PPP1R3E

Summary

PPP1R3E (protein phosphatase 1 regulatory subunit 3E, HGNC:14943) is a protein-coding gene on chromosome 14q11.2, encoding Protein phosphatase 1 regulatory subunit 3E (Q9H7J1). Acts as a glycogen-targeting subunit for PP1.

Predicted to enable [phosphorylase] phosphatase activity; glycogen binding activity; and protein phosphatase 1 binding activity. Predicted to be involved in positive regulation of glycogen biosynthetic process. Predicted to be located in glycogen granule. Predicted to be part of protein phosphatase type 1 complex.

Source: NCBI Gene 90673 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• MANE Select transcript: NM_001276318

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14943
Approved symbol	PPP1R3E
Name	protein phosphatase 1 regulatory subunit 3E
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ00089
Ensembl gene	ENSG00000235194
Ensembl biotype	protein_coding
OMIM	619540
Entrez	90673

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000452015, ENST00000558058, ENST00000559314, ENST00000559942, ENST00000560073, ENST00000560913, ENST00000561178, ENST00000561426, ENST00000561437, ENST00000879497

RefSeq mRNA: 1 — MANE Select: NM_001276318 NM_001276318

CCDS: CCDS61403

Canonical transcript exons

ENST00000452015 — 5 exons

Exon	Start	End
ENSE00000889206	23301298	23301858
ENSE00000889207	23302160	23302859
ENSE00000930088	23299401	23299541
ENSE00000930089	23300758	23300864
ENSE00001625062	23295652	23298917

Expression profiles

Bgee: expression breadth ubiquitous, 238 present calls, max score 96.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.9129 / max 100.4753, expressed in 1423 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142341	3.0445	839
142344	1.5856	573
142343	1.2828	824

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	96.97	gold quality
cerebellar hemisphere	UBERON:0002245	96.83	gold quality
cerebellar cortex	UBERON:0002129	96.74	gold quality
cerebellum	UBERON:0002037	95.92	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.04	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.53	gold quality
right frontal lobe	UBERON:0002810	94.50	gold quality
pituitary gland	UBERON:0000007	93.76	gold quality
right uterine tube	UBERON:0001302	93.62	gold quality
spinal cord	UBERON:0002240	93.43	gold quality
hypothalamus	UBERON:0001898	93.42	gold quality
adenohypophysis	UBERON:0002196	93.21	gold quality
anterior cingulate cortex	UBERON:0009835	93.11	gold quality
putamen	UBERON:0001874	92.99	gold quality
nucleus accumbens	UBERON:0001882	92.82	gold quality
substantia nigra	UBERON:0002038	92.82	gold quality
caudate nucleus	UBERON:0001873	92.80	gold quality
right testis	UBERON:0004534	92.53	gold quality
left testis	UBERON:0004533	92.48	gold quality
right lobe of thyroid gland	UBERON:0001119	92.34	gold quality
amygdala	UBERON:0001876	92.09	gold quality
left lobe of thyroid gland	UBERON:0001120	91.65	gold quality
midbrain	UBERON:0001891	91.60	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.26	gold quality
thyroid gland	UBERON:0002046	91.19	gold quality
brain	UBERON:0000955	90.98	gold quality
spleen	UBERON:0002106	90.70	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.54	gold quality
forebrain	UBERON:0001890	90.52	gold quality
left ovary	UBERON:0002119	90.38	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-7303	no	107.29
E-ANND-3	no	3.16

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

104 targeting PPP1R3E, 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-6748-5P	100.00	65.81	1057
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ppp1r3e	ENSMUSG00000072494

Paralogs (6): PPP1R3F (ENSG00000049769), PPP1R3C (ENSG00000119938), PPP1R3D (ENSG00000132825), PPP1R3A (ENSG00000154415), PPP1R3B (ENSG00000173281), PPP1R3G (ENSG00000219607)

Protein

Protein identifiers

Protein phosphatase 1 regulatory subunit 3E — Q9H7J1 (reviewed: Q9H7J1)

All UniProt accessions (6): Q9H7J1, H0YLE3, H0YM26, H0YMB9, H0YMS8, H0YNQ2

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a glycogen-targeting subunit for PP1. PP1 is involved in glycogen metabolism and contributes to the activation of glycogen synthase leading to an increase in glycogen synthesis.

Tissue specificity. Expressed in skeletal muscle and heart with barely detectable levels in liver.

Domain organisation. The CBM21 domain is known to be involved in the localization to glycogen and is characteristic of some regulatory subunit of phosphatase complexes.

