PPP1R1C

Summary

PPP1R1C (protein phosphatase 1 regulatory inhibitor subunit 1C, HGNC:14940) is a protein-coding gene on chromosome 2q31.3-q32.1, encoding Protein phosphatase 1 regulatory subunit 1C (Q8WVI7). May increase cell susceptibility to TNF-induced apoptosis.

Protein phosphatase-1 (PP1) is a major serine/threonine phosphatase that regulates a variety of cellular functions. PP1 consists of a catalytic subunit (see PPP1CA; MIM 176875) and regulatory subunits that determine the subcellular localization of PP1 or regulate its function. PPP1R1C belongs to a group of PP1 inhibitory subunits that are themselves regulated by phosphorylation (Wang et al., 2008 [PubMed 18310074]).

Source: NCBI Gene 151242 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 22 total
• MANE Select transcript: NM_001080545

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14940
Approved symbol	PPP1R1C
Name	protein phosphatase 1 regulatory inhibitor subunit 1C
Location	2q31.3-q32.1
Locus type	gene with protein product
Status	Approved
Aliases	Inhibitor-1-like
Ensembl gene	ENSG00000150722
Ensembl biotype	protein_coding
OMIM	613240
Entrez	151242

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 8 protein_coding_CDS_not_defined, 5 protein_coding, 1 retained_intron

ENST00000280295, ENST00000409137, ENST00000409702, ENST00000461410, ENST00000464264, ENST00000465612, ENST00000475249, ENST00000479855, ENST00000486067, ENST00000490645, ENST00000494189, ENST00000495820, ENST00000682840, ENST00000952657

RefSeq mRNA: 3 — MANE Select: NM_001080545 NM_001080545, NM_001261424, NM_001261425

CCDS: CCDS46468, CCDS58740

Canonical transcript exons

ENST00000682840 — 5 exons

Exon	Start	End
ENSE00003467361	182061442	182061479
ENSE00003497515	182063731	182063791
ENSE00003640909	181987839	181987899
ENSE00003917706	182117207	182117756
ENSE00003919281	181985853	181986191

Expression profiles

Bgee: expression breadth ubiquitous, 174 present calls, max score 92.47.

FANTOM5 (CAGE): breadth broad, TPM avg 1.8966 / max 254.1408, expressed in 487 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
24043	1.1137	344
24050	0.1749	31
24045	0.1167	34
24048	0.0934	31
24049	0.0770	27
24047	0.0719	22
24041	0.0713	9
24046	0.0523	17
24042	0.0465	14
24044	0.0428	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	92.47	gold quality
heart right ventricle	UBERON:0002080	91.63	gold quality
right testis	UBERON:0004534	91.43	gold quality
testis	UBERON:0000473	89.71	gold quality
pancreatic ductal cell	CL:0002079	88.75	silver quality
sperm	CL:0000019	86.11	gold quality
cardiac ventricle	UBERON:0002082	84.28	gold quality
heart left ventricle	UBERON:0002084	84.22	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.88	gold quality
dorsal root ganglion	UBERON:0000044	81.55	gold quality
right lobe of liver	UBERON:0001114	80.33	gold quality
sural nerve	UBERON:0015488	80.07	gold quality
heart	UBERON:0000948	79.62	gold quality
apex of heart	UBERON:0002098	79.32	gold quality
buccal mucosa cell	CL:0002336	79.30	silver quality
gall bladder	UBERON:0002110	78.99	gold quality
liver	UBERON:0002107	77.95	gold quality
trigeminal ganglion	UBERON:0001675	77.79	gold quality
right atrium auricular region	UBERON:0006631	77.15	gold quality
tibial nerve	UBERON:0001323	77.07	gold quality
adult organism	UBERON:0007023	77.00	gold quality
cardiac atrium	UBERON:0002081	76.34	gold quality
islet of Langerhans	UBERON:0000006	75.92	gold quality
myocardium	UBERON:0002349	75.85	gold quality
tibialis anterior	UBERON:0001385	75.65	silver quality
mucosa of paranasal sinus	UBERON:0005030	75.20	gold quality
ileal mucosa	UBERON:0000331	73.00	silver quality
stromal cell of endometrium	CL:0002255	72.97	gold quality
deltoid	UBERON:0001476	72.09	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-56	yes	252.36
E-ANND-3	yes	4.33

