PPP6R1

gene
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Also known as SAP190

Summary

PPP6R1 (protein phosphatase 6 regulatory subunit 1, HGNC:29195) is a protein-coding gene on chromosome 19q13.42, encoding Serine/threonine-protein phosphatase 6 regulatory subunit 1 (Q9UPN7). Regulatory subunit of protein phosphatase 6 (PP6).

Protein phosphatase regulatory subunits, such as SAPS1, modulate the activity of protein phosphatase catalytic subunits by restricting substrate specificity, recruiting substrates, and determining the intracellular localization of the holoenzyme. SAPS1 is a regulatory subunit for the protein phosphatase-6 catalytic subunit (PPP6C; MIM 612725) (Stefansson and Brautigan, 2006 [PubMed 16769727]).

Source: NCBI Gene 22870 — RefSeq curated summary.

At a glance

  • GWAS associations: 4
  • Clinical variants (ClinVar): 208 total
  • Druggable target: yes
  • MANE Select transcript: NM_014931

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:29195
Approved symbolPPP6R1
Nameprotein phosphatase 6 regulatory subunit 1
Location19q13.42
Locus typegene with protein product
StatusApproved
AliasesSAP190
Ensembl geneENSG00000105063
Ensembl biotypeprotein_coding
OMIM610875
Entrez22870

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 35 protein_coding, 5 retained_intron

ENST00000412770, ENST00000586690, ENST00000587283, ENST00000587457, ENST00000589343, ENST00000591323, ENST00000591602, ENST00000592242, ENST00000875996, ENST00000875997, ENST00000875998, ENST00000875999, ENST00000876000, ENST00000876001, ENST00000876002, ENST00000876003, ENST00000876004, ENST00000876005, ENST00000938391, ENST00000938392, ENST00000938393, ENST00000938394, ENST00000938395, ENST00000938396, ENST00000938397, ENST00000938398, ENST00000938399, ENST00000938400, ENST00000938401, ENST00000938402, ENST00000961708, ENST00000961709, ENST00000961710, ENST00000961711, ENST00000961712, ENST00000961713, ENST00000961714, ENST00000961715, ENST00000961716, ENST00000961717

RefSeq mRNA: 1 — MANE Select: NM_014931 NM_014931

CCDS: CCDS46186

Canonical transcript exons

ENST00000412770 — 24 exons

ExonStartEnd
ENSE000007280705524512055245185
ENSE000007280735524237655242488
ENSE000008564765523664355236821
ENSE000008564785523940555239502
ENSE000008564795523959455239683
ENSE000008564805523982655239911
ENSE000008564815523999955240114
ENSE000011793595524526555245402
ENSE000012497315523207555232211
ENSE000014327075524687755247109
ENSE000014338045524549255245678
ENSE000017583035525843555259017
ENSE000035521485524216655242279
ENSE000035583445523159855231668
ENSE000035786165523077455230884
ENSE000035800205523061355230684
ENSE000035884165523141055231491
ENSE000035978495522977955230531
ENSE000036337245524147755241639
ENSE000036434645524023655240300
ENSE000036520725523691355236970
ENSE000036538615524094555241079
ENSE000036682055524123955241391
ENSE000036738295523180255231982

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 97.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.7630 / max 773.4901, expressed in 1821 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter IDTPM avgSamples expressed
18276731.25731816
1827633.82691500
1827610.9709196
1827660.6704273
1827650.2999131
1827640.2866128
1827600.2664107
1827590.108136
1827580.054810
1827570.02174

