PPP1R18

Summary

PPP1R18 (protein phosphatase 1 regulatory subunit 18, HGNC:29413) is a protein-coding gene on chromosome 6p21.33, encoding Phostensin (Q6NYC8). May target protein phosphatase 1 to F-actin cytoskeleton.

Protein phosphatase-1 (PP1; see MIM 176875) interacts with regulatory subunits that target the enzyme to different cellular locations and change its activity toward specific substrates. Phostensin is a regulatory subunit that targets PP1 to F-actin (see MIM 102610) cytoskeleton (Kao et al., 2007 [PubMed 17374523]).

Source: NCBI Gene 170954 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 104 total — 1 pathogenic
• MANE Select transcript: NM_133471

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29413
Approved symbol	PPP1R18
Name	protein phosphatase 1 regulatory subunit 18
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Aliases	phostensin
Ensembl gene	ENSG00000146112
Ensembl biotype	protein_coding
OMIM	610990
Entrez	170954

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000274853, ENST00000399199, ENST00000467662, ENST00000488324, ENST00000615527, ENST00000615892, ENST00000860729

RefSeq mRNA: 2 — MANE Select: NM_133471 NM_001134870, NM_133471

CCDS: CCDS43444

Canonical transcript exons

ENST00000274853 — 3 exons

Exon	Start	End
ENSE00003476910	30676389	30677288
ENSE00003582917	30679179	30679389
ENSE00003847644	30684408	30686645

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 98.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 109.1830 / max 2586.3070, expressed in 1826 samples.

FANTOM5 promoters (21 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72572	49.1676	1783
72563	17.2640	1472
72573	12.2677	1755
72574	10.7580	1750
72568	4.5489	1496
72571	3.4061	1305
72565	1.6147	538
72575	1.5168	1063
72561	1.3243	447
72577	1.2540	767

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.93	gold quality
blood	UBERON:0000178	98.65	gold quality
lymph node	UBERON:0000029	98.24	gold quality
spleen	UBERON:0002106	97.74	gold quality
leukocyte	CL:0000738	97.46	gold quality
monocyte	CL:0000576	97.30	gold quality
vermiform appendix	UBERON:0001154	97.18	gold quality
right coronary artery	UBERON:0001625	96.68	gold quality
descending thoracic aorta	UBERON:0002345	96.18	gold quality
ascending aorta	UBERON:0001496	95.94	gold quality
thoracic aorta	UBERON:0001515	95.92	gold quality
cortical plate	UBERON:0005343	95.86	gold quality
bone element	UBERON:0001474	95.47	gold quality
bone marrow	UBERON:0002371	95.47	gold quality
gall bladder	UBERON:0002110	95.29	gold quality
bone marrow cell	CL:0002092	95.13	gold quality
upper lobe of left lung	UBERON:0008952	95.00	gold quality
ganglionic eminence	UBERON:0004023	94.89	gold quality
embryo	UBERON:0000922	94.88	gold quality
left coronary artery	UBERON:0001626	94.86	gold quality
myometrium	UBERON:0001296	94.80	gold quality
urinary bladder	UBERON:0001255	94.64	gold quality
placenta	UBERON:0001987	94.63	gold quality
tibial artery	UBERON:0007610	94.56	gold quality
popliteal artery	UBERON:0002250	94.55	gold quality
stromal cell of endometrium	CL:0002255	94.54	gold quality
omental fat pad	UBERON:0010414	94.52	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.49	gold quality
left uterine tube	UBERON:0001303	94.48	gold quality
mucosa of stomach	UBERON:0001199	94.34	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-8271	yes	15.06
E-MTAB-8410	yes	12.42
E-MTAB-10042	yes	9.29
E-ANND-3	yes	5.70

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

56 targeting PPP1R18, 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-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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-12124	99.68	69.17	2700

Literature-anchored findings (GeneRIF, showing 5)

