PPP1R9B

Summary

PPP1R9B (protein phosphatase 1 regulatory subunit 9B, HGNC:9298) is a protein-coding gene on chromosome 17q21.33, encoding Neurabin-2 (Q96SB3). Seems to act as a scaffold protein in multiple signaling pathways.

This gene encodes a scaffold protein that functions as a regulatory subunit of protein phosphatase 1a. Expression of this gene is particularly high in dendritic spines, suggesting that the encoded protein may play a role in receiving signals from the central nervous system. The encoded protein has putative tumor suppressor function and decreased expression has been observed in tumors.

Source: NCBI Gene 84687 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 167 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_032595

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9298
Approved symbol	PPP1R9B
Name	protein phosphatase 1 regulatory subunit 9B
Location	17q21.33
Locus type	gene with protein product
Status	Approved
Aliases	Spn, SPINO
Ensembl gene	ENSG00000108819
Ensembl biotype	protein_coding
OMIM	603325
Entrez	84687

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000513579, ENST00000612501, ENST00000962426, ENST00000962427

RefSeq mRNA: 1 — MANE Select: NM_032595 NM_032595

CCDS: CCDS74102

Canonical transcript exons

ENST00000612501 — 10 exons

Exon	Start	End
ENSE00003712514	50140093	50140228
ENSE00003713208	50133737	50135384
ENSE00003714063	50135553	50135649
ENSE00003714704	50145113	50145245
ENSE00003723514	50139429	50139581
ENSE00003742978	50143598	50143718
ENSE00003745842	50135968	50136197
ENSE00003746640	50149143	50150677
ENSE00003747983	50141269	50141373
ENSE00003748577	50139263	50139316

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 97.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.8379 / max 242.5439, expressed in 1795 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166852	9.5498	1759
166851	2.7215	1446
166850	0.5666	282

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	97.03	gold quality
granulocyte	CL:0000094	97.02	gold quality
anterior cingulate cortex	UBERON:0009835	96.99	gold quality
cerebellar hemisphere	UBERON:0002245	96.84	gold quality
cerebellar cortex	UBERON:0002129	96.82	gold quality
monocyte	CL:0000576	96.73	gold quality
leukocyte	CL:0000738	96.72	gold quality
right frontal lobe	UBERON:0002810	96.69	gold quality
amygdala	UBERON:0001876	96.02	gold quality
cerebellum	UBERON:0002037	95.96	gold quality
cortical plate	UBERON:0005343	95.74	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.38	gold quality
prefrontal cortex	UBERON:0000451	95.34	gold quality
nucleus accumbens	UBERON:0001882	95.26	gold quality
putamen	UBERON:0001874	95.22	gold quality
caudate nucleus	UBERON:0001873	95.10	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.73	gold quality
frontal cortex	UBERON:0001870	94.36	gold quality
neocortex	UBERON:0001950	94.28	gold quality
vermiform appendix	UBERON:0001154	94.05	gold quality
spleen	UBERON:0002106	93.63	gold quality
ganglionic eminence	UBERON:0004023	93.54	gold quality
cerebral cortex	UBERON:0000956	93.27	gold quality
lymph node	UBERON:0000029	93.16	gold quality
Ammon’s horn	UBERON:0001954	92.99	gold quality
stromal cell of endometrium	CL:0002255	92.91	gold quality
right coronary artery	UBERON:0001625	92.83	gold quality
brain	UBERON:0000955	92.73	gold quality
hypothalamus	UBERON:0001898	92.70	gold quality
forebrain	UBERON:0001890	92.62	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.94
E-GEOD-124858	no	2.85

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXC1, GATA4, SP1

miRNA regulators (miRDB)

185 targeting PPP1R9B, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
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-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-1271-5P	99.91	71.99	1972

Literature-anchored findings (GeneRIF, showing 23)

