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PPP6R3 (protein phosphatase 6 regulatory subunit 3)

Written2019-03Luigi Cristiano
Aesthetic and medical biotechnologies research unit, Prestige, Terranuova Bracciolini, Italy.;

Abstract Protein phosphatase 6 regulatory subunit 3 (PPP6R3) is a regulatory subunit of the PP6 holoenzyme complex involved in the turnover of serine and threonine phosphorylation events during mitosis. PPP6R3 shows abundant mRNA splicing variants and numerous functional protein isoforms. PPP6R3 gene is often involved in abnormal chromosomal translocations and it is found as a fusion gene partner in different kind of cancers.

Keywords PPP6R3, protein phosphatase 6 regulatory subunit 3, C11orf23, SAPS, phosphorylation, breast cancer, bladder cancer, lung cancer, nodular fasciitis

(Note : for Links provided by Atlas : click)


chromosome 11 open reading frame 23
SAPS domain family, member 3
protein phosphatase 6, regulatory subunit 3
Alias_symbol (synonym)SAPLa
Other aliasSerine/threonine-protein phosphatase 6 regulatory subunit 3
chromosome 11 open reading frame 23 C11orf23
SAPS domain family member 3, SAPS3
sporulation-induced transcript 4-associated protein
HGNC (Hugo) PPP6R3
LocusID (NCBI) 55291
Atlas_Id 54550
Location 11q13.2  [Link to chromosome band 11q13]
Location_base_pair Starts at 68460718 and ends at 68615333 bp from pter ( according to hg19-Feb_2009)  [Mapping PPP6R3.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)


  Figure. 1. PPP6R3 gene and splicing variants/isoforms. The figure shows the locus on chromosome 11 of the PPP6R3 gene (reworked from;;
Description PPP6R3, alias protein phosphatase 6 regulatory subunit 3, is a protein coding gene that starts at 68,460,718 nt and ends at 68,615,334 nt from qter (RefSeq NC_000011.10) and with a length of 154617 bp. It is proximal to LRP5 (LDL receptor related protein 5) gene. Around the genomic locus of PPP6R3 take place different promoter or enhancer transcriptional elements that are located at +0.5 kb, +837.9 kb and -359.7 kb.
Transcription Exists a high number of spliced version of PPP6R3 (Stefansson and Brautigan, 2006) and their main characteristics are reported in Table.1
Name Variant RefSeq (1) Transcript ID Exons Type Lenght (bp) Isoform Alias RefSeq (2) Lenght (aa) MW (kDa) pI
PPP6R3-201 (PPP6R3-003)Var.5 NM_018312ENST00000265636.923protein coding4992Isoform 5-NP_06078279388.954.49
PPP6R3-202  (PPP6R3-021)Var.44NR_147968.1ENST00000265637.822ncRNA5124------
PPP6R3-203 (PPP6R3-001)Var.6NM_001164161ENST00000393800.624protein coding5127Isoform 6-NP_00115763387397.674.50
Var.21NM_0013523614873Isoform 18-NP_00133929078286.884.52
Var.28NM_0013523685211Isoform 6-NP_00133929787397.674.50
Var. 35NM_0013523755233Isoform 6-NP_00133930487397.674.50
Var.45NR_147969 5235------
Var.46NR_147970 4978------
PPP6R3-204 (PPP6R3-005)Var.4NM_001164160 ENST00000393801.725protein coding5145Isoform 4A, C11orf23a, SAPLaNP_001157632 87998.494.54
Var.7NM_001352347 5052Isoform 7-NP_001339276 66473.154.44
Var.10NM_001352350 5037Isoform 8-NP_001339279 85095.264.55
Var.12NM_001352352 5073Isoform 10-NP_001339281 86296.454.55
Var.13NM_001352353 4704Isoform 11-NP_001339282 71779.534.49
Var.14NM_001352354 5281Isoform 12-NP_001339283 88999.474.53
Var.16NM_001352356 5154Isoform 12-NP_001339285 88999.474.53
Var.20NM_001352360 5194Isoform 17-NP_001339289 86096.254.54
Var.24NM_001352364 5251Isoform 4A, C11orf23a, SAPLaNP_001339293 87998.494.54
Var.29NM_001352369 5149Isoform 20-NP_001339298 65472.164.45
Var.30NM_001352370 4891Isoform 21-NP_001339299 78887.694.56
Var.31NM_001352371 5200Isoform 10-NP_001339300 86296.454.55
Var.32NM_001352372 5233Isoform 24-NP_001339301 87397.734.54
Var.33NM_001352373 5067Isoform 17-NP_001339302 86096.254.54
Var.34NM_001352374 4804Isoform 22-NP_001339303 75984.474.58
Var.36NM_001352376 5164Isoform 8-NP_001339305 85095.264.55
Var.37NM_001352377 5106Isoform 24-NP_001339306 87397.734.54
Var.38NM_001352378 4931Isoform 22-NP_001339307 75984.474.58
Var.39NM_001352379 5390Isoform 4A, C11orf23a, SAPLaNP_001339308 87998.494.54
Var.40NM_001352380 5142Isoform 8-NP_001339309 85095.264.55
PPP6R3-205 (PPP6R3-026)Var.2NM_001164163 ENST00000524845.5 23protein coding5040Isoform 2-NP_001157635 84494.444.51
Var.15NM_001352355 4786Isoform 13-NP_001339284 75383.654.54
Var.23NM_0013523635146Isoform 2-NP_00133929284494.444.51
PPP6R3-206  (PPP6R3-007)Var.1NM_001164162 ENST00000524904.524protein coding5109Isoform 1-NP_001157634 86796.964.51
Var.8NM_001352348 5284Isoform 1-NP_001339277 86796.964.51
Var.11NM_001352351 4822Isoform 9-NP_001339280 76584.844.54
Var.18NM_001352358 4902Isoform 15-NP_001339287 80590.144.49
Var.19NM_001352359 4885Isoform 16-NP_001339288 78687.154.52
Var.22NM_001352362 5129Isoform 19-NP_001339291 85695.634.52
Var.25NM_0013523655055Isoform 19-NP_00133929485695.634.52
PPP6R3-207--ENST00000525050.5 4retained intron513------
PPP6R3-208--ENST00000525152.12retained intron582------
PPP6R3-209--ENST00000525421.5 8nonsense md830------
PPP6R3-210--ENST00000526307.510retained intron4134------
PPP6R3-211--ENST00000526574.1 4retained intron489------
PPP6R3-212--ENST00000526593.15nonsense md570------
PPP6R3-213--ENST00000527069.5 4retained intron573------
PPP6R3-214  (PPP6R3-020)Var.26NM_001352366ENST00000527403.622protein coding5019Isoform 23-NP_00133929584494.554.56
PPP6R3-215  (PPP6R3-012)--ENST00000528635.55(?)538------
PPP6R3-216--ENST00000529172.1 4retained intron500------
PPP6R3-217  (PPP6R3-011)--ENST00000529344.5 4(?)603------
PPP6R3-218  (PPP6R3-004)Var.3NM_001164164ENST00000529710.5 23protein coding3426Isoform 3B, C11orf23b, SAPLbNP_00115763679188.914.48
PPP6R3-219  (PPP6R3-009)--ENST00000529907.5 7(?)826------
PPP6R3-220--ENST00000530427.55processed transcript560------
PPP6R3-221 (PPP6R3-025)--ENST00000530734.1 2(?)576------
PPP6R3-222  (PPP6R3-013)--ENST00000531244.1 5(?)687------
PPP6R3-223--ENST00000531432.12retained intron590------
PPP6R3-224 (PPP6R3-027)--ENST00000533127.5 4(?)551------
PPP6R3-225  (PPP6R3-018)Var.17NM_001352357ENST00000534190.5 16protein coding5150Isoform 14-NP_00133928661968.124.42
PPP6R3-226  (PPP6R3-008)--ENST00000534534.5 19(?)2968------