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
left testisUBERON:000453397.36gold quality
right testisUBERON:000453497.27gold quality
granulocyteCL:000009496.95gold quality
lymph nodeUBERON:000002996.77gold quality
bloodUBERON:000017896.45gold quality
testisUBERON:000047395.97gold quality
bone marrowUBERON:000237195.94gold quality
vermiform appendixUBERON:000115495.49gold quality
spleenUBERON:000210695.34gold quality
bone marrow cellCL:000209295.28gold quality
leukocyteCL:000073894.70gold quality
prefrontal cortexUBERON:000045194.67gold quality
monocyteCL:000057694.56gold quality
frontal cortexUBERON:000187094.42gold quality
Ammon’s hornUBERON:000195494.36gold quality
putamenUBERON:000187494.23gold quality
anterior cingulate cortexUBERON:000983594.23gold quality
right frontal lobeUBERON:000281094.18gold quality
right uterine tubeUBERON:000130294.10gold quality
temporal lobeUBERON:000187194.07gold quality
amygdalaUBERON:000187694.05gold quality
superior frontal gyrusUBERON:000266193.95gold quality
cerebral cortexUBERON:000095693.82gold quality
caudate nucleusUBERON:000187393.82gold quality
lower esophagus mucosaUBERON:003583493.59gold quality
nucleus accumbensUBERON:000188293.51gold quality
small intestineUBERON:000210893.18gold quality
small intestine Peyer’s patchUBERON:000345493.13gold quality
dorsolateral prefrontal cortexUBERON:000983493.06gold quality
right adrenal gland cortexUBERON:003582793.05gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes3.43
E-MTAB-7381no646.25
E-CURD-89no126.43

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

56 targeting PPP6R1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-6873-3P100.0071.422626
HSA-MIR-7110-3P100.0073.182486
HSA-MIR-5692B100.0071.322622
HSA-MIR-5692C100.0071.322622
HSA-MIR-1277-5P100.0073.955056
HSA-MIR-5011-5P100.0083.465820
HSA-MIR-19A-3P99.9875.332762
HSA-MIR-19B-3P99.9875.442754
HSA-MIR-185-3P99.9567.011743
HSA-MIR-450B-5P99.9271.483175
HSA-MIR-454-3P99.9174.011925
HSA-MIR-374A-5P99.9071.342923
HSA-MIR-374B-5P99.9069.982734
HSA-MIR-130A-3P99.9073.311861
HSA-MIR-130B-3P99.9073.271850
HSA-MIR-301A-3P99.9073.151839
HSA-MIR-301B-3P99.9073.191836
HSA-MIR-366699.9073.241833
HSA-MIR-429599.9073.111838
HSA-MIR-369-3P99.8570.522264
HSA-MIR-444799.8567.812900
HSA-MIR-6756-5P99.8267.972466
HSA-MIR-6515-3P99.8268.191933
HSA-MIR-7110-5P99.8067.841712
HSA-MIR-6842-5P99.8067.541587
HSA-MIR-6817-3P99.7968.352126
HSA-MIR-148A-3P99.7473.771700
HSA-MIR-148B-3P99.7473.751700
HSA-MIR-152-3P99.7473.751703
HSA-MIR-430699.7270.503630

Literature-anchored findings (GeneRIF, showing 1)

  • PP6 regulatory subunit R1 is bidentate anchor for targeting protein phosphatase-6 to DNA-dependent protein kinase. (PMID:22298787)

Cross-species orthologs

4 orthologs

OrganismSymbolGene ID
mus_musculusPpp6r1ENSMUSG00000052296
rattus_norvegicusPpp6r1ENSRNOG00000018090
drosophila_melanogasterfmtFBGN0035688
caenorhabditis_elegansWBGENE00008166

Paralogs (2): PPP6R2 (ENSG00000100239), PPP6R3 (ENSG00000110075)

Protein

Protein identifiers

Serine/threonine-protein phosphatase 6 regulatory subunit 1Q9UPN7 (reviewed: Q9UPN7)

Alternative names: SAPS domain family member 1

All UniProt accessions (2): Q9UPN7, K7EM28

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of protein phosphatase 6 (PP6). May function as a scaffolding PP6 subunit. Involved in the PP6-mediated dephosphorylation of NFKBIE opposing its degradation in response to TNF.

Subunit / interactions. Protein phosphatase 6 (PP6) holoenzyme is proposed to be a heterotrimeric complex formed of the catalytic subunit, a SAPS domain-containing subunit (PP6R) and an ankyrin repeat-domain containing regulatory subunit (ARS). Interacts with PPP6C and NFKBIE. Interacts with ANKRD28, ANKRD44 and ANKRD52.

Subcellular location. Cytoplasm.

Tissue specificity. Ubiquitous with higher expression in testis.

