PPP1R14B

Summary

PPP1R14B (protein phosphatase 1 regulatory inhibitor subunit 14B, HGNC:9057) is a protein-coding gene on chromosome 11q13.1, encoding Protein phosphatase 1 regulatory subunit 14B (Q96C90). Inhibitor of PPP1CA. It is a selective cancer dependency (DepMap: 60.3% of cell lines).

Predicted to enable protein serine/threonine phosphatase inhibitor activity. Predicted to be involved in innate immune response. Predicted to be located in cytoplasm.

Source: NCBI Gene 26472 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 20 total
• Cancer dependency (DepMap): dependent in 60.3% of screened cell lines
• MANE Select transcript: NM_138689

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9057
Approved symbol	PPP1R14B
Name	protein phosphatase 1 regulatory inhibitor subunit 14B
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	SOM172, PNG, PHI-1
Ensembl gene	ENSG00000173457
Ensembl biotype	protein_coding
OMIM	601140
Entrez	26472

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000309318, ENST00000392210, ENST00000542235, ENST00000912829

RefSeq mRNA: 1 — MANE Select: NM_138689 NM_138689

CCDS: CCDS31596

Canonical transcript exons

ENST00000309318 — 4 exons

Exon	Start	End
ENSE00001195861	64244930	64244962
ENSE00001232542	64246416	64246943
ENSE00001334162	64244479	64244822
ENSE00003606403	64245204	64245287

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 98.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.4613 / max 312.0720, expressed in 1821 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120371	28.0495	1812
120369	5.9378	1642
120362	1.9571	697
120370	1.8345	1173
120365	0.7036	439
120368	0.5633	309
120364	0.5127	306
120363	0.4731	269
120361	0.2692	96
120366	0.0890	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	98.83	gold quality
ganglionic eminence	UBERON:0004023	98.75	gold quality
embryo	UBERON:0000922	98.74	gold quality
lower esophagus mucosa	UBERON:0035834	98.72	gold quality
body of pancreas	UBERON:0001150	98.00	gold quality
right coronary artery	UBERON:0001625	97.96	gold quality
esophagus mucosa	UBERON:0002469	97.62	gold quality
stromal cell of endometrium	CL:0002255	97.53	gold quality
apex of heart	UBERON:0002098	97.48	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.37	gold quality
mucosa of transverse colon	UBERON:0004991	97.21	gold quality
skin of abdomen	UBERON:0001416	97.12	gold quality
zone of skin	UBERON:0000014	96.98	gold quality
skin of leg	UBERON:0001511	96.92	gold quality
gastrocnemius	UBERON:0001388	96.64	gold quality
ventricular zone	UBERON:0003053	96.45	gold quality
skeletal muscle tissue	UBERON:0001134	96.34	gold quality
muscle of leg	UBERON:0001383	96.34	gold quality
left coronary artery	UBERON:0001626	96.32	gold quality
ascending aorta	UBERON:0001496	96.13	gold quality
thoracic aorta	UBERON:0001515	95.99	gold quality
pancreas	UBERON:0001264	95.78	gold quality
cortex of kidney	UBERON:0001225	95.77	gold quality
placenta	UBERON:0001987	95.40	gold quality
metanephros cortex	UBERON:0010533	95.25	gold quality
heart left ventricle	UBERON:0002084	95.16	gold quality
aorta	UBERON:0000947	95.15	gold quality
left adrenal gland cortex	UBERON:0035825	95.12	gold quality
esophagus	UBERON:0001043	94.89	gold quality
left adrenal gland	UBERON:0001234	94.83	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-GEOD-149689	yes	1816.88
E-HCAD-13	yes	1352.09
E-MTAB-10553	yes	797.82
E-CURD-79	yes	625.63
E-MTAB-6701	yes	588.38
E-MTAB-8221	yes	473.84
E-HCAD-4	yes	62.64
E-MTAB-9467	yes	18.26
E-CURD-112	yes	14.39
E-MTAB-8498	yes	14.30
E-CURD-122	yes	13.67
E-ANND-3	yes	12.30
E-MTAB-9067	yes	12.08
E-CURD-46	yes	10.01
E-CURD-114	yes	6.63

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting PPP1R14B, 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-3148	99.97	75.06	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-593-5P	99.34	69.50	965

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 60.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 8)