Table.1 Alterative splicing variants and isoforms of PPP6R3. (reworked from; ttps://;;
ncRNA = non-coding RNA; nonsense md = nonsense mediated decay; (?) = undetermined; MW = molecular weight; pI = theoretical pI.
Pseudogene Currently, pseudogenes for PPP6R3 have not been detected in the human genome.


  Figure.2 PPP6R3 protein isoforms. Graphical representation of the PPP6R3 protein isoforms with highlight of the main verified post-translational modifications (reworked from;; Stefansson and Brautigan, 2006).
Description PPP6R3 encodes the protein phosphatase 6 regulatory subunit 3, which belongs to protein phosphatase 6 (PP6) complex (York et al., 2014; Guergnon et al., 2009) in which there are also PPP6R1, PPP6R2 and PPP6C proteins. PP6 complex is a member of the PP2A subfamily of protein phosphatases and shows a Sit4-associated protein domain (SAPS domain) (Stefansson and Brautigan, 2006). There are evidence about many functioning isoforms for PPP6R3 protein (Table.1) that maintain the SAPS main domain.
Expression PPP6R3 is ubiquitously expressed in human tissues and mRNA levels are highly expressed in heart (Ziembik et al., 2017; Stefansson and Brautigan, 2006) and also in immune cells and lymphoid tissues, in particular in T helper cells, cytotoxic T cells and monocytes (Ziembik et al., 2017). On the contrary, PPP6R3 protein is found at high levels in lung, bladder, spleen and pancreas (Ziembik et al., 2017).
Localisation PPP6R3 localize in various subcellular compartments: it is present mainly in the cytoplasm but it is also found in Golgi apparatus, nucleoplasm, nucleus and associated with the plasma membrane (Stefansson et al., 2008;
Function PPP6R3 is a subunit of protein phosphatase 6 (PP6), a trimeric holoenzyme of the family of phosphoprotein phosphatases (PPPs), involved in the turnover of serine and threonine phosphorylation events during mitosis so much to be able to regulate the cell cycle progression (Stefansson and Brautigan, 2007). PPP6R3 acts as a regulatory element in the PP6 protein complex and could function as a scaffold for PP6 subunits. It was observed that a high amount of PPP6R3 in cell result in a great destabilization, upon depletion, of the catalytic subunit of PP6 (Rusin et al.,2017). Moreover, PPP6R3 could have an important role in maintaining immune self-tolerance through the control of the nuclear factor kappaB (NF-kB) (Ziembik et al., 2017) and the TNF- α/NF-kB pathway (Bouwmeester et al., 2004).
Pediatric musculoskeletal development. PPP6R3, along with other genes, seems to be involved in bone mineralization and myogenensis during pediatric development (Medina-Gomez et al., 2017). However, the inner significance of this relation, such as the impact on musculoskeletal structure, on strength or weakness and on the predisposition to develop the related pathologies, needs to be clarified.
Interactions with the influenza A virus transcription/replication machinery. PPP6R3 is a member of PP6 complex and some authors found that PP6 interact directly with two subunits, i.e. PB1 and PB2, of the viral RNA-dependent RNA polymerase (RdRP) of the influenza A virus. This suggest a role of PP6 complex, and for regulatory subunit PPP6R3, in the regulation of phosphorylation also in the influenza A virus transcription/replication machinery (York et al., 2014).
Homology PPP6R3 is highly and abundant conserved in many species and its homology between the species is reported in Table.2
OrganismSpeciesSymbol DNA Identity (%)Prot Identity (%)
Mouse M.musculus Ppp6r390.596.3
RatR.norvegicus Ppp6r390.695.5
Xenopus tropicalisX.tropicalis Ppp6r375.680.3
Zebrafish D.rerio Ppp6r371.679.0

