PPP1CB

Summary

PPP1CB (protein phosphatase 1 catalytic subunit beta, HGNC:9282) is a protein-coding gene on chromosome 2p23.2, encoding Serine/threonine-protein phosphatase PP1-beta catalytic subunit (P62140). Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. It is a selective cancer dependency (DepMap: 89.6% of cell lines).

The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). PP1 is a serine/threonine specific protein phosphatase known to be involved in the regulation of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. Mouse studies suggest that PP1 functions as a suppressor of learning and memory. Two alternatively spliced transcript variants encoding distinct isoforms have been observed.

Source: NCBI Gene 5500 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Noonan syndrome-like disorder with loose anagen hair (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 8
• Clinical variants (ClinVar): 366 total — 4 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 99
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 89.6% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_002709

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9282
Approved symbol	PPP1CB
Name	protein phosphatase 1 catalytic subunit beta
Location	2p23.2
Locus type	gene with protein product
Status	Approved
Aliases	PP1Cbeta, PPP1CD, PP1Cdelta, PP1B, PP-1B, PP1beta, PP1c, MP, PPP1beta
Ensembl gene	ENSG00000213639
Ensembl biotype	protein_coding
OMIM	600590
Entrez	5500

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 28 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000296122, ENST00000395366, ENST00000418910, ENST00000420282, ENST00000427786, ENST00000441461, ENST00000455580, ENST00000464273, ENST00000703171, ENST00000703172, ENST00000703173, ENST00000703174, ENST00000703175, ENST00000703176, ENST00000703177, ENST00000703183, ENST00000868409, ENST00000868410, ENST00000868411, ENST00000868412, ENST00000868413, ENST00000868414, ENST00000930106, ENST00000941104, ENST00000941105, ENST00000941106, ENST00000941107, ENST00000941108, ENST00000941109, ENST00000941110, ENST00000941111, ENST00000941112, ENST00000941113, ENST00000941114

RefSeq mRNA: 2 — MANE Select: NM_002709 NM_002709, NM_206876

CCDS: CCDS33169

Canonical transcript exons

ENST00000395366 — 8 exons

Exon	Start	End
ENSE00001623145	28781738	28781842
ENSE00001906903	28799199	28802940
ENSE00001932380	28751830	28752176
ENSE00003512678	28776851	28776982
ENSE00003786696	28783907	28783978
ENSE00003789746	28778809	28779039
ENSE00003988242	28788658	28788809
ENSE00003988257	28793863	28793997

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 77.1754 / max 868.3864, expressed in 1825 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19485	45.8500	1796
19482	32.5463	1810
19484	30.1879	1812
19481	4.4724	1598
19480	4.0847	1495
19477	2.2340	1020
19478	1.3363	797
19479	1.0931	655
19487	0.6681	337
19483	0.5526	313

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.17	gold quality
amniotic fluid	UBERON:0000173	99.11	gold quality
buccal mucosa cell	CL:0002336	99.10	gold quality
ventricular zone	UBERON:0003053	99.03	gold quality
descending thoracic aorta	UBERON:0002345	98.98	gold quality
tendon	UBERON:0000043	98.91	gold quality
lower esophagus	UBERON:0013473	98.91	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.91	gold quality
popliteal artery	UBERON:0002250	98.90	gold quality
tibial artery	UBERON:0007610	98.90	gold quality
aorta	UBERON:0000947	98.83	gold quality
artery	UBERON:0001637	98.82	gold quality
thoracic aorta	UBERON:0001515	98.74	gold quality
ascending aorta	UBERON:0001496	98.73	gold quality
ganglionic eminence	UBERON:0004023	98.73	gold quality
caput epididymis	UBERON:0004358	98.73	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.72	gold quality
choroid plexus epithelium	UBERON:0003911	98.71	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.67	gold quality
mucosa of stomach	UBERON:0001199	98.65	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.61	gold quality
parotid gland	UBERON:0001831	98.60	gold quality
muscle of leg	UBERON:0001383	98.58	gold quality
cauda epididymis	UBERON:0004360	98.56	gold quality
gastrocnemius	UBERON:0001388	98.55	gold quality
blood vessel layer	UBERON:0004797	98.51	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.51	gold quality
left coronary artery	UBERON:0001626	98.45	gold quality
esophagus	UBERON:0001043	98.44	gold quality
skeletal muscle organ	UBERON:0014892	98.44	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-8498	yes	14099.04
E-GEOD-111727	yes	6032.78
E-MTAB-10287	yes	44.11
E-GEOD-135922	yes	26.94
E-GEOD-134144	yes	11.19
E-HCAD-9	yes	5.45
E-CURD-97	no	11764.67
E-CURD-6	no	10867.14
E-GEOD-76312	no	7474.83
E-CURD-89	no	2696.07
E-MTAB-9154	no	627.41
E-MTAB-6524	no	307.68
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI2, TEAD4

miRNA regulators (miRDB)

