PPP1R10

Summary

PPP1R10 (protein phosphatase 1 regulatory subunit 10, HGNC:9284) is a protein-coding gene on chromosome 6p21.33, encoding Serine/threonine-protein phosphatase 1 regulatory subunit 10 (Q96QC0). Substrate-recognition component of the PNUTS-PP1 protein phosphatase complex, a protein phosphatase 1 (PP1) complex that promotes RNA polymerase II transcription pause-release, allowing transcription elongation. It is a common-essential gene (DepMap: required in 99.3% of cancer cell lines).

This gene encodes a protein phosphatase 1 binding protein. The encoded protein plays a role in many cellular processes including cell cycle progression, DNA repair and apoptosis by regulating the activity of protein phosphatase 1. This gene lies within the major histocompatibility complex class I region on chromosome 6, and alternatively spliced transcript variants have been observed for this gene.

Source: NCBI Gene 5514 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 121 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_002714

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9284
Approved symbol	PPP1R10
Name	protein phosphatase 1 regulatory subunit 10
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Aliases	PNUTS, FB19, CAT53, p99
Ensembl gene	ENSG00000204569
Ensembl biotype	protein_coding
OMIM	603771
Entrez	5514

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 9 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000376511, ENST00000461593, ENST00000468181, ENST00000473954, ENST00000476704, ENST00000484449, ENST00000496955, ENST00000913675, ENST00000913676, ENST00000913677, ENST00000913678, ENST00000913679, ENST00000913680, ENST00000913681, ENST00000951331

RefSeq mRNA: 2 — MANE Select: NM_002714 NM_001376195, NM_002714

CCDS: CCDS4681

Canonical transcript exons

ENST00000376511 — 20 exons

Exon	Start	End
ENSE00001596300	30608779	30608914
ENSE00001622301	30603210	30603285
ENSE00001633026	30609838	30609955
ENSE00001657351	30606779	30606856
ENSE00001663842	30616478	30616998
ENSE00001672203	30609077	30609163
ENSE00001691022	30604994	30605094
ENSE00001692556	30603780	30603843
ENSE00001707124	30606468	30606641
ENSE00001710220	30607840	30607891
ENSE00001721337	30602846	30602959
ENSE00001754211	30603472	30603666
ENSE00001773728	30604353	30604511
ENSE00001794313	30601936	30602691
ENSE00001795769	30604588	30604735
ENSE00001795970	30604008	30604254
ENSE00001883804	30600413	30601658
ENSE00003600751	30606138	30606243
ENSE00003671260	30605923	30606035
ENSE00003848169	30617224	30617243

Expression profiles

Bgee: expression breadth ubiquitous, 136 present calls, max score 96.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.4290 / max 1105.9705, expressed in 1818 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72545	38.5577	1818
72542	0.7789	455
72544	0.6020	339
72541	0.4783	220
72547	0.2545	94
72543	0.1543	74
72549	0.1529	68
72551	0.1373	68
72546	0.1350	31
72550	0.1220	45

