PPP2R5A

Summary

PPP2R5A (protein phosphatase 2 regulatory subunit B’alpha, HGNC:9309) is a protein-coding gene on chromosome 1q32.3, encoding Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform (Q15172). The B regulatory subunit might modulate substrate selectivity and catalytic activity, and might also direct the localization of the catalytic enzyme to a particular subcellular compartment.

The product of this gene belongs to the phosphatase 2A regulatory subunit B family. 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. The B regulatory subunit might modulate substrate selectivity and catalytic activity. This gene encodes an alpha isoform of the regulatory subunit B56 subfamily. Alternative transcript variants encoding distinct isoforms have been found for this gene.

Source: NCBI Gene 5525 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 53 total
• Druggable target: yes
• MANE Select transcript: NM_006243

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9309
Approved symbol	PPP2R5A
Name	protein phosphatase 2 regulatory subunit B’alpha
Location	1q32.3
Locus type	gene with protein product
Status	Approved
Aliases	PR61A, B56A, B56alpha
Ensembl gene	ENSG00000066027
Ensembl biotype	protein_coding
OMIM	601643
Entrez	5525

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000261461, ENST00000479259, ENST00000498123, ENST00000498129, ENST00000537030, ENST00000886945, ENST00000886946, ENST00000886947, ENST00000886948, ENST00000886949, ENST00000886950, ENST00000932454, ENST00000970523

RefSeq mRNA: 2 — MANE Select: NM_006243 NM_001199756, NM_006243

CCDS: CCDS1503, CCDS55686

Canonical transcript exons

ENST00000261461 — 13 exons

Exon	Start	End
ENSE00001159031	212360638	212361853
ENSE00001196909	212285410	212286291
ENSE00003695918	212347347	212347406
ENSE00003696142	212342188	212342280
ENSE00003697358	212348389	212348497
ENSE00003697989	212349189	212349242
ENSE00003698654	212333497	212333598
ENSE00003700605	212358686	212358787
ENSE00003700781	212356626	212356676
ENSE00003701322	212356950	212357069
ENSE00003701846	212357157	212357284
ENSE00003702090	212345803	212345933
ENSE00003702293	212329135	212329331

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 94.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.9533 / max 1740.3528, expressed in 1820 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8442	22.9558	1810
8443	5.7574	1556
8446	3.8895	1235
8444	0.8646	552
8445	0.4642	249
8447	0.0154	4
201944	0.0065	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	94.91	gold quality
leukocyte	CL:0000738	94.80	gold quality
mononuclear cell	CL:0000842	94.77	gold quality
rectum	UBERON:0001052	94.29	gold quality
bone marrow	UBERON:0002371	94.25	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.20	gold quality
adipose tissue	UBERON:0001013	94.14	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.08	gold quality
right lung	UBERON:0002167	94.01	gold quality
connective tissue	UBERON:0002384	93.95	gold quality
esophagus squamous epithelium	UBERON:0006920	93.87	gold quality
esophagus mucosa	UBERON:0002469	93.76	gold quality
bone element	UBERON:0001474	93.68	gold quality
blood	UBERON:0000178	93.66	gold quality
tongue squamous epithelium	UBERON:0006919	93.66	gold quality
right coronary artery	UBERON:0001625	93.60	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.55	gold quality
cervix epithelium	UBERON:0004801	93.55	gold quality
lower esophagus mucosa	UBERON:0035834	93.38	gold quality
squamous epithelium	UBERON:0006914	93.36	gold quality
body of pancreas	UBERON:0001150	93.32	gold quality
trabecular bone tissue	UBERON:0002483	93.28	gold quality
lung	UBERON:0002048	93.16	gold quality
epithelium of esophagus	UBERON:0001976	93.11	gold quality
heart left ventricle	UBERON:0002084	93.04	gold quality
cardiac ventricle	UBERON:0002082	93.03	gold quality
granulocyte	CL:0000094	92.99	gold quality
vena cava	UBERON:0004087	92.92	gold quality
lower lobe of lung	UBERON:0008949	92.79	gold quality
left ventricle myocardium	UBERON:0006566	92.78	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	19.56
E-ANND-3	yes	18.08
E-CURD-97	no	1360.58
E-GEOD-100618	no	410.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

