PPP1R3G

Summary

PPP1R3G (protein phosphatase 1 regulatory subunit 3G, HGNC:14945) is a protein-coding gene on chromosome 6p25.1, encoding Protein phosphatase 1 regulatory subunit 3G (B7ZBB8). Glycogen-targeting subunit for protein phosphatase 1 (PP1).

Predicted to enable glycogen binding activity and protein phosphatase 1 binding activity. Predicted to be involved in regulation of glycogen biosynthetic process. Predicted to act upstream of or within glucose homeostasis; positive regulation of glycogen (starch) synthase activity; and positive regulation of glycogen biosynthetic process. Predicted to be located in cytoplasm. Predicted to be part of protein phosphatase type 1 complex.

Source: NCBI Gene 648791 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_001145115

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14945
Approved symbol	PPP1R3G
Name	protein phosphatase 1 regulatory subunit 3G
Location	6p25.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000219607
Ensembl biotype	protein_coding
OMIM	619541
Entrez	648791

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000405617

RefSeq mRNA: 1 — MANE Select: NM_001145115 NM_001145115

CCDS: CCDS47366

Canonical transcript exons

ENST00000405617 — 1 exons

Exon	Start	End
ENSE00001552642	5085341	5089487

Expression profiles

Bgee: expression breadth ubiquitous, 123 present calls, max score 79.87.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0764 / max 9.8166, expressed in 18 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65586	0.0764	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	79.87	gold quality
heart left ventricle	UBERON:0002084	76.06	gold quality
right atrium auricular region	UBERON:0006631	75.10	gold quality
heart	UBERON:0000948	73.99	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.88	gold quality
right adrenal gland cortex	UBERON:0035827	72.16	gold quality
lower esophagus mucosa	UBERON:0035834	71.78	gold quality
right adrenal gland	UBERON:0001233	71.06	gold quality
popliteal artery	UBERON:0002250	70.75	gold quality
tibial artery	UBERON:0007610	70.72	gold quality
left adrenal gland	UBERON:0001234	70.11	gold quality
left adrenal gland cortex	UBERON:0035825	69.95	gold quality
nucleus accumbens	UBERON:0001882	69.42	gold quality
stromal cell of endometrium	CL:0002255	68.96	gold quality
putamen	UBERON:0001874	68.36	gold quality
adrenal gland	UBERON:0002369	67.97	gold quality
ascending aorta	UBERON:0001496	67.85	gold quality
thoracic aorta	UBERON:0001515	67.65	gold quality
right coronary artery	UBERON:0001625	67.56	gold quality
descending thoracic aorta	UBERON:0002345	67.18	gold quality
temporal lobe	UBERON:0001871	66.97	gold quality
amygdala	UBERON:0001876	66.97	gold quality
lower esophagus	UBERON:0013473	66.60	gold quality
lower esophagus muscularis layer	UBERON:0035833	66.53	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	66.50	gold quality
caudate nucleus	UBERON:0001873	66.38	gold quality
subcutaneous adipose tissue	UBERON:0002190	66.31	gold quality
endometrium	UBERON:0001295	66.06	gold quality
urinary bladder	UBERON:0001255	65.92	gold quality
endocervix	UBERON:0000458	65.89	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.74

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SMAD3, TGFB1

miRNA regulators (miRDB)

20 targeting PPP1R3G, 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-520G-5P	99.99	66.76	658
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-1245B-5P	98.88	66.55	576
HSA-MIR-3142	98.88	66.09	529
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-6819-5P	97.96	66.59	1071
HSA-MIR-3921	97.81	67.45	1431
HSA-MIR-6737-5P	97.75	66.54	1044
HSA-MIR-6812-5P	97.56	65.39	1059
HSA-MIR-342-5P	97.25	64.10	817
HSA-MIR-4653-5P	97.22	67.72	1429
HSA-MIR-4288	97.11	67.23	1636
HSA-MIR-4264	96.35	64.76	1480
HSA-MIR-6747-5P	96.17	64.99	743

Literature-anchored findings (GeneRIF, showing 2)

• Protein phosphatase 1 regulatory subunit 3G (PPP1R3G) correlates with poor prognosis and immune infiltration in lung adenocarcinoma. (PMID:34592886)
• RIPK1 dephosphorylation and kinase activation by PPP1R3G/PP1gamma promote apoptosis and necroptosis. (PMID:34862394)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	PPP1R3G	ENSDARG00000104576
mus_musculus	Ppp1r3g	ENSMUSG00000050423
rattus_norvegicus	Ppp1r3g	ENSRNOG00000088982
drosophila_melanogaster	Gbs-70E	FBGN0036428
caenorhabditis_elegans		WBGENE00019211