165 targeting PPP1CB, 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-340-5P	100.00	72.50	4437
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-3148	99.97	75.06	6478

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 89.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 31)

• In this study, we show that protein phosphatase-1 (PP1) inhibitor-3 (Inh3) is localized to the nucleoli and centrosomes in interphase HEK 293 cells. (PMID:16256067)
• R16A at the membrane may mediate the PB signal to initiate CAR nuclear translocation, through a mechanism including its dimerization and inhibition of PP1beta activity. (PMID:18202305)
• PP-1 ( PP-1alpha or PP-1beta ) acts as a major phosphatase to dephosphorylate AKT1 at Thr-450 and thus modulate its functions in regulating gene expression, cell survival and differentiation. (PMID:20186153)
• 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)
• serine/threonine protein phosphatase PP1beta is a physiological Nucleophosmin (NPM) phosphatase under both the genotoxic stress and growth conditions. (PMID:20962268)
• Data suggest that double-thiophosphorylation of TIMAP has minor effect on its binding ability to PP1c, but considerably attenuates its inhibitory effect on the activity of PP1c. (PMID:21466834)
• PPP1CB is over expressed in malignant melanoma. (PMID:21566537)
• Protein phosphatase 1beta (PP1beta) is identified as a phosphatase for the cluster of phosphorylated threonines ((353)TTETQRT(359)) within the sst(2A) somatostatin receptor carboxyl terminus that mediates beta-arrestin binding using siRNA knock-down screening. (PMID:21795688)
• Studies suggest that any change in substrate specificity of the spinophilin : PP1 holoenzyme complex was probably due to direct modification of a PP1 substrate binding surface. (PMID:22284538)
• Studies indicate that the Ser/Thr phosphatases PP1 and PP2A are responsible for the dephosphorylation and activation of Rb proteins. (PMID:22299668)
• Studies indicate that the diversity of the PP1 interactome and the properties of the PP1 binding code account for the exquisite specificity of PP1 in vivo. (PMID:22360570)
• These findings provide evidence for the involvement of a particular PP1 complex, PPP1R12A/PP1cdelta, in insulin signaling. (PMID:22728334)
• Interaction between protein phosphatase 1 beta and myosin phosphatase (MYPT)1 results in exclusion of Nkx2.5 from the cell nucleus. (PMID:23168335)
• PPP1C isoforms have distinct contribution to the outside-in alphaIIbbeta3 signalling-dependent functions in HEK293 alphaIIbbeta3 cells. (PMID:23197154)
• results indicate that SCN-iPS cells provide a useful disease model for SCN, and the activation of the Wnt3a/beta-catenin pathway may offer a novel therapy for SCN with ELANE mutation (PMID:23382248)
• Findings show that PP1cbeta plays a role in endothelial cell migration through a mechanism involving the interplay of actin cytoskeleton proteins and focal adhesion molecules signaling. (PMID:25967976)
• These results suggest a unique functional role for the PP1beta isoform in affecting cardiac contractile function (PMID:26334248)
• Missense mutations in PPP1CB are associated with a phenotype resembling NS-LAH. Based on this phenotype and PPP1CB’s known role within the RAS/MAPK pathway, we think that this condition is a novel rasopathy, which may be provisionally termed “PPP1CB-related Noonan syndrome with loose anagen hair” (P-NS-LAH). (PMID:27264673)
• this study shows a pivotal role for PP1 in impeding IRF7-mediated IFN-alpha production in host immune responses (PMID:27469204)
• Our data suggest that our heterozygous de novo PPP1CB pathogenic variants are associated with syndromic intellectual disability. (PMID:27681385)
• This report gives further support that this novel RASopathy-PPP1CB-related Noonan syndrome with loose anagen hair-shares great similarity to Noonan syndrome-like disorder with loose anagen hair, and expands the phenotypic spectrum by adding the cranial vault abnormality. (PMID:28211982)
• PPP1CB mutation is associated with Noonan syndrome. (PMID:30368668)
• Activating MRAS mutations cause Noonan syndrome associated with hypertrophic cardiomyopathy. (PMID:31108500)
• The association of MYPT1 with PP1cbeta was profoundly reduced in the presence of excess TIMAP, leading to proteasomal MYPT1 degradation. (PMID:31315927)
• our experiments support that PPP1CB and KPC2 together inhibit the activity of HOXA2 by activating its nuclear export, but favored HOXA2 de-ubiquitination and stabilization thereby establishing a store of HOXA2 in the cytoplasm. (PMID:31323436)
• Integrative genomics analysis of eQTL and GWAS summary data identifies PPP1CB as a novel bone mineral density risk genes. (PMID:32266926)
• A case report of Noonan syndrome-like disorder with loose anagen hair 2 treated with recombinant human growth hormone. (PMID:32476286)
• Noonan syndrome with loose anagen hair with variants in the PPP1CB gene: First familial case reported. (PMID:33491856)
• The expression and clinical prognostic value of protein phosphatase 1 catalytic subunit beta in pancreatic cancer. (PMID:34125004)
• PP-1beta and PP-2Aalpha modulate cAMP response element-binding protein (CREB) functions in aging control and stress response through de-regulation of alphaB-crystallin gene and p300-p53 signaling axis. (PMID:34425033)
• Histones Methyltransferase NSD3 Inhibits Lung Adenocarcinoma Glycolysis Through Interacting with PPP1CB to Decrease STAT3 Signaling Pathway. (PMID:39119928)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppp1cb	ENSDARG00000044153
danio_rerio	ppp1cbl	ENSDARG00000102012
mus_musculus	Ppp1cb	ENSMUSG00000014956
rattus_norvegicus	Ppp1cb	ENSRNOG00000004612
rattus_norvegicus		ENSRNOG00000069573
rattus_norvegicus		ENSRNOG00000084581
drosophila_melanogaster	flw	FBGN0000711
caenorhabditis_elegans		WBGENE00001747