71 targeting PPP2R5A, 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-656-3P	100.00	72.15	2788
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-3682-3P	99.58	67.63	865
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-520A-5P	99.35	66.72	1632

Literature-anchored findings (GeneRIF, showing 22)

• PKR regulates B56(alpha)-mediated BCL2 phosphatase activity in acute lymphoblastic leukemia-derived REH cells. (PMID:18957415)
• The B’alpha1 subunit of the serine/threonine protein phosphatase 2A, which binds to cyclin G1, can stabilize cyclin G1 under unstressed conditions and upon DNA damage, as well as inhibit the ability of cyclin G1 to be ubiquitinated. (PMID:18981217)
• these data indicate that the B subunits alpha and delta are essential for the interaction of PP2A with CaMKIV. (PMID:19538941)
• The B’alpha subunit of protein phosphatase 2A (PP 2A) as a CHK2 binding partner shows that their interaction is modulated by DNA damage. (PMID:20160490)
• B56alpha has a role in nuclear export of the catalytic subunit of PP2A (PMID:20378546)
• Following TGF-beta1 treatment, recruitment of PP2A-Balpha by TbetaRI increased in benign cells, but not in malignant cells. Inhibition of PP2A in benign cells resulted in an increase in ERK activation and in TGF-beta1 auto-induction after TGF-beta1 treatment. (PMID:21030067)
• The PP2A-B’alpha holoenzyme appears to function as an important endogenous regulator of SK1. (PMID:21075214)
• Reveal that PPP2R5A, an essential tumour suppressor, tunes the balance of phosphorylation to promote chromosome-spindle interactions during cell division. (PMID:21874008)
• reversible phosphorylation of Dzip1, which is controlled by the antagonistic action of CK2 and B56-containing PP2As, has an important impact on the stability of Gli transcription factors and Hh signaling. (PMID:21878643)
• PP2A regulatory subunit Balpha controls endothelial contractility and vessel lumen integrity via regulation of HDAC7. (PMID:23955003)
• results suggest that PKCalpha can modify PP2A activity by phosphorylation of B56alpha at Ser(41). This interplay between PKCalpha and PP2A represents a new mechanism to regulate important cellular functions like cellular Ca(2+) homeostasis. (PMID:24225947)
• structure of the PP2A B56-BubR1 complex provides important insights into how the B56 subunit directs the recruitment of PP2A to specific targets. (PMID:27350047)
• Results report that BubR1 and RepoMan bind directly to PP2A-B56 using an LSPIxE short linear motif (SLiM), where phosphorylation of the Ser residue enhances binding. RepoMan and BubR1 bind B56 using both hydrophobic and electrostatic interactions. (PMID:27998540)
• cyclin E is specifically dephosphorylated at S384 by the PP2A-B56 phosphatase, thereby uncoupling cyclin E degradation from cyclin E-CDK2 activity (PMID:28137908)
• A mitotic phosphorylation site on Cdc20, known to be a substrate of PP2A(B56), modulates APC/C(Cdc20) assembly. (PMID:28404789)
• Overexpression of miR-218 led to inhibition of PPP2R5A expression, whereas knockdown of miR-218 increased PPP2R5A levels. Introduction of PPP2R5A abrogated miR218-mediated cell survival and drug resistance. (PMID:28849187)
• Studies indicate protein phosphatase 2, regulatory subunit B’, alpha isoform protein (PPP2R5A) plays an important role in many cellular activities. (PMID:29175459)
• PP1 and PP2A Use Opposite Phospho-dependencies to Control Distinct Processes at the Kinetochore. (PMID:31433993)
• HIV-1 Vif Triggers Cell Cycle Arrest by Degrading Cellular PPP2R5 Phospho-regulators. (PMID:31665623)
• Selective PP2A Enhancement through Biased Heterotrimer Stabilization. (PMID:32315618)
• Functional and Structural Insights into a Vif/PPP2R5 Complex Elucidated Using Patient HIV-1 Isolates and Computational Modeling. (PMID:32847850)
• A complex of BRCA2 and PP2A-B56 is required for DNA repair by homologous recombination. (PMID:34593815)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppp2r5a	ENSDARG00000027017
mus_musculus	Ppp2r5a	ENSMUSG00000026626
rattus_norvegicus	Ppp2r5a	ENSRNOG00000000068
drosophila_melanogaster	wdb	FBGN0027492
caenorhabditis_elegans		WBGENE00007554
caenorhabditis_elegans		WBGENE00012348