Similarity. Belongs to the SAPS family.

RefSeq proteins (1): NP_055746* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR007587SAPSFamily
IPR016024ARM-type_foldHomologous_superfamily

Pfam: PF04499

UniProt features (18 total): modified residue 11, compositionally biased region 4, region of interest 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9UPN7-F167.960.43

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 (11): 530, 531, 635, 638, 702, 726, 759, 846, 232, 524, 529

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

IDPathway
R-HSA-204005COPII-mediated vesicle transport

MSigDB gene sets: 139 (showing top): TATTATA_MIR374, REACTOME_MEMBRANE_TRAFFICKING, GOMF_GTPASE_BINDING, TTTGCAC_MIR19A_MIR19B, GOCC_LAMELLIPODIUM, GOMF_PROTEIN_PHOSPHATASE_BINDING, GOCC_CELL_LEADING_EDGE, GOMF_PHOSPHATASE_BINDING, GOMF_ENZYME_REGULATOR_ACTIVITY, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GOMF_PHOSPHATASE_REGULATOR_ACTIVITY, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, PURBEY_TARGETS_OF_CTBP1_NOT_SATB1_UP, GHANDHI_DIRECT_IRRADIATION_UP, REACTOME_ER_TO_GOLGI_ANTEROGRADE_TRANSPORT

GO Biological Process (1): regulation of signal transduction (GO:0009966)

GO Molecular Function (4): protein phosphatase regulator activity (GO:0019888), protein phosphatase binding (GO:0019903), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), cytosol (GO:0005829), lamellipodium (GO:0030027), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

CategoryPathways
ER to Golgi Anterograde Transport1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure2
signal transduction1
regulation of cell communication1
regulation of signaling1
regulation of response to stimulus1
phosphoprotein phosphatase activity1
phosphatase regulator activity1
protein phosphatase binding1
phosphatase binding1
GTPase binding1
binding1
intracellular membrane-bounded organelle1
cytoplasm1
cell leading edge1
plasma membrane bounded cell projection1
intracellular anatomical structure1

Protein interactions and networks

STRING

1268 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
PPP6R1PPP6CO00743992
PPP6R1SF3B1O75533924
PPP6R1ANKRD28O15084853
PPP6R1NFKBIEO00221838
PPP6R1ANKRD44Q8N8A2774
PPP6R1PPP2CAP05323764
PPP6R1ANKRD52Q8NB46683
PPP6R1DPH3Q96FX2683
PPP6R1KTI12Q96EK9637
PPP6R1PPP4CP33172620
PPP6R1ELP6Q0PNE2551
PPP6R1PPP4R2Q9NY27519
PPP6R1PPP4R4Q6NUP7518
PPP6R1PRKDCP78527510
PPP6R1ZNF579Q8NAF0504

IntAct

195 interactions, top by confidence:

ABTypeScore
PPP6CPPP6R1psi-mi:“MI:0915”(physical association)0.920
PPP6R1PPP6Cpsi-mi:“MI:0914”(association)0.920
PIK3CAPIK3R2psi-mi:“MI:0914”(association)0.900
PPP6CANKRD28psi-mi:“MI:0914”(association)0.870
ANKRD28PPP6Cpsi-mi:“MI:0914”(association)0.870
PPP6R1ANKRD44psi-mi:“MI:0914”(association)0.800
ANKRD52PPP6Cpsi-mi:“MI:0914”(association)0.790
ANKRD44PPP6Cpsi-mi:“MI:0914”(association)0.790
ANKRD28PPP6R1psi-mi:“MI:0914”(association)0.750
ANKRD28PPP6R1psi-mi:“MI:0915”(physical association)0.750
PPP6R1ANKRD28psi-mi:“MI:0915”(physical association)0.750
CFTRESYT2psi-mi:“MI:2364”(proximity)0.710
CFTRESYT2psi-mi:“MI:0914”(association)0.710

