PPP1R14C

Summary

PPP1R14C (protein phosphatase 1 regulatory inhibitor subunit 14C, HGNC:14952) is a protein-coding gene on chromosome 6q25.1, encoding Protein phosphatase 1 regulatory subunit 14C (Q8TAE6). Inhibitor of the PP1 regulatory subunit PPP1CA.

The degree of protein phosphorylation is regulated by a balance of protein kinase and phosphatase activities. Protein phosphatase-1 (PP1; see MIM 176875) is a signal-transducing phosphatase that influences neuronal activity, protein synthesis, metabolism, muscle contraction, and cell division. PPP1R14C is an inhibitor of PP1 (Liu et al., 2002 [PubMed 11812771]).

Source: NCBI Gene 81706 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 29 total
• MANE Select transcript: NM_030949

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14952
Approved symbol	PPP1R14C
Name	protein phosphatase 1 regulatory inhibitor subunit 14C
Location	6q25.1
Locus type	gene with protein product
Status	Approved
Aliases	CPI17-like, NY-BR-81, KEPI
Ensembl gene	ENSG00000198729
Ensembl biotype	protein_coding
OMIM	613242
Entrez	81706

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000361131, ENST00000893449, ENST00000952229

RefSeq mRNA: 1 — MANE Select: NM_030949 NM_030949

CCDS: CCDS5226

Canonical transcript exons

ENST00000361131 — 4 exons

Exon	Start	End
ENSE00000765171	150214744	150214827
ENSE00001023413	150216824	150216856
ENSE00001128709	150248746	150250392
ENSE00001869103	150143044	150143498

Expression profiles

Bgee: expression breadth ubiquitous, 229 present calls, max score 99.19.

FANTOM5 (CAGE): breadth broad, TPM avg 5.2562 / max 206.8097, expressed in 711 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
70509	4.9975	697
70508	0.1436	80
70512	0.1151	50

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	99.19	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.03	gold quality
left ventricle myocardium	UBERON:0006566	98.54	gold quality
secondary oocyte	CL:0000655	98.20	gold quality
cartilage tissue	UBERON:0002418	98.13	gold quality
bronchial epithelial cell	CL:0002328	97.33	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.79	gold quality
myocardium	UBERON:0002349	96.75	gold quality
upper leg skin	UBERON:0004262	96.46	gold quality
bronchus	UBERON:0002185	96.27	gold quality
skin of abdomen	UBERON:0001416	96.12	gold quality
skin of hip	UBERON:0001554	95.83	gold quality
zone of skin	UBERON:0000014	95.71	gold quality
oocyte	CL:0000023	95.65	gold quality
tibialis anterior	UBERON:0001385	95.65	gold quality
cardiac atrium	UBERON:0002081	95.56	gold quality
skin of leg	UBERON:0001511	95.41	gold quality
right atrium auricular region	UBERON:0006631	95.37	gold quality
deltoid	UBERON:0001476	94.83	gold quality
heart left ventricle	UBERON:0002084	94.44	gold quality
cardiac ventricle	UBERON:0002082	94.42	gold quality
apex of heart	UBERON:0002098	94.38	gold quality
heart right ventricle	UBERON:0002080	93.99	gold quality
quadriceps femoris	UBERON:0001377	93.33	gold quality
penis	UBERON:0000989	93.22	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.91	gold quality
vastus lateralis	UBERON:0001379	92.72	gold quality
left lobe of thyroid gland	UBERON:0001120	92.10	gold quality
mammalian vulva	UBERON:0000997	92.05	gold quality
thyroid gland	UBERON:0002046	92.01	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	16.59
E-HCAD-5	yes	15.28
E-CURD-10	no	766.35

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

102 targeting PPP1R14C, 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-3163	100.00	77.23	8605
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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-6809-3P	99.91	71.45	3814

Literature-anchored findings (GeneRIF, showing 5)

• PPP1R14C gene encodes a PKC-potentiated inhibitory protein, KEPI, for type-1 Ser/Thr protein phosphatase (PP1). KEPI mRNA and protein were enriched in brain, heart and skeletal muscle. (PMID:11812771)
• regulation by morphine (PMID:11812771)
• analysis of antibodies generated against the protein phosphatase 1 inhibitor KEPI and characterization of the epitope (PMID:20592344)
• KEPI plays a negative role in the repression that accompanies translational inhibition guided by the uORF element of human CHOP transcript during stress response. (PMID:35031423)
• Attempted replication of pharmacogenetic association of variants in PPP1R14C and CCDC148 with aromatase inhibitor-induced musculoskeletal symptoms. (PMID:38359166)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppp1r14c	ENSDARG00000077341
mus_musculus	Ppp1r14c	ENSMUSG00000040653
rattus_norvegicus	Ppp1r14c	ENSRNOG00000016368
drosophila_melanogaster	CG17124	FBGN0032297
caenorhabditis_elegans		WBGENE00010109

Paralogs (3): PPP1R14D (ENSG00000166143), PPP1R14A (ENSG00000167641), PPP1R14B (ENSG00000173457)

Protein

Protein identifiers

Protein phosphatase 1 regulatory subunit 14C — Q8TAE6 (reviewed: Q8TAE6)

Alternative names: Kinase-enhanced PP1 inhibitor, PKC-potentiated PP1 inhibitory protein, Serologically defined breast cancer antigen NY-BR-81

All UniProt accessions (1): Q8TAE6

UniProt curated annotations — full annotation on UniProt →

Function. Inhibitor of the PP1 regulatory subunit PPP1CA.