Paralogs (6): PPP1R3F (ENSG00000049769), PPP1R3C (ENSG00000119938), PPP1R3D (ENSG00000132825), PPP1R3A (ENSG00000154415), PPP1R3B (ENSG00000173281), PPP1R3E (ENSG00000235194)

Protein

Protein identifiers

Protein phosphatase 1 regulatory subunit 3G — B7ZBB8 (reviewed: B7ZBB8)

All UniProt accessions (1): B7ZBB8

UniProt curated annotations — full annotation on UniProt →

Function. Glycogen-targeting subunit for protein phosphatase 1 (PP1). Involved in the regulation of hepatic glycogenesis in a manner coupled to the fasting-feeding cycle and distinct from other glycogen-targeting subunits.

RefSeq proteins (1): NP_001138587* (*=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 (8 total): region of interest 2, compositionally biased region 2, chain 1, domain 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-B7ZBB8-F1	69.09	0.27

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 (1): 86

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 65 (showing top): GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS, SHEPARD_BMYB_MORPHOLINO_DN, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, chr6p25, 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_CARBOHYDRATE_HOMEOSTASIS, GOBP_REGULATION_OF_POLYSACCHARIDE_METABOLIC_PROCESS, GOBP_REGULATION_OF_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY

GO Biological Process (4): glycogen biosynthetic process (GO:0005978), regulation of glycogen biosynthetic process (GO:0005979), glucose homeostasis (GO:0042593), positive regulation of glycogen biosynthetic process (GO:0045725)

GO Molecular Function (4): protein phosphatase 1 binding (GO:0008157), glycogen binding (GO:2001069), protein binding (GO:0005515), protein phosphatase binding (GO:0019903)

GO Cellular Component (2): protein phosphatase type 1 complex (GO:0000164), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glycogen biosynthetic process	2
glycogen metabolic process	1
glucan biosynthetic process	1
regulation of glucan biosynthetic process	1
regulation of glycogen metabolic process	1
carbohydrate homeostasis	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
polysaccharide binding	1
binding	1
phosphatase binding	1
cytoplasm	1
protein serine/threonine phosphatase complex	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

452 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPP1R3G	DPY19L3	Q6ZPD9	517
PPP1R3G	PRPSAP1	Q14558	495
PPP1R3G	PPP1R3A	Q16821	466
PPP1R3G	CHST10	O43529	462
PPP1R3G	NLRP13	Q86W25	462
PPP1R3G	ZC3H8	Q8N5P1	459
PPP1R3G	MTMR1	Q13613	447
PPP1R3G	PRDM13	Q9H4Q3	443
PPP1R3G	SOHLH1	Q5JUK2	435
PPP1R3G	CMTM4	Q8IZR5	433
PPP1R3G	SLC30A3	Q99726	429
PPP1R3G	RAB11FIP5	Q9BXF6	427
PPP1R3G	AP3B1	O00203	418
PPP1R3G	GNAI1	P04898	408
PPP1R3G	IRS4	O14654	406
PPP1R3G	H3BTC1	H3BTC1	406

IntAct

126 interactions, top by confidence:

A	B	Type	Score
PPP1R3G	NOS1	psi-mi:“MI:0407”(direct interaction)	0.440
NHERF4	PPP1R3G	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R3G	HTRA4	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	PPP1R3G	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R3G	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R3G	PALS2	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R3G	LIN7C	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R3G	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R3G	PICK1	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R3G	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R3G	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R3G	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R3G	LIN7A	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R3G	TJP1	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R3G	LIN7B	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R3G	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R3G	APBA2	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R3G	HTRA3	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R3G	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R3G	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R3G	PDZRN3	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R3G	FRMPD1	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R3G	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R3G	MPP7	psi-mi:“MI:0407”(direct interaction)	0.440
GRIP1	PPP1R3G	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R3G	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R3G	MPP2	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R3G	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (1): PPP1R3G (Two-hybrid)