Table.2 PPP6R3 homology (reworked from ps://

Implicated in

Note PPP6R3 is involved in many and heterogeneous genomic translocations in different kind of tumors (Table. 3) and it has been proposed that this happens because it possess a potent promotor activity (Guo et al., 2016).
Name 5' end 3' end Loc1 Loc2 Description Type Disease Organ Code Ref.
C11orf80/PPP6R3C11orf80PPP6R3 11q13.211q13.2 t(11;11)(q13;q13)Fusion geneAdenocarcinomaBreastBRCAHu et al., 2018
CCDC132/PPP6R3 CCDC132PPP6R3 7q21.2 11q13.2t(7;11)(q21;q13)TranslocationAdenocarcinomaLungLUAD-
CTTN/PPP6R3CTTNPPP6R317q23.311q13.2t(11;11)(q13;q13)Fusion geneMalignant melanomaSkinSKCMHu et al., 2018
CSHL1/PPP6R3CSHL1PPP6R3 17q23.311q13.2t(11:17)(q13;q23)Translocation(?)(?)(?)-
DPP9/PPP6R3DPP9PPP6R3 19p13.311q13.2t(11;19)(q13;p13) TranslocationAdenocarcinomaOvaryOVCASmebye et al., 2017
EEF1G/PPP6R3 EEF1GPPP6R311q12.311q13.2t(11;11)(q12;q13)Fusion geneSquamous cell carcinomaLungLUSCHammerman et al., 2012
ITGB5 /PPP6R3ITGB5 PPP6R33q21.211q13.2t(3;11)(q21;q13)Translocation(?)(?)(?)-
KDM2A/PPP6R3 KDM2APPP6R311q13.211q13.2t(11;11)(q13;q13)Fusion geneAdenocarcinomaBreastBRCAYoshihara et al., 2015
MKL2/PPP6R3MKL2 PPP6R316p13.1211q13.2t(11;16)(q13;p13)Translocation(?)(?)(?)-
NADSYN1/PPP6R3NADSYN1PPP6R3 11q13.411q13.2t(11;11)(q13;q13)Fusion geneMalignant melanomaSkinSKCMHu et al., 2018; Klijn et al., 2015
PC/PPP6R3PCPPP6R311q13.211q13.2t(11;11)(q13;q13)Fusion geneAdenocarcinomaBreastBRCAYoshihara et al., 2015
PPP6R3/ACER3PPP6R3ACER311q13.2 11q13.5t(11;11)(q13;q13)Fusion geneMalignant melanomaSkinSKCMHu et al., 2018
PPP6R3/ARHGAP1PPP6R3ARHGAP111q13.211p11.2t(11;11)(p11;q13)Fusion geneSquamous cell carcinomaLungLUSCYoshihara et al., 2015
PPP6R3/ATP6V0D2PPP6R3ATP6V0D211q13.2 8q21.3t(8;11)(q21;q13)TranslocationSarcomaSoft tissueSARC-
PPP6R3/CNTN5PPP6R3CNTN511q13.211q22.1t(11;11)(q13;q22)Fusion geneSquamous cell carcinomaLungLUSCHammerman et al., 2012
PPP6R3/DPP3PPP6R3DPP311q13.211q13.2 t(11;11)(q13;q13)Fusion geneGerm cell tumor, NOSTestisTGCTHoff et al., 2016
PPP6R3/FADD PPP6R3FADD 11q13.211q13.3 t(11;11)(q13;q13)Fusion geneAdenocarcinomaBreastBRCAYoshihara et al., 2015
PPP6R3/EIF4G3PPP6R3EIF4G311q13.2 1p36.12t(1;11)(p36;q13)TranslocationMalignant melanomaSkinSKCM-
PPP6R3/INTS4 PPP6R3INTS4 11q13.2 11q14.1t(11;11)(q13;q14) Fusion geneAcute lymphoblastic leukemia/lymphoblastic lymphoma (T-Lineage)BloodT-ALLLiu et al., 2017
PPP6R3/LRP5PPP6R3LRP511q13.211q13.2 t(11;11)(q13;q13)Fusion geneSquamous cell carcinomaLungLUSCYoshihara et al., 2015
PPP6R3/MGAMPPP6R3MGAM11q13.2 7q34t(7;11)(q34;q13)TranslocationSquamous cell carcinomaLungLUSC-
PPP6R3/MTL5PPP6R3MTL511q13.211q13.3 t(11;11)(q13;q13)Fusion geneAdenocarcinomaBreastBRCAYoshihara et al., 2015
PPP6R3/POLD3PPP6R3POLD311q13.211q13.4t(11;11)(q13;q13)Fusion geneAdenocarcinomaBreastBRCAYoshihara et al., 2015
 PPP6R3/RHODPPP6R3RHOD11q13.2 11q13.2 t(11;11)(q13;q13)Fusion geneAdenocarcinomaStomachSTADHu et al., 2018
PPP6R3/SHANK2PPP6R3SHANK211q13.2 11q13.3 t(11;11)(q13;q13)Fusion gene Transitional cell carcinomaBladderBLCAHu et al., 2018
PPP6R3/SPTBN2PPP6R3SPTBN211q13.211q13.2t(11;11)(q13;q13)Fusion geneAdenocarcinomaBreastBRCAYoshihara et al., 2015
PPP6R3/SSH2PPP6R3SSH211q13.217q11.2t(11;17)(q13;q11)TranslocationAdenocarcinomaBreastBRCAYoshihara et al., 2015
NeuroblastomaSoft tissueNBLMcRobert et al., 1992
Acute lymphoblastic leukemia/lymphoblastic lymphomaBloodALLSchmiegelow et al., 2012
PPP6R3/SSH3PPP6R3SSH311q13.2 11q13.2  t(11;11)(q13;q13)Fusion geneAdenocarcinomaPancreasPAADHu et al., 2018
PPP6R3/USP6 PPP6R3USP6 11q13.2 17p13.2 t(11;17)(q13;p13) TranslocationNodular fasciitisSoft tissueNFGuo et al., 2016
Hairy cell leukemiaBloodHCLNacheva et al., 1992
Multiple myelomaBloodMMSawyer et al., 1995; Sawyer et al., 2014
 Chronic myeloid leukemiaBloodCMLStopera et al., 1990
PPP6R3/YAP1PPP6R3YAP111q13.211q22.1 t(11;11)(q13;q22)Fusion gene Transitional cell carcinomaBladderBLCAYoshihara et al., 2015
RAB11A/PPP6R3RAB11APPP6R3 15q22.31 11q13.2t(11;15)(q13;q22)TranslocationCell carcinoma and endocervical adenocarcinomaCervicalCESC-
RNF121/PPP6R3 RNF121PPP6R311q13.411q13.2t(11;11)(q13;q13)Fusion geneAdenocarcinomaBreastBRCAYoshihara et al., 2015
SSBP1/PPP6R3SSBP1PPP6R3 7q3411q13.2t(7;11)(q34;q13)TranslocationSquamous cell carcinomaLungLUSC-
STRN3/PPP6R3 STRN3PPP6R314q1211q13.2 t(11;14)(q13;q12)TranslocationAdenocarcinomaBreastBRCAYoshihara et al., 2015
TMPRSS6/PPP6R3TMPRSS6PPP6R3 22q12.311q13.2t(11;22)(q13;q12)TranslocationLiver hepatocellular carcinomaLiver LIHC-
TNFRSF21/PPP6R3TNFRSF21PPP6R3 6p12.3 11q13.2t(6;11)(p12;q13)TranslocationAdenocarcinomaBreastBRCABanerji et al., 2012