Paralogs (4): PPP2R5B (ENSG00000068971), PPP2R5C (ENSG00000078304), PPP2R5D (ENSG00000112640), PPP2R5E (ENSG00000154001)

Protein

Protein identifiers

Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform — Q15172 (reviewed: Q15172)

Alternative names: PP2A B subunit isoform B’-alpha, PP2A B subunit isoform B56-alpha, PP2A B subunit isoform PR61-alpha, PP2A B subunit isoform R5-alpha

All UniProt accessions (1): Q15172

UniProt curated annotations — full annotation on UniProt →

Function. The B regulatory subunit might modulate substrate selectivity and catalytic activity, and might also direct the localization of the catalytic enzyme to a particular subcellular compartment.

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 or 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. Interacts with SGO1.

Subcellular location. Cytoplasm. Nucleus. Chromosome. Centromere.

Tissue specificity. Widely expressed with the highest expression in heart and skeletal muscle.

Post-translational modifications. Phosphorylated on serine residues.

Similarity. Belongs to the phosphatase 2A regulatory subunit B56 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15172-1	1	yes
Q15172-2	2

RefSeq proteins (2): NP_001186685, NP_006234* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002554	PP2A_B56	Family
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily

Pfam: PF01603

UniProt features (16 total): sequence conflict 5, modified residue 4, compositionally biased region 3, initiator methionine 1, chain 1, splice variant 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8SZK	ELECTRON MICROSCOPY	3.58
6NTS	ELECTRON MICROSCOPY	3.63

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15172-F1	89.18	0.79

Functional residue map

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

Post-translational modifications (4): 2, 41, 42, 49

Function

Pathways and Gene Ontology

Reactome pathways

59 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-195253	Degradation of beta-catenin by the destruction complex
R-HSA-196299	Beta-catenin phosphorylation cascade
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-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-68877	Mitotic Prometaphase
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-9833482	PKR-mediated signaling
R-HSA-109582	Hemostasis
R-HSA-1169410	Antimicrobial mechanism of IFN-stimulated genes
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1280218	Adaptive Immune System
R-HSA-141424	Amplification of signal from the kinetochores

MSigDB gene sets: 330 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GGGTGGRR_PAX4_03, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, REACTOME_CO_STIMULATION_BY_CD28, GOCC_MICROTUBULE_ORGANIZING_CENTER, PATIL_LIVER_CANCER, WATANABE_RECTAL_CANCER_RADIOTHERAPY_RESPONSIVE_UP, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_UP, MODULE_239, RAMALHO_STEMNESS_DN, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, GOCC_CENTROSOME, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_6

GO Biological Process (2): signal transduction (GO:0007165), negative regulation of protein localization to plasma membrane (GO:1903077)

GO Molecular Function (5): protein phosphatase regulator activity (GO:0019888), kinase binding (GO:0019900), protein binding (GO:0005515), kinase inhibitor activity (GO:0019210), protein phosphatase activator activity (GO:0072542)