ESM2 similar proteins: A2VDX9, A6NCS6, A6NEL2, A6NJG2, A6NK89, A6NLJ0, A8MVW0, B2RU40, B7ZBB8, C9JH25, D3YXK1, D4A9R4, M0QZC1, O15049, P03971, P03972, P0C1Z6, P0CG25, P0DPE3, P27106, P49000, P79295, Q17QH7, Q1HCM0, Q1LZD1, Q29RM6, Q2M3G4, Q2M3V2, Q3SX20, Q4G0M1, Q6NY19, Q6PCT2, Q6PJ61, Q6ZS72, Q6ZW31, Q717R9, Q86SH2, Q8BLS7, Q8N4B5, Q8N9M5

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, P28006, Q06216, Q16821

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 79 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
Ras activation upon Ca2+ influx through NMDA receptor	5	53.9×	1e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	51.3×	1e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	51.3×	1e-06
Assembly and cell surface presentation of NMDA receptors	10	47.9×	5e-13
Dopamine Neurotransmitter Release Cycle	5	46.8×	2e-06
Long-term potentiation	5	44.9×	2e-06
Neurexins and neuroligins	11	40.9×	3e-13
Protein-protein interactions at synapses	7	35.1×	6e-08

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	84.1×	1e-16
protein localization to synapse	6	60.5×	8e-08
receptor clustering	7	57.5×	6e-09
regulation of postsynaptic membrane neurotransmitter receptor levels	6	39.1×	7e-07
protein-containing complex assembly	9	13.5×	2e-06
cell-cell adhesion	10	13.4×	4e-07
protein localization to plasma membrane	5	7.2×	1e-02
chemical synaptic transmission	7	7.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

12 predictions. Top by Δscore:

Variant	Effect	Δscore
6:5085430:T:G	donor_gain	0.5500
6:5086569:A:T	donor_gain	0.4300
6:5085696:G:GT	donor_gain	0.4000
6:5085672:G:GT	donor_gain	0.3700
6:5085645:C:G	donor_gain	0.2500
6:5085507:C:G	donor_gain	0.2400
6:5085578:G:GA	donor_gain	0.2300
6:5085422:GGA:G	donor_gain	0.2100
6:5085423:GAG:G	donor_gain	0.2100
6:5085506:GC:G	donor_gain	0.2000
6:5086956:TAGCC:T	acceptor_gain	0.2000
6:5088112:C:CA	acceptor_gain	0.2000

AlphaMissense

2271 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:5085885:T:C	F134L	1.000
6:5085887:C:A	F134L	1.000
6:5085887:C:G	F134L	1.000
6:5085886:T:C	F134S	0.999
6:5085886:T:G	F134C	0.999
6:5086254:T:A	W257R	0.998
6:5086254:T:C	W257R	0.998
6:5086256:G:C	W257C	0.998
6:5086256:G:T	W257C	0.998
6:5086465:T:C	F327S	0.997
6:5086502:G:C	W339C	0.997
6:5086502:G:T	W339C	0.997
6:5086504:A:T	D340V	0.997
6:5085885:T:A	F134I	0.996
6:5085901:G:A	G139E	0.996
6:5085927:T:C	F148L	0.996
6:5085929:C:A	F148L	0.996
6:5085929:C:G	F148L	0.996
6:5085885:T:G	F134V	0.995
6:5085892:A:T	D136V	0.995
6:5086239:T:G	Y252D	0.995
6:5086389:T:C	F302L	0.995
6:5086390:T:C	F302S	0.995
6:5086391:C:A	F302L	0.995
6:5086391:C:G	F302L	0.995
6:5085891:G:C	D136H	0.994
6:5085893:C:A	D136E	0.994
6:5085893:C:G	D136E	0.994
6:5086503:G:C	D340H	0.994
6:5085892:A:C	D136A	0.993

dbSNP variants (sampled 300 via entrez): RS1000040795 (6:5087750 G>A), RS1000113569 (6:5086536 T>C), RS1000229711 (6:5084895 C>G,T), RS1000296485 (6:5085112 G>A), RS1000644652 (6:5089329 G>A,T), RS1000911405 (6:5088954 G>A), RS1001381654 (6:5085791 G>A), RS1001592064 (6:5086169 C>T), RS1001912507 (6:5087392 G>A), RS1002598241 (6:5085044 C>T), RS1003691341 (6:5087070 C>A,T), RS1003693407 (6:5084916 C>G), RS1003844556 (6:5084795 G>A,T), RS1004128839 (6:5086725 C>A,T), RS1004362616 (6:5084327 G>A)

Disease associations

OMIM: gene MIM:619541 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
fluorene-9-bisphenol	increases expression	1
bisphenol A	decreases methylation	1
ferrous chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Caffeine	increases phosphorylation	1
Camptothecin	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Oxygen	increases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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