PPP1R17

Summary

PPP1R17 (protein phosphatase 1 regulatory subunit 17, HGNC:16973) is a protein-coding gene on chromosome 7p14.3, encoding Protein phosphatase 1 regulatory subunit 17 (O96001). Inhibits phosphatase activities of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) complexes.

The protein encoded by this gene is found primarily in cerebellar Purkinje cells, where it functions as a protein phosphatase inhibitor. The encoded protein is a substrate for cGMP-dependent protein kinase. An allele of this gene was discovered that increases susceptibility to hypercholesterolemia. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10842 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• Phenotypes (HPO): 7
• MANE Select transcript: NM_006658

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16973
Approved symbol	PPP1R17
Name	protein phosphatase 1 regulatory subunit 17
Location	7p14.3
Locus type	gene with protein product
Status	Approved
Aliases	GSBS
Ensembl gene	ENSG00000106341
Ensembl biotype	protein_coding
OMIM	604088
Entrez	10842

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000342032, ENST00000409146, ENST00000498609, ENST00000927588, ENST00000927589

RefSeq mRNA: 2 — MANE Select: NM_006658 NM_001145123, NM_006658

CCDS: CCDS47570, CCDS5436

Canonical transcript exons

ENST00000342032 — 5 exons

Exon	Start	End
ENSE00000675073	31695469	31695621
ENSE00000832250	31707204	31708455
ENSE00001366428	31692406	31692523
ENSE00001577301	31687215	31687306
ENSE00003689443	31696965	31697117

Expression profiles

Bgee: expression breadth broad, 100 present calls, max score 99.02.

FANTOM5 (CAGE): breadth broad, TPM avg 0.7521 / max 108.8187, expressed in 200 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
78046	0.7224	194
78045	0.0297	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.02	gold quality
lateral nuclear group of thalamus	UBERON:0002736	91.67	gold quality
embryo	UBERON:0000922	89.67	gold quality
cerebellar vermis	UBERON:0004720	89.24	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.74	gold quality
ventricular zone	UBERON:0003053	81.22	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.05	gold quality
cerebellum	UBERON:0002037	78.31	gold quality
cerebellar cortex	UBERON:0002129	77.30	gold quality
cerebellar hemisphere	UBERON:0002245	77.02	gold quality
hypothalamus	UBERON:0001898	75.86	gold quality
cortical plate	UBERON:0005343	73.19	gold quality
diaphragm	UBERON:0001103	70.30	gold quality
pons	UBERON:0000988	69.94	silver quality
adenohypophysis	UBERON:0002196	67.76	gold quality
dorsal plus ventral thalamus	UBERON:0001897	66.83	gold quality
adult organism	UBERON:0007023	66.00	gold quality
olfactory bulb	UBERON:0002264	65.83	gold quality
type B pancreatic cell	CL:0000169	64.75	gold quality
granulocyte	CL:0000094	64.20	gold quality
hair follicle	UBERON:0002073	64.07	gold quality
leukocyte	CL:0000738	63.43	gold quality
monocyte	CL:0000576	63.19	gold quality
cingulate cortex	UBERON:0003027	63.17	gold quality
anterior cingulate cortex	UBERON:0009835	63.15	gold quality
mononuclear cell	CL:0000842	63.06	gold quality
pituitary gland	UBERON:0000007	62.56	gold quality
prefrontal cortex	UBERON:0000451	62.40	gold quality
epithelium of nasopharynx	UBERON:0001951	61.85	gold quality
right testis	UBERON:0004534	61.22	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-56	yes	1003.17
E-ANND-3	no	3.60

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting PPP1R17, 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-5193	100.00	67.26	1744
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-6794-3P	98.76	66.99	894
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-4712-3P	98.52	65.39	822
HSA-MIR-640	98.44	66.93	644
HSA-MIR-758-3P	98.42	68.60	1122
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-224-5P	98.33	70.12	1256
HSA-MIR-6509-3P	98.32	67.33	1343

Literature-anchored findings (GeneRIF, showing 2)

• Single nucleotide polymorphism in the GSBS gene is associated with hypercholesterolemia (PMID:12955585)
• G-substrate plays a role in the NO-sGC-cGMP-PKG pathway, cerebellum-dependent long-term memory, & neuroprotection of the ventral tegmentum and retina. Review. (PMID:22340725)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ppp1r17	ENSMUSG00000002930
rattus_norvegicus	Ppp1r17	ENSRNOG00000012235

Protein

Protein identifiers

Protein phosphatase 1 regulatory subunit 17 — O96001 (reviewed: O96001)

Alternative names: G-substrate

All UniProt accessions (2): O96001, A0A090N8N7

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits phosphatase activities of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) complexes.