• The actin-binding domain of spinophilin is necessary and sufficient for targeting of spinophilin to dendrites and dendritic spines. (PMID:12230305)
• Decreased spinophilin but unchanged MAP2 expression provides molecular evidence for a hippocampal dendritic pathology in schizophrenia that preferentially affects the spines. (PMID:15465982)
• PPP1R9B is required for synapse formation in the NK cells and suggest that it may be involved in the maintenance of cellular architecture by regulation of actin assembly, possibly acting to stabilize the NKIS until granule release is eminent. (PMID:19130477)
• Asef2, Neurabin2 and APC cooperatively regulate actin cytoskeletal organization and are required for HGF-induced cell migration. (PMID:19151759)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• IRSp53 and spinophilin regulate localized Rac activation by T-lymphocyte invasion and metastasis protein 1 (PMID:20360004)
• The molecular size and subcellular location of myotube glycogen particles is determined by the PPP1R6, PTG and G(M) scaffolding. (PMID:22054094)
• Data show that that SPL/RGS/SHP1 complexes are present in resting platelets where constitutive phosphorylation of SPL(Y398) creates an atypical binding site for SHP-1. (PMID:22210881)
• 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)
• Spinophilin-deficient mice have enhanced antidepressant response to desipramine compared with wild-type controls. (PMID:22369787)
• Spinophilin associates with both delta- and mu-OmicronR and G protein subunits in HEK293 cells participating in a multimeric signaling complex that displays a differential regulatory role in opioid receptor signaling. (PMID:22922354)
• study found a substantial number of hepatocellular carcinomas (HCC) show reduced or absent Spn expression; the low expression of Spn in tumour tissue is an independent negative prognostic factor for clinical outcome in HCC; spinophilin expression inversely correlates with proliferative activity (PMID:23591196)
• Spn downregulation contributes to a more aggressive biologic behavior, induces chemoresistance, and is associated with a poorer survival in patients with advanced stages of colorectal carcinoma. (PMID:23729363)
• spinophilin might play a previously unrecognized role in the pathogenesis of head and neck squamous cell carcinoma (PMID:24565202)
• Colorectal carcinoma expression of spinophilin expression determines cellular growth, cancer stemness and 5-flourouracil resistance. (PMID:25261368)
• Low spinophilin expression enhances aggressive biological behavior of breast cancer. (PMID:25857299)
• The increased cancer stem cells-like properties induced by the downregulation of Spn might account for the increased malignant phenotype observed in Spn-null breast tumors. (PMID:26387546)
• results indicate that spinophilin plays an important role in regulating the activity of Group I mGluRs as well as their influence on synaptic activity. (PMID:27358397)
• Data identify Spn as a critical adhesion and signaling protein that is essential for modulating glioblastoma cell invasion in the brain microenvironment. Spn suppresses brain tumor cell invasion, in part, via control of Rac1 GTPase activities and invadopodia disassembly. Its C-terminus binds directly to the beta 8 integrin cytoplasmic tail. (PMID:27655131)
• Clinical onset of AD is marked by the loss of PreC spinophilin-ir dendritic spines that is related to Abeta pathology and may contribute to cognitive symptoms early in the disease. (PMID:28259365)
• Study determined that spinophilin binding to neurofilament medium required overexpression of the catalytic subunit of protein kinase A and was decreased by cyclin-dependent protein kinase 5. (PMID:28634551)
• homo-oligomerization of neurabin is required for stabilizing RGS4 on the plasma membrane to attenuate A1R signaling (PMID:28954816)
• Mutation of SPINOPHILIN (PPP1R9B) found in human tumors promotes the tumorigenic and stemness properties of cells. (PMID:33537097)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppp1r9bb	ENSDARG00000071709
danio_rerio	ppp1r9ba	ENSDARG00000079366
mus_musculus	Ppp1r9b	ENSMUSG00000038976
rattus_norvegicus	Ppp1r9b	ENSRNOG00000052113
drosophila_melanogaster	Spn	FBGN0010905
caenorhabditis_elegans	nab-1	WBGENE00003516