GO Cellular Component (10): protein phosphatase type 2A complex (GO:0000159), chromosome, centromeric region (GO:0000775), nucleus (GO:0005634), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), Z disc (GO:0030018), M band (GO:0031430), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Signaling by CTNNB1 phospho-site mutants	4
Regulation of T cell activation by CD28 family	2
RAF/MAP kinase cascade	2
Amplification of signal from the kinetochores	1
Signaling by WNT	1
Degradation of beta-catenin by the destruction complex	1
Mitotic Anaphase	1
Mitotic Prometaphase	1
Platelet homeostasis	1
TCF dependent signaling in response to WNT	1
Signaling by WNT in cancer	1
Signaling by APC mutants	1
Signaling by AXIN mutants	1
Signaling by AMER1 mutants	1
RHO GTPase Effectors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
phosphoprotein phosphatase activity	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
protein localization to plasma membrane	1
regulation of protein localization to plasma membrane	1
negative regulation of protein localization to cell periphery	1
negative regulation of protein localization to membrane	1
phosphatase regulator activity	1
protein phosphatase binding	1
enzyme binding	1
binding	1
enzyme inhibitor activity	1
kinase activity	1
kinase regulator activity	1
phosphatase activator activity	1
protein phosphatase regulator activity	1
protein serine/threonine phosphatase complex	1
chromosomal region	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
cytoplasm	1
membrane	1
cell periphery	1
I band	1
A band	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1373 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPP2R5A	PPP2R2A	P50409	922
PPP2R5A	PPP2R1A	P30153	908
PPP2R5A	PPP2R2D	Q66LE6	863
PPP2R5A	LPGAT1	Q92604	851
PPP2R5A	PPP2CA	P05323	823
PPP2R5A	A0A1W2PPA2	A0A1W2PPA2	796
PPP2R5A	KCNH1	O95259	781
PPP2R5A	BUB1B	O60566	778
PPP2R5A	ANK2	Q01484	776
PPP2R5A	PPP2R3C	Q969Q6	763
PPP2R5A	PPP2R3A	Q06190	754
PPP2R5A	PPP2R3B	Q9Y5P8	750
PPP2R5A	POPDC1	Q8NE79	740
PPP2R5A	LAMB3	Q13751	664
PPP2R5A	PPP2R5E	Q16537	662

IntAct

122 interactions, top by confidence:

A	B	Type	Score
PPP2CA	PPP2R5A	psi-mi:“MI:0915”(physical association)	0.900
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
PPP2R1A	STRN	psi-mi:“MI:2364”(proximity)	0.880
PPP2R5A	PPP2R1A	psi-mi:“MI:0914”(association)	0.870
PPP2R1A	PPP2R5A	psi-mi:“MI:0915”(physical association)	0.870
PPP2CA	STRN	psi-mi:“MI:0914”(association)	0.840
PPP2CB	STRN	psi-mi:“MI:0914”(association)	0.790
PRR14	PPP2R1A	psi-mi:“MI:0914”(association)	0.790
MOS	PPP2R5A	psi-mi:“MI:0915”(physical association)	0.740
PPP2CB	CEP43	psi-mi:“MI:0914”(association)	0.730
PPP2R5A	SGO1	psi-mi:“MI:0915”(physical association)	0.730
SGO1	PPP2R5A	psi-mi:“MI:0403”(colocalization)	0.730
PPP2R5A	PPP2R1B	psi-mi:“MI:0915”(physical association)	0.670
PPP2R5A	DZIP1	psi-mi:“MI:0915”(physical association)	0.670
PPP2R5A	C1orf21	psi-mi:“MI:0915”(physical association)	0.670
PPP2R1A	PPFIA3	psi-mi:“MI:0914”(association)	0.670
PPP2R5A	PPP2R1B	psi-mi:“MI:0914”(association)	0.670
CHEK2	PPP2R5A	psi-mi:“MI:0915”(physical association)	0.660
PPP2R5A	CHEK2	psi-mi:“MI:0407”(direct interaction)	0.660
AXIN1	MYC	psi-mi:“MI:0914”(association)	0.620
MYC	AXIN1	psi-mi:“MI:0914”(association)	0.620
PPP2R5A	SGO2	psi-mi:“MI:0915”(physical association)	0.610
PPP2R5A	USHBP1	psi-mi:“MI:0915”(physical association)	0.560
PPP2R5A	AXIN2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (154): PPP2R5A (Affinity Capture-Western), DAPK1 (Affinity Capture-Western), PPP2CA (Affinity Capture-Western), PPP2R1A (Affinity Capture-Western), PPP2R2D (Affinity Capture-Western), PPP2R5A (Affinity Capture-Western), DAPK1 (Biochemical Activity), PPP2R5A (Affinity Capture-MS), PPP2R5A (Affinity Capture-MS), PPP2R5A (Affinity Capture-MS), PPP2R5A (Affinity Capture-MS), PPP2R5A (Co-fractionation), PPP2R5A (Co-fractionation), PPP2R5D (Co-fractionation), PPP2R5A (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5P556, A6H7I5, B0DOB5, D3ZGS3, F1M386, F1MSG6, F1PBJ0, G5EGS5, H2KZZ6, O95466, P21575, P23678, P27619, P39052, P39053, P39054, P39055, P48608, P50570, P78344, P79398, Q01968, Q05193, Q08877, Q08DF4, Q15057, Q15172, Q24564, Q2KI89, Q5R629, Q5R7J9, Q5ZK62, Q62448, Q6IVG4, Q6NXC0, Q6ZQK5, Q7SIG6, Q7XPJ0, Q80U19, Q86T65