Tissue specificity. Highly expressed in cerebellum.

Post-translational modifications. Substrate for cGMP-dependent protein kinase. Phosphorylated by PRKG1 isoform alpha. Phosphorylation of Thr-68 and Thr-119 is required for its phosphatase activity. Substrate for cGMP-dependent protein kinase.

Isoforms (2)

UniProt ID	Names	Canonical?
O96001-1	1	yes
O96001-2	2

RefSeq proteins (2): NP_001138595, NP_006649* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR033242	PPP1R17	Family

UniProt features (8 total): modified residue 2, sequence variant 2, chain 1, region of interest 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O96001-F1	66.49	0.03

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 (2): 68, 119

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 134 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_REGULATION_OF_PHOSPHATASE_ACTIVITY, GCANCTGNY_MYOD_Q6, CAGCTG_AP4_Q5, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, GOBP_REGULATION_OF_HYDROLASE_ACTIVITY, JAZAG_TGFB1_SIGNALING_VIA_SMAD4_UP, GOBP_REGULATION_OF_DEPHOSPHORYLATION, AACTTT_UNKNOWN, GOBP_DEPHOSPHORYLATION, RFX1_02, MODULE_207, GOBP_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, RYTGCNWTGGNR_UNKNOWN, GOMF_PHOSPHATASE_INHIBITOR_ACTIVITY

GO Biological Process (3): central nervous system development (GO:0007417), regulation of phosphatase activity (GO:0010921), intracellular signal transduction (GO:0035556)

GO Molecular Function (3): protein serine/threonine phosphatase inhibitor activity (GO:0004865), protein phosphatase inhibitor activity (GO:0004864), phosphatase inhibitor activity (GO:0019212)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphatase activity	2
nervous system development	1
system development	1
regulation of dephosphorylation	1
regulation of hydrolase activity	1
intracellular anatomical structure	1
signal transduction	1
protein serine/threonine phosphatase activity	1
protein phosphatase inhibitor activity	1
phosphoprotein phosphatase activity	1
phosphatase inhibitor activity	1
protein phosphatase regulator activity	1
enzyme inhibitor activity	1
phosphatase regulator activity	1

Protein interactions and networks

STRING

670 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPP1R17	PCSK9	Q8NBP7	650
PPP1R17	EPHX2	P34913	587
PPP1R17	APOA2	P02652	572
PPP1R17	GHR	P10912	510
PPP1R17	GRXCR2	A6NFK2	505
PPP1R17	CLRN2	A0PK11	504
PPP1R17	ITIH4	Q14624	492
PPP1R17	EFR3A	Q14156	475
PPP1R17	APEX1	P27695	473
PPP1R17	STRC	Q7RTU9	453
PPP1R17	CHRNA10	Q9GZZ6	443
PPP1R17	ANKUB1	A6NFN9	429
PPP1R17	APOB	P04114	427
PPP1R17	MTTP	P55157	423
PPP1R17	ZNF843	Q8N446	419

IntAct

0 interactions, top by confidence:

BioGRID (3): PPP1R17 (Biochemical Activity), PPP1R17 (Affinity Capture-MS), APP (Reconstituted Complex)

ESM2 similar proteins: A0A0P0XCU3, A0A1P8BH59, A1YFC1, A1YGK6, A2T7F2, A6NJ88, B7SY83, F1QU13, F4HXQ7, F4ICX9, F4INW9, F4KCE9, O04251, O81472, O96001, P0CV01, P0CV36, P0CV42, P0CV43, P0CV45, P0CV46, P0CV55, P0CV57, P0CV58, P10322, P16531, P48786, Q0DVU4, Q10P83, Q2EI21, Q3URU2, Q5JY77, Q5QNA6, Q5R7U0, Q5SRN2, Q5U4C1, Q5XPK0, Q6K5K2, Q7T2B3, Q8N3K9

Diamond homologs: O96001, Q9Z2E4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PRKG1	up-regulates	PPP1R17	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

1 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

667 predictions. Top by Δscore:

Variant	Effect	Δscore
7:31692404:A:AG	acceptor_gain	1.0000
7:31692405:G:GA	acceptor_gain	1.0000
7:31692405:GT:G	acceptor_gain	1.0000
7:31692405:GTGCT:G	acceptor_gain	1.0000
7:31692400:CCTTA:C	acceptor_loss	0.9900
7:31692401:CTTA:C	acceptor_loss	0.9900
7:31692403:TAGTG:T	acceptor_loss	0.9900
7:31692404:A:C	acceptor_loss	0.9900
7:31692404:AGT:A	acceptor_gain	0.9900
7:31692405:GTG:G	acceptor_gain	0.9900
7:31692519:CTTAG:C	donor_loss	0.9900
7:31692520:TTAG:T	donor_loss	0.9900
7:31692521:TAG:T	donor_loss	0.9900
7:31692522:AG:A	donor_loss	0.9900
7:31692523:GGT:G	donor_loss	0.9900
7:31692524:G:A	donor_loss	0.9900
7:31692525:T:A	donor_loss	0.9900
7:31707198:TTGCA:T	acceptor_loss	0.9900
7:31707199:TGCAG:T	acceptor_loss	0.9900
7:31707200:GCAG:G	acceptor_loss	0.9900
7:31707201:CAGGT:C	acceptor_loss	0.9900
7:31707202:A:AT	acceptor_loss	0.9900
7:31707203:GGT:G	acceptor_gain	0.9900
7:31707260:G:GT	donor_gain	0.9900
7:31707265:TGAC:T	donor_gain	0.9900
7:31707202:A:AG	acceptor_gain	0.9800
7:31707203:G:GG	acceptor_gain	0.9800
7:31707203:GGTGT:G	acceptor_gain	0.9800
7:31707261:A:T	donor_gain	0.9800
7:31707272:A:G	donor_gain	0.9800

AlphaMissense

1032 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:31695581:G:C	R65S	0.984
7:31695581:G:T	R65S	0.984
7:31697077:A:C	R116S	0.980
7:31697077:A:T	R116S	0.980
7:31695580:G:C	R65T	0.960
7:31695584:A:C	K66N	0.955
7:31695584:A:T	K66N	0.955
7:31697076:G:C	R116T	0.952
7:31697080:A:C	K117N	0.950
7:31697080:A:T	K117N	0.950
7:31697074:G:C	R115S	0.941
7:31697074:G:T	R115S	0.941
7:31695585:G:C	D67H	0.940
7:31695583:A:T	K66I	0.928
7:31695578:G:C	R64S	0.925
7:31695578:G:T	R64S	0.925
7:31695580:G:T	R65M	0.918
7:31697079:A:T	K117I	0.912
7:31695586:A:C	D67A	0.895
7:31695579:A:G	R65G	0.894
7:31695583:A:C	K66T	0.890
7:31697079:A:C	K117T	0.882
7:31695587:T:A	D67E	0.878
7:31695587:T:G	D67E	0.878
7:31697075:A:G	R116G	0.878
7:31695586:A:T	D67V	0.877
7:31697076:G:T	R116I	0.875
7:31695582:A:G	K66E	0.872
7:31697081:G:C	D118H	0.872
7:31697078:A:G	K117E	0.841

dbSNP variants (sampled 300 via entrez): RS1000064606 (7:31687830 G>A,C), RS1000096450 (7:31695559 C>A,T), RS1000253925 (7:31704128 G>A), RS1000283888 (7:31692626 C>A,T), RS1000362218 (7:31692808 G>A,C), RS1000392702 (7:31698065 T>G), RS1000426510 (7:31698624 T>C), RS1000539069 (7:31705736 A>C), RS1000567775 (7:31691838 A>G), RS1000666797 (7:31697193 G>C), RS1000694169 (7:31694370 T>G), RS1000975181 (7:31694636 G>A), RS1001114171 (7:31693943 A>C), RS1001206113 (7:31702813 T>C), RS1001236923 (7:31688375 C>T)

Disease associations

OMIM: gene MIM:604088 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0001084	Corneal arcus
HP:0001114	Xanthelasma
HP:0001677	Coronary artery atherosclerosis
HP:0003141	Increased LDL cholesterol concentration
HP:0010874	Tendon xanthomatosis

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

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, affects cotreatment	5
mercuric bromide	decreases expression, affects cotreatment	2
trichostatin A	increases expression	1
deguelin	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	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
pyrimidifen	decreases expression	1
thifluzamide	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
gardiquimod	decreases reaction, increases expression	1
Antimycin A	decreases expression	1
Benzene	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Fluorouracil	increases expression	1
Rotenone	decreases expression	1
Tretinoin	increases expression	1
Permethrin	increases expression	1
Protein Kinase Inhibitors	decreases reaction, increases expression	1

Clinical trials (associated diseases)

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