	Score
PPP2R2A	PPP2R1A	psi-mi:“MI:2364”(proximity)	0.970
PPME1	PPP2R1A	psi-mi:“MI:0914”(association)	0.950
IGBP1	PPP6C	psi-mi:“MI:0914”(association)	0.940
PPP2R1A	PPP2CB	psi-mi:“MI:0407”(direct interaction)	0.940
STK25	STRN	psi-mi:“MI:0914”(association)	0.900
STK24	STK25	psi-mi:“MI:0914”(association)	0.890
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
PPP2R1A	STRN	psi-mi:“MI:2364”(proximity)	0.880
PPP2CB	IGBP1	psi-mi:“MI:0915”(physical association)	0.880
STRIP1	PPP2CB	psi-mi:“MI:0915”(physical association)	0.870
STK24	STRN	psi-mi:“MI:0914”(association)	0.870
STRIP1	PPP2CB	psi-mi:“MI:0914”(association)	0.870
ANKLE2	PPP2R1A	psi-mi:“MI:0914”(association)	0.850
PPP2CB	STRN	psi-mi:“MI:0914”(association)	0.790
CDCA4	PPP2R1A	psi-mi:“MI:0914”(association)	0.790
STK26	STK25	psi-mi:“MI:0914”(association)	0.790
STRIP1	STRN	psi-mi:“MI:0915”(physical association)	0.770
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
PPP2CB	CEP43	psi-mi:“MI:0914”(association)	0.730
PPP2R2C	PPP2R1A	psi-mi:“MI:0914”(association)	0.730
PPP2R2D	YEATS4	psi-mi:“MI:0914”(association)	0.730
LRFN4	NCK2	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710

BioGRID (544): PPP2CB (Affinity Capture-RNA), PPP2CB (Two-hybrid), CEP350 (Affinity Capture-MS), STRIP2 (Affinity Capture-MS), STRIP1 (Affinity Capture-MS), PRR14 (Affinity Capture-MS), PRR14L (Affinity Capture-MS), STRN (Affinity Capture-MS), STRN3 (Affinity Capture-MS), STRN4 (Affinity Capture-MS), CCDC6 (Affinity Capture-MS), TBCCD1 (Affinity Capture-MS), SIKE1 (Affinity Capture-MS), NDUFAF1 (Affinity Capture-MS), FGFR1OP (Affinity Capture-MS)

ESM2 similar proteins: A0C1E4, A0CCD2, A0DJ90, A2XN40, A6H772, A8WGP3, A9JRC7, O04860, O04951, O76932, P11084, P11611, P20604, P23696, P23778, P32345, P36614, P48463, P48528, P48529, P48577, P48578, P49576, P60510, P62714, P62715, P62716, P63330, P63331, P67774, P67775, P67776, P67777, P97470, Q06009, Q07098, Q07099, Q07100, Q0P594, Q10BT5

Diamond homologs: A0C1E4, A0CCD2, A0CNL9, A0DJ90, A2X2G3, A2XN40, A2YEB4, A3C4N5, A6H772, A8WGP3, A8XE00, A9JRC7, G5EGK8, O00743, O04860, O04951, O74789, O76932, P0C5D7, P11084, P11493, P11611, P20604, P23594, P23595, P23635, P23636, P23696, P23778, P30366, P32345, P32598, P32838, P36614, P48463, P48480, P48483, P48528, P48529, P48577

SIGNOR signaling

51 interactions.

A	Effect	B	Mechanism
PPP2R1A	up-regulates	PPP2CB	binding
PPP2CB	down-regulates	MYC	dephosphorylation
PLAAT3	down-regulates	PPP2CB
PPP2CB	down-regulates	RALA	dephosphorylation
SET	down-regulates	PPP2CB	binding
TLX1	“down-regulates activity”	PPP2CB	binding
PPP2CB	“down-regulates activity”	CHEK1	dephosphorylation
PPP2CB	“down-regulates activity”	IKBKB	dephosphorylation
PPP2CB	“up-regulates activity”	CHEK2	dephosphorylation
PPP2CB	“up-regulates quantity by stabilization”	TP53	dephosphorylation
PPP2CB	unknown	KRT8	dephosphorylation
PPP2CB	“up-regulates activity”	BCL2	dephosphorylation
PPP2CB	“down-regulates activity”	ELF1	dephosphorylation
PPP2CB	“down-regulates activity”	SNCA	dephosphorylation
PPP2CB	“down-regulates activity”	ATM	dephosphorylation
PPP2CB	“up-regulates activity”	HDAC7	dephosphorylation
PPP2CB	“down-regulates activity”	CARD11	dephosphorylation
PPP2CB	“down-regulates activity”	AKT3	dephosphorylation
PPP2CB	“down-regulates activity”	AKT	dephosphorylation
PPP2CB	down-regulates	AKT1	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 198 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
Cyclin A/B1/B2 associated events during G2/M transition	7	16.2×	9e-05
MAP kinase activation	6	13.9×	5e-04
Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	5	13.4×	1e-03
RAF activation	5	12.6×	2e-03
Interleukin-17 signaling	6	11.4×	8e-04
Regulation of TP53 Degradation	5	11.0×	2e-03
MyD88 cascade initiated on plasma membrane	7	10.7×	5e-04
Glycolysis	5	10.7×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of hippo signaling	7	27.9×	5e-06
positive regulation of miRNA transcription	7	11.6×	1e-03
protein phosphorylation	13	5.0×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1002 predictions. Top by Δscore:

Variant	Effect	Δscore
8:30791195:A:AC	donor_gain	1.0000
8:30791196:C:CA	donor_gain	1.0000
8:30791196:CA:C	donor_gain	1.0000
8:30791196:CAA:C	donor_gain	1.0000
8:30791196:CAAG:C	donor_gain	1.0000
8:30791196:CAAGG:C	donor_gain	1.0000
8:30791313:TCCC:T	acceptor_loss	1.0000
8:30791314:CC:C	acceptor_gain	1.0000
8:30791315:CC:C	acceptor_gain	1.0000
8:30791316:C:CC	acceptor_gain	1.0000
8:30791316:CTG:C	acceptor_loss	1.0000
8:30791317:T:A	acceptor_loss	1.0000
8:30793913:ATACC:A	donor_loss	1.0000
8:30793914:TACC:T	donor_loss	1.0000
8:30793915:A:AC	donor_gain	1.0000
8:30793915:A:T	donor_loss	1.0000
8:30793915:ACCT:A	donor_gain	1.0000
8:30793916:C:CC	donor_gain	1.0000
8:30793916:CCT:C	donor_gain	1.0000
8:30793916:CCTC:C	donor_gain	1.0000
8:30794074:GGGCC:G	acceptor_gain	1.0000
8:30794076:GCC:G	acceptor_gain	1.0000
8:30794077:CC:C	acceptor_gain	1.0000
8:30794077:CCC:C	acceptor_gain	1.0000
8:30794077:CCCTG:C	acceptor_loss	1.0000
8:30794078:CC:C	acceptor_gain	1.0000
8:30794079:C:CC	acceptor_gain	1.0000
8:30794079:CTGGC:C	acceptor_loss	1.0000
8:30794084:C:CT	acceptor_gain	1.0000
8:30794084:C:T	acceptor_gain	1.0000

AlphaMissense

2021 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:30791234:C:G	A274P	1.000
8:30791241:G:C	N271K	1.000
8:30791241:G:T	N271K	1.000
8:30791252:G:T	R268S	1.000
8:30791256:A:C	C266W	1.000
8:30791257:C:T	C266Y	1.000
8:30791258:A:G	C266R	1.000
8:30791260:T:C	Y265C	1.000
8:30791261:A:G	Y265H	1.000
8:30791262:A:C	N264K	1.000
8:30791262:A:T	N264K	1.000
8:30791266:G:T	P263H	1.000
8:30791271:A:C	S261R	1.000
8:30791271:A:T	S261R	1.000
8:30791273:T:G	S261R	1.000
8:30791274:G:C	F260L	1.000
8:30791274:G:T	F260L	1.000
8:30791276:A:C	F260V	1.000
8:30791276:A:G	F260L	1.000
8:30791276:A:T	F260I	1.000
8:30791314:C:A	G247V	1.000
8:30791314:C:T	G247E	1.000
8:30791315:C:G	G247R	1.000
8:30791315:C:T	G247R	1.000
8:30793927:A:T	L243H	1.000
8:30793929:C:A	Q242H	1.000
8:30793929:C:G	Q242H	1.000
8:30793932:G:C	H241Q	1.000
8:30793932:G:T	H241Q	1.000
8:30793933:T:C	H241R	1.000

dbSNP variants (sampled 300 via entrez): RS1000034624 (8:30806210 G>A), RS1000154240 (8:30812288 C>T), RS1000227299 (8:30789005 C>A), RS1000323652 (8:30806421 G>A,C,T), RS1000324121 (8:30799860 C>T), RS1000473796 (8:30805425 T>C,G), RS1000670617 (8:30793013 G>A), RS1000870162 (8:30804153 A>G), RS1000952353 (8:30788249 C>A,T), RS1001022453 (8:30809379 G>A), RS1001036069 (8:30801134 A>T), RS1001072575 (8:30794895 C>G), RS1001172787 (8:30787154 A>T), RS1001288889 (8:30786912 G>A), RS1001327538 (8:30798217 T>C)

Disease associations

OMIM: gene MIM:176916 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003518_18	Daytime sleep phenotypes	2.000000e-06
GCST012489_62	Heel bone mineral density x serum urate levels interaction	1.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2435 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects binding, increases reaction, affects cotreatment, increases abundance, increases expression (+2 more)	5
Tobacco Smoke Pollution	affects expression, increases expression	3
bisphenol A	affects expression, decreases expression	2
Arsenic Trioxide	increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Smoke	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
echimidine	increases expression, increases metabolic processing	1
lasiocarpine	increases expression, increases metabolic processing	1
pirinixic acid	decreases expression, increases activity, affects binding	1
riddelliine	increases expression, increases metabolic processing	1
tetrahydropalmatine	decreases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
bufalin	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
potassium chromate(VI)	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
obeticholic acid	increases expression	1
morroniside	decreases activity, decreases methylation, decreases reaction, increases phosphorylation, increases activity (+1 more)	1
bisphenol B	increases expression	1
abrine	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Air Pollutants, Occupational	decreases expression	1
Atrazine	increases expression	1
Chelating Agents	affects binding, increases expression	1
Cocaine	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4119016	Binding	Binding affinity to PPP2CB in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1PZ	Abcam K-562 PPP2CB KO	Cancer cell line	Female
CVCL_D2LL	Abcam Raji PPP2CB KO	Cancer cell line	Male
CVCL_TF90	HAP1 PPP2CB (-) 1	Cancer cell line	Male
CVCL_TF91	HAP1 PPP2CB (-) 2	Cancer cell line	Male
CVCL_TF92	HAP1 PPP2CB (-) 3	Cancer cell line	Male
CVCL_WQ36	Abcam Jurkat PPP2CB KO	Cancer cell line	Male

Clinical trials (associated diseases)

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