RefSeq proteins (1): NP_001263247* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005036	CBM21_dom	Domain
IPR038175	CBM21_dom_sf	Homologous_superfamily
IPR050782	PP1_regulatory_subunit_3	Family

Pfam: PF03370

UniProt features (10 total): region of interest 3, modified residue 3, chain 1, domain 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H7J1-F1	72.88	0.39

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 (3): 16, 33, 66

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 87 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_POSITIVE_REGULATION_OF_GLYCOGEN_METABOLIC_PROCESS, GOBP_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_REGULATION_OF_GLUCOSE_METABOLIC_PROCESS, GOBP_REGULATION_OF_GLYCOGEN_METABOLIC_PROCESS, GOBP_GLUCOSE_METABOLIC_PROCESS, GOBP_REGULATION_OF_CARBOHYDRATE_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_POLYSACCHARIDE_METABOLIC_PROCESS, GOBP_REGULATION_OF_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_MONOSACCHARIDE_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_GLUCOSE_METABOLIC_PROCESS

GO Biological Process (3): glycogen metabolic process (GO:0005977), regulation of glycogen biosynthetic process (GO:0005979), positive regulation of glycogen biosynthetic process (GO:0045725)

GO Molecular Function (5): protein phosphatase 1 binding (GO:0008157), [phosphorylase] phosphatase activity (GO:0050196), glycogen binding (GO:2001069), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515)

GO Cellular Component (2): protein phosphatase type 1 complex (GO:0000164), glycogen granule (GO:0042587)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glycogen biosynthetic process	2
cytoplasm	2
energy reserve metabolic process	1
glucan metabolic process	1
regulation of glucan biosynthetic process	1
regulation of glycogen metabolic process	1
regulation of glycogen biosynthetic process	1
positive regulation of macromolecule biosynthetic process	1
positive regulation of glycogen metabolic process	1
protein phosphatase binding	1
phosphoprotein phosphatase activity	1
polysaccharide binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
protein serine/threonine phosphatase complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

442 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPP1R3E	PPP1CC	P36873	557
PPP1R3E	PPP1CB	P37140	550
PPP1R3E	DCXR	Q7Z4W1	492
PPP1R3E	PPP1R3A	Q16821	471
PPP1R3E	PPP1R3F	Q6ZSY5	433
PPP1R3E	GYS2	P54840	389
PPP1R3E	GPATCH2L	Q9NWQ4	370
PPP1R3E	PPP1R3B	Q86XI6	358
PPP1R3E	TAS2R42	Q7RTR8	350
PPP1R3E	PYGB	P11216	342
PPP1R3E	SLC35E3	Q7Z769	339
PPP1R3E	PDK2	Q15119	339
PPP1R3E	RPS6KA2	Q15349	335
PPP1R3E	PYGM	P11217	330
PPP1R3E	ABTB3	A6QL63	329

IntAct

16 interactions, top by confidence:

A	B	Type	Score
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
PPP1CA	PPP1R3E	psi-mi:“MI:0915”(physical association)	0.550
YWHAB	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAE	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAZ	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
	PPP1R3E	psi-mi:“MI:0915”(physical association)	0.370
SFN	SHTN1	psi-mi:“MI:0914”(association)	0.350
YWHAH	SHTN1	psi-mi:“MI:0914”(association)	0.350
YWHAQ	SHTN1	psi-mi:“MI:0914”(association)	0.350
YWHAQ	MCRIP1	psi-mi:“MI:0914”(association)	0.350
CREB3L2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (12): PPP1R3E (Affinity Capture-MS), PPP1R3E (Affinity Capture-MS), PPP1R3E (Affinity Capture-RNA), PPP1R3E (Affinity Capture-MS), PPP1R3E (Affinity Capture-MS), PPP1R3E (Affinity Capture-MS), PPP1R3E (Affinity Capture-MS), PPP1R3E (Affinity Capture-MS), PPP1R3E (Affinity Capture-MS), PPP1R3E (Affinity Capture-MS), PPP1R3E (Protein-RNA), PPP1R3E (Two-hybrid)

ESM2 similar proteins: A0A0U1RQ45, A5PKL7, A6NCL7, A6NCS6, A6NJG2, A6NL88, A6NLJ0, B7Z1M9, B7ZBB8, B8ZZ34, C9J069, D3ZZN9, J3QNX5, P0C7L8, P0CG09, P0CG25, P98077, Q0PHV7, Q14934, Q2KJ18, Q2M3V2, Q2MJR0, Q3B7L1, Q3LUD4, Q5HZI2, Q64355, Q69YZ2, Q6NY19, Q6P6N5, Q6PAJ3, Q6PB97, Q6PCT2, Q6PJ61, Q6ZW31, Q75VX8, Q7Z736, Q86UD0, Q8BLS7, Q8BRJ4, Q8IYJ3

Diamond homologs: B7ZBB8, O95685, P0C7L8, Q6GL23, Q8BRJ4, Q9CW07, Q9H7J1, A6QNP3, P40036, P40187, Q0VCR4, Q28E28, Q5BL87, Q5U2R5, Q6GQ68, Q6IN01, Q6P950, Q7TMB3, Q803M0, Q86XI6, Q8C767, Q9UQK1, Q9VVY3, T1SFR8, Q00756, Q6DDQ5, Q6ZSY5, Q99MR9, Q9JIG4, Q16821

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 14 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
Activation of BAD and translocation to mitochondria	7	409.9×	2e-16
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	361.7×	2e-16
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	361.7×	2e-16
Activation of BH3-only proteins	7	267.4×	2e-15
RHO GTPases activate PKNs	7	170.8×	7e-14
Intrinsic Pathway for Apoptosis	7	157.7×	1e-13
FOXO-mediated transcription	5	129.2×	1e-09
SARS-CoV-1-host interactions	7	94.6×	4e-12