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	96.56	gold quality
sural nerve	UBERON:0015488	95.28	gold quality
adrenal tissue	UBERON:0018303	94.65	gold quality
tonsil	UBERON:0002372	93.95	gold quality
gall bladder	UBERON:0002110	93.83	gold quality
lower esophagus mucosa	UBERON:0035834	93.73	gold quality
granulocyte	CL:0000094	93.29	gold quality
vermiform appendix	UBERON:0001154	92.97	gold quality
urinary bladder	UBERON:0001255	92.83	gold quality
right uterine tube	UBERON:0001302	92.72	gold quality
rectum	UBERON:0001052	92.70	gold quality
calcaneal tendon	UBERON:0003701	92.34	gold quality
smooth muscle tissue	UBERON:0001135	92.32	gold quality
liver	UBERON:0002107	92.26	gold quality
cortical plate	UBERON:0005343	92.10	gold quality
colonic epithelium	UBERON:0000397	92.06	gold quality
right lobe of liver	UBERON:0001114	92.01	gold quality
pituitary gland	UBERON:0000007	91.94	gold quality
stomach	UBERON:0000945	91.94	gold quality
uterine cervix	UBERON:0000002	91.88	gold quality
blood	UBERON:0000178	91.85	gold quality
body of pancreas	UBERON:0001150	91.78	gold quality
bone marrow	UBERON:0002371	91.76	gold quality
cortex of kidney	UBERON:0001225	91.75	gold quality
fallopian tube	UBERON:0003889	91.58	gold quality
left uterine tube	UBERON:0001303	91.57	gold quality
right adrenal gland	UBERON:0001233	91.55	gold quality
pancreas	UBERON:0001264	91.53	gold quality
right lobe of thyroid gland	UBERON:0001119	91.43	gold quality
mucosa of transverse colon	UBERON:0004991	91.42	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIF1A

miRNA regulators (miRDB)

126 targeting PPP1R10, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
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-570-3P	99.96	72.41	4910
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-302E	99.96	70.74	2669
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-335-3P	99.93	73.36	4958

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 21)

• PNUTS has a role in protein kinase A-regulated targeting of PP1 to specific RNA-associated complexes in the nucleus (PMID:12574161)
• PNUTS, encoded by CAT 53 on 6p21.3, may have a role in the progression of AD. (PMID:15894402)
• results illustrate an involvement of the PNUTS:PP1 holoenzyme in chromosome decondensation in vitro and argue that PNUTS functions as a PP1-targeting subunit in this process (PMID:15907195)
• Findings suggest that PNUTS may play an important role in controlling cell death in response to cellular stresses such as hypoxia through the post-translational modification of p53 and MDM2. (PMID:17318220)
• reduced expression of PNUTS leads to activation of Rb-phosphatase and caspase-mediated apoptosis (PMID:18360108)
• the coordinated spatial and temporal regulation of LCP1 and PNUTS may be a novel mechanism to control the expression of genes that are critical for certain physiological and pathological processes. (PMID:19293638)
• no evidence found of association between a CAT53 polymorphism and Alzheimer’s Disease (AD), but found a significant negative association of the C282Y HFE mutation with AD (PMID:19429178)
• stimulation of PP1 activity via siRNA mediated knockdown of its interacting protein PNUTS (Phosphatase Nuclear Targeting Subunit) leads to Rb dephosphorylation and apoptosis in cancer cells (PMID:20372802)
• mammalian Wdr82 functions in a variety of cellular processes; PTW/PP1 phosphatase complex (PNUTS, Tox4, Wdr82, PP1) has a role in the regulation of chromatin structure during the transition from mitosis into interphase (PMID:20516061)
• PNUTS is identified as a new and integral component of the DNA damage response involved in DNA repair. (PMID:20890310)
• our studies reveal PNUTS as a novel PTEN regulator and a likely oncogene. (PMID:23117887)
• PNUTS was a valid target of miR-383 and was involved in the inhibition of gammaH2AX. (PMID:24462707)
• PNUTS inhibits the PP1-mediated dephosphorylation of critical substrates, especially retinoblastoma protein, by blocking their binding sites on PP1. (PMID:24591642)
• Biophysical analysis of PNUTS suggests an extended transcription factor TFIIS-like fold. (PMID:27591855)
• PNUTS is a bifunctional RNA encoding both PNUTS mRNA and lncRNA-PNUTS, each eliciting distinct biological functions. While PNUTS mRNA is ubiquitously expressed, lncRNA-PNUTS appears to be tightly regulated dependent on the status of hnRNP E1 and tumour context. (PMID:28825698)
• A -31 G to A “hot zone” putative functional noncoding variant of PPP1R10 was found in an AML patient. It perturbs the binding activities of E2F1, E2F4, ZBTB33, and TBP. SRSF1 and PPP1R10 genes are interacting partners in a protein-protein interaction network. (PMID:29764005)
• The work demonstrates that PP1/PNUTS stabilizes chromatin-bound MYC in proliferating cells. (PMID:30158517)
• PNUTS depletion suppresses the activation of Aurora A/B kinases, and disrupts the spatiotemporal regulation of the chromosomal passenger complex (CPC). PNUTS dynamically localizes to kinetochores, and is required for the activation of the spindle assembly checkpoint. (PMID:30190438)
• Poly(A) site-dependent deceleration caused by PNUTS-PP1 and Spt5 dephosphorylation is required to convert Pol II into a viable target for the Xrn2 terminator exonuclease, leading to transcription termination. (PMID:31677974)
• Upregulation of Phosphatase 1 Nuclear-Targeting Subunit (PNUTS) Is an Independent Predictor of Poor Prognosis in Prostate Cancer. (PMID:32377272)
• Alternatively-spliced lncRNA-PNUTS promotes HCC cell EMT via regulating ZEB1 expression. (PMID:35139713)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppp1r10	ENSDARG00000032651
mus_musculus	Ppp1r10	ENSMUSG00000039220
rattus_norvegicus	Ppp1r10	ENSRNOG00000059268
drosophila_melanogaster	PNUTS	FBGN0053526