Table.3 PPP6R3 rearrangements: translocations and fusion genes (reworked from ps://;;;
[ (?) ] unknown; [ - ] no reference
Entity Acute lymphoblastic leukemia (ALL)
Hybrid/Mutated Gene The fusion gene PPP6R3/ INTS4 has been found in T-ALL (Liu et al., 2017), while a t(11;17)(q13;q11) PPP6R3/ SSH2 was discovered in a childhood T/BCP (T/ B-cell precursor) ALL (Schmiegelow et al., 2012).
Entity Bladder cancer
Hybrid/Mutated Gene The fusion genes PPP6R3/ SHANK2 and PPP6R3/ YAP1 have been found in transitional cell carcinoma of the bladder (Hu et al., 2018; Yoshihara et al., 2015;
Entity Breast cancer
Hybrid/Mutated Gene Many fusion genes and abnormal translocation was discovered. C11orf80 /PPP6R3, KDM2A/PPP6R3, PC/PPP6R3, PPP6R3/ FADD, PPP6R3/ MTL5, PPP6R3/ POLD3, PPP6R3/ SPTBN2, t(11;17)(q13;q11) PPP6R3/SSH2, RNF121/PPP6R3, t(11;14)(q13;q12) STRN3/PPP6R3 and t(6;11)(p12;q13) TNFRSF21/PPP6R3 have been found in breast adenocarcinoma (Hu et al., 2018; Yoshihara et al., 2015;
Entity Cervical carcinoma
Hybrid/Mutated Gene A t(11;15)(q13;q22) RAB11A/PPP6R3 has been found in cervical carcinoma (
Entity Gastric cancer
Hybrid/Mutated Gene The fusion gene PPP6R3/ RHOD has been found in gastric adenocarcinoma (Hu et al., 2018;
Entity t(11;17)(q13;p13)PPP6R3/USP6 in hematological malignancies.
Hybrid/Mutated Gene A t(11;17)(q13;p13)PPP6R3/ USP6 has been found in Hairy cell leukemia, Multiple myeloma, and Chronic myeloid leukemia (Sawyer et al., 2014 ; Sawyer et al., 1995 ; Nacheva et al., 1992; Stopera et al., 1990
Entity Hepatocellular carcinoma
Entity Lung squamous cell carcinoma
Hybrid/Mutated Gene In squamous cell carcinoma of the lung was discovered the fusion gene EEF1G/PPP6R3 (Hammerman et al., 2012). Other detected are: a t(7;11)(q21;q13) CCDC132/PPP6R3, PPP6R3/ ARHGAP1 fusion gene, PPP6R3/ CNTN5 fusion gene, PPP6R3/ LRP5 fusion gene, a t(7;11)(q13;q34)PPP6R3/ MGAM and a t(7;11)(q34;q13) SSBP1/PPP6R3 (Yoshihara et al., 2015; Hammerman et al., 2012;
In squamous cell carcinoma of the lung was found the presence of the fusion gene 5' EEF1G- 3' PPP6R3 deriving by the genomic translocation and fusion of a part of EEF1G gene with a portion of PPP6R3 gene, both located on chromosome 11 (Hammerman et al., 2012).
Entity Malignant melanoma
Hybrid/Mutated Gene The fusion genes CTTN/PPP6R3, NADSYN1/PPP6R3 and PPP6R3/ ACER3 have been found in malignant melanoma. In addition, a t(1;11)( p36;q13) PPP6R3/ EIF4G3 has also been found (Hu et al., 2018; Klijn et al., 2015;
Entity Malignant Nodular Fasciitis
Disease Nodular fasciitis (NF) occurs in subcutaneous tissue and it is generally a benign self-limiting myofibroblastic proliferation (Bernstein and Lattes, 1982). Sometimes was found USP6 gene rearrangements (Erickson-Johnson et al., 2011) and surprendently in one case was revealed the presence of PPP6R3/USP6 fusion gene with both genomic amplification and overexpression (Guo et al., 2016) that could explain the more aggressive behavior seen in malignant NF case report.
Hybrid/Mutated Gene It was described the fusion gene 5' PPP6R3 / 3' USP6 deriving by the genomic translocation and fusion of a part of PPP6R3 gene, situated on chromosome 11, with a portion of USP6 gene, instead located on chromosome 17. In particular, the breakpoint reside at the end of exon 1 of PPP6R3 (non-coding) and 155 bp upstream of coding sequence of USP6 gene (Guo et al., 2016).