Paralogs (12): PPP5C (ENSG00000011485), PPEF1 (ENSG00000086717), PPP2CB (ENSG00000104695), PPP3CB (ENSG00000107758), PPP2CA (ENSG00000113575), PPP6C (ENSG00000119414), PPP3CC (ENSG00000120910), PPP3CA (ENSG00000138814), PPP4C (ENSG00000149923), PPEF2 (ENSG00000156194), PPP1CA (ENSG00000172531), PPP1CC (ENSG00000186298)

Protein

Protein identifiers

Serine/threonine-protein phosphatase PP1-beta catalytic subunit — P62140 (reviewed: P62140)

All UniProt accessions (10): A0A8V8TQ71, A0A8V8TR83, A0A8V8TRH9, B4DJ75, C9J9S3, C9JP48, P62140, F8WE71, H0Y3Y6, V9HW04

UniProt curated annotations — full annotation on UniProt →

Function. Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase (PP1) is essential for cell division, it participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E. Dephosphorylates the ‘Ser-418’ residue of FOXP3 in regulatory T-cells (Treg) from patients with rheumatoid arthritis, thereby inactivating FOXP3 and rendering Treg cells functionally defective. Core component of the SHOC2-MRAS-PP1c (SMP) holophosphatase complex that regulates the MAPK pathway activation. The SMP complex specifically dephosphorylates the inhibitory phosphorylation at ‘Ser-259’ of RAF1 kinase, ‘Ser-365’ of BRAF kinase and ‘Ser-214’ of ARAF kinase, stimulating their kinase activities. The SMP complex enhances the dephosphorylation activity and substrate specificity of PP1c.

Subunit / interactions. PP1 comprises a catalytic subunit, PPP1CA, PPP1CB or PPP1CC, which is folded into its native form by inhibitor 2 and glycogen synthetase kinase 3, and then complexed to one or several targeting or regulatory subunits. The targeting or regulatory subunits determine the substrate specificity of PP1. PPP1R12A, PPP1R12B and PPP1R12C mediate binding to myosin. PPP1R3A (in skeletal muscle), PPP1R3B (in liver), PPP1R3C, PPP1R3D and PPP1R3F (in brain) mediate binding to glycogen. Part of a complex containing PPP1R15B, PP1 and NCK1/2. Interacts with PPP1R7 and PPP1R12C. PPP1R15A and PPP1R15B mediate binding to EIF2S1. Interacts with PPP1R16B. Component of the PTW/PP1 phosphatase complex, composed of PPP1R10/PNUTS, TOX4, WDR82, and PPP1CA or PPP1CB or PPP1CC. Interacts with PPP1R8. Interacts with TRIM28; the interaction is weak. Interacts with PPP1R12A and NUAK1; the interaction is direct. Interacts with FOXP3. Interacts with RRP1B. Interacts with SERPINE1. Interacts with LZTR1. Component of the SHOC2-MRAS-PP1c (SMP) complex consisting of SHOC2, GTP-bound M-Ras/MRAS and the catalytic subunit of protein phosphatase 1 (either PPP1CA, PPP1CB or PPP1CC). SHOC2 and PP1c preferably bind M-Ras/MRAS, but they also bind K-Ras/KRAS, N-Ras/NRAS and H-Ras/HRAS; these interactions are GTP-dependent and both SHOC2 and PP1c are required to form a stable complex. Interacts with SHOC2 in the absence of Ras GTPases.

Subcellular location. Cytoplasm. Nucleus. Nucleoplasm. Nucleolus.