Paralogs (2): PPP1R9A (ENSG00000158528), SAMD14 (ENSG00000167100)

Protein

Protein identifiers

Neurabin-2 — Q96SB3 (reviewed: Q96SB3)

Alternative names: Neurabin-II, Protein phosphatase 1 regulatory subunit 9B, Spinophilin

All UniProt accessions (1): Q96SB3

UniProt curated annotations — full annotation on UniProt →

Function. Seems to act as a scaffold protein in multiple signaling pathways. Modulates excitatory synaptic transmission and dendritic spine morphology. Binds to actin filaments (F-actin) and shows cross-linking activity. Binds along the sides of the F-actin. May play an important role in linking the actin cytoskeleton to the plasma membrane at the synaptic junction. Believed to target protein phosphatase 1/PP1 to dendritic spines, which are rich in F-actin, and regulates its specificity toward ion channels and other substrates, such as AMPA-type and NMDA-type glutamate receptors. Plays a role in regulation of G-protein coupled receptor signaling, including dopamine D2 receptors and alpha-adrenergic receptors. May establish a signaling complex for dopaminergic neurotransmission through D2 receptors by linking receptors downstream signaling molecules and the actin cytoskeleton. Binds to ADRA1B and RGS2 and mediates regulation of ADRA1B signaling. May confer to Rac signaling specificity by binding to both, RacGEFs and Rac effector proteins. Probably regulates p70 S6 kinase activity by forming a complex with TIAM1. Required for hepatocyte growth factor (HGF)-induced cell migration.

Subunit / interactions. Interacts with DCLK2. Possibly exists as a homodimer, homotrimer or a homotetramer. Interacts with F-actin, PPP1CA, neurabin-1, TGN38 and D(2) dopamine receptor. Interacts with RGS1, RGS2, RGS4, RGS19 and ADRA1B, ADRA2A, ADRA2B, ADRA2C, CDKN2A, PPP1R2, RASGFR1 and TIAM1. Interacts (via C-terminus) with SPATA13 (via C-terminal tail). Interacts with ADRA2B.

Subcellular location. Cytoplasm. Cytoskeleton. Nucleus. Cell projection. Dendritic spine. Postsynaptic density. Synapse. Cell junction. Adherens junction. Cell membrane. Lamellipodium. Filopodium. Ruffle membrane.

Post-translational modifications. Stimulation of D1 (but not D2) dopamine receptors induces Ser-94 phosphorylation. Dephosphorylation of Ser-94 is mediated mainly by PP1 and to a lesser extent by PP2A. Phosphorylation of spinophilin disrupts its association with F-actin, but does not affect its binding to PP1.

Domain organisation. The PP1 binding region is natively unstructured, upon PP1 binding, it acquires structure, blocks a substrate-binding site, and restricts PP1 phosphatase specificity to a subset of substrates.

RefSeq proteins (1): NP_115984* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR036034	PDZ_sf	Homologous_superfamily
IPR040645	Neurabin-1/2_PDZ	Domain
IPR043446	Neurabin-like	Family

Pfam: PF00595, PF17817

UniProt features (36 total): modified residue 11, region of interest 9, compositionally biased region 7, sequence conflict 4, chain 1, domain 1, coiled-coil region 1, short sequence motif 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96SB3-F1	63.67	0.30

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): 15, 17, 94, 100, 116, 192, 193, 205, 207, 438, 658

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 692 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_DENDRITE_DEVELOPMENT, GGGACCA_MIR133A_MIR133B, GOBP_REGULATION_OF_CELL_ACTIVATION, E2F_Q4_01, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, AP1_01, GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, GOBP_COGNITION, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_BEHAVIOR, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_RESPONSE_TO_ESTRADIOL