Oncogenesis The presence of the novel PPP6R3/USP6 fusion gene was linked to the increase of malignancy of the nodular faciitis (NF). Other tumors were tested for the presence of this chimeric gene, such as aggressive angiomyxoma , malignant peripheral nerve sheath tumor, dermatofibroma/ benign fibrous histiocytoma and melanoma. In that cases the results were negatives (Guo et al., 2016). Some authors detect PPP6R3/USP6 in hairy cell leukemia, multiple myeloma and chronic myeloid leukemia (Sawyer et al., 2014; Sawyer et al., 1995; Nacheva et al., 1992 ; Stopera et al., 1990).
Entity Nervous system tumors
Disease Malignant peripheral nerve sheath tumors (MPNSTs), also called neurofibrosarcomas, are a rare aggressive, metastatic, nerve-associated cancer type. It was found that in about 10% of this malignancy there are mutations on PPP6R3 gene that cause disrupt gene transcription (Rahrmann et al., 2013). In addition a t(8;11)(q21;q13)PPP6R3/ ATP6V0D2 is found in sarcoma ( and a t(11;17)(q13;q11)PPP6R3/SSH2 is detected in neuroblastoma (McRobert et al., 1992).
Entity Ovarian carcinoma
Disease Ovarian malignancies, a type of gynecological cancer, show high genomic instability and structural chromosomal aberrations which are believed to be common mechanisms for both the inactivation of tumour suppressor genes and the production of fusion genes useful for cancer vitality. The precise roles and functions of these chimeric gene are not always understood (Smebye et al., 2017). The fusion gene DPP9 /PPP6R3 play a role in tumorigenesis and/or cancer progression through the loss-of-function of the DPP9 protein, a serine protease that act as a tumour suppressor and is a inducer of apoptosis.
Hybrid/Mutated Gene A fusion gene 5' DPP9 / 3' PPP6R3 deriving from the genomic translocation and fusion of a part of DPP9 (dipeptidyl peptidase 9) gene, situated on chromosome 19 with a portion of PPP6R3 gene, located on chromosome 11 was found in a high-grade serous ovarian carcinoma. The fusion occured between DPP9 exon 11 and PPP6R3 exon 18. DPP9 is a serine protease that act as a tumor suppressor and as a inducer of apoptosis (Smebye et al., 2017).
Abnormal Protein The fusion between DPP9 and PPP6R3 leads to disruption and deregulation of expression of DPP9 gene due to the introduction of a stop codon (TAG) directly after the junction that leads to the production of truncated form of DPP9 protein. This protein loss some functional domains, i.e. the peptidase and esterase-lipase domains (Smebye et al., 2017) and this causes its loss-of-function.
Entity Pancreatic cancer
Hybrid/Mutated Gene The fusion genes PPP6R3/LRP5 and PPP6R3/ SSH3 have been found in pancreas adenocarcinoma (Hu et al., 2018;
Entity Testicular germ cell tumors
Disease Testicular germ cell tumors (TGCTs) are the most frequently diagnosed solid malignancies in young males and men by 15 to 44 years old and that includes two main subtypes: seminomas and non-seminomas (Hoff et al., 2016; Znaor et al., 2014). Some authors found a novel fusion gene 5' PPP6R3 - 3' DPP3 in pluripotent embryonal carcinomas (EC) cell lines (Hoff et al., 2016).
Hybrid/Mutated Gene The fusion gene 5' PPP6R3 / 3' DPP3 resulting by the translocation t(11;11)(q13;q13) and PPP6R3/DPP3 is a novel genomic chimeric rearrangement occurs in vitro. However more studies are need to characterize it and to elucidate its exact role in testicular germ cell tumors.
Abnormal Protein PPP6R3-DPP3 fusion gene encodes a protein of 198 amino acids long (Hoff et al., 2016). The functions of this chimeric protein are unknown.
Entity Type 1 diabetes mellitus 4
Note The IDDM4 locus has been localized to chromosome 11q13 and PPP6R3 gene is linked with type 1 diabetes mellitus 4 (Twells et al., 2001).
Entity Effects on HIV-1 replication
Note Knockdown of PPP6R3 by short interfering RNAs (siRNA) library screening inhibits HIV-1 replication in cultured Jurkat T-cells (Yeung et al., 2009).


