CPPED1

Summary

CPPED1 (calcineurin like phosphoesterase domain containing 1, HGNC:25632) is a protein-coding gene on chromosome 16p13.12, encoding Serine/threonine-protein phosphatase CPPED1 (Q9BRF8). Protein phosphatase that dephosphorylates AKT family kinase specifically at ‘Ser-473’, blocking cell cycle progression and promoting cell apoptosis.

Predicted to enable metal ion binding activity and phosphoprotein phosphatase activity. Predicted to be involved in chromatin remodeling and regulation of transcription by RNA polymerase II. Located in cytosol and plasma membrane.

Source: NCBI Gene 55313 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 88 total
• MANE Select transcript: NM_018340

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25632
Approved symbol	CPPED1
Name	calcineurin like phosphoesterase domain containing 1
Location	16p13.12
Locus type	gene with protein product
Status	Approved
Aliases	CSTP1, FLJ11151
Ensembl gene	ENSG00000103381
Ensembl biotype	protein_coding
OMIM	615603
Entrez	55313

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000261660, ENST00000381774, ENST00000433677, ENST00000539677, ENST00000898262

RefSeq mRNA: 2 — MANE Select: NM_018340 NM_001099455, NM_018340

CCDS: CCDS42119, CCDS42120

Canonical transcript exons

ENST00000381774 — 4 exons

Exon	Start	End
ENSE00001203053	12659799	12665115
ENSE00001554127	12803707	12803887
ENSE00001691316	12704624	12705049
ENSE00002324269	12781185	12781403

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 97.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.2924 / max 1467.8545, expressed in 1730 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156354	34.2924	1730

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	97.82	gold quality
mononuclear cell	CL:0000842	97.65	gold quality
leukocyte	CL:0000738	97.55	gold quality
blood	UBERON:0000178	96.92	gold quality
granulocyte	CL:0000094	93.96	gold quality
oral cavity	UBERON:0000167	90.71	gold quality
buccal mucosa cell	CL:0002336	89.64	gold quality
placenta	UBERON:0001987	87.09	gold quality
amniotic fluid	UBERON:0000173	86.89	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.81	gold quality
palpebral conjunctiva	UBERON:0001812	86.54	gold quality
esophagus mucosa	UBERON:0002469	86.54	gold quality
thoracic aorta	UBERON:0001515	86.20	gold quality
ascending aorta	UBERON:0001496	86.10	gold quality
descending thoracic aorta	UBERON:0002345	85.87	gold quality
esophagus squamous epithelium	UBERON:0006920	85.79	gold quality
right lobe of liver	UBERON:0001114	85.69	gold quality
spleen	UBERON:0002106	85.51	gold quality
spinal cord	UBERON:0002240	85.50	gold quality
rectum	UBERON:0001052	85.34	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.12	gold quality
lower esophagus mucosa	UBERON:0035834	84.94	gold quality
liver	UBERON:0002107	84.64	gold quality
bone marrow	UBERON:0002371	84.52	gold quality
duodenum	UBERON:0002114	84.30	gold quality
jejunal mucosa	UBERON:0000399	83.61	gold quality
epithelium of esophagus	UBERON:0001976	83.58	gold quality
lower lobe of lung	UBERON:0008949	83.41	gold quality
esophagus	UBERON:0001043	83.36	gold quality
right coronary artery	UBERON:0001625	83.10	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	25.38
E-ANND-3	yes	10.49
E-GEOD-36552	no	121.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

171 targeting CPPED1, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4747-5P	100.00	67.90	2681
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-5196-5P	100.00	67.98	2761
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-545-3P	99.95	70.74	2783

Literature-anchored findings (GeneRIF, showing 2)

• CPPED1 is involved in glucose uptake in adipocytes (PMID:23939394)
• functions regulated by CPPED1 in trophoblasts at choriodecidual interphase have a role in the induction of term labour, but it may be independent of AKT1. (PMID:29193784)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cpped1	ENSMUSG00000065979

Protein

Protein identifiers

Serine/threonine-protein phosphatase CPPED1 — Q9BRF8 (reviewed: Q9BRF8)

Alternative names: Calcineurin-like phosphoesterase domain-containing protein 1, Complete S-transactivated protein 1

All UniProt accessions (1): Q9BRF8

UniProt curated annotations — full annotation on UniProt →

Function. Protein phosphatase that dephosphorylates AKT family kinase specifically at ‘Ser-473’, blocking cell cycle progression and promoting cell apoptosis. May play an inhibitory role in glucose uptake by adipocytes.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in subcutaneous adipose tissue.

Cofactor. Binds 2 divalent metal cations.

Induction. Transactivated by the large envelope protein of the hepatitis B virus (HBV).