Disease relevance. Noonan syndrome-like disorder with loose anagen hair 2 (NSLH2) [MIM:617506] A syndrome characterized by Noonan dysmorphic features such as macrocephaly, high forehead, hypertelorism, palpebral ptosis, low-set and posteriorly rotated ears, short and webbed neck, pectus anomalies, in association with pluckable, sparse, thin and slow-growing hair. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by the toxins okadaic acid, tautomycin and microcystin Leu-Arg. The phosphatase activity of the PPP1R15A-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress.

Cofactor. Binds 2 manganese ions per subunit.

Induction. Up-regulated in synovial fluid mononuclear cells and peripheral blood mononuclear cells from patients with rheumatoid arthritis.

Similarity. Belongs to the PPP phosphatase family. PP-1 subfamily.

RefSeq proteins (2): NP_002700, NP_996759 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004843	Calcineurin-like_PHP	Domain
IPR006186	Ser/Thr-sp_prot-phosphatase	Domain
IPR029052	Metallo-depent_PP-like	Homologous_superfamily
IPR031675	STPPase_N	Domain
IPR050341	PP1_catalytic_subunit	Family

Pfam: PF00149, PF16891

Enzyme classification (BRENDA):

• EC 3.1.3.16 — protein-serine/threonine phosphatase (BRENDA: 92 organisms, 641 substrates, 468 inhibitors, 127 Km, 67 kcat entries)

Substrate kinetics (BRENDA)

59 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
6,8-DIFLUORO-4-METHYLUMBELLIFERYL PHOSPHATE	0.023–0.862	22
4-NITROPHENYL PHOSPHATE	0.0028–12.7	13
P-NITROPHENYL PHOSPHATE	3–200	11
RRAPTVA	0.058–1.954	4
PHOSPHOCASEIN	0.0001–0.002	3
PHOSPHOHISTONE	0.0023–0.0723	3
PHOSPHORYLATED MYOSIN LIGHT CHAIN PEPTIDE	0.01–0.11	3
PHOSPHOSERINE-MYELIN BASIC PROTEIN	0.0004–0.022	3
DLDVPIPGRFDRRVSVAAE	0.0006–0.0138	2
DLDVPIPGRFDRRVY(P)VAAE	0.0025–0.023	2
PHOSPHORYLASE A	0.004–0.021	2
RRA(PT)VA	0.0536–0.308	2
80S-RIBOSOME	0.0027	1
AAAPTVA	0.206	1
AGPALSPVPPV	0.357	1

Catalyzed reactions (Rhea), 4 shown:

• O-phospho-L-seryl-[myosin light chain] + H2O = L-seryl-[myosin light chain] + phosphate (RHEA:12849)
• O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate (RHEA:20629)
• O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate (RHEA:47004)
• O-phospho-L-threonyl-[myosin light chain] + H2O = L-threonyl-[myosin light chain] + phosphate (RHEA:53988)

UniProt features (20 total): binding site 7, sequence variant 6, modified residue 2, initiator methionine 1, chain 1, sequence conflict 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62140-F1	91.91	0.87

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 124 (proton donor)

Ligand- & substrate-binding residues (7): 247; 63; 65; 91; 91; 123; 172

Post-translational modifications (2): 2, 316

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-163560	Triglyceride catabolism
R-HSA-2173788	Downregulation of TGF-beta receptor signaling
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-5625740	RHO GTPases activate PKNs
R-HSA-5625900	RHO GTPases activate CIT
R-HSA-5627117	RHO GTPases Activate ROCKs
R-HSA-5627123	RHO GTPases activate PAKs
R-HSA-5673000	RAF activation
R-HSA-9726840	SHOC2 M1731 mutant abolishes MRAS complex function
R-HSA-9726842	Gain-of-function MRAS complexes activate RAF signaling
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9828806	Maturation of hRSV A proteins
R-HSA-9931530	Phosphorylation and nuclear translocation of the CRY:PER:kinase complex

MSigDB gene sets: 522 (showing top): GOBP_CIRCADIAN_RHYTHM, REACTOME_TRIGLYCERIDE_CATABOLISM, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, MOOTHA_GLYCOGEN_METABOLISM, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, HNF3ALPHA_Q6, MODULE_255, GOBP_PHOTOPERIODISM, TTTGTAG_MIR520D, YANG_BREAST_CANCER_ESR1_LASER_DN, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, TGACCTY_ERR1_Q2, GOBP_CIRCADIAN_REGULATION_OF_GENE_EXPRESSION, HNF1_Q6, FOXO1_01

GO Biological Process (9): MAPK cascade (GO:0000165), glycogen metabolic process (GO:0005977), protein dephosphorylation (GO:0006470), regulation of cell adhesion (GO:0030155), circadian regulation of gene expression (GO:0032922), regulation of circadian rhythm (GO:0042752), entrainment of circadian clock by photoperiod (GO:0043153), cell division (GO:0051301), rhythmic process (GO:0048511)