Sequence analysis of mutations and translocations across breast cancer subtypes
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A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway
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PMID 22960745
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PMID 19835610
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Nat Biotechnol 2015 Mar;33(3):306-12
PMID 25485619
The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia
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Nat Genet 2017 Aug;49(8):1211-1218
PMID 28671688
Detection of MYCN amplification in three neuroblastoma cell lines by non-radioactive chromosomal in situ hybridization
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Cancer Genet Cytogenet 1992 Apr;59(2):128-34
PMID 1581879
Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus
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Nat Commun 2017 Jul 25;8(1):121
PMID 28743860
Complex chromosomal rearrangements in an unusual variant of hairy cell leukemia
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Cancer Genet Cytogenet 1992 Sep;62(2):186-90
PMID 1394107
Forward genetic screen for malignant peripheral nerve sheath tumor formation identifies new genes and pathways driving tumorigenesis
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This paper should be referenced as such :
Cristiano L.
PPP6R3 (protein phosphatase 6 regulatory subunit 3);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version :

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(11;11)(q13;q14) PPP6R3/INTS4

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 16 ]
  Lung: Translocations in Squamous Cell Carcinoma
t(11;11)(p11;q13) PPP6R3/ARHGAP1
t(11;11)(q12;q13) EEF1G/PPP6R3
KDM2A/PPP6R3 (11q13)
PC/PPP6R3 (11q13)
PPP6R3/DPP3 (11q13)
PPP6R3/FADD (11q13)
PPP6R3/LRP5 (11q13)
PPP6R3/POLD3 (11q13)
PPP6R3/SPTBN2 (11q13)
RNF121/PPP6R3 (11q13)
t(11;11)(q13;q22) PPP6R3/YAP1
t(11;11)(q13;q22) PPP6R3/CNTN5
t(11;14)(q13;q12) STRN3/PPP6R3
t(11;17)(q13;p13) PPP6R3/USP6
t(11;17)(q13;q11) PPP6R3/SSH2