Subcellular location. Cytoplasm. Membrane.

Tissue specificity. Detected in breast cancer.

Post-translational modifications. Has over 600-fold higher inhibitory activity when phosphorylated, creating a molecular switch for regulating the phosphorylation status of PPP1CA substrates and smooth muscle contraction. The main inhibitory site appears to be Thr-73.

Similarity. Belongs to the PP1 inhibitor family.

RefSeq proteins (1): NP_112211* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF05361

UniProt features (11 total): modified residue 5, compositionally biased region 2, initiator methionine 1, chain 1, sequence variant 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TAE6-F1	64.37	0.00

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, 25, 27, 33, 73

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 125 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, AGGAAGC_MIR5163P, BENPORATH_ES_WITH_H3K27ME3, WWTAAGGC_UNKNOWN, NKX25_02, GCANCTGNY_MYOD_Q6, AREB6_03, RACCACAR_AML_Q6, chr6q25, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_UP, AML_Q6, PU1_Q6, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_DN, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, PIT1_Q6

GO Biological Process (1): regulation of phosphorylation (GO:0042325)

GO Molecular Function (4): protein serine/threonine phosphatase inhibitor activity (GO:0004865), protein phosphatase inhibitor activity (GO:0004864), phosphatase inhibitor activity (GO:0019212), protein phosphatase regulator activity (GO:0019888)

GO Cellular Component (2): cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphoprotein phosphatase activity	2
phosphatase regulator activity	2
cellular anatomical structure	2
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
enzyme inhibitor activity	1
phosphatase activity	1
protein phosphatase binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

518 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPP1R14C	PPP1R14D	Q9NXH3	924
PPP1R14C	PPP1CA	P08129	805
PPP1R14C	OPRM1	P35372	656
PPP1R14C	IYD	Q6PHW0	591
PPP1R14C	PPP2CA	P05323	524
PPP1R14C	PCMT1	P22061	485
PPP1R14C	NAALADL2	Q58DX5	464
PPP1R14C	KATNA1	O75449	458
PPP1R14C	TIPE1	Q8WVP5	445
PPP1R14C	PRTFDC1	Q9NRG1	433
PPP1R14C	ENPP5	Q9UJA9	409
PPP1R14C	ZBTB2	Q8N680	406
PPP1R14C	SRSF12	Q8WXF0	392
PPP1R14C	RGS17	Q9UGC6	374
PPP1R14C	LNX1	Q8TBB1	366

IntAct

5 interactions, top by confidence:

A	B	Type	Score
ESR1	PGK2	psi-mi:“MI:0914”(association)	0.530
PPP1R14C	CCDC190	psi-mi:“MI:0915”(physical association)	0.400
PPP1R14C	HMGCS1	psi-mi:“MI:0915”(physical association)	0.400
PPP1R14C	SELENOH	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (17): PPP1R14C (Affinity Capture-MS), HMGCS1 (Affinity Capture-MS), PPP1R14C (Synthetic Lethality), PPP1R14C (Proximity Label-MS), PPP1R14C (Affinity Capture-RNA), C11orf31 (Affinity Capture-MS), PPP1R14C (Reconstituted Complex), RPL4 (Cross-Linking-MS (XL-MS)), PPP1R14C (Cross-Linking-MS (XL-MS)), PPP1R14A (Cross-Linking-MS (XL-MS)), PPP1R14C (Proximity Label-MS), PPP1R14C (Proximity Label-MS), PPP1R14C (Proximity Label-MS), PPP1R14C (Proximity Label-MS), PPP1R14C (Affinity Capture-MS)

ESM2 similar proteins: A3KMV1, A4IFA8, A8ID74, A8INQ0, A8JBB2, B4FR29, D3ZKV9, F5A894, O60292, P46062, P97287, Q07820, Q2KIL7, Q2QNS6, Q2T9W0, Q3TQF0, Q4VBF2, Q4VC12, Q53JI9, Q566Q8, Q580W5, Q5E9N0, Q5QD03, Q5XUX0, Q60764, Q69T21, Q6NWH0, Q6P7W2, Q6R2V6, Q6Z690, Q750K9, Q7YRZ9, Q8HYS5, Q8JZP9, Q8N8M0, Q8R4R9, Q8R4S0, Q8TAE6, Q8TBC3, Q8VD62

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

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ILK	“up-regulates activity”	PPP1R14C	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1741 predictions. Top by Δscore:

Variant	Effect	Δscore
6:150156226:TTAA:T	donor_gain	1.0000
6:150214732:A:AG	acceptor_gain	1.0000
6:150214734:T:A	acceptor_gain	1.0000
6:150214824:ACAGG:A	donor_loss	1.0000
6:150214825:CAGG:C	donor_loss	1.0000
6:150214826:AGG:A	donor_loss	1.0000
6:150214827:GGTAA:G	donor_loss	1.0000
6:150214829:T:A	donor_loss	1.0000
6:150216816:A:AG	acceptor_gain	1.0000
6:150216817:A:G	acceptor_gain	1.0000
6:150216818:TTCTA:T	acceptor_loss	1.0000
6:150216819:TCTA:T	acceptor_loss	1.0000
6:150216820:CTAG:C	acceptor_loss	1.0000
6:150216821:TAGG:T	acceptor_loss	1.0000
6:150216822:A:AG	acceptor_gain	1.0000
6:150216822:AGGA:A	acceptor_loss	1.0000
6:150216823:G:GG	acceptor_gain	1.0000
6:150216823:GGAA:G	acceptor_gain	1.0000
6:150216854:GAG:G	donor_gain	1.0000
6:150216855:AGG:A	donor_loss	1.0000
6:150216856:GGT:G	donor_loss	1.0000
6:150216857:G:GG	donor_gain	1.0000
6:150216857:GTA:G	donor_loss	1.0000
6:150216858:T:G	donor_loss	1.0000
6:150248742:TTAG:T	acceptor_loss	1.0000
6:150248743:TAGG:T	acceptor_loss	1.0000
6:150248744:A:AG	acceptor_gain	1.0000
6:150248744:A:C	acceptor_loss	1.0000
6:150248744:AG:A	acceptor_gain	1.0000
6:150248745:G:A	acceptor_loss	1.0000

AlphaMissense

1064 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:150143415:A:G	K75E	1.000
6:150143417:A:C	K75N	1.000
6:150143417:A:T	K75N	1.000
6:150143418:T:C	Y76H	1.000
6:150143418:T:G	Y76D	1.000
6:150143419:A:C	Y76S	1.000
6:150143419:A:G	Y76C	1.000
6:150143424:C:A	R78S	1.000
6:150143434:T:A	L81H	1.000
6:150143434:T:C	L81P	1.000
6:150143446:T:A	L85Q	1.000
6:150143446:T:C	L85P	1.000
6:150143452:T:C	L87P	1.000
6:150143454:G:A	E88K	1.000
6:150143455:A:T	E88V	1.000
6:150143456:G:C	E88D	1.000
6:150143456:G:T	E88D	1.000
6:150143460:T:A	W90R	1.000
6:150143460:T:C	W90R	1.000
6:150143462:G:C	W90C	1.000
6:150143462:G:T	W90C	1.000
6:150214769:T:G	I111S	1.000
6:150214775:T:A	I113N	1.000
6:150214778:A:T	D114V	1.000
6:150214784:T:C	L116P	1.000
6:150214823:T:C	L129S	1.000
6:150216841:C:G	C136W	1.000
6:150248749:T:C	F143L	1.000
6:150248750:T:C	F143S	1.000
6:150248751:T:A	F143L	1.000

dbSNP variants (sampled 300 via entrez): RS1000044510 (6:150208790 A>C), RS1000052024 (6:150141118 C>G,T), RS1000059672 (6:150158495 G>A,C), RS1000059921 (6:150248070 T>C), RS1000123756 (6:150165135 G>T), RS1000168359 (6:150184466 C>T), RS1000173982 (6:150214055 C>T), RS1000215442 (6:150142024 G>A), RS1000238497 (6:150241311 C>A,T), RS1000241997 (6:150164818 C>A), RS1000269876 (6:150181742 G>A), RS1000295926 (6:150166035 G>A), RS1000398927 (6:150197604 G>A,C), RS1000400860 (6:150149142 T>C,G), RS1000431861 (6:150149461 T>A,C,G)

Disease associations

OMIM: gene MIM:613242 | 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
GCST001251_15	Pulmonary function	4.000000e-06
GCST005183_8	Common carotid intima-media thickness	4.000000e-06
GCST006464_10	Endometrial cancer	6.000000e-06
GCST006465_18	Endometrial cancer (endometrioid histology)	9.000000e-08
GCST008554_3	Atorvastatin-induced myopathy	9.000000e-07
GCST012481_2	Cerebral amyloid angiopathy in Alzheimer’s disease	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004314	forced expiratory volume

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
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	8
Benzo(a)pyrene	increases expression, decreases expression	4
Aflatoxin B1	affects expression, affects methylation, increases expression	4
trichostatin A	affects cotreatment, affects expression, affects methylation, increases expression	2
Calcitriol	increases expression, affects cotreatment, decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	2
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
bisphenol A	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	increases methylation	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Decitabine	affects cotreatment, affects expression, affects methylation	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Ethanol	affects cotreatment, increases abundance, increases expression	1
Arsenic	affects methylation	1
Cadmium	increases expression	1
Camptothecin	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Estradiol	affects cotreatment, increases expression	1
Gasoline	affects cotreatment, increases abundance, increases 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_TF64	HAP1 PPP1R14C (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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