PPP3CC

Summary

PPP3CC (protein phosphatase 3 catalytic subunit gamma, HGNC:9316) is a protein-coding gene on chromosome 8p21.3, encoding Serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform (P48454). Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals.

Calcineurin is a calcium-dependent, calmodulin-stimulated protein phosphatase involved in the downstream regulation of dopaminergic signal transduction. Calcineurin is composed of a regulatory subunit and a catalytic subunit. The protein encoded by this gene represents one of the regulatory subunits that has been found for calcineurin. Three transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5533 — RefSeq curated summary.

At a glance

• Gene–disease (curated): schizophrenia (No Known Disease Relationship, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 85 total
• Phenotypes (HPO): 1
• MANE Select transcript: NM_005605

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9316
Approved symbol	PPP3CC
Name	protein phosphatase 3 catalytic subunit gamma
Location	8p21.3
Locus type	gene with protein product
Status	Approved
Aliases	CALNA3, PP2Bgamma
Ensembl gene	ENSG00000120910
Ensembl biotype	protein_coding
OMIM	114107
Entrez	5533

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 29 protein_coding

ENST00000240139, ENST00000289963, ENST00000397775, ENST00000518852, ENST00000521651, ENST00000522000, ENST00000522034, ENST00000523620, ENST00000898949, ENST00000898950, ENST00000898951, ENST00000898952, ENST00000898953, ENST00000898954, ENST00000898955, ENST00000898956, ENST00000898957, ENST00000898958, ENST00000968564, ENST00000968565, ENST00000968566, ENST00000968567, ENST00000968568, ENST00000968569, ENST00000968570, ENST00000968571, ENST00000968572, ENST00000968573, ENST00000968574

RefSeq mRNA: 3 — MANE Select: NM_005605 NM_001243974, NM_001243975, NM_005605

CCDS: CCDS34859, CCDS59093, CCDS59094

Canonical transcript exons

ENST00000240139 — 14 exons

Exon	Start	End
ENSE00000683876	22511086	22511231
ENSE00000818468	22532921	22533018
ENSE00000818469	22532225	22532306
ENSE00000818470	22528506	22528577
ENSE00000818472	22522655	22522749
ENSE00000818474	22513293	22513432
ENSE00001203665	22539469	22539498
ENSE00001204020	22474954	22475151
ENSE00001355444	22441078	22441458
ENSE00001382826	22540615	22541125
ENSE00001596992	22522491	22522568
ENSE00001703946	22475500	22475624
ENSE00001783856	22498001	22498112
ENSE00001796829	22527392	22527517

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 95.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.7130 / max 319.7694, expressed in 1814 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87765	15.0641	1800
87764	2.1005	1063
87767	1.4014	716
87769	1.0205	639
87768	0.7125	303
87766	0.4140	216

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	95.80	gold quality
muscle of leg	UBERON:0001383	95.52	gold quality
calcaneal tendon	UBERON:0003701	94.96	gold quality
skeletal muscle organ	UBERON:0014892	94.27	gold quality
muscle organ	UBERON:0001630	94.26	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.80	