• our data shows that phostensin targets PP1 to F-actin cytoskeleton. (PMID:17374523)
• phostensin is an actin filament pointed end-capping protein that is capable of modulating actin dynamics. (PMID:19622346)
• phostensin is a ubiquitous protein in leukocytes, and it may play an important role in modulating the cellular functions of leukocytes. (PMID:21804078)
• Authors identified an actin-regulatory protein, protein phosphatase 1 regulatory subunit 18 (PPP1r18), as an Src-binding protein in an Src-, Yes-, and Fyn-deficient fibroblast (SYF) cell line overexpressing a constitutively active form of Src. PPP1r18 was localized in the nucleus and actin ring. (PMID:29158294)
• Identification of phostensin in association with Eps 15 homology domain-containing protein 1 (EHD1) and EHD4. (PMID:32800345)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppp1r18	ENSDARG00000071251
mus_musculus	Ppp1r18	ENSMUSG00000034595
rattus_norvegicus	Ppp1r18	ENSRNOG00000071251

Paralogs (1): TPRN (ENSG00000176058)

Protein

Protein identifiers

Phostensin — Q6NYC8 (reviewed: Q6NYC8)

Alternative names: Protein phosphatase 1 F-actin cytoskeleton-targeting subunit, Protein phosphatase 1 regulatory subunit 18

All UniProt accessions (2): Q6NYC8, A0A024RCJ8

UniProt curated annotations — full annotation on UniProt →

Function. May target protein phosphatase 1 to F-actin cytoskeleton. May target protein phosphatase 1 to F-actin cytoskeleton.

Subunit / interactions. Interacts with Protein phosphatase 1 (PP1).

Subcellular location. Cytoplasm. Cytoskeleton Cytoplasm. Cytoskeleton.

Tissue specificity. Isoform 4 is predominantly expressed in leukocytes and spleen.

Isoforms (4)

UniProt ID	Names	Canonical?
Q6NYC8-1	1, 110 kDa, phostensin-beta	yes
Q6NYC8-2	2
Q6NYC8-3	3
Q6NYC8-4	4, 26kDa, phostensin-alpha

RefSeq proteins (2): NP_001128342, NP_597728* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025903	Phostensin/Taperin_N_dom	Domain
IPR025907	Phostensin/Taperin_PP1-bd_dom	Domain
IPR026671	PPP1R18/Tprn	Family

Pfam: PF13914, PF13916

UniProt features (42 total): compositionally biased region 13, modified residue 12, splice variant 5, region of interest 3, sequence variant 3, sequence conflict 3, mutagenesis site 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NYC8-F1	54.16	0.06

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 (12): 54, 125, 133, 175, 195, 199, 224, 368, 432, 457, 490, 530

Mutagenesis-validated functional residues (2):

Position	Phenotype
540	decrease binding to pp1. complete inhibition of pp1 binding; when associated with g-542.
542	decrease binding to pp1. decrease binding to pp1. complete inhibition of pp1 binding; when associated with g-540.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 162 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, JOHANSSON_GLIOMAGENESIS_BY_PDGFB_UP, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOMF_ACTIN_BINDING, GARY_CD5_TARGETS_UP, GEORGES_TARGETS_OF_MIR192_AND_MIR215, GOMF_PHOSPHATASE_BINDING, GOMF_CYTOSKELETAL_PROTEIN_BINDING, WONG_ADULT_TISSUE_STEM_MODULE, PASINI_SUZ12_TARGETS_DN, PEDERSEN_METASTASIS_BY_ERBB2_ISOFORM_7, FORTSCHEGGER_PHF8_TARGETS_DN, LIM_MAMMARY_STEM_CELL_UP, ELLWOOD_MYC_TARGETS_UP, GSE10240_CTRL_VS_IL17_STIM_PRIMARY_BRONCHIAL_EPITHELIAL_CELLS_DN

GO Biological Process (0):

GO Molecular Function (3): actin binding (GO:0003779), phosphatase binding (GO:0019902), protein binding (GO:0005515)

GO Cellular Component (2): cytoskeleton (GO:0005856), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoskeletal protein binding	1
enzyme binding	1
binding	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

928 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPP1R18	PPP1CA	P08129	833
PPP1R18	CARNS1	A5YM72	560
PPP1R18	TMEM44	Q2T9K0	517
PPP1R18	NPDC1	Q9NQX5	445
PPP1R18	PPP1R2	P41236	429
PPP1R18	GRXCR2	A6NFK2	411
PPP1R18	BABAM1	Q9NWV8	406
PPP1R18	APBA1	Q02410	400
PPP1R18	B3GALT4	O96024	398
PPP1R18	KRABD1	C9JBD0	397
PPP1R18	MCHR1	Q99705	387
PPP1R18	TOPAZ1	Q8N9V7	379
PPP1R18	MUCL3	Q3MIW9	367
PPP1R18	DHX16	O60231	366
PPP1R18	NCOR2	Q9Y618	362