GO Biological Process (43): regulation of cell growth by extracellular stimulus (GO:0001560), response to amphetamine (GO:0001975), developmental process involved in reproduction (GO:0003006), actin filament organization (GO:0007015), regulation of exit from mitosis (GO:0007096), learning (GO:0007612), RNA splicing (GO:0008380), dendrite development (GO:0016358), cell migration (GO:0016477), calcium-mediated signaling (GO:0019722), hippocampus development (GO:0021766), cerebral cortex development (GO:0021987), actin filament depolymerization (GO:0030042), negative regulation of cell growth (GO:0030308), neuron projection development (GO:0031175), response to prostaglandin E (GO:0034695), response to nicotine (GO:0035094), response to immobilization stress (GO:0035902), regulation of cell population proliferation (GO:0042127), filopodium assembly (GO:0046847), response to steroid hormone (GO:0048545), regulation of cell cycle (GO:0051726), male mating behavior (GO:0060179), reproductive system development (GO:0061458), cellular response to morphine (GO:0071315), cellular response to epidermal growth factor stimulus (GO:0071364), cellular response to estradiol stimulus (GO:0071392), cellular response to xenobiotic stimulus (GO:0071466), regulation of postsynapse assembly (GO:0150052), cellular response to peptide (GO:1901653), positive regulation of protein localization to plasma membrane (GO:1903078), protein localization to actin cytoskeleton (GO:1903119), positive regulation of protein localization to actin cortical patch (GO:1904372), response to kainic acid (GO:1904373), response to L-phenylalanine derivative (GO:1904386), protein localization to cell periphery (GO:1990778), regulation of opioid receptor signaling pathway (GO:2000474), nervous system development (GO:0007399), response to xenobiotic stimulus (GO:0009410), cell differentiation (GO:0030154)

GO Molecular Function (10): protein kinase activity (GO:0004672), protein phosphatase inhibitor activity (GO:0004864), protein phosphatase 1 binding (GO:0008157), kinase binding (GO:0019900), D2 dopamine receptor binding (GO:0031749), transmembrane transporter binding (GO:0044325), actin filament binding (GO:0051015), actin binding (GO:0003779), protein binding (GO:0005515), protein-containing complex binding (GO:0044877)

GO Cellular Component (29): protein phosphatase type 1 complex (GO:0000164), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), plasma membrane (GO:0005886), adherens junction (GO:0005912), postsynaptic density (GO:0014069), actin cytoskeleton (GO:0015629), lamellipodium (GO:0030027), filopodium (GO:0030175), dendrite (GO:0030425), growth cone (GO:0030426), cortical actin cytoskeleton (GO:0030864), ruffle membrane (GO:0032587), neuronal cell body (GO:0043025), dendritic spine neck (GO:0044326), dendritic spine head (GO:0044327), spine apparatus (GO:0097444), extrinsic component of postsynaptic membrane (GO:0098890), glutamatergic synapse (GO:0098978), cytoplasmic side of dendritic spine plasma membrane (GO:1990780), nucleus (GO:0005634), cytoskeleton (GO:0005856), membrane (GO:0016020), dendritic spine membrane (GO:0032591), cell projection (GO:0042995), dendritic spine (GO:0043197), synapse (GO:0045202), anchoring junction (GO:0070161), plasma membrane bounded cell projection (GO:0120025)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
anatomical structure development	3
dendritic spine	3
regulation of cell growth	2
pallium development	2
binding	2
cellular response to stimulus	1
response to amine	1
reproductive process	1
developmental process	1
actin cytoskeleton organization	1
supramolecular fiber organization	1
exit from mitosis	1
regulation of mitotic cell cycle phase transition	1
learning or memory	1
RNA processing	1
neuron projection development	1
cell motility	1
intracellular signaling cassette	1
limbic system development	1
actin polymerization or depolymerization	1
protein depolymerization	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
neuron development	1
plasma membrane bounded cell projection organization	1
response to prostaglandin	1
response to alcohol	1
response to ketone	1
response to chemical	1
response to stress	1
cell population proliferation	1
regulation of cellular process	1
plasma membrane bounded cell projection assembly	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
phosphoprotein phosphatase activity	1
phosphatase inhibitor activity	1

