PPP1R3D

Summary

PPP1R3D (protein phosphatase 1 regulatory subunit 3D, HGNC:9294) is a protein-coding gene on chromosome 20q13.33, encoding Protein phosphatase 1 regulatory subunit 3D (O95685). Seems to act as a glycogen-targeting subunit for PP1.

Phosphorylation of serine and threonine residues in proteins is a crucial step in the regulation of many cellular functions ranging from hormonal regulation to cell division and even short-term memory. The level of phosphorylation is controlled by the opposing actions of protein kinases and protein phosphatases. Protein phosphatase 1 (PP1) is 1 of 4 major serine/threonine-specific protein phosphatases which have been identified in eukaryotic cells. PP1 associates with various regulatory subunits that dictate its subcellular localization and modulate its substrate specificity. Several subunits that target PP1 to glycogen have been identified. This gene encodes a glycogen-targeting subunit of PP1.

Source: NCBI Gene 5509 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 5 total
• MANE Select transcript: NM_006242

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9294
Approved symbol	PPP1R3D
Name	protein phosphatase 1 regulatory subunit 3D
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000132825
Ensembl biotype	protein_coding
OMIM	603326
Entrez	5509

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000370996

RefSeq mRNA: 1 — MANE Select: NM_006242 NM_006242

CCDS: CCDS13483

Canonical transcript exons

ENST00000370996 — 1 exons

Exon	Start	End
ENSE00001454080	59936663	59940305

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 95.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.0507 / max 51.0592, expressed in 1579 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188224	2.8248	1188
188223	2.2260	1086

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	95.54	gold quality
oocyte	CL:0000023	93.70	gold quality
blood	UBERON:0000178	84.79	gold quality
bronchial epithelial cell	CL:0002328	83.27	gold quality
trabecular bone tissue	UBERON:0002483	82.62	gold quality
bone marrow	UBERON:0002371	82.12	gold quality
oral cavity	UBERON:0000167	82.08	gold quality
jejunal mucosa	UBERON:0000399	80.89	gold quality
hindlimb stylopod muscle	UBERON:0004252	80.65	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	79.81	silver quality
monocyte	CL:0000576	79.72	gold quality
leukocyte	CL:0000738	79.66	gold quality
mononuclear cell	CL:0000842	79.43	gold quality
heart right ventricle	UBERON:0002080	79.41	gold quality
biceps brachii	UBERON:0001507	79.28	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	79.20	gold quality
palpebral conjunctiva	UBERON:0001812	77.73	gold quality
epithelium of bronchus	UBERON:0002031	77.26	gold quality
epithelium of esophagus	UBERON:0001976	77.05	gold quality
bronchus	UBERON:0002185	77.00	gold quality
esophagus squamous epithelium	UBERON:0006920	76.94	gold quality
upper leg skin	UBERON:0004262	76.91	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.90	gold quality
muscle of leg	UBERON:0001383	76.89	gold quality
gastrocnemius	UBERON:0001388	76.78	gold quality
granulocyte	CL:0000094	76.25	gold quality
jejunum	UBERON:0002115	76.14	gold quality
heart left ventricle	UBERON:0002084	76.09	gold quality
cardiac ventricle	UBERON:0002082	76.07	gold quality
bone marrow cell	CL:0002092	76.05	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-36552	yes	183.17
E-ANND-3	no	2.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

118 targeting PPP1R3D, 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-7110-3P	100.00	73.18	2486
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-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-383-3P	99.85	65.84	1359

Literature-anchored findings (GeneRIF, showing 4)

• In this work we present evidence that PPP1R3D (R6), one of the PP1 glycogenic targeting subunits, interacts physically with laforin, a glucan phosphatase involved in Lafora disease, a fatal type of progressive myoclonus epilepsy. (PMID:23624058)
• These results define binding to 14-3-3 proteins as an additional pathway in the control of the glycogenic properties of PPP1R3D (R6). (PMID:26114292)
• These data are in accordance with R6 binding directly to AMPKbeta2 when both proteins detach from the diminishing glycogen particle, which is simultaneous with increased AMPKbeta2 Thr-148 autophosphorylation. (PMID:26831516)
• Host miR-4301 promotes rotavirus replication via PPP1R3D in Caco-2 cells. (PMID:34260071)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppp1r3db	ENSDARG00000076248
danio_rerio	ppp1r3da	ENSDARG00000077513
mus_musculus	Ppp1r3d	ENSMUSG00000049999
rattus_norvegicus	Ppp1r3d	ENSRNOG00000053869
drosophila_melanogaster	Gbs-70E	FBGN0036428
caenorhabditis_elegans		WBGENE00019211

Paralogs (6): PPP1R3F (ENSG00000049769), PPP1R3C (ENSG00000119938), PPP1R3A (ENSG00000154415), PPP1R3B (ENSG00000173281), PPP1R3G (ENSG00000219607), PPP1R3E (ENSG00000235194)

Protein

Protein identifiers

Protein phosphatase 1 regulatory subunit 3D — O95685 (reviewed: O95685)

Alternative names: Protein phosphatase 1 regulatory subunit 6, Protein phosphatase 1-binding subunit R6

All UniProt accessions (1): O95685

UniProt curated annotations — full annotation on UniProt →

Function. Seems to act as a glycogen-targeting subunit for PP1. PP1 is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis.

Subunit / interactions. Interacts with PPP1CC catalytic subunit of PP1, and associates with glycogen. Interacts with EPM2A; in the presence of NHLC1/malin the interaction leads to PPP1R3D ubiquitination and autophagic degradation.

Tissue specificity. Expressed in all tissues tested. High expression in skeletal muscle and heart.

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_006233* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005036	CBM21_dom	Domain
IPR017434	Pase-1_reg-su_3B/C/D_met	Family
IPR038175	CBM21_dom_sf	Homologous_superfamily
IPR050782	PP1_regulatory_subunit_3	Family

Pfam: PF03370

UniProt features (13 total): modified residue 5, compositionally biased region 3, region of interest 2, chain 1, domain 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95685-F1	71.03	0.37

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 (5): 28, 74, 133, 23, 25

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 162 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, MOOTHA_GLYCOGEN_METABOLISM, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, MORF_MSH3, MORF_BRCA1, MORF_ATRX, MEF2_02, MORF_ESR1, CAGCTG_AP4_Q5, TTGCWCAAY_CEBPB_02, CEBPB_01, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GTGCCTT_MIR506, GOBP_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS, TGIF_01

GO Biological Process (3): glycogen metabolic process (GO:0005977), regulation of glycogen biosynthetic process (GO:0005979), regulation of glycogen catabolic process (GO:0005981)

GO Molecular Function (6): protein serine/threonine phosphatase activity (GO:0004722), protein phosphatase 1 binding (GO:0008157), glycogen binding (GO:2001069), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), enzyme binding (GO:0019899)

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

Protein interactions and networks

STRING

468 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPP1R3D	NHLRC1	Q6VVB1	506
PPP1R3D	EPM2A	O95278	506
PPP1R3D	PRKAB1	Q9Y478	494
PPP1R3D	PPP1R3A	Q16821	454
PPP1R3D	FAM217B	Q9NTX9	448
PPP1R3D	GYS2	P54840	438
PPP1R3D	PYGL	P06737	424
PPP1R3D	PYGB	P11216	419
PPP1R3D	SYCP2	Q9BX26	406
PPP1R3D	GYG1	P46976	403
PPP1R3D	PYGM	P11217	401
PPP1R3D	AGL	P35573	401
PPP1R3D	PPP1CB	P37140	398
PPP1R3D	GYS1	P13807	395
PPP1R3D	PPP1R27	Q86WC6	391

IntAct

42 interactions, top by confidence:

A	B	Type	Score
STBD1	GABARAP	psi-mi:“MI:0914”(association)	0.760
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PPP1CC	CCDC85C	psi-mi:“MI:2364”(proximity)	0.740
PPP1R3D	PPP1CA	psi-mi:“MI:0915”(physical association)	0.740
PPP1R3D	YWHAZ	psi-mi:“MI:0915”(physical association)	0.680
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
STBD1	MID1	psi-mi:“MI:0914”(association)	0.530
PPP1R3C	STBD1	psi-mi:“MI:0914”(association)	0.530
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
PYGB	STBD1	psi-mi:“MI:0914”(association)	0.530
NAA10	OFD1	psi-mi:“MI:0914”(association)	0.480
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
PPP1R3D	FYN	psi-mi:“MI:0915”(physical association)	0.400
PPP1R3D	SFN	psi-mi:“MI:0915”(physical association)	0.400
Prkab1	PPP1R3D	psi-mi:“MI:0915”(physical association)	0.400
Ppp1r3b		psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (39): PPP1R3D (Affinity Capture-MS), PPP1R3D (Affinity Capture-MS), PPP1R3D (Affinity Capture-MS), PPP1R3D (Affinity Capture-MS), PPP1R3D (Affinity Capture-MS), PPP1R3D (Affinity Capture-MS), PPP1R3D (Affinity Capture-MS), PPP1R3D (Affinity Capture-MS), PPP1R3D (Affinity Capture-MS), PPP1R3D (Affinity Capture-MS), PPP1R3D (Affinity Capture-MS), PPP1R3D (Affinity Capture-MS), PPP1R3D (Affinity Capture-MS), PPP1R3D (Proximity Label-MS), PPP1R3D (Two-hybrid)

ESM2 similar proteins: D3YZZ2, E7ERA6, F2Z333, H3BV60, O00292, O18796, O43508, O43612, O54907, O55232, O55241, O60391, O75462, O75610, O77668, O95633, O95685, P13224, P41155, P56717, Q02833, Q06643, Q14626, Q1LZB9, Q2TBM7, Q4V892, Q5RF19, Q5TM22, Q6IA17, Q6UXT9, Q6ZMM2, Q862Z7, Q86VR8, Q86YD3, Q8BQB4, Q8NBV8, Q8TAD2, Q99640, Q99MF4, Q9BZR6

Diamond homologs: A6QNP3, O95685, P40036, P40187, Q00756, Q0VCR4, Q16821, Q28E28, Q5BL87, Q5U2R5, Q6DDQ5, Q6GL23, Q6GQ68, Q6IN01, Q6P950, Q7TMB3, Q803M0, Q86XI6, Q8C767, Q99MR9, Q9UQK1, Q9VVY3, T1SFR8, B7ZBB8, P0C7L8, Q8BRJ4, Q9CW07, Q9H7J1, Q6ZSY5, Q9JIG4, P28006, Q06216, P07683

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 31 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	231.7×	3e-14
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	204.4×	5e-14
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	204.4×	5e-14
Activation of BH3-only proteins	7	151.1×	5e-13
RHO GTPases activate PKNs	7	96.5×	1e-11
Intrinsic Pathway for Apoptosis	7	89.1×	2e-11
FOXO-mediated transcription	5	73.0×	6e-08
Apoptosis	8	58.4×	1e-11

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	84.5×	2e-08
intracellular protein localization	7	28.2×	5e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	5
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

228 predictions. Top by Δscore:

Variant	Effect	Δscore
20:59937988:A:AG	acceptor_gain	0.9400
20:59937989:G:GG	acceptor_gain	0.9400
20:59940130:TTA:T	donor_gain	0.8400
20:59937989:GT:G	acceptor_gain	0.7600
20:59940230:G:C	acceptor_gain	0.7300
20:59940114:C:A	donor_gain	0.7200
20:59940141:G:GG	donor_gain	0.7200
20:59940227:TTGG:T	acceptor_gain	0.7200
20:59939513:TCC:T	donor_gain	0.6900
20:59939963:G:T	donor_gain	0.6900
20:59936696:GCTC:G	donor_gain	0.6800
20:59939953:A:G	donor_gain	0.6800
20:59939962:GGA:G	donor_gain	0.6700
20:59937988:AGT:A	acceptor_gain	0.6600
20:59937989:GTG:G	acceptor_gain	0.6600
20:59940226:CTTGG:C	acceptor_gain	0.6600
20:59940067:GCCC:G	donor_gain	0.6400
20:59940113:T:TA	donor_gain	0.6400
20:59939959:C:T	donor_gain	0.6200
20:59937978:T:G	acceptor_loss	0.6000
20:59937984:CTCCA:C	acceptor_loss	0.6000
20:59937985:TCCAG:T	acceptor_loss	0.6000
20:59937986:CCAGT:C	acceptor_loss	0.6000
20:59937987:CA:C	acceptor_loss	0.6000
20:59937977:A:AG	acceptor_loss	0.5900
20:59937973:A:AG	acceptor_loss	0.5800
20:59937974:A:AG	acceptor_loss	0.5800
20:59939949:G:GT	donor_gain	0.5800
20:59940151:G:T	donor_gain	0.5800
20:59940228:TGG:T	acceptor_gain	0.5600

AlphaMissense

1911 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:59939617:G:C	F105L	0.999
20:59939617:G:T	F105L	0.999
20:59939619:A:G	F105L	0.999
20:59939038:G:C	F298L	0.998
20:59939038:G:T	F298L	0.998
20:59939040:A:G	F298L	0.998
20:59939618:A:C	F105C	0.998
20:59939618:A:G	F105S	0.998
20:59939575:G:C	F119L	0.997
20:59939575:G:T	F119L	0.997
20:59939577:A:G	F119L	0.997
20:59939129:T:A	D268V	0.996
20:59939157:A:C	Y259D	0.996
20:59939168:A:G	F255S	0.996
20:59939224:G:C	F236L	0.996
20:59939224:G:T	F236L	0.996
20:59939226:A:G	F236L	0.996
20:59939310:A:C	Y208D	0.996
20:59939576:A:G	F119S	0.996
20:59939326:C:A	K202N	0.995
20:59939326:C:G	K202N	0.995
20:59939360:C:T	G191D	0.995
20:59939131:C:A	W267C	0.994
20:59939131:C:G	W267C	0.994
20:59939619:A:T	F105I	0.994
20:59939045:A:G	I296T	0.993
20:59939130:C:G	D268H	0.993
20:59939225:A:G	F236S	0.993
20:59939039:A:G	F298S	0.992
20:59939102:A:G	L277P	0.992

dbSNP variants (sampled 300 via entrez): RS1000034704 (20:59936647 A>G), RS1000085208 (20:59936479 G>A), RS1000471616 (20:59938574 T>G), RS1000892571 (20:59941985 C>G), RS1000945651 (20:59941401 A>G), RS1001709804 (20:59938281 T>C), RS1002147210 (20:59939791 C>T), RS1002653259 (20:59936568 T>C), RS1002775512 (20:59941723 A>C), RS1002830092 (20:59941909 C>T), RS1003405058 (20:59940041 T>C), RS1003769479 (20:59940481 G>A), RS1004128050 (20:59939155 G>A,C), RS1004278586 (20:59937632 GCTT>G), RS1004632023 (20:59937342 A>G)

Disease associations

OMIM: gene MIM:603326 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005851_8	Delirium	5.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	4
trichostatin A	increases expression, affects cotreatment	3
entinostat	increases expression, affects cotreatment	2
Panobinostat	increases expression, affects cotreatment	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Quercetin	decreases expression, decreases phosphorylation	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
monomethylarsonous acid	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
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Arsenic Trioxide	decreases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Cyclosporine	decreases expression	1
Asbestos, Crocidolite	increases expression	1
Lactic Acid	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TF82	HAP1 PPP1R3D (-) 1	Cancer cell line	Male
CVCL_TF83	HAP1 PPP1R3D (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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