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	130.8×	2e-08
intracellular protein localization	7	52.3×	3e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

829 predictions. Top by Δscore:

Variant	Effect	Δscore
14:23301323:C:CA	donor_gain	0.9900
14:23302154:GCCTA:G	donor_loss	0.9900
14:23302155:CCTAC:C	donor_loss	0.9900
14:23302156:CTACC:C	donor_loss	0.9900
14:23302157:TAC:T	donor_loss	0.9900
14:23302158:A:AT	donor_loss	0.9900
14:23302159:C:CG	donor_loss	0.9900
14:23299537:CCCTT:C	acceptor_gain	0.9800
14:23299538:CCTTC:C	acceptor_gain	0.9800
14:23299539:CTT:C	acceptor_gain	0.9800
14:23299572:A:C	acceptor_gain	0.9800
14:23301409:T:A	donor_gain	0.9800
14:23301358:A:AC	donor_gain	0.9700
14:23301358:ACT:A	donor_gain	0.9700
14:23301359:C:CC	donor_gain	0.9700
14:23301359:CTC:C	donor_gain	0.9700
14:23301327:TGG:T	donor_gain	0.9600
14:23299542:C:CC	acceptor_gain	0.9500
14:23301324:C:A	donor_gain	0.9500
14:23301336:C:CA	donor_gain	0.9500
14:23301344:T:TA	donor_gain	0.9500
14:23301354:T:A	donor_gain	0.9500
14:23301424:AGGCG:A	donor_gain	0.9500
14:23301511:G:C	donor_gain	0.9500
14:23301540:CGTG:C	donor_gain	0.9500
14:23301364:C:CA	donor_gain	0.9400
14:23301857:TCCTG:T	acceptor_gain	0.9400
14:23301538:CTCG:C	donor_gain	0.9300
14:23301539:TCGT:T	donor_gain	0.9300
14:23301542:TG:T	donor_gain	0.9300

AlphaMissense

1769 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:23301613:G:C	F221L	0.999
14:23301613:G:T	F221L	0.999
14:23301615:A:G	F221L	0.999
14:23302307:G:C	F90L	0.999
14:23302307:G:T	F90L	0.999
14:23302308:A:C	F90C	0.999
14:23302309:A:G	F90L	0.999
14:23301530:T:A	D249V	0.998
14:23301532:C:A	W248C	0.998
14:23301532:C:G	W248C	0.998
14:23301569:A:G	F236S	0.998
14:23301608:A:G	F223S	0.998
14:23301614:A:G	F221S	0.998
14:23302308:A:G	F90S	0.998
14:23301607:G:C	F223L	0.997
14:23301607:G:T	F223L	0.997
14:23301609:A:G	F223L	0.997
14:23301682:C:A	W198C	0.997
14:23301682:C:G	W198C	0.997
14:23301715:C:A	K187N	0.997
14:23301715:C:G	K187N	0.997
14:23301531:C:G	D249H	0.996
14:23301534:A:G	W248R	0.996
14:23301534:A:T	W248R	0.996
14:23301442:A:C	F278L	0.995
14:23301442:A:T	F278L	0.995
14:23301444:A:G	F278L	0.995
14:23301558:A:C	Y240D	0.995
14:23301614:A:C	F221C	0.995
14:23301716:T:A	K187M	0.995

dbSNP variants (sampled 300 via entrez): RS1000334659 (14:23303372 A>G), RS1000897641 (14:23297287 C>T), RS1000898912 (14:23298856 T>C), RS1001014738 (14:23297043 G>A), RS1001074988 (14:23304715 AATAT>A,AAT), RS1001564313 (14:23300650 T>A), RS1001680133 (14:23300353 T>C,G), RS1001707563 (14:23298145 G>A), RS1001866831 (14:23304779 C>T), RS1001901235 (14:23298868 A>G), RS1002015658 (14:23298471 T>G), RS1002438278 (14:23299645 C>T), RS1002545893 (14:23301775 G>A,C), RS1002652546 (14:23304564 G>A), RS1002701120 (14:23301600 G>A)

Disease associations

OMIM: gene MIM:619540 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST007096_169	Pulse pressure	2.000000e-12
GCST007097_35	Pulse pressure	2.000000e-08
GCST007097_36	Pulse pressure	5.000000e-08
GCST007099_33	Systolic blood pressure	3.000000e-07
GCST90011900_110	Serum alkaline phosphatase levels	5.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases methylation	7
entinostat	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
propionaldehyde	decreases expression	1
bisphenol A	increases expression	1
trichostatin A	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Leflunomide	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Aldehydes	decreases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	affects cotreatment, increases expression	1
Demecolcine	decreases expression	1
Doxorubicin	decreases expression	1
Ozone	affects expression, increases abundance	1
Thimerosal	decreases expression	1
Tunicamycin	increases expression	1
Vincristine	decreases expression	1

Clinical trials (associated diseases)

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