External links

HGNC (Hugo)PPP6R3   1173
Entrez_Gene (NCBI)PPP6R3  55291  protein phosphatase 6 regulatory subunit 3
AliasesC11orf23; PP6R3; SAP190; SAPL; 
GeneCards (Weizmann)PPP6R3
Ensembl hg19 (Hinxton)ENSG00000110075 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000110075 [Gene_View]  ENSG00000110075 [Sequence]  chr11:68460718-68615333 [Contig_View]  PPP6R3 [Vega]
ICGC DataPortalENSG00000110075
TCGA cBioPortalPPP6R3
AceView (NCBI)PPP6R3
Genatlas (Paris)PPP6R3
SOURCE (Princeton)PPP6R3
Genetics Home Reference (NIH)PPP6R3
Genomic and cartography
GoldenPath hg38 (UCSC)PPP6R3  -     chr11:68460718-68615333 +  11q13.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PPP6R3  -     11q13.2   [Description]    (hg19-Feb_2009)
GoldenPathPPP6R3 - 11q13.2 [CytoView hg19]  PPP6R3 - 11q13.2 [CytoView hg38]
Mapping of homologs : NCBIPPP6R3 [Mapview hg19]  PPP6R3 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AB046778 AF264779 AF264780 AK001920 AK023950
RefSeq transcript (Entrez)NM_001164160 NM_001164161 NM_001164162 NM_001164163 NM_001164164 NM_001352347 NM_001352348 NM_001352350 NM_001352351 NM_001352352 NM_001352353 NM_001352354 NM_001352355 NM_001352356 NM_001352357 NM_001352358 NM_001352359 NM_001352360 NM_001352361 NM_001352362 NM_001352363 NM_001352364 NM_001352365 NM_001352366 NM_001352368 NM_001352369 NM_001352370 NM_001352371 NM_001352372 NM_001352373 NM_001352374 NM_001352375 NM_001352376 NM_001352377 NM_001352378 NM_001352379 NM_001352380 NM_018312
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)PPP6R3
Cluster EST : UnigeneHs.503022 [ NCBI ]
CGAP (NCI)Hs.503022
Alternative Splicing GalleryENSG00000110075
Gene ExpressionPPP6R3 [ NCBI-GEO ]   PPP6R3 [ EBI - ARRAY_EXPRESS ]   PPP6R3 [ SEEK ]   PPP6R3 [ MEM ]
Gene Expression Viewer (FireBrowse)PPP6R3 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)55291
GTEX Portal (Tissue expression)PPP6R3
Human Protein AtlasENSG00000110075-PPP6R3 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ5H9R7   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ5H9R7  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ5H9R7
Splice isoforms : SwissVarQ5H9R7
Domains : Interpro (EBI)ARM-type_fold    SAPS   
Domain families : Pfam (Sanger)SAPS (PF04499)   
Domain families : Pfam (NCBI)pfam04499   
Conserved Domain (NCBI)PPP6R3
DMDM Disease mutations55291
Blocks (Seattle)PPP6R3
Human Protein Atlas [tissue]ENSG00000110075-PPP6R3 [tissue]
Peptide AtlasQ5H9R7
IPIIPI00719821   IPI00719553   IPI00719345   IPI00019540   IPI00719725   IPI00030624   IPI00909546   IPI00975695   IPI01015850   IPI00985268   IPI00976160   IPI00984704   IPI00985128   IPI00983215   IPI00977455   IPI00983893   IPI00983242   IPI00976813   IPI00985067   
Protein Interaction databases
IntAct (EBI)Q5H9R7
Ontologies - Pathways
Ontology : AmiGOGolgi membrane  protein binding  nucleoplasm  cytosol  cytosol  plasma membrane  protein phosphatase binding  regulation of phosphoprotein phosphatase activity  COPII vesicle coating  
Ontology : EGO-EBIGolgi membrane  protein binding  nucleoplasm  cytosol  cytosol  plasma membrane  protein phosphatase binding  regulation of phosphoprotein phosphatase activity  COPII vesicle coating  
REACTOMEQ5H9R7 [protein]
REACTOME PathwaysR-HSA-204005 [pathway]   
NDEx NetworkPPP6R3
Atlas of Cancer Signalling NetworkPPP6R3
Wikipedia pathwaysPPP6R3
Orthology - Evolution
GeneTree (enSembl)ENSG00000110075
Phylogenetic Trees/Animal Genes : TreeFamPPP6R3
Homologs : HomoloGenePPP6R3
Homology/Alignments : Family Browser (UCSC)PPP6R3
Gene fusions - Rearrangements
Fusion : MitelmanCCDC132/11q13.2 [PPP6R3/t(7;11)(q21;q13)]  
Fusion : MitelmanEEF1G/PPP6R3 [11q12.3/11q13.2]  [t(11;11)(q12;q13)]  
Fusion : MitelmanKDM2A/PPP6R3 [11q13.2/11q13.2]  [t(11;11)(q13;q13)]  
Fusion : MitelmanPC/PPP6R3 [11q13.2/11q13.2]  [t(11;11)(q13;q13)]  
Fusion : MitelmanPPP6R3/ARHGAP1 [11q13.2/11p11.2]  [t(11;11)(p11;q13)]  
Fusion : MitelmanPPP6R3/CNTN5 [11q13.2/11q22.1]  [t(11;11)(q13;q22)]  
Fusion : MitelmanPPP6R3/FADD [11q13.2/11q13.3]  [t(11;11)(q13;q13)]  