GO Molecular Function (9): protein serine/threonine phosphatase activity (GO:0004722), phosphatase activity (GO:0016791), myosin phosphatase activity (GO:0017018), protein kinase binding (GO:0019901), metal ion binding (GO:0046872), myosin-light-chain-phosphatase activity (GO:0050115), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), focal adhesion (GO:0005925), extracellular exosome (GO:0070062), PTW/PP1 phosphatase complex (GO:0072357), chromosome, telomeric region (GO:0000781)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
RHO GTPase Effectors	4
Signaling by MRAS-complex mutants	2
Triglyceride metabolism	1
TGF-beta receptor signaling activates SMADs	1
G2/M Transition	1
RAF/MAP kinase cascade	1
mRNA 3’-end processing	1
Respiratory syncytial virus (RSV) genome replication, transcription and translation	1
Circadian clock	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
circadian rhythm	2
phosphoprotein phosphatase activity	2
nuclear lumen	2
intracellular signaling cassette	1
energy reserve metabolic process	1
glucan metabolic process	1
dephosphorylation	1
protein modification process	1
cell adhesion	1
regulation of cellular process	1
regulation of gene expression	1
regulation of biological process	1
photoperiodism	1
entrainment of circadian clock	1
cellular process	1
biological_process	1
phosphoric ester hydrolase activity	1
protein serine/threonine phosphatase activity	1
kinase binding	1
cation binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cytoplasm	1
cell-substrate junction	1
extracellular vesicle	1
protein phosphatase type 1 complex	1
chromosomal region	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

332 interactions, top by confidence:

A	B	Type	Score
PPP1CB	SH2D4A	psi-mi:“MI:0915”(physical association)	0.960
SH2D4A	PPP1CB	psi-mi:“MI:0915”(physical association)	0.960
PPP1CB	PPP1R7	psi-mi:“MI:0915”(physical association)	0.930
PPP1R11	PPP1CB	psi-mi:“MI:0915”(physical association)	0.920
PPP1R16A	PPP1CB	psi-mi:“MI:0915”(physical association)	0.830
PPP1CB	PPP1R16A	psi-mi:“MI:0915”(physical association)	0.830
PPP1CB	PPP1R16B	psi-mi:“MI:0915”(physical association)	0.790
PPP1R16B	PPP1CB	psi-mi:“MI:0915”(physical association)	0.790
PPP1CB	PPP1R3C	psi-mi:“MI:0915”(physical association)	0.780
PPP1R3C	PPP1CB	psi-mi:“MI:0915”(physical association)	0.780
PPP1CB	CCDC85C	psi-mi:“MI:0914”(association)	0.750
PPP1CB	CCDC85C	psi-mi:“MI:2364”(proximity)	0.750
CSRNP2	PPP1CB	psi-mi:“MI:0915”(physical association)	0.740
PPP1CB	CSRNP2	psi-mi:“MI:0915”(physical association)	0.740
PPP1CB	PPP1R2B	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (712): PPP1R3C (Two-hybrid), TP53BP2 (Two-hybrid), SH2D4A (Two-hybrid), CSRNP2 (Two-hybrid), PPP1R16A (Two-hybrid), PPP1R2P3 (Two-hybrid), PPP1CB (Affinity Capture-MS), AKT1 (Affinity Capture-Western), PPP1CB (Affinity Capture-Western), PPP1CB (Affinity Capture-MS), PPP1CB (Affinity Capture-MS), PPP1CB (Two-hybrid), PPP1CB (Two-hybrid), PPP1CB (Two-hybrid), RORC (Two-hybrid)

ESM2 similar proteins: A2YEB4, A3C4N5, O00743, O02658, O04856, O04857, O04860, O04951, P0C5D7, P20604, P23696, P23778, P36614, P36874, P48462, P48481, P48482, P48485, P48486, P48487, P48529, P48578, P48580, P61292, P62140, P62141, P62142, P62143, P62207, P91420, Q06009, Q07098, Q07099, Q07100, Q0DBD3, Q27497, Q3SWW9, Q5I085, Q5R740, Q61JR3

Diamond homologs: A0C1E4, A0CCD2, A6H772, A8XE00, A9JRC7, B0XUR7, G5EGK8, O02658, O04856, O04857, O04858, O15757, O76932, O82733, O82734, P11084, P11493, P11611, P11612, P12982, P13681, P20654, P22198, P23696, P23733, P23734, P23777, P23880, P26570, P30366, P32598, P32945, P33329, P36873, P36874, P48458, P48459, P48461, P48462, P48463

SIGNOR signaling

18 interactions.