Paralogs (2): ZC3H18 (ENSG00000158545), PRR3 (ENSG00000204576)

Protein

Protein identifiers

Serine/threonine-protein phosphatase 1 regulatory subunit 10 — Q96QC0 (reviewed: Q96QC0)

Alternative names: MHC class I region proline-rich protein CAT53, PP1-binding protein of 114 kDa, Phosphatase 1 nuclear targeting subunit, p99

All UniProt accessions (2): Q96QC0, Q2L6I0

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-recognition component of the PNUTS-PP1 protein phosphatase complex, a protein phosphatase 1 (PP1) complex that promotes RNA polymerase II transcription pause-release, allowing transcription elongation. Promoter-proximal pausing by RNA polymerase II is a transcription halt following transcription initiation but prior to elongation, which acts as a checkpoint to control that transcripts are favorably configured for transcriptional elongation. The PNUTS-PP1 complex mediates the release of RNA polymerase II from promoter-proximal region of genes by catalyzing dephosphorylation of proteins involved in transcription, such as AFF4, CDK9, MEPCE, INTS12, NCBP1, POLR2M/GDOWN1 and SUPT6H. The PNUTS-PP1 complex also regulates RNA polymerase II transcription termination by mediating dephosphorylation of SUPT5H in termination zones downstream of poly(A) sites, thereby promoting deceleration of RNA polymerase II transcription. PNUTS-PP1 complex is also involved in the response to replication stress by mediating dephosphorylation of POLR2A at ‘Ser-5’ of the CTD, promoting RNA polymerase II degradation. The PNUTS-PP1 complex also plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. PNUTS-PP1 complex mediates dephosphorylation of MYC, promoting MYC stability by preventing MYC ubiquitination by the SCF(FBXW7) complex. In addition to acts as a substrate-recognition component, PPP1R10/PNUTS also acts as a nuclear targeting subunit for the PNUTS-PP1 complex. In some context, PPP1R10/PNUTS also acts as an inhibitor of protein phosphatase 1 (PP1) activity by preventing access to substrates, such as RB.

Subunit / interactions. Component of the PNUTS-PP1 complex (also named PTW/PP1 complex), composed of PPP1R10/PNUTS, TOX4, WDR82, and PPP1CA (or PPP1CB or PPP1CC).

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Post-translational modifications. Phosphorylated on Ser-398 by PKA within the region necessary for interaction with PPP1CA.

Domain organisation. The TFIIS N-terminal domain specifically recognizes disordered sequences in protein substrates that are then dephosphorylated by PPP1CA (or PPP1CB or PPP1CC).