Protein interactions and networks

STRING

1580 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPP1R9B	PPP1CC	P36873	904
PPP1R9B	RGS2	P41220	875
PPP1R9B	RGS4	P49798	874
PPP1R9B	SAG	P10523	863
PPP1R9B	PPP1CB	P37140	818
PPP1R9B	SPATA13	Q96N96	818
PPP1R9B	DCX	O43602	797
PPP1R9B	NEXN	Q0ZGT2	758
PPP1R9B	ARR3	P36575	753
PPP1R9B	PPP1CA	P08129	703
PPP1R9B	DBN1	Q16643	702
PPP1R9B	PPP1R1B	Q9UD71	678
PPP1R9B	ARRB2	P32121	668
PPP1R9B	PPP2R3A	Q06190	661
PPP1R9B	GRK2	P25098	632

IntAct

177 interactions, top by confidence:

A	B	Type	Score
CCM2	KRIT1	psi-mi:“MI:0914”(association)	0.960
PPP1CA	PPP1R9B	psi-mi:“MI:0915”(physical association)	0.890
PPP1CC	PPP1R9B	psi-mi:“MI:0915”(physical association)	0.860
BRCA1	ABRAXAS1	psi-mi:“MI:0914”(association)	0.860
MED23	MED19	psi-mi:“MI:2364”(proximity)	0.770
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
BRCA1	BRCA1	psi-mi:“MI:0914”(association)	0.650
POP4	POP7	psi-mi:“MI:0914”(association)	0.640
OSBPL5	NAGLU	psi-mi:“MI:0914”(association)	0.640
PPP1R9B	PPP1CB	psi-mi:“MI:0915”(physical association)	0.560
RPS14	MAGEB2	psi-mi:“MI:0914”(association)	0.560
POP4	NME2P1	psi-mi:“MI:0914”(association)	0.530
DCLK1	DCX	psi-mi:“MI:0914”(association)	0.530
KXD1	HIP1	psi-mi:“MI:0914”(association)	0.530
CASQ2	PES1	psi-mi:“MI:0914”(association)	0.530
YJU2B	RCCD1	psi-mi:“MI:0914”(association)	0.530
CACNB3	CACNB4	psi-mi:“MI:0914”(association)	0.530
KXD1	TRAK2	psi-mi:“MI:0914”(association)	0.530

BioGRID (304): PPP1R9B (Affinity Capture-MS), PPP1R9B (Affinity Capture-MS), PPP1R9B (Affinity Capture-MS), PPP1R9B (Affinity Capture-MS), PPP1R9B (Affinity Capture-MS), PPP1R9B (Affinity Capture-MS), PPP1R9B (Proximity Label-MS), PPP1R9B (Proximity Label-MS), PPP1R9B (Affinity Capture-MS), PPP1R9B (Affinity Capture-MS), PPP1R9B (Affinity Capture-MS), PPP1R9B (Affinity Capture-MS), PPP1R9B (Affinity Capture-MS), PPP1R9B (Affinity Capture-MS), PPP1R9B (Affinity Capture-MS)

ESM2 similar proteins: A0A088MLT8, A0A0G2K0D3, A2AQ19, B3KU38, D3ZTQ1, E1BTG2, E6ZGB4, E9PSK7, O35274, O60271, O75151, O75376, P12755, P22682, P29536, P49140, Q08DA0, Q13191, Q3B7T9, Q3TTA7, Q3UHZ5, Q3USH5, Q3YEC7, Q4KKX4, Q58A65, Q5SFM8, Q5U3K5, Q60698, Q60974, Q62415, Q640N2, Q6P5Q4, Q6R891, Q70E73, Q80XA6, Q86YP4, Q8BVA4, Q8CHY6, Q8K4S7, Q8R3Y5