Fusion : MitelmanPPP6R3/LRP5 [11q13.2/11q13.2]  [t(11;11)(q13;q13)]  
Fusion : MitelmanPPP6R3/MTL5 [11q13.2/11q13.3]  [t(11;11)(q13;q13)]  
Fusion : MitelmanPPP6R3/POLD3 [11q13.2/11q13.4]  [t(11;11)(q13;q13)]  
Fusion : MitelmanPPP6R3/SPTBN2 [11q13.2/11q13.2]  [t(11;11)(q13;q13)]  
Fusion : MitelmanPPP6R3/SSH2 [11q13.2/17q11.2]  [t(11;17)(q13;q11)]  
Fusion : MitelmanPPP6R3/YAP1 [11q13.2/11q22.1]  [t(11;11)(q13;q22)]  
Fusion : MitelmanRNF121/PPP6R3 [11q13.4/11q13.2]  [t(11;11)(q13;q13)]  
Fusion : MitelmanSTRN3/PPP6R3 [14q12/11q13.2]  [t(11;14)(q13;q12)]  
Fusion PortalCCDC132 PPP6R3 11q13.2 LUAD
Fusion PortalKDM2A 11q13.2 PPP6R3 11q13.2 BRCA
Fusion PortalPC 11q13.2 PPP6R3 11q13.2 BRCA
Fusion PortalPPP6R3 11q13.2 ARHGAP1 11p11.2 LUSC
Fusion PortalPPP6R3 11q13.2 FADD 11q13.3 BRCA
Fusion PortalPPP6R3 11q13.2 LRP5 11q13.2 LUSC
Fusion PortalPPP6R3 11q13.2 MTL5 11q13.3 BRCA
Fusion PortalPPP6R3 11q13.2 POLD3 11q13.4 BRCA
Fusion PortalPPP6R3 11q13.2 SPTBN2 11q13.2 BRCA
Fusion PortalPPP6R3 11q13.2 SSH2 17q11.2 BRCA
Fusion PortalPPP6R3 11q13.2 YAP1 11q22.1 BLCA
Fusion PortalRNF121 11q13.4 PPP6R3 11q13.2 BRCA
Fusion PortalSTRN3 14q12 PPP6R3 11q13.2 BRCA
Fusion : FusionGDB17886    18409    19272    22089    23362    26332    28532    28533    28534    28535    28536    28537    28538    28539    28540   
28541    28542    28543    28544    28545    28546    28547    28548    28549    29870    31401    33690    34732    38775    43074   
4651    8606    8955   
Fusion : Fusion_HubANTXR1--PPP6R3    BCCIP--PPP6R3    C11ORF80--PPP6R3    CCDC132--PPP6R3    CSHL1--PPP6R3    CTTN--PPP6R3    DDAH1--PPP6R3    DPP3--PPP6R3    DPP9--PPP6R3    FAM168A--PPP6R3    FCHSD2--PPP6R3    FGFR1OP2--PPP6R3    FOXJ3--PPP6R3    ITGB5--PPP6R3    KDM2A--PPP6R3   
KDM4C--PPP6R3    KRT5--PPP6R3    LRP5--PPP6R3    MKL2--PPP6R3    NADSYN1--PPP6R3    NAPG--PPP6R3    OPA1--PPP6R3    PC--PPP6R3    PHF21A--PPP6R3    PPP6R3--ACER3    PPP6R3--ACTB    PPP6R3--ANAPC4    PPP6R3--ARHGAP1    PPP6R3--ATG2A    PPP6R3--ATP6V0D2   
PPP6R3--C11ORF63    PPP6R3--C17ORF67    PPP6R3--CAPZB    PPP6R3--CDK19    PPP6R3--CHMP3    PPP6R3--DPP3    PPP6R3--DRG1    PPP6R3--EIF4G3    PPP6R3--FADD    PPP6R3--GNB2L1    PPP6R3--GOLGA8A    PPP6R3--KDM2A    PPP6R3--KLC1    PPP6R3--LOC338694    PPP6R3--LRP5   
PPP6R3--LRTM1    PPP6R3--MGAM    PPP6R3--MTL5    PPP6R3--POLD3    PPP6R3--PPFIA1    PPP6R3--PPP1CB    PPP6R3--PREPL    PPP6R3--RHOD    PPP6R3--SERINC1    PPP6R3--SHANK2    PPP6R3--SIK2    PPP6R3--SPTBN2    PPP6R3--SS18    PPP6R3--SSH2    PPP6R3--SSH3   
PPP6R3--TBC1D15    PPP6R3--YAP1    RAB11A--PPP6R3    RNF121--PPP6R3    SCARB1--PPP6R3    SCCPDH--PPP6R3    SH3RF1--PPP6R3    SHANK2--PPP6R3    SMAD2--PPP6R3    SSBP1--PPP6R3    STRN3--PPP6R3    TMPRSS6--PPP6R3   
Fusion : QuiverPPP6R3
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPPP6R3 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PPP6R3
Exome Variant ServerPPP6R3
ExAC (Exome Aggregation Consortium)ENSG00000110075
GNOMAD BrowserENSG00000110075
Varsome BrowserPPP6R3
Genetic variants : HAPMAP55291
Genomic Variants (DGV)PPP6R3 [DGVbeta]
DECIPHERPPP6R3 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPPP6R3 
ICGC Data PortalPPP6R3 
TCGA Data PortalPPP6R3 
Broad Tumor PortalPPP6R3
OASIS PortalPPP6R3 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPPP6R3  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDPPP6R3
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch PPP6R3
DgiDB (Drug Gene Interaction Database)PPP6R3
DoCM (Curated mutations)PPP6R3 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PPP6R3 (select a term)
NCG5 (London)PPP6R3
Cancer3DPPP6R3(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry PPP6R3
NextProtQ5H9R7 [Medical]
Target ValidationPPP6R3
Huge Navigator PPP6R3 [HugePedia]
snp3D : Map Gene to Disease55291
BioCentury BCIQPPP6R3
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD55291
Chemical/Pharm GKB GenePA25487
Clinical trialPPP6R3
canSAR (ICR)PPP6R3 (select the gene name)
DataMed IndexPPP6R3
PubMed67 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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