A	Effect	B	Mechanism
PPP1CB	up-regulates	NF2	dephosphorylation
PPP1CB	down-regulates	AKT1	dephosphorylation
PPP1CB	up-regulates	IKZF1	dephosphorylation
PPP1CB	“down-regulates activity”	AXIN1	dephosphorylation
PPP1CB	“down-regulates activity”	TP53	dephosphorylation
PPP1CB	“up-regulates activity”	NOS3	dephosphorylation
PPP1CB	“down-regulates activity”	AKT	dephosphorylation
PPP1CB	“up-regulates quantity by stabilization”	MDM2	dephosphorylation
PPP1CB	“down-regulates activity”	AKT1	dephosphorylation
PPP1R1B	“down-regulates activity”	PPP1CB	binding
PPP1CB	unknown	AHCYL1	dephosphorylation
PPP1CB	“up-regulates activity”	CASP2	dephosphorylation
PPP1R14A	“down-regulates activity”	PPP1CB	binding
PPP1R14B	“down-regulates activity”	PPP1CB	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 118 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
Mitotic G1 phase and G1/S transition	5	15.3×	6e-04
MITF-M-dependent gene expression	5	15.1×	6e-04
EML4 and NUDC in mitotic spindle formation	8	12.4×	2e-05
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	6	11.7×	4e-04
Resolution of Sister Chromatid Cohesion	8	11.5×	3e-05
RHO GTPase Effectors	10	11.3×	4e-06
Regulation of TP53 Activity	5	11.1×	2e-03
RHO GTPases Activate Formins	8	10.4×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
glycogen metabolic process	5	27.4×	7e-04
G1/S transition of mitotic cell cycle	6	12.5×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	8
Uncertain significance	95
Likely benign	220
Benign	18

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
254648	NM_002709.3(PPP1CB):c.146C>G (p.Pro49Arg)	Pathogenic
254651	NM_002709.3(PPP1CB):c.548A>T (p.Glu183Val)	Pathogenic
254652	NM_002709.3(PPP1CB):c.548A>C (p.Glu183Ala)	Pathogenic
4282429	NM_002709.3(PPP1CB):c.569G>A (p.Arg190Lys)	Pathogenic
1727054	NM_002709.3(PPP1CB):c.493G>C (p.Asp165His)	Likely pathogenic
2231503	NM_002709.3(PPP1CB):c.755A>G (p.Asp252Gly)	Likely pathogenic
254649	NM_002709.3(PPP1CB):c.754G>T (p.Asp252Tyr)	Likely pathogenic
254653	NM_002709.3(PPP1CB):c.820G>A (p.Glu274Lys)	Likely pathogenic
3256555	NM_002709.3(PPP1CB):c.493G>A (p.Asp165Asn)	Likely pathogenic
4075297	NM_002709.3(PPP1CB):c.515A>G (p.His172Arg)	Likely pathogenic
427633	NM_002709.3(PPP1CB):c.166G>C (p.Ala56Pro)	Likely pathogenic
546861	NM_002709.3(PPP1CB):c.255C>A (p.Asn85Lys)	Likely pathogenic

SpliceAI

1533 predictions. Top by Δscore:

Variant	Effect	Δscore
2:28751857:G:GT	donor_gain	1.0000
2:28752172:GGAGG:G	donor_gain	1.0000
2:28752173:GAGG:G	donor_gain	1.0000
2:28752173:GAGGG:G	donor_gain	1.0000
2:28752175:GG:G	donor_gain	1.0000
2:28752176:GG:G	donor_gain	1.0000
2:28752177:G:A	donor_loss	1.0000
2:28752178:T:G	donor_loss	1.0000
2:28776841:C:A	acceptor_gain	1.0000
2:28776845:T:TA	acceptor_gain	1.0000
2:28776846:GTCA:G	acceptor_loss	1.0000
2:28776848:CAG:C	acceptor_loss	1.0000
2:28776849:A:AG	acceptor_gain	1.0000
2:28776849:A:AT	acceptor_loss	1.0000
2:28776849:AGTAC:A	acceptor_gain	1.0000
2:28776850:G:GT	acceptor_gain	1.0000
2:28776850:GT:G	acceptor_gain	1.0000
2:28776850:GTA:G	acceptor_gain	1.0000
2:28776850:GTAC:G	acceptor_gain	1.0000
2:28776850:GTACG:G	acceptor_gain	1.0000
2:28776852:ACGAG:A	acceptor_gain	1.0000
2:28776961:G:GT	donor_gain	1.0000
2:28776980:GTG:G	donor_gain	1.0000
2:28776983:G:C	donor_loss	1.0000
2:28776983:G:GG	donor_gain	1.0000
2:28776984:T:A	donor_loss	1.0000
2:28778803:TTTTA:T	acceptor_loss	1.0000
2:28778804:TTTAG:T	acceptor_loss	1.0000
2:28778805:TTAG:T	acceptor_loss	1.0000
2:28778808:G:GT	acceptor_loss	1.0000