BioGRID (253): PPP6R1 (Affinity Capture-MS), PPP6R1 (Affinity Capture-MS), PPP6R1 (Affinity Capture-MS), PPP6R1 (Affinity Capture-MS), PPP6R1 (Affinity Capture-MS), PPP6R1 (Affinity Capture-MS), PPP6R1 (Proximity Label-MS), PPP6R1 (Affinity Capture-MS), PPP6R1 (Affinity Capture-MS), PPP6R1 (Affinity Capture-MS), PPP6R1 (Affinity Capture-MS), PPP6R1 (Affinity Capture-MS), PPP6R1 (Affinity Capture-MS), PPP6R1 (Proximity Label-MS), PPP6R1 (Affinity Capture-MS)

ESM2 similar proteins: A0A571BF63, A0A8M9QN10, A1L1K1, A1YER0, A2ARM1, A2AVJ5, A2CI98, A2CJ06, A2D5H2, A7YY97, B5DEB9, C9JE40, O00443, O43147, O43149, O93307, O95475, P59729, Q15475, Q2KHT9, Q32N92, Q4V7K4, Q5E9R0, Q5EB20, Q5PQS0, Q5R6T6, Q5RAY1, Q5RJH6, Q5U464, Q61194, Q62231, Q6AW68, Q6DGF9, Q6MZQ0, Q6TNU3, Q6ZUJ8, Q7TSI1, Q7TSI3, Q7Z3E5, Q80U12

Diamond homologs: O75170, Q5F471, Q5H9R7, Q6NRF1, Q6NRI0, Q7TSI3, Q8R3Q2, Q922D4, Q9UPN7, B5VMH6, C8ZCJ2, P36123, P40856

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 195 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:

PathwayPartnersFoldFDR
Lysosphingolipid and LPA receptors530.4×3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance162
Likely benign7
Benign2

Top pathogenic / likely-pathogenic (0)

SpliceAI

4283 predictions. Top by Δscore:

VariantEffectΔscore
19:55230611:A:ACdonor_gain1.0000
19:55230612:C:CCdonor_gain1.0000
19:55230769:CTCA:Cdonor_loss1.0000
19:55230770:TCAC:Tdonor_loss1.0000
19:55230771:CACCT:Cdonor_loss1.0000
19:55230772:A:ACdonor_gain1.0000
19:55230773:C:Adonor_loss1.0000
19:55230773:C:CCdonor_gain1.0000
19:55230773:CCT:Cdonor_gain1.0000
19:55230880:TTGCA:Tacceptor_gain1.0000
19:55230881:TGCA:Tacceptor_gain1.0000
19:55230883:CA:Cacceptor_gain1.0000
19:55230883:CACTG:Cacceptor_loss1.0000
19:55230885:C:CAacceptor_loss1.0000
19:55230885:C:CCacceptor_gain1.0000
19:55231487:AGGGG:Aacceptor_gain1.0000
19:55231488:GGGG:Gacceptor_gain1.0000
19:55231489:GGG:Gacceptor_gain1.0000
19:55231490:GG:Gacceptor_gain1.0000
19:55231492:C:CCacceptor_gain1.0000
19:55231797:CTCA:Cdonor_loss1.0000
19:55231798:TCAC:Tdonor_loss1.0000
19:55231800:A:Tdonor_loss1.0000
19:55231801:CCT:Cdonor_loss1.0000
19:55236641:A:ACdonor_gain1.0000
19:55236642:C:CCdonor_gain1.0000
19:55236723:C:Adonor_gain1.0000
19:55236818:TGGG:Tacceptor_gain1.0000
19:55236911:A:ACdonor_gain1.0000
19:55236911:ACGTT:Adonor_gain1.0000

AlphaMissense

5798 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
19:55245323:A:GL165P0.999
19:55245326:T:GD164A0.999
19:55245335:G:TA161D0.999
19:55245528:C:AK126N0.999
19:55245528:C:GK126N0.999
19:55245531:G:CS125R0.999
19:55245531:G:TS125R0.999
19:55245533:T:GS125R0.999
19:55245537:G:CF123L0.999
19:55245537:G:TF123L0.999
19:55245539:A:GF123L0.999
19:55245540:G:CS122R0.999
19:55245540:G:TS122R0.999
19:55245542:T:GS122R0.999
19:55245652:A:GL85P0.999
19:55245652:A:TL85Q0.999
19:55245664:G:TA81D0.999
19:55247095:C:AW3C0.999
19:55247095:C:GW3C0.999
19:55247097:A:GW3R0.999
19:55247097:A:TW3R0.999
19:55247098:A:CF2L0.999
19:55247098:A:TF2L0.999
19:55247100:A:GF2L0.999
19:55245181:A:GL186P0.998
19:55245326:T:CD164G0.998
19:55245327:C:GD164H0.998
19:55245530:T:CK126E0.998
19:55245544:G:TA121D0.998
19:55245652:A:CL85R0.998

dbSNP variants (sampled 300 via entrez): RS1000127376 (19:55232946 C>T), RS1000142373 (19:55257063 T>A,C), RS1000146061 (19:55247819 A>G), RS1000312501 (19:55238692 C>T), RS1000342168 (19:55238959 T>C), RS1000460725 (19:55234025 C>T), RS1000467452 (19:55255898 A>G), RS1000499245 (19:55253535 C>T), RS1000646035 (19:55234238 T>C), RS1000668015 (19:55230441 G>A), RS1000730868 (19:55234202 C>T), RS1000817228 (19:55248797 A>C,T), RS1000883294 (19:55253818 G>A), RS1000920777 (19:55242099 G>A), RS1000932862 (19:55249038 G>A)

Disease associations

OMIM: gene MIM:610875 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

StudyTraitp-value
GCST010653_3Thyroid stimulating hormone levels1.000000e-08
GCST011739_12Cutaneous leishmaniasis5.000000e-06
GCST90002390_663Mean corpuscular hemoglobin3.000000e-12
GCST90002392_79Mean corpuscular volume6.000000e-09

EFO canonical traits (1, from GWAS)

EFO IDTrait name
EFO:0004527mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105774 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
8.85Kd1.421nMCHEMBL5653589
8.85ED501.421nMCHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 6 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2149058: Binding affinity to human PPP6R1 incubated for 45 mins by Kinobead based pull down assaykd0.0014uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
sodium arsenitedecreases expression, increases expression2
Air Pollutantsaffects cotreatment, increases abundance, increases oxidation, decreases expression2
aristolochic acid Iincreases expression1
FR900359increases phosphorylation1
dicrotophosincreases expression1
2,4,6-tribromophenoldecreases expression1
alpha-pineneincreases abundance, affects cotreatment, increases oxidation1
bisphenol Adecreases expression1
sodium arsenatedecreases expression1
decabromobiphenyl etherdecreases expression1
beta-lapachonedecreases expression1
cobaltous chlorideincreases expression1
tetrabromobisphenol Adecreases expression1
benzo(e)pyrenedecreases methylation1
cupric chlorideincreases expression1
methacrylaldehydeaffects cotreatment, increases oxidation, increases abundance1
di-n-butylphosphoric acidaffects expression1
CGP 52608affects binding, increases reaction1
2-palmitoylglycerolincreases expression1
ICG 001decreases expression1
2,2’,4,4’-tetrabromodiphenyl etherdecreases expression1
pentabrominated diphenyl ether 100decreases expression1
hexabrominated diphenyl ether 153decreases expression1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic aciddecreases expression1
Temozolomidedecreases expression1
Acroleinaffects cotreatment, increases oxidation, increases abundance1
Estradiolaffects expression1
Leaddecreases expression1
Methapyrilenedecreases methylation1
Nickelincreases expression1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL4012582BindingBinding affinity to PP6R1 protein in human INA-6 cells after 3 hrs by nanoLC-MS/MS methodUgi Reaction-Derived α-Acyl Aminocarboxamides Bind to Phosphatidylinositol 3-Kinase-Related Kinases, Inhibit HSF1-Dependent Heat Shock Response, and Induce Apoptosis in Multiple Myeloma Cells. — J Med Chem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

CellosaurusNameCategorySex
CVCL_B3ENAbcam HEK293T PPP6R1 KOTransformed cell lineFemale
CVCL_TG30HAP1 PPP6R1 (-) 1Cancer cell lineMale
CVCL_TG31HAP1 PPP6R1 (-) 2Cancer cell lineMale

Clinical trials (associated diseases)

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

  • Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): cutaneous leishmaniasis