Diamond homologs: A4FV68, O04375, O04376, O18178, P38903, P78759, Q10428, Q13362, Q14738, Q15172, Q15173, Q16537, Q28647, Q28651, Q28653, Q28654, Q54VB6, Q60996, Q61151, Q6I621, Q6PD03, Q6PD28, Q80W83, Q8LF36, Q8RW96, Q93YV6, Q9LU89, Q9LVE2, Q9SV41, Q9ZQY6

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
EIF2AK2	up-regulates	PPP2R5A	phosphorylation
ANK2	“up-regulates quantity”	PPP2R5A	relocalization
PPP2R5A	up-regulates	TGFBR1	binding
PRKCA	“down-regulates activity”	PPP2R5A	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 85 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 GSK3beta mutants	6	83.0×	2e-09
CTNNB1 S33 mutants aren’t phosphorylated	6	83.0×	2e-09
CTNNB1 S37 mutants aren’t phosphorylated	6	83.0×	2e-09
CTNNB1 S45 mutants aren’t phosphorylated	6	83.0×	2e-09
CTNNB1 T41 mutants aren’t phosphorylated	6	83.0×	2e-09
Beta-catenin phosphorylation cascade	6	73.3×	5e-09
ERK/MAPK targets	6	73.3×	5e-09
Platelet sensitization by LDL	5	61.1×	3e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2652 predictions. Top by Δscore:

Variant	Effect	Δscore
1:212329129:TTATA:T	acceptor_loss	1.0000
1:212329130:TATA:T	acceptor_loss	1.0000
1:212329132:TAGAT:T	acceptor_loss	1.0000
1:212329133:A:AG	acceptor_gain	1.0000
1:212329133:A:T	acceptor_loss	1.0000
1:212329134:G:GA	acceptor_gain	1.0000
1:212329134:GAT:G	acceptor_gain	1.0000
1:212329265:GGT:G	donor_gain	1.0000
1:212329266:GTTGA:G	donor_gain	1.0000
1:212329267:T:G	donor_gain	1.0000
1:212329271:G:GG	donor_gain	1.0000
1:212333494:CA:C	acceptor_loss	1.0000
1:212333495:A:AG	acceptor_gain	1.0000
1:212333495:AG:A	acceptor_loss	1.0000
1:212333496:G:GT	acceptor_gain	1.0000
1:212333496:GA:G	acceptor_gain	1.0000
1:212333496:GAT:G	acceptor_gain	1.0000
1:212333496:GATC:G	acceptor_gain	1.0000
1:212333496:GATCA:G	acceptor_gain	1.0000
1:212333597:AGG:A	donor_loss	1.0000
1:212333598:GGTAT:G	donor_loss	1.0000
1:212333599:G:GG	donor_gain	1.0000
1:212333599:GTATG:G	donor_loss	1.0000
1:212342186:AGTT:A	acceptor_gain	1.0000
1:212342187:GTTG:G	acceptor_gain	1.0000
1:212345934:G:GA	donor_loss	1.0000
1:212345934:G:GG	donor_gain	1.0000
1:212345935:T:A	donor_loss	1.0000
1:212347342:TTCA:T	acceptor_loss	1.0000
1:212347343:TCA:T	acceptor_loss	1.0000