RefSeq proteins (2): NP_001363124, NP_002705* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000571	Znf_CCCH	Domain
IPR003617	TFIIS/CRSP70_N_sub	Domain
IPR017923	TFIIS_N	Domain
IPR035441	TFIIS/LEDGF_dom_sf	Homologous_superfamily
IPR036855	Znf_CCCH_sf	Homologous_superfamily

Pfam: PF00642, PF08711

UniProt features (54 total): compositionally biased region 11, helix 11, region of interest 9, modified residue 9, sequence conflict 3, cross-link 2, strand 2, chain 1, domain 1, short sequence motif 1, zinc finger region 1, sequence variant 1, mutagenesis site 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8SW5	X-RAY DIFFRACTION	2.39
6ZV2	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96QC0-F1	58.34	0.16

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): 256, 313, 382, 398, 545, 591, 665, 693, 738, 179, 262

Mutagenesis-validated functional residues (1):

Position	Phenotype
140	abolished interaction with ppp1ca, preventing ability to regulate transcription-pause release and transcription terminat

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9770562	mRNA Polyadenylation

MSigDB gene sets: 350 (showing top): RNGTGGGC_UNKNOWN, GOBP_CHROMOSOME_ORGANIZATION, GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, TAATAAT_MIR126, TGCGCANK_UNKNOWN, GOBP_DNA_TEMPLATED_TRANSCRIPTION_TERMINATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, TGCACTT_MIR519C_MIR519B_MIR519A, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_TELOMERE_ORGANIZATION, CREBP1_Q2, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE

GO Biological Process (11): RNA polymerase II promoter clearance (GO:0001111), protein import into nucleus (GO:0006606), negative regulation of cardiac muscle cell apoptotic process (GO:0010667), positive regulation of telomere maintenance (GO:0032206), positive regulation of transcription elongation by RNA polymerase II (GO:0032968), negative regulation of transcription elongation by RNA polymerase II (GO:0034244), protein stabilization (GO:0050821), negative regulation of mitotic DNA damage checkpoint (GO:1904290), positive regulation of termination of RNA polymerase II transcription, poly(A)-coupled (GO:2000806), transcription by RNA polymerase II (GO:0006366), transcription elongation by RNA polymerase II (GO:0006368)

GO Molecular Function (9): DNA binding (GO:0003677), RNA binding (GO:0003723), protein phosphatase inhibitor activity (GO:0004864), protein phosphatase 1 binding (GO:0008157), zinc ion binding (GO:0008270), protein phosphatase regulator activity (GO:0019888), enzyme-substrate adaptor activity (GO:0140767), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (7): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear body (GO:0016604), PTW/PP1 phosphatase complex (GO:0072357), chromosome, telomeric region (GO:0000781), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
mRNA 3’-end processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
transcription elongation by RNA polymerase II	2
regulation of transcription elongation by RNA polymerase II	2
nucleic acid binding	2
phosphoprotein phosphatase activity	2
protein phosphatase binding	2
cellular anatomical structure	2
intracellular membraneless organelle	2
promoter clearance during DNA-templated transcription	1
intracellular protein transport	1
protein localization to nucleus	1
import into nucleus	1
establishment of protein localization to organelle	1
cardiac muscle cell apoptotic process	1
negative regulation of striated muscle cell apoptotic process	1
regulation of cardiac muscle cell apoptotic process	1
telomere maintenance	1
regulation of telomere maintenance	1
positive regulation of DNA metabolic process	1
positive regulation of chromosome organization	1
positive regulation of DNA-templated transcription, elongation	1
positive regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription, elongation	1
regulation of protein stability	1
negative regulation of cell cycle process	1
mitotic DNA damage checkpoint signaling	1
positive regulation of mitotic cell cycle	1
regulation of mitotic DNA damage checkpoint	1
negative regulation of DNA damage checkpoint	1
termination of RNA polymerase II transcription, poly(A)-coupled	1
positive regulation of termination of RNA polymerase II transcription	1
regulation of termination of RNA polymerase II transcription, poly(A)-coupled	1
DNA-templated transcription	1
DNA-templated transcription elongation	1
phosphatase inhibitor activity	1
protein phosphatase regulator activity	1
transition metal ion binding	1
phosphatase regulator activity	1
protein-macromolecule adaptor activity	1
binding	1