AlphaMissense

2136 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:28776982:G:A	G62R	1.000
2:28776982:G:C	G62R	1.000
2:28778809:G:A	G62E	1.000
2:28778809:G:T	G62V	1.000
2:28778811:G:C	D63H	1.000
2:28778812:A:C	D63A	1.000
2:28778812:A:G	D63G	1.000
2:28778812:A:T	D63V	1.000
2:28778813:T:A	D63E	1.000
2:28778813:T:G	D63E	1.000
2:28778817:C:A	H65N	1.000
2:28778817:C:G	H65D	1.000
2:28778819:T:A	H65Q	1.000
2:28778819:T:G	H65Q	1.000
2:28778820:G:A	G66R	1.000
2:28778820:G:C	G66R	1.000
2:28778821:G:A	G66E	1.000
2:28778821:G:T	G66V	1.000
2:28778884:T:A	L87H	1.000
2:28778884:T:C	L87P	1.000
2:28778892:G:A	G90R	1.000
2:28778892:G:C	G90R	1.000
2:28778893:G:A	G90E	1.000
2:28778893:G:T	G90V	1.000
2:28778895:G:C	D91H	1.000
2:28778896:A:C	D91A	1.000
2:28778896:A:G	D91G	1.000
2:28778896:A:T	D91V	1.000
2:28778897:T:A	D91E	1.000
2:28778897:T:G	D91E	1.000

dbSNP variants (sampled 300 via entrez): RS1000022162 (2:28773012 A>G), RS1000087650 (2:28766834 C>A), RS1000112033 (2:28788158 T>TG), RS1000190200 (2:28760743 A>G), RS1000193450 (2:28771119 T>A,G), RS1000219865 (2:28760974 C>T), RS1000283818 (2:28800443 G>A), RS1000335883 (2:28793566 A>C,T), RS1000374327 (2:28754573 CA>C), RS1000411380 (2:28760042 C>A), RS1000459962 (2:28766651 T>A), RS1000478203 (2:28749659 T>C,G), RS1000511063 (2:28750008 A>G), RS1000547592 (2:28787874 C>G,T), RS1000644011 (2:28783088 C>A)

Disease associations

OMIM: gene MIM:600590 | disease phenotypes: MIM:617506, MIM:220200, MIM:163950, MIM:607721

GenCC curated gene-disease

Disease	Classification	Inheritance
Noonan syndrome-like disorder with loose anagen hair	Definitive	Autosomal dominant
Noonan syndrome-like disorder with loose anagen hair 2	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Noonan syndrome-like disorder with loose anagen hair	Definitive	AD

Mondo (6): Noonan syndrome-like disorder with loose anagen hair 2 (MONDO:0054588), Dandy-Walker syndrome (MONDO:0009072), Noonan syndrome (MONDO:0018997), RASopathy (MONDO:0021060), Noonan syndrome-like disorder with loose anagen hair (MONDO:0011899), intellectual disability (MONDO:0001071)

Orphanet (5): Isolated Dandy-Walker malformation (Orphanet:217), RASopathy (Orphanet:536391), Noonan syndrome (Orphanet:648), Noonan syndrome-like disorder with loose anagen hair (Orphanet:2701), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

99 total (30 of 99 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000174	Abnormal palate morphology
HP:0000179	Thick lower lip vermilion
HP:0000193	Bifid uvula
HP:0000207	Triangular mouth
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000233	Thin vermilion border
HP:0000238	Hydrocephalus
HP:0000256	Macrocephaly
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000329	Facial hemangioma
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000391	Thickened helices
HP:0000396	Overfolded helix
HP:0000400	Macrotia
HP:0000430	Underdeveloped nasal alae
HP:0000445	Wide nose
HP:0000463	Anteverted nares
HP:0000465	Webbed neck
HP:0000470	Short neck
HP:0000475	Broad neck

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002783_312	Body mass index	9.000000e-07
GCST006090_1	Excessive sweating	2.000000e-11
GCST006288_419	Heel bone mineral density	4.000000e-08
GCST006288_569	Heel bone mineral density	1.000000e-11
GCST006979_916	Heel bone mineral density	1.000000e-21
GCST007656_7	Chronic obstructive pulmonary disease or resting heart rate (pleiotropy)	9.000000e-12
GCST008523_1	Pure non-grapefruit juice consumption	2.000000e-07
GCST008758_32	Pre-treatment viral load in HIV-1 infection	4.000000e-19

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0009270	heel bone mineral density
EFO:0010095	non-grapefruit juice consumption measurement
EFO:0010125	viral load