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting PPP1R1C, 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-8485	100.00	77.57	4731
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-3168	99.08	67.75	1384
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-4744	99.01	69.91	1581
HSA-MIR-16-1-3P	98.70	69.23	1538
HSA-MIR-633	98.35	69.45	1167
HSA-MIR-4704-3P	98.28	69.33	1300
HSA-MIR-10226	98.25	66.50	811
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-510-5P	97.66	65.82	916
HSA-MIR-512-5P	97.47	66.48	591
HSA-MIR-5000-5P	97.40	66.11	1055
HSA-MIR-342-5P	97.25	64.10	817
HSA-MIR-4509	96.19	65.80	900
HSA-MIR-675-3P	95.77	69.27	675

Literature-anchored findings (GeneRIF, showing 4)

• Overexpression of active mutant IPP5 inhibited anchorage-dependent growth and induced apoptosis in HeLa cells, which may be attributed to the up-regulation of p21, p53 and Bcl-2-antagonist/killer, and down-regulation of Bcl-2 and Bcl-X(L). (PMID:19874272)
• The effect of IPP5 on tumor growth and the underlying molecular mechanisms were investigated by overexpression of IPP5 in HeLa cells, a human cervical carcinoma cell line. (PMID:22939397)
• The data demonstrate a novel role for 8-60hIPP5(m) in the control of G2/M cell cycle progression, a process that involves the activation of ATM/p53/p21cip1/waf1/Cdc2/ cyclin B1 pathways. (PMID:24935604)
• IPP5 mutations are associated with response to paclitaxel in cervical cancer. (PMID:25339026)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppp1r1c	ENSDARG00000038941
mus_musculus	Ppp1r1c	ENSMUSG00000034683
rattus_norvegicus	Ppp1r1c	ENSRNOG00000024990

Paralogs (2): PPP1R1B (ENSG00000131771), PPP1R1A (ENSG00000135447)

Protein

Protein identifiers

Protein phosphatase 1 regulatory subunit 1C — Q8WVI7 (reviewed: Q8WVI7)

Alternative names: Inhibitor-5 of protein phosphatase 1

All UniProt accessions (1): Q8WVI7

UniProt curated annotations — full annotation on UniProt →

Function. May increase cell susceptibility to TNF-induced apoptosis.

Subcellular location. Cytoplasm.

Similarity. Belongs to the protein phosphatase inhibitor 1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WVI7-1	1	yes
Q8WVI7-2	2

RefSeq proteins (3): NP_001074014, NP_001248353, NP_001248354 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008466	PPP1R1A/B/C	Family

Pfam: PF05395

UniProt features (7 total): compositionally biased region 3, chain 1, region of interest 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WVI7-F1	68.69	0.12

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 69 (showing top): CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, GOBP_CELL_DIVISION, GOMF_PHOSPHATASE_INHIBITOR_ACTIVITY, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, GOMF_PHOSPHATASE_REGULATOR_ACTIVITY, LI_INDUCED_T_TO_NATURAL_KILLER_DN, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A, MIR8485, MIR548E_5P, MIR30B_5P_MIR30C_5P, MIR30D_5P, MIR30E_5P, MIR30A_5P

GO Biological Process (3): intracellular signal transduction (GO:0035556), cell division (GO:0051301), signal transduction (GO:0007165)

GO Molecular Function (2): protein phosphatase inhibitor activity (GO:0004864), protein binding (GO:0005515)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	2
cellular process	2
signal transduction	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
phosphoprotein phosphatase activity	1
phosphatase inhibitor activity	1
protein phosphatase regulator activity	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

380 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPP1R1C	PPP1CA	P08129	701
PPP1R1C	CCNE1	P24864	608
PPP1R1C	DPH6	Q7L8W6	459
PPP1R1C	HYDIN	Q4G0P3	415
PPP1R1C	MYO3B	Q8WXR4	403
PPP1R1C	MGAT4C	Q9UBM8	396
PPP1R1C	CPNE4	Q96A23	383
PPP1R1C	CSMD3	Q7Z407	374
PPP1R1C	PDE1A	P54750	371
PPP1R1C	KIAA0408	Q6ZU52	363
PPP1R1C	PPP1R14D	Q9NXH3	359
PPP1R1C	LDLRAD3	Q86YD5	357
PPP1R1C	PP2D1	A8MPX8	348
PPP1R1C	B3GALT2	O43825	337
PPP1R1C	TRAPPC3L	Q5T215	325