Protein interactions and networks

STRING

1909 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPP1R10	PPP1CA	P08129	762
PPP1R10	WDR82	Q6UXN9	760
PPP1R10	PPP1R8	Q12972	755
PPP1R10	SNIP1	Q8TAD8	748
PPP1R10	CDCA2	Q69YH5	709
PPP1R10	PPP1CC	P36873	701
PPP1R10	PPP1CB	P37140	683
PPP1R10	HLA-E	P13747	674
PPP1R10	TOX4	O94842	660
PPP1R10	CD99	P14209	636
PPP1R10	PPP1R7	Q15435	552
PPP1R10	TERF2	Q15554	527
PPP1R10	PGK1	P00558	507
PPP1R10	PPP1R9B	Q96SB3	507
PPP1R10	BTK	Q06187	497

IntAct

144 interactions, top by confidence:

A	B	Type	Score
TERF2IP	TERF2	psi-mi:“MI:0914”(association)	0.970
PIK3CA	PIK3R2	psi-mi:“MI:0914”(association)	0.900
CAPN1	CAPNS1	psi-mi:“MI:0914”(association)	0.840
MED23	MED19	psi-mi:“MI:2364”(proximity)	0.770
PPP1R10	PPP1CA	psi-mi:“MI:0915”(physical association)	0.760
PPP1CB	CCDC85C	psi-mi:“MI:0914”(association)	0.750
PPP1CB	CCDC85C	psi-mi:“MI:2364”(proximity)	0.750
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PPP1CC	CCDC85C	psi-mi:“MI:2364”(proximity)	0.740
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
PPP1CA	CCDC85C	psi-mi:“MI:2364”(proximity)	0.670
TERF2	MCPH1	psi-mi:“MI:0914”(association)	0.580
TOX4	PPP1CA	psi-mi:“MI:0914”(association)	0.570
RSPH9	EIF3H	psi-mi:“MI:0914”(association)	0.530
WDR82	SETD1A	psi-mi:“MI:0914”(association)	0.530
SUPT5H	POLR2D	psi-mi:“MI:0914”(association)	0.530
KCTD17	CBX4	psi-mi:“MI:0914”(association)	0.530

BioGRID (266): PPP1R10 (Affinity Capture-MS), PPP1R10 (Affinity Capture-MS), PPP1R10 (Affinity Capture-MS), PPP1R10 (Affinity Capture-MS), PPP1R10 (Affinity Capture-MS), PPP1R10 (Affinity Capture-MS), PPP1R10 (Affinity Capture-MS), PPP1R10 (Affinity Capture-MS), PPP1R10 (Affinity Capture-MS), PPP1R10 (Affinity Capture-MS), PPP1R10 (Reconstituted Complex), PPP1R10 (Affinity Capture-MS), PPP1R10 (Proximity Label-MS), PPP1R10 (Affinity Capture-MS), PPP1R10 (Affinity Capture-MS)

ESM2 similar proteins: A2AJK6, A2VDB3, A5PJN8, C5XYW4, F1R5H6, F4NYQ2, G3CHK5, O55000, O60885, O95104, P0CB49, P49750, P51532, P75330, Q06A37, Q08D75, Q10124, Q15428, Q3TKT4, Q4R7I8, Q4V7X9, Q5TM61, Q5ZHZ4, Q62203, Q63623, Q63627, Q66KL9, Q6AXT8, Q6DFF2, Q6DID3, Q6DRG1, Q75N03, Q767K9, Q7TSH6, Q7YR38, Q80W00, Q8CFT2, Q8CGZ0, Q8IWX8, Q8K1P7