Similarity. Belongs to the metallophosphoesterase superfamily. CPPED1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BRF8-1	1	yes
Q9BRF8-2	2
Q9BRF8-3	3

RefSeq proteins (2): NP_001092925, NP_060810* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004843	Calcineurin-like_PHP	Domain
IPR029052	Metallo-depent_PP-like	Homologous_superfamily
IPR041867	MPP_CSTP1	Domain
IPR051918	STPP_CPPED1	Family

Pfam: PF00149

Catalyzed reactions (Rhea), 2 shown:

• O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate (RHEA:20629)
• O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate (RHEA:47004)

UniProt features (20 total): binding site 5, sequence variant 4, sequence conflict 4, splice variant 3, modified residue 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BRF8-F1	95.46	0.92

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5): 53; 90; 90; 127; 247

Post-translational modifications (2): 2, 294

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 189 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GNF2_CD1D, MODULE_285, CHIANG_LIVER_CANCER_SUBCLASS_CTNNB1_UP, GOCC_SECRETORY_VESICLE, GOCC_VESICLE_LUMEN, GOCC_VACUOLAR_LUMEN, ZHENG_GLIOBLASTOMA_PLASTICITY_UP, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_PROTEIN_SERINE_THREONINE_PHOSPHATASE_ACTIVITY, chr20p11, GOMF_PHOSPHORIC_ESTER_HYDROLASE_ACTIVITY, DODD_NASOPHARYNGEAL_CARCINOMA_DN, BOYAULT_LIVER_CANCER_SUBCLASS_G56_UP

GO Biological Process (0):

GO Molecular Function (3): protein serine/threonine phosphatase activity (GO:0004722), metal ion binding (GO:0046872), hydrolase activity (GO:0016787)

GO Cellular Component (5): extracellular region (GO:0005576), cytosol (GO:0005829), plasma membrane (GO:0005886), azurophil granule lumen (GO:0035578), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
phosphoprotein phosphatase activity	1
cation binding	1
catalytic activity	1
cytoplasm	1
membrane	1
cell periphery	1
vacuolar lumen	1
secretory granule lumen	1
azurophil granule	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1754 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPPED1	CST1	P01037	938
CPPED1	CST2	P09228	916
CPPED1	CST3	P01034	756
CPPED1	ARB2A	Q8WUF8	486
CPPED1	LIPT1	Q9Y234	466
CPPED1	PUDP	Q08623	461
CPPED1	PNPLA4	P41247	453
CPPED1	CST4	P01036	448
CPPED1	SYT10	Q6XYQ8	447
CPPED1	KLHL2	O95198	443
CPPED1	RNPEP	Q9H4A4	436
CPPED1	DRC7	Q8IY82	414
CPPED1	TXNDC11	Q6PKC3	408
CPPED1	CST5	P28325	402
CPPED1	IPP	Q9Y573	402

IntAct

10 interactions, top by confidence:

A	B	Type	Score
	CPPED1	psi-mi:“MI:0915”(physical association)	0.560
	CPPED1	psi-mi:“MI:0915”(physical association)	0.400
CPPED1	SEPSECS	psi-mi:“MI:0915”(physical association)	0.400
CPPED1	NARS1	psi-mi:“MI:0915”(physical association)	0.400
POT1	CPPED1	psi-mi:“MI:0915”(physical association)	0.370
HTRA4	PSMD12	psi-mi:“MI:0914”(association)	0.350
PAAT	HIP1	psi-mi:“MI:0914”(association)	0.350

BioGRID (27): SEPSECS (Affinity Capture-MS), CPPED1 (Co-fractionation), PFKM (Co-fractionation), CPPED1 (Affinity Capture-MS), SEPSECS (Affinity Capture-MS), CPPED1 (Proximity Label-MS), CPPED1 (Proximity Label-MS), CPPED1 (Proximity Label-MS), CPPED1 (Proximity Label-MS), CPPED1 (Affinity Capture-MS), NARS (Affinity Capture-MS), CPPED1 (Affinity Capture-MS), ASPM (Negative Genetic), CPPED1 (Co-fractionation), CPPED1 (Co-fractionation)

ESM2 similar proteins: A0A1P8AWH8, A2RU49, A4FUP9, A5PJU6, M4IRL9, O80574, O82730, P13255, P37287, Q14749, Q1PET6, Q29513, Q29555, Q2KIR8, Q58DC0, Q58DM7, Q5F480, Q5HZ68, Q5IH13, Q5IH14, Q5R7E8, Q5RAF1, Q5U3W0, Q64323, Q6DHV7, Q6DIQ1, Q6DJF8, Q6NYU2, Q6PBF6, Q6YXW6, Q71N41, Q7ZXG7, Q80SY6, Q8BFS6, Q8CCT7, Q8R164, Q90WG6, Q91W63, Q94AH8, Q94AS5

Diamond homologs: Q28FE0, Q58DC0, Q5RCR9, Q5U3W0, Q66H71, Q8BFS6, Q9BRF8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1700 predictions. Top by Δscore:

Variant	Effect	Δscore
16:12664939:G:C	donor_gain	1.0000
16:12665113:CAC:C	acceptor_gain	1.0000
16:12704618:CTCTA:C	donor_loss	1.0000
16:12704619:TCTAC:T	donor_loss	1.0000
16:12704620:CTACC:C	donor_loss	1.0000
16:12704621:TAC:T	donor_loss	1.0000
16:12704622:ACCTG:A	donor_loss	1.0000
16:12704623:C:CA	donor_loss	1.0000
16:12704654:T:TA	donor_gain	1.0000
16:12781179:TCTTA:T	donor_loss	1.0000
16:12781180:CTTAC:C	donor_loss	1.0000
16:12781181:TTAC:T	donor_loss	1.0000
16:12781182:TA:T	donor_loss	1.0000
16:12781183:A:AC	donor_gain	1.0000
16:12781184:C:CA	donor_loss	1.0000
16:12781184:C:CC	donor_gain	1.0000
16:12781184:CCTGG:C	donor_gain	1.0000
16:12781399:CTTTT:C	acceptor_gain	1.0000
16:12781400:TTTTC:T	acceptor_loss	1.0000
16:12781401:TTT:T	acceptor_gain	1.0000
16:12781402:TT:T	acceptor_gain	1.0000
16:12781402:TTCTT:T	acceptor_loss	1.0000
16:12781403:TCTT:T	acceptor_loss	1.0000
16:12781404:C:CA	acceptor_loss	1.0000
16:12781404:C:CC	acceptor_gain	1.0000
16:12781405:T:C	acceptor_gain	1.0000
16:12781405:T:TC	acceptor_gain	1.0000
16:12664935:CTCAG:C	donor_gain	0.9900
16:12665114:ACC:A	acceptor_loss	0.9900
16:12665115:CCTGC:C	acceptor_loss	0.9900

AlphaMissense

2082 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:12781205:T:A	D90V	0.992
16:12665086:G:C	H249D	0.989
16:12704712:G:C	F209L	0.988
16:12704712:G:T	F209L	0.988
16:12704714:A:G	F209L	0.988
16:12781204:G:C	D90E	0.987
16:12781204:G:T	D90E	0.987
16:12781205:T:G	D90A	0.987
16:12704847:G:C	N164K	0.986
16:12704847:G:T	N164K	0.986
16:12704962:C:A	G126V	0.986
16:12781208:C:A	G89V	0.985
16:12781343:C:T	G44E	0.984
16:12704958:G:C	N127K	0.983
16:12704958:G:T	N127K	0.983
16:12781205:T:C	D90G	0.983
16:12781206:C:G	D90H	0.982
16:12704964:G:C	S125R	0.981
16:12704964:G:T	S125R	0.981
16:12704966:T:G	S125R	0.981
16:12781293:A:G	W61R	0.981
16:12781293:A:T	W61R	0.981
16:12704789:A:G	W184R	0.980
16:12704789:A:T	W184R	0.980
16:12704734:A:T	V202D	0.978
16:12705016:A:G	L108P	0.978
16:12781291:C:A	W61C	0.978
16:12781291:C:G	W61C	0.978
16:12781344:C:A	G44W	0.978
16:12704724:G:C	H205Q	0.977

dbSNP variants (sampled 300 via entrez): RS1000007581 (16:12702188 G>A), RS1000011067 (16:12756374 T>G), RS1000058334 (16:12743078 C>G), RS1000069912 (16:12775150 G>A), RS1000088702 (16:12742820 C>T), RS1000109573 (16:12675742 G>A,C), RS1000153654 (16:12680439 G>A), RS1000159233 (16:12721223 G>A), RS1000196704 (16:12683288 G>C,T), RS1000213492 (16:12785893 C>A,T), RS1000230903 (16:12778852 G>T), RS1000242975 (16:12747611 C>A,T), RS1000247516 (16:12694722 A>T), RS1000257947 (16:12783514 A>T), RS1000267788 (16:12689689 G>A)

Disease associations

OMIM: gene MIM:615603 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002806_14	Type 2 diabetes	8.000000e-06
GCST003518_21	Daytime sleep phenotypes	2.000000e-06
GCST005839_17	Depression	2.000000e-08
GCST008839_112	Height	7.000000e-10
GCST009391_1809	Metabolite levels	9.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement
EFO:0010403	triacylglycerol 48:0 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases expression	2
Benzo(a)pyrene	decreases expression	2
Tretinoin	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
Cadmium Chloride	increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
arsenite	increases methylation	1
cobaltous chloride	decreases expression	1
manganese chloride	increases abundance, increases expression	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
entinostat	increases expression	1
nutlin 3	increases secretion, affects cotreatment	1
bisphenol B	increases expression	1
bisphenol S	affects cotreatment, increases methylation	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Air Pollutants	decreases expression, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Dimethyl Sulfoxide	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Formaldehyde	decreases expression	1

Clinical trials (associated diseases)

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