IntAct

4 interactions, top by confidence:

A	B	Type	Score
TNPO3	PPP1R1C	psi-mi:“MI:0915”(physical association)	0.560
PPP1R1C	TNPO3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (1): PPP1R1C (Two-hybrid)

ESM2 similar proteins: A0A1B0GTR3, A1L429, A3GGV1, A6NDE8, A6NER3, A6NGK3, A9WSI2, B8H8L5, O08664, O14598, O60829, O76087, P0C1C6, P0CL80, P0CL81, P0CL82, P0DPH9, P0DSO3, P0DTW1, P12507, P14379, P22421, P34493, Q08561, Q13066, Q13069, Q13070, Q4V321, Q4V326, Q5JRK9, Q5JUK9, Q6I7R5, Q6IPX3, Q6NT46, Q7Z2X7, Q8AIH8, Q8CCT4, Q8IYN2, Q8R0A5, Q8WTP9

Diamond homologs: P01099, P07516, P19103, Q13522, Q29277, Q5R853, Q60829, Q6J4I0, Q8BKK4, Q8WMS3, Q8WVI7, Q9ERT9, Q9UD71

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PPP1R1C	“down-regulates activity”	PP1	binding
PPP1R1C	“down-regulates activity”	PPP1CA	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1681 predictions. Top by Δscore:

Variant	Effect	Δscore
2:182061440:A:AG	acceptor_gain	1.0000
2:182061441:G:GG	acceptor_gain	1.0000
2:182061477:G:GT	donor_gain	1.0000
2:182061480:G:GG	donor_gain	1.0000
2:182063726:CACA:C	acceptor_loss	1.0000
2:182063729:A:AC	acceptor_loss	1.0000
2:182063729:A:AG	acceptor_gain	1.0000
2:182063730:G:GA	acceptor_gain	1.0000
2:182063730:G:GT	acceptor_loss	1.0000
2:182117465:C:CG	donor_gain	1.0000
2:182061436:TTACA:T	acceptor_loss	0.9900
2:182061437:TACA:T	acceptor_loss	0.9900
2:182061438:ACAG:A	acceptor_loss	0.9900
2:182061439:CAG:C	acceptor_loss	0.9900
2:182061440:AGAA:A	acceptor_loss	0.9900
2:182061441:GAA:G	acceptor_gain	0.9900
2:182061441:GAAAT:G	acceptor_gain	0.9900
2:182061475:GGGAA:G	donor_gain	0.9900
2:182061476:GGAA:G	donor_gain	0.9900
2:182061476:GGAAG:G	donor_gain	0.9900
2:182061477:G:T	donor_gain	0.9900
2:182061477:GAA:G	donor_gain	0.9900
2:182063728:C:G	acceptor_gain	0.9900
2:182063730:GT:G	acceptor_gain	0.9900
2:182063730:GTT:G	acceptor_gain	0.9900
2:182063730:GTTA:G	acceptor_gain	0.9900
2:182063730:GTTAC:G	acceptor_gain	0.9900
2:182117325:G:GT	donor_gain	0.9900
2:182117439:G:GT	donor_gain	0.9900
2:182117465:C:G	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000027173 (2:182038669 G>A), RS1000027845 (2:182118155 T>C), RS1000055424 (2:181955205 T>C), RS1000071722 (2:182102846 T>C), RS1000086613 (2:182079759 T>C), RS1000144492 (2:182077094 A>G), RS1000148218 (2:181993725 T>C), RS1000153908 (2:181960479 C>G), RS1000170776 (2:182013376 G>A,C,T), RS1000215659 (2:181991623 A>AT), RS1000235047 (2:181980611 T>G), RS1000242760 (2:182075216 C>T), RS1000259823 (2:182070800 C>T), RS1000262027 (2:181987201 CAAAT>C), RS1000262666 (2:182032887 C>G,T)

Disease associations

OMIM: gene MIM:613240 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007267_35	Systolic blood pressure	5.000000e-17
GCST008156_128	Hip circumference adjusted for BMI	7.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1913896	PPP1R1C		0.00	0

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	4
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	affects cotreatment, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Vorinostat	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Calcitriol	increases expression	1
Cisplatin	decreases expression, affects cotreatment	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Mifepristone	increases expression	1
Aflatoxin B1	decreases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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