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D003616	Dandy-Walker Syndrome	C10.228.140.252.300; C10.228.140.602.500; C10.500.205; C16.131.666.205
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009634	Noonan Syndrome	C05.660.207.690; C14.240.400.787; C14.280.400.787; C16.131.240.400.784; C16.131.621.207.690; C17.300.690
C564342	Noonan-Like Syndrome With Loose Anagen Hair (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4546 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	decreases expression, increases expression	3
Valproic Acid	decreases methylation, affects expression, decreases expression	3
bisphenol A	increases expression, affects cotreatment	2
Air Pollutants	decreases expression, increases abundance	2
Benzene	increases expression	2
Rotenone	decreases expression, increases expression	2
Smoke	increases abundance, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Cadmium Chloride	increases abundance, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	increases expression, decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
moringin	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
oxybenzone	increases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
tamibarotene	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
deguelin	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
pyrimidifen	increases expression	1
nutlin 3	increases secretion, affects cotreatment	1
bisphenol B	increases expression	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4221651	Binding	Binding affinity to full length recombinant human N-terminal His6-tagged PP1cdelta expressed in Escherichia coli M15 assessed as inhibition of protein interaction with GST-tagged MYPT1 at 10 to 50 uM by surface plasmon resonance method	Aralkyl selenoglycosides and related selenosugars in acetylated form activate protein phosphatase-1 and -2A. — Bioorg Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00452725	PHASE3	COMPLETED	Effect of MAXOMAT ® on the Growth of Small Children to NOONAN’s Syndrome
NCT01529840	PHASE3	COMPLETED	Somatropin Effect on Linear Growth and Final Height in Subjects With Noonan Syndrome
NCT01529944	PHASE3	COMPLETED	Genetic Testing of Noonan Subjects Previously Treated With Norditropin®. An Extension to Trial GHNOO-1658
NCT01927861	PHASE3	COMPLETED	Investigating the Long-term Efficacy and Safety of Two Doses of NN-220 (Somatropin) in Short Stature Due to Noonan Syndrome
NCT02713945	PHASE3	COMPLETED	Treatment With HMG-COA Reductase Inhibitor of Growth and Bone Abnormalities in Children With Noonan Syndrome
NCT05723835	PHASE3	ACTIVE_NOT_RECRUITING	A Research Study Looking at How Safe Somapacitan is and How Well it Works in Children Who Need Help to Grow - REAL 9
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00351221	PHASE2	TERMINATED	Research Study Using Recombinant Human Insulin-Like Growth Factor-1/Recombinant Human Insulin-Like Growth Factor Binding Protein-3 for Children With Noonan Syndrome
NCT06555237	PHASE2	RECRUITING	MEK Inhibitors for the Treatment of Hypertrophic Cardiomyopathy in Patients With RASopathies
NCT06668805	PHASE2	RECRUITING	A Study of Vosoritide in Children With Noonan Syndrome With Inadequate Growth During or After Human Growth Hormone Treatment
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT00960128	Not specified	COMPLETED	Observational Prospective Study on Patients Treated With Norditropin®
NCT02486731	Not specified	COMPLETED	Hormonal Sensitivity in Patients With Noonan and LEOPARD Syndromes
NCT03435627	Not specified	COMPLETED	Post Marketing Surveillance on Long-term Use With Norditropin® (Short Stature Due to Noonan Syndrome)
NCT04395495	Not specified	RECRUITING	RASopathy Biorepository
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes
NCT04888936	Not specified	RECRUITING	Clinical, Genetic, and Epidemiologic Study of Children and Adults With RASopathies
NCT05202210	Not specified	RECRUITING	Constitution of a Biological Collection to Study the Pathophysiology in Noonan Syndrome
NCT05308927	Not specified	ENROLLING_BY_INVITATION	French Registry of Children Treated With Norditropin® for Short Stature Associated With Noonan Syndrome
NCT05361811	Not specified	RECRUITING	Acceptance and Commitment Therapy for Caregivers of Children With a RASopathy: An Internal Pilot Feasibility Study and Follow-up Randomized Controlled Trial
NCT05761314	Not specified	RECRUITING	Solid Tumors in RASopathies
NCT06267807	Not specified	COMPLETED	Lymphatic Phenotype in Noonan Syndrome Spectrum Disorders
NCT06331117	Not specified	UNKNOWN	Effect of RAS/MAPK Pathway Hyperactivation on Growth’ and Bone’ Profile of the RASopathies
NCT06355622	Not specified	UNKNOWN	Prevalence and Characterization of Pain in RASopathies
NCT06550635	Not specified	COMPLETED	Joint and Hematologic Disorders of Noonan Syndrome: French Descriptive Cross-sectional Study
NCT06938542	Not specified	ENROLLING_BY_INVITATION	Palliative Care Needs of Children With Rare Diseases and Their Families
NCT07259135	Not specified	NOT_YET_RECRUITING	Link Between Abnormal Bleeding and Coagulation Disorders in Noonan Syndromes
NCT07336394	Not specified	RECRUITING	Precision Diagnosis and Risk Stratification of Rare Cardiomyopathies Based on Novel Cardiac Magnetic Resonance Techniques