Diamond homologs: O55000, P79522, Q5TM61, Q6GLQ4, Q6MG07, Q767K9, Q767L1, Q7YR36, Q7YR38, Q80W00, Q811B5, Q96QC0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NUAK1	“up-regulates activity”	PPP1R10	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 170 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
Pausing and recovery of Tat-mediated HIV elongation	5	16.2×	8e-04
Tat-mediated HIV elongation arrest and recovery	5	16.2×	8e-04
HIV elongation arrest and recovery	5	15.2×	9e-04
Pausing and recovery of HIV elongation	5	15.2×	9e-04
HIV Transcription Elongation	5	14.7×	9e-04
Formation of RNA Pol II elongation complex	7	11.9×	2e-04
RNA Polymerase II Transcription Elongation	7	11.9×	2e-04
Formation of HIV-1 elongation complex containing HIV-1 Tat	5	11.4×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
entrainment of circadian clock by photoperiod	5	24.6×	4e-04
positive regulation of transcription elongation by RNA polymerase II	8	16.2×	2e-05
mRNA splicing, via spliceosome	13	8.0×	1e-05
RNA splicing	12	7.1×	4e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	91
Likely benign	11
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2037 predictions. Top by Δscore:

Variant	Effect	Δscore
6:30601654:CATGT:C	acceptor_gain	1.0000
6:30601659:C:CC	acceptor_gain	1.0000
6:30601930:CCTCA:C	donor_loss	1.0000
6:30601931:CTCAC:C	donor_loss	1.0000
6:30601932:TCA:T	donor_loss	1.0000
6:30601933:CA:C	donor_loss	1.0000
6:30601934:A:AC	donor_gain	1.0000
6:30601934:ACCT:A	donor_gain	1.0000
6:30601935:C:CC	donor_gain	1.0000
6:30601935:C:CT	donor_loss	1.0000
6:30601935:CCT:C	donor_gain	1.0000
6:30601935:CCTC:C	donor_gain	1.0000
6:30601937:T:TA	donor_gain	1.0000
6:30602687:GGGAC:G	acceptor_gain	1.0000
6:30602688:GGAC:G	acceptor_gain	1.0000
6:30602689:GAC:G	acceptor_gain	1.0000
6:30602690:AC:A	acceptor_gain	1.0000
6:30602690:ACC:A	acceptor_loss	1.0000
6:30602691:CCTG:C	acceptor_gain	1.0000
6:30602692:C:CC	acceptor_gain	1.0000
6:30602694:G:C	acceptor_gain	1.0000
6:30602694:G:GC	acceptor_gain	1.0000
6:30602703:C:CT	acceptor_gain	1.0000
6:30602704:A:T	acceptor_gain	1.0000
6:30602960:C:CC	acceptor_gain	1.0000
6:30603204:GATTA:G	donor_loss	1.0000
6:30603205:ATTAC:A	donor_loss	1.0000
6:30603206:TTAC:T	donor_loss	1.0000
6:30603207:TA:T	donor_loss	1.0000
6:30603208:A:AC	donor_gain	1.0000