• An inhibitory phosphoprotein that inhibits the myosin- and glycogen-associated holoenzyme versions of protein type-1 phosphatase (PP1) as well as the monomeric catalytic subunit of PP1 in multiple tissues. (PMID:10606530)
• Whereas CPI-17 staining was diffuse, PHI-1 was concentrated along the cell membrane in distinct foci. The common tissue distribution but different cellular localization of PHI-1 and CPI-17 suggest distinctive physiological roles for these PP1 inhibitors. (PMID:15083373)
• PHI-1 participates in regulatory events at the trailing edge of migrating cells and modulates retraction of endothelial and epithelial cells (PMID:15522888)
• In vitro assessment of roles of PPP1R14B in cervical and endometrial cancer. (PMID:35679681)
• Protein Phosphatase 1 Subunit PPP1R14B Stabilizes STMN1 to Promote Progression and Paclitaxel Resistance in Triple-Negative Breast Cancer. (PMID:36484700)
• Upregulated PPP1R14B is connected to cancer progression and immune infiltration in kidney renal clear cell carcinoma. (PMID:37261660)
• PHI-1, an Endogenous Inhibitor Protein for Protein Phosphatase-1 and a Pan-Cancer Marker, Regulates Raf-1 Proteostasis. (PMID:38136612)
• PPP1R14B-mediated phosphorylation enhances protein stability of RPS6KA1 to promote hepatocellular carcinoma tumorigenesis. (PMID:39216602)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppp1r14bb	ENSDARG00000030161
danio_rerio	ppp1r14ba	ENSDARG00000044541
mus_musculus	Ppp1r14bl	ENSMUSG00000073730
rattus_norvegicus	Ppp1r14bl	ENSRNOG00000014123
drosophila_melanogaster	CG17124	FBGN0032297
caenorhabditis_elegans		WBGENE00010109

Paralogs (3): PPP1R14D (ENSG00000166143), PPP1R14A (ENSG00000167641), PPP1R14C (ENSG00000198729)

Protein

Protein identifiers

Protein phosphatase 1 regulatory subunit 14B — Q96C90 (reviewed: Q96C90)

Alternative names: Phospholipase C-beta-3 neighbouring gene protein

All UniProt accessions (3): Q96C90, F5GXC4, F5H2U0

UniProt curated annotations — full annotation on UniProt →

Function. Inhibitor of PPP1CA. Has over 50-fold higher inhibitory activity when phosphorylated.

Subcellular location. Cytoplasm.

Tissue specificity. Ubiquitous. Expressed at low levels.

Post-translational modifications. Phosphorylated primarily on Thr-57 by PKC (in vitro). An unknown Ser is also phosphorylated by PKC (in vitro).

Similarity. Belongs to the PP1 inhibitor family.

RefSeq proteins (1): NP_619634* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008025	CPI-17	Family
IPR036658	CPI-17_sf	Homologous_superfamily

Pfam: PF05361

UniProt features (9 total): modified residue 5, initiator methionine 1, chain 1, region of interest 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96C90-F1	73.06	0.10

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 (5): 2, 21, 29, 32, 57

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 218 (showing top): TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HONMA_DOCETAXEL_RESISTANCE, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, JOHANSSON_GLIOMAGENESIS_BY_PDGFB_UP, chr11q13, DAVICIONI_RHABDOMYOSARCOMA_PAX_FOXO1_FUSION_UP, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, LE_EGR2_TARGETS_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, BROWN_MYELOID_CELL_DEVELOPMENT_DN, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, CUI_TCF21_TARGETS_2_UP, BERENJENO_TRANSFORMED_BY_RHOA_UP, SANSOM_APC_TARGETS_REQUIRE_MYC

GO Biological Process (2): innate immune response (GO:0045087), regulation of phosphorylation (GO:0042325)

GO Molecular Function (5): protein serine/threonine phosphatase inhibitor activity (GO:0004865), protein phosphatase inhibitor activity (GO:0004864), protein binding (GO:0005515), phosphatase inhibitor activity (GO:0019212), protein phosphatase regulator activity (GO:0019888)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphoprotein phosphatase activity	2
phosphatase regulator activity	2
immune response	1
defense response to symbiont	1
phosphorylation	1
regulation of metabolic process	1
protein serine/threonine phosphatase activity	1
protein phosphatase inhibitor activity	1
phosphatase inhibitor activity	1
protein phosphatase regulator activity	1
binding	1
enzyme inhibitor activity	1
phosphatase activity	1
protein phosphatase binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

882 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPP1R14B	PPP1R14D	Q9NXH3	882
PPP1R14B	PPP1CA	P08129	644
PPP1R14B	NUDT22	Q9BRQ3	609
PPP1R14B	PPP2CA	P05323	547
PPP1R14B	TMEM86A	Q8N2M4	466
PPP1R14B	PPP1R27	Q86WC6	445
PPP1R14B	TASP1	Q9H6P5	420
PPP1R14B	TRPT1	Q86TN4	408
PPP1R14B	DNAJC4	Q9NNZ3	381
PPP1R14B	OSTF1	Q92882	368
PPP1R14B	VAC14	Q08AM6	361
PPP1R14B	NEU4	Q8WWR8	361
PPP1R14B	MAP2K5	Q13163	357
PPP1R14B	SOBP	A7XYQ1	352
PPP1R14B	DLST	P36957	341

IntAct

7 interactions, top by confidence:

A	B	Type	Score
PPP1R14B	LIMK2	psi-mi:“MI:0915”(physical association)	0.560
HSD17B6	NME2P1	psi-mi:“MI:0914”(association)	0.530
PPP1R14B	ROCK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
PPP1R14B	PPP1CC	psi-mi:“MI:0915”(physical association)	0.400
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
LIMK2	HAX1	psi-mi:“MI:0914”(association)	0.350

BioGRID (37): PPP1R14B (Co-fractionation), PPP1R14B (Co-fractionation), PPP1R14B (Co-fractionation), SEPT10 (Co-fractionation), PPP1R14B (Affinity Capture-MS), LIMK2 (Affinity Capture-MS), ATP6V1D (Co-fractionation), PPP1R14B (Affinity Capture-MS), PPP1R14B (Affinity Capture-MS), PPP1R14B (Affinity Capture-MS), PPP1R14B (Affinity Capture-MS), RPS27A (Affinity Capture-MS), ANXA2P2 (Affinity Capture-MS), DPM1 (Affinity Capture-MS), RAP1B (Affinity Capture-MS)

ESM2 similar proteins: A0JN53, D3ZND0, F1MX48, O95400, Q0V8M0, Q17QX2, Q28H71, Q29407, Q2YD98, Q3T1I9, Q4R992, Q58CQ5, Q5FVH7, Q5PPF5, Q5R8S0, Q62084, Q64327, Q66H85, Q66HA5, Q6P0I6, Q80TE0, Q80UU1, Q8BIW9, Q8BIY1, Q8BRN9, Q8K1A6, Q8K3F3, Q8MIK9, Q8N163, Q8N5A5, Q8N9T8, Q8VC31, Q8VDM1, Q8VDQ9, Q8WVB6, Q92917, Q95313, Q96C90, Q96F63, Q96I76

Diamond homologs: O18734, Q62084, Q7TT52, Q8K3F3, Q8K3F4, Q8MIK9, Q8R4R9, Q8R4S0, Q8TAE6, Q91VC7, Q96A00, Q96C90, Q99MC0, Q9NXH3

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
PRKCD	“up-regulates activity”	PPP1R14B	phosphorylation
PKC	“up-regulates activity”	PPP1R14B	phosphorylation
ILK	“up-regulates activity”	PPP1R14B	phosphorylation
PPP1R14B	“down-regulates activity”	PPP1CB	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

605 predictions. Top by Δscore:

Variant	Effect	Δscore
11:64244819:AGGC:A	acceptor_gain	1.0000
11:64244820:GGC:G	acceptor_gain	1.0000
11:64244823:C:CA	acceptor_loss	1.0000
11:64244823:C:CC	acceptor_gain	1.0000
11:64245198:CCTCA:C	donor_loss	1.0000
11:64245199:CTCA:C	donor_loss	1.0000
11:64245201:CA:C	donor_loss	1.0000
11:64245202:A:C	donor_loss	1.0000
11:64245203:C:CT	donor_loss	1.0000
11:64245203:CCT:C	donor_gain	1.0000
11:64245205:TTG:T	donor_gain	1.0000
11:64245206:TG:T	donor_gain	1.0000
11:64245235:T:A	donor_gain	1.0000
11:64245284:CTTC:C	acceptor_gain	1.0000
11:64245285:TTC:T	acceptor_gain	1.0000
11:64245286:TC:T	acceptor_gain	1.0000
11:64245287:CC:C	acceptor_gain	1.0000
11:64245288:C:CA	acceptor_loss	1.0000
11:64245288:C:CC	acceptor_gain	1.0000
11:64245293:G:C	acceptor_gain	1.0000
11:64245293:G:GC	acceptor_gain	1.0000
11:64245299:G:C	acceptor_gain	1.0000
11:64245299:G:GC	acceptor_gain	1.0000
11:64246411:CACA:C	donor_loss	1.0000
11:64246412:ACAC:A	donor_loss	1.0000
11:64246413:CACCT:C	donor_loss	1.0000
11:64246414:ACCTG:A	donor_loss	1.0000
11:64246415:C:G	donor_loss	1.0000
11:64244818:AAGGC:A	acceptor_gain	0.9900
11:64244821:GC:G	acceptor_gain	0.9900

AlphaMissense

948 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:64244817:G:C	F127L	1.000
11:64244817:G:T	F127L	1.000
11:64244819:A:G	F127L	1.000
11:64244945:A:C	C120W	1.000
11:64244946:C:T	C120Y	1.000
11:64245244:A:G	L101P	1.000
11:64245247:A:G	L100P	1.000
11:64245247:A:T	L100H	1.000
11:64245253:T:A	D98V	1.000
11:64245253:T:C	D98G	1.000
11:64245253:T:G	D98A	1.000
11:64245254:C:A	D98Y	1.000
11:64245254:C:G	D98H	1.000
11:64245254:C:T	D98N	1.000
11:64245259:T:A	D96V	1.000
11:64245259:T:C	D96G	1.000
11:64245262:A:C	I95S	1.000
11:64245262:A:T	I95N	1.000
11:64246438:A:G	L79P	1.000
11:64246450:A:G	I75T	1.000
11:64246452:C:A	W74C	1.000
11:64246452:C:G	W74C	1.000
11:64246454:A:G	W74R	1.000
11:64246454:A:T	W74R	1.000
11:64246458:C:A	E72D	1.000
11:64246458:C:G	E72D	1.000
11:64246459:T:A	E72V	1.000
11:64246460:C:T	E72K	1.000
11:64246462:A:G	L71P	1.000
11:64246468:A:G	L69P	1.000

dbSNP variants (sampled 300 via entrez): RS1000379419 (11:64246632 G>A), RS1000981937 (11:64244972 G>A,C), RS1001294271 (11:64248221 A>AC), RS1001341927 (11:64244465 A>C), RS1001394854 (11:64247238 T>C), RS1001714431 (11:64244345 T>C), RS1002449735 (11:64245544 G>T), RS1002481694 (11:64248356 G>C), RS1002797010 (11:64248654 A>G), RS1003274829 (11:64244455 C>G,T), RS1003325768 (11:64244186 C>T), RS1003730572 (11:64247444 A>T), RS1004168098 (11:64247193 G>A), RS1004738401 (11:64244635 G>A), RS1004829574 (11:64244446 G>C)

Disease associations

OMIM: gene MIM:601140 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004132_98	Crohn’s disease	5.000000e-06
GCST004785_38	Vitiligo	5.000000e-08
GCST010136_47	Fruit consumption	9.000000e-10
GCST90002389_365	Lymphocyte percentage of white cells	4.000000e-10
GCST90002397_526	Mean spheric corpuscular volume	8.000000e-21
GCST90002402_351	Platelet count	6.000000e-15

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
beauvericin	decreases expression	1
bisphenol A	decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
ochratoxin A	increases acetylation, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
chloropicrin	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
K 7174	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
jinfukang	decreases expression, affects cotreatment	1
(+)-JQ1 compound	decreases 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
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Benztropine	affects cotreatment, decreases expression	1
Cannabidiol	affects cotreatment, decreases expression	1
Carbamazepine	affects expression	1
Cisplatin	affects cotreatment, decreases expression	1
Clozapine	decreases expression	1
Cuprizone	affects cotreatment, decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diclofenac	affects expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TF63	HAP1 PPP1R14B (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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