IntAct

354 interactions, top by confidence:

A	B	Type	Score
PPP1R18	TRIM27	psi-mi:“MI:0915”(physical association)	0.780
TRIM27	PPP1R18	psi-mi:“MI:0915”(physical association)	0.780
PPP1R18	CCDC102B	psi-mi:“MI:0915”(physical association)	0.720
FSD2	PPP1R18	psi-mi:“MI:0915”(physical association)	0.720
HOMER3	PPP1R18	psi-mi:“MI:0915”(physical association)	0.720
PPP1R18	STX11	psi-mi:“MI:0915”(physical association)	0.720
DES	PPP1R18	psi-mi:“MI:0915”(physical association)	0.720
PPP1R18	KRT15	psi-mi:“MI:0915”(physical association)	0.720
PPP1R18	GOLGA2	psi-mi:“MI:0915”(physical association)	0.720
PPP1R18	KRT31	psi-mi:“MI:0915”(physical association)	0.720
VPS52	PPP1R18	psi-mi:“MI:0915”(physical association)	0.720
KASH5	PPP1R18	psi-mi:“MI:0915”(physical association)	0.720
PPP1R18	TRIM54	psi-mi:“MI:0915”(physical association)	0.720
PPP1R18	MID2	psi-mi:“MI:0915”(physical association)	0.720
CCDC102B	PPP1R18	psi-mi:“MI:0915”(physical association)	0.720
PPP1R18	FSD2	psi-mi:“MI:0915”(physical association)	0.720
STX11	PPP1R18	psi-mi:“MI:0915”(physical association)	0.720
KRT31	PPP1R18	psi-mi:“MI:0915”(physical association)	0.720
PPP1R18	VPS52	psi-mi:“MI:0915”(physical association)	0.720
PPP1R18	KASH5	psi-mi:“MI:0915”(physical association)	0.720
TRIM54	PPP1R18	psi-mi:“MI:0915”(physical association)	0.720
PPP1R18	DES	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (195): PPP1R18 (Two-hybrid), PPP1R18 (Two-hybrid), PPP1R18 (Two-hybrid), PPP1R18 (Two-hybrid), PPP1R18 (Two-hybrid), PPP1R18 (Two-hybrid), PPP1R18 (Two-hybrid), PPP1R18 (Two-hybrid), PPP1R18 (Two-hybrid), PPP1R18 (Two-hybrid), PPP1R18 (Two-hybrid), PPP1R18 (Two-hybrid), PPP1R18 (Two-hybrid), PPP1R18 (Two-hybrid), PPP1R18 (Two-hybrid)

ESM2 similar proteins: A0A1B0GUA9, A2TJV2, A4FU49, A6NDB9, A6X8Z5, D3ZAQ5, P0C671, P10636, P10637, P48681, P58871, Q14676, Q2YDF7, Q3MI48, Q4R729, Q5EBJ4, Q5PSV9, Q5S6V2, Q5SWP3, Q5TM66, Q5TM68, Q5U2M8, Q5YCV9, Q5YCW0, Q5YCW1, Q640N3, Q68A65, Q68DA7, Q6NYC8, Q6ZW13, Q767L8, Q7YR40, Q7Z6I6, Q811Q2, Q8BHB9, Q8BHW6, Q8BQ30, Q8CB87, Q8CC96, Q8IXJ9

Diamond homologs: A2AI08, Q4KMQ1, Q5TM66, Q5XHX2, Q6NYC8, Q767M0, Q8BQ30

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 93 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
Formation of the cornified envelope	8	13.3×	5e-05
Keratinization	8	8.4×	8e-04

GO biological processes:

GO term	Partners	Fold	FDR
intermediate filament organization	12	36.6×	3e-13
morphogenesis of an epithelium	8	34.8×	2e-08
epithelial cell differentiation	7	15.6×	7e-05
regulation of apoptotic process	7	7.4×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	83
Likely benign	6
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
155430	GRCh38/hg38 6p25.3-12.3(chr6:156974-46789291)x3	Pathogenic

SpliceAI

559 predictions. Top by Δscore:

Variant	Effect	Δscore
6:30677284:CTCAT:C	acceptor_gain	1.0000
6:30677286:CAT:C	acceptor_gain	1.0000
6:30679173:GCTTA:G	donor_loss	1.0000
6:30679174:CTTA:C	donor_loss	1.0000
6:30679176:TA:T	donor_loss	1.0000
6:30679177:A:AC	donor_gain	1.0000
6:30679177:AC:A	donor_gain	1.0000
6:30679177:ACC:A	donor_gain	1.0000
6:30679178:C:CA	donor_gain	1.0000
6:30679178:CC:C	donor_gain	1.0000
6:30679178:CCC:C	donor_gain	1.0000
6:30679178:CCCA:C	donor_gain	1.0000
6:30679241:T:TA	donor_gain	1.0000
6:30679385:TTAAG:T	acceptor_gain	1.0000
6:30679386:TAAG:T	acceptor_gain	1.0000
6:30679387:AAG:A	acceptor_gain	1.0000
6:30679388:AG:A	acceptor_gain	1.0000
6:30679390:C:CC	acceptor_gain	1.0000
6:30677285:TCAT:T	acceptor_gain	0.9900
6:30677286:CATC:C	acceptor_gain	0.9900
6:30677286:CATCT:C	acceptor_loss	0.9900
6:30677287:ATC:A	acceptor_loss	0.9900
6:30677288:TC:T	acceptor_loss	0.9900
6:30677289:C:CC	acceptor_gain	0.9900
6:30677290:T:G	acceptor_loss	0.9900
6:30679386:TAAGC:T	acceptor_gain	0.9900
6:30679387:AAGCT:A	acceptor_gain	0.9900
6:30679388:AGCT:A	acceptor_gain	0.9900
6:30679389:GCT:G	acceptor_gain	0.9900
6:30679390:C:A	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000005903 (6:30682159 C>T), RS1001319286 (6:30687330 G>A,C), RS1001329182 (6:30687140 G>A), RS1001462517 (6:30678476 C>T), RS1001513380 (6:30678201 G>A), RS1001850437 (6:30676247 A>G,T), RS1001869753 (6:30682080 T>C), RS1001874138 (6:30681782 G>C), RS1002510794 (6:30678534 C>T), RS1002516262 (6:30679800 T>C), RS1002971851 (6:30678212 G>GT), RS1003055500 (6:30687128 C>T), RS1003665689 (6:30685792 G>A), RS1003675447 (6:30685525 C>T), RS1003968291 (6:30685092 T>C)

Disease associations

OMIM: gene MIM:610990 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

21 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_48	Autism spectrum disorder or schizophrenia	1.000000e-09
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
GCST004748_103	Lung cancer	4.000000e-18
GCST010083_151	Hemoglobin levels	3.000000e-28
GCST011766_17	Chronic obstructive pulmonary disease	1.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs9262143	Toxicity	3	carboplatin;gemcitabine	Non-Small Cell Lung Carcinoma;Thrombocytopenia

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9262143	PPP1R18	3	2.50	1	carboplatin;gemcitabine

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression, decreases expression	4
sodium arsenite	increases abundance, increases expression, affects cotreatment	3
Benzo(a)pyrene	increases expression, increases methylation	3
bisphenol F	increases expression, affects cotreatment	2
bisphenol A	decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Nickel	increases expression	2
Tobacco Smoke Pollution	increases expression	2
Tretinoin	increases expression	2
Aflatoxin B1	affects expression, increases expression	2
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
lead acetate	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
potassium chromate(VI)	affects cotreatment, increases expression	1
ferrous chloride	increases expression	1
cupric chloride	increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
avobenzone	increases expression	1
2-palmitoylglycerol	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
bisphenol B	increases expression	1
NSC 689534	affects binding, increases expression	1
PCI 5002	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Decitabine	affects expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TF68	HAP1 PPP1R18 (-) 1	Cancer cell line	Male
CVCL_TF69	HAP1 PPP1R18 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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