AlphaMissense

6078 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:30604050:C:G	R489P	1.000
6:30604135:A:G	W461R	1.000
6:30604135:A:T	W461R	1.000
6:30604194:C:G	R441P	1.000
6:30604222:C:G	A432P	1.000
6:30604229:A:C	F429L	1.000
6:30604229:A:T	F429L	1.000
6:30604230:A:C	F429C	1.000
6:30604230:A:G	F429S	1.000
6:30604231:A:G	F429L	1.000
6:30604248:A:T	V423E	1.000
6:30604250:A:C	N422K	1.000
6:30604250:A:T	N422K	1.000
6:30604357:T:A	E419D	1.000
6:30604357:T:G	E419D	1.000
6:30604358:T:A	E419V	1.000
6:30604375:A:C	F413L	1.000
6:30604375:A:T	F413L	1.000
6:30604377:A:G	F413L	1.000
6:30604411:C:A	W401C	1.000
6:30604411:C:G	W401C	1.000
6:30604413:A:G	W401R	1.000
6:30604413:A:T	W401R	1.000
6:30605064:A:G	L295P	1.000
6:30605064:A:T	L295H	1.000
6:30605075:A:C	F291L	1.000
6:30605075:A:T	F291L	1.000
6:30605076:A:G	F291S	1.000
6:30605077:A:G	F291L	1.000
6:30606477:G:T	R209S	1.000

dbSNP variants (sampled 300 via entrez): RS1000157407 (6:30614454 A>C), RS1000442325 (6:30616660 C>A,T), RS1000473154 (6:30616508 G>A), RS1000483702 (6:30608257 G>A), RS1000549684 (6:30613169 C>T), RS1000765872 (6:30606257 C>A), RS1000844072 (6:30612630 G>A,C,T), RS1000899909 (6:30612989 G>C), RS1000949312 (6:30605775 G>T), RS1000967267 (6:30617785 G>C,T), RS1001162827 (6:30615784 C>T), RS1001440459 (6:30609552 C>G,T), RS1002067532 (6:30619090 G>A,C,T), RS1002285542 (6:30602649 A>G), RS1002416888 (6:30618809 C>T)

Disease associations

OMIM: gene MIM:603771 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST004521_114	Autism spectrum disorder or schizophrenia	3.000000e-17
GCST004521_117	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_121	Autism spectrum disorder or schizophrenia	3.000000e-13
GCST004521_132	Autism spectrum disorder or schizophrenia	2.000000e-09
GCST004521_171	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_2	Autism spectrum disorder or schizophrenia	2.000000e-16
GCST004521_209	Autism spectrum disorder or schizophrenia	5.000000e-16
GCST004521_210	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_211	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_263	Autism spectrum disorder or schizophrenia	7.000000e-17
GCST004521_265	Autism spectrum disorder or schizophrenia	7.000000e-14
GCST004521_269	Autism spectrum disorder or schizophrenia	7.000000e-11
GCST004521_295	Autism spectrum disorder or schizophrenia	6.000000e-18
GCST004521_3	Autism spectrum disorder or schizophrenia	2.000000e-15
GCST004521_56	Autism spectrum disorder or schizophrenia	1.000000e-22
GCST004521_70	Autism spectrum disorder or schizophrenia	8.000000e-20
GCST004521_79	Autism spectrum disorder or schizophrenia	1.000000e-16
GCST004602_50	Mean corpuscular volume	6.000000e-16
GCST007201_387	Schizophrenia	1.000000e-14

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725163 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.04	IC50	910	nM	MOLIBRESIB

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.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178715: Inhibition of PPP1R10 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.9100	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression, affects expression	4
Cadmium Chloride	decreases methylation, increases expression	4
Arsenic	increases abundance, increases expression, affects methylation, affects cotreatment	2
Nickel	decreases expression, increases expression	2
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
FR900359	affects phosphorylation	1
urushiol	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	increases expression	1
cinnamaldehyde	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
pyrrolidine dithiocarbamic acid	affects cotreatment, increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
bathocuproine sulfonate	affects cotreatment, increases expression	1
ferrous chloride	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	decreases phosphorylation	1
vanadyl sulfate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
vanillin	decreases expression	1
ICG 001	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Acetaldehyde	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants, Occupational	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697445	Binding	Inhibition of PPP1R10 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C303	Mel285	Cancer cell line	Female
CVCL_C304	Mel290	Cancer cell line	Female

Clinical trials (associated diseases)

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