AlphaMissense

3238 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:212329235:A:C	K94N	1.000
1:212329235:A:T	K94N	1.000
1:212329244:A:C	K97N	1.000
1:212329244:A:T	K97N	1.000
1:212329255:T:C	L101P	1.000
1:212329264:T:C	L104P	1.000
1:212333584:T:A	W156R	1.000
1:212333584:T:C	W156R	1.000
1:212333586:G:C	W156C	1.000
1:212333586:G:T	W156C	1.000
1:212345804:T:C	L192P	1.000
1:212345827:G:C	D200H	1.000
1:212345834:G:T	R202I	1.000
1:212345835:A:C	R202S	1.000
1:212345835:A:T	R202S	1.000
1:212345839:C:A	R204S	1.000
1:212345840:G:C	R204P	1.000
1:212345849:T:C	L207P	1.000
1:212345851:A:G	K208E	1.000
1:212345853:G:C	K208N	1.000
1:212345853:G:T	K208N	1.000
1:212345861:T:C	L211P	1.000
1:212345863:C:A	H212N	1.000
1:212345863:C:G	H212D	1.000
1:212345864:A:G	H212R	1.000
1:212345865:C:A	H212Q	1.000
1:212345865:C:G	H212Q	1.000
1:212345867:G:C	R213P	1.000
1:212345872:T:C	Y215H	1.000
1:212345875:G:A	G216R	1.000

dbSNP variants (sampled 300 via entrez): RS1000014943 (1:212341226 C>T), RS1000032992 (1:212296234 A>C,G), RS1000049739 (1:212290203 T>G), RS1000108083 (1:212346557 T>C), RS1000201381 (1:212314842 A>G), RS1000237813 (1:212315621 G>A), RS1000263329 (1:212361082 CTTT>C), RS1000272128 (1:212354185 AAAAT>A,AAAATAAAT), RS1000362774 (1:212294013 A>G), RS1000375033 (1:212332187 T>C), RS1000476868 (1:212347777 C>T), RS1000553295 (1:212313230 C>T), RS1000561361 (1:212326723 G>A), RS1000573603 (1:212317382 A>G), RS1000605706 (1:212359686 A>G)

Disease associations

OMIM: gene MIM:601643 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002928_11	Nickel levels	9.000000e-06
GCST010242_443	HDL cholesterol levels	3.000000e-11
GCST010727_1	Deep white matter hyperintensities	6.000000e-06
GCST90020025_1242	Waist-to-hip ratio adjusted for BMI	3.000000e-08
GCST90020025_1243	Waist-to-hip ratio adjusted for BMI	4.000000e-09
GCST90020027_1930	Waist-hip index	1.000000e-08
GCST90020027_1931	Waist-hip index	8.000000e-10
GCST90020029_1017	Waist circumference adjusted for body mass index	5.000000e-09
GCST90020029_1018	Waist circumference adjusted for body mass index	3.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0005665	white matter hyperintensity measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4763 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
10.15	IC50	0.07	nM	OKADAIC ACID
10.00	IC50	0.1	nM	MICROCYSTIN-LR
9.89	IC50	0.13	nM	CALYCULIN A

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	7
sodium arsenite	increases expression	2
Benzo(a)pyrene	affects methylation	2
Tretinoin	increases expression	2
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
hydroquinone	affects localization, affects reaction, decreases phosphorylation, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	affects reaction, decreases phosphorylation, increases expression, affects binding, increases reaction (+1 more)	1
Ethanol	increases expression, affects localization, affects reaction, decreases phosphorylation	1
Atrazine	increases expression	1
Calcitriol	increases expression	1
Carbamazepine	affects expression	1
Chelating Agents	affects binding, increases expression	1
Copper	affects binding, increases expression	1
Diclofenac	affects expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL764181	Binding	Binding affinity against Purine Nucleoside Phosphatase	SMall Molecule Growth 2001 (SMoG2001): an improved knowledge-based scoring function for protein-ligand interactions. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7Y7	Ubigene A-549 PPP2R5A KO	Cancer cell line	Male
CVCL_TG05	HAP1 PPP2R5A (-) 1	Cancer cell line	Male
CVCL_TG06	HAP1 PPP2R5A (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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