Diamond homologs: A0A140LI67, A5PKA5, A7UA95, E1JIT7, O14910, O15018, O19132, O35274, O35867, O35889, O62666, O62674, O62675, O62676, O62677, O62678, O88951, O88952, P11434, P29475, P29476, P31016, P51140, P55196, P57105, P78352, Q07436, Q0P5F3, Q12923, Q14005, Q29498, Q2KIB6, Q32LM6, Q3T0C9, Q3UHD6, Q4KL35, Q5F425, Q5RAA5, Q62108, Q64512

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
MAPK1	unknown	PPP1R9B	phosphorylation
PRKACA	“down-regulates activity”	PPP1R9B	phosphorylation
PPP1R9B	“up-regulates activity”	SPATA13	binding
PPP1R9B	“up-regulates activity”	PP1	binding
CDK5	“down-regulates quantity”	PPP1R9B	phosphorylation
PPP1R9B	“up-regulates activity”	ARHGEF2	binding
PPP1R9B	up-regulates	F-actin_assembly
PPP1R9B	“up-regulates quantity”	TIAM1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 208 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
RHO GTPases activate PAKs	6	23.5×	1e-04
Sensory processing of sound	6	13.3×	1e-03
Parasite infection	5	12.4×	4e-03
Leishmania phagocytosis	5	12.4×	4e-03
FCGR3A-mediated phagocytosis	7	9.4×	2e-03
Regulation of actin dynamics for phagocytic cup formation	7	9.3×	2e-03
Signaling by ALK fusions and activated point mutants	8	8.7×	1e-03
Sensory processing of sound by inner hair cells of the cochlea	7	8.2×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
actin filament-based movement	5	21.2×	2e-03
actin cytoskeleton organization	14	5.9×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	76
Likely benign	29
Benign	14

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
253525	GRCh37/hg19 16p11.2(chr16:29060171-30197341)x3	Pathogenic

SpliceAI

1613 predictions. Top by Δscore:

Variant	Effect	Δscore
17:50135384:TC:T	acceptor_loss	1.0000
17:50135385:C:A	acceptor_loss	1.0000
17:50135385:C:CC	acceptor_gain	1.0000
17:50135548:CCCA:C	donor_loss	1.0000
17:50135549:CCAC:C	donor_loss	1.0000
17:50135550:CAC:C	donor_loss	1.0000
17:50135551:A:AT	donor_loss	1.0000
17:50135578:T:TA	donor_gain	1.0000
17:50135646:CTCC:C	acceptor_gain	1.0000
17:50135647:TCC:T	acceptor_gain	1.0000
17:50135648:CC:C	acceptor_gain	1.0000
17:50135648:CCC:C	acceptor_gain	1.0000
17:50135649:CC:C	acceptor_gain	1.0000
17:50135649:CCTG:C	acceptor_loss	1.0000
17:50135650:C:CC	acceptor_gain	1.0000
17:50135650:C:T	acceptor_gain	1.0000
17:50135650:CTGGG:C	acceptor_loss	1.0000
17:50135655:C:CT	acceptor_gain	1.0000
17:50135657:C:CT	acceptor_gain	1.0000
17:50135658:A:T	acceptor_gain	1.0000
17:50135661:C:CT	acceptor_gain	1.0000
17:50135662:A:T	acceptor_gain	1.0000
17:50135963:CGTA:C	donor_gain	1.0000
17:50135964:GTA:G	donor_loss	1.0000
17:50135965:TA:T	donor_loss	1.0000
17:50135966:A:AC	donor_gain	1.0000
17:50135966:ACTT:A	donor_gain	1.0000
17:50135967:C:CG	donor_gain	1.0000
17:50135967:CT:C	donor_gain	1.0000
17:50135967:CTT:C	donor_gain	1.0000

AlphaMissense

5310 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:50135974:T:G	Q766P	1.000
17:50135989:A:G	L761P	1.000
17:50135998:G:T	A758D	1.000
17:50135999:C:G	A758P	1.000
17:50136008:A:C	Y755D	1.000
17:50136019:A:G	L751P	1.000
17:50136049:A:G	L741P	1.000
17:50136073:A:G	L733P	1.000
17:50136083:C:G	A730P	1.000
17:50136103:A:G	L723P	1.000
17:50139273:A:G	L688P	1.000
17:50139289:C:G	A683P	1.000
17:50139297:A:T	V680D	1.000
17:50139301:C:G	A679P	1.000
17:50139303:T:G	H678P	1.000
17:50139305:C:A	K677N	1.000
17:50139305:C:G	K677N	1.000
17:50139315:A:G	L674P	1.000
17:50140169:T:G	Q597P	1.000
17:50140175:A:C	I595S	1.000
17:50140175:A:G	I595T	1.000
17:50140175:A:T	I595N	1.000
17:50140178:A:G	L594P	1.000
17:50140214:C:G	R582P	1.000
17:50140217:C:T	G581D	1.000
17:50140218:C:G	G581R	1.000
17:50140220:A:T	I580N	1.000
17:50140226:A:G	F578S	1.000
17:50141290:C:G	R570P	1.000
17:50141293:A:G	L569P	1.000

dbSNP variants (sampled 300 via entrez): RS1000131713 (17:50137486 C>G,T), RS1000301346 (17:50138424 G>A), RS1000506458 (17:50148085 T>C), RS1000572271 (17:50149180 G>A,C,T), RS1000592078 (17:50138180 G>A), RS1000889364 (17:50148040 G>A,C), RS1001180957 (17:50143779 C>A), RS1001233161 (17:50143509 G>A,C), RS1001295577 (17:50136956 G>A), RS1001649685 (17:50136653 A>T), RS1001679298 (17:50148629 G>T), RS1001769530 (17:50148921 G>A), RS1001966458 (17:50147769 G>A), RS1002030414 (17:50137357 A>G), RS1002079820 (17:50148947 C>T)

Disease associations

OMIM: gene MIM:603325 | disease phenotypes: MIM:611913

GenCC curated gene-disease

Mondo (1): proximal 16p11.2 microdeletion syndrome (MONDO:0012756)

Orphanet (1): Proximal 16p11.2 microdeletion syndrome (Orphanet:261197)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST009723_46	Vertical cup-disc ratio (adjusted for vertical disc diameter)	2.000000e-08
GCST009724_70	Vertical cup-disc ratio (multi-trait analysis)	4.000000e-12
GCST90002401_551	Platelet distribution width	1.000000e-20

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006939	cup-to-disc ratio measurement
EFO:0007984	platelet component distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C579850	16p11.2 Deletion Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725188 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, affects expression, increases abundance, increases expression	3
Nickel	increases expression	2
Smoke	decreases expression, increases abundance	2
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
trichostatin A	affects expression	1
sodium arsenite	increases expression	1
aflatoxin B2	increases methylation	1
coumarin	decreases phosphorylation	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
1-Methyl-3-isobutylxanthine	increases expression, affects cotreatment	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cadmium Chloride	decreases expression	1
Lactic Acid	increases expression	1
Particulate Matter	increases abundance, increases 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
CHEMBL5697372	Binding	Inhibition of PPP1R9B (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_TF88	HAP1 PPP1R9B (-) 1	Cancer cell line	Male
CVCL_TF89	HAP1 PPP1R9B (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04271332	PHASE2	ACTIVE_NOT_RECRUITING	Safety, Tolerability, and Efficacy of Arbaclofen in 16p11.2 Deletion
NCT01238250	Not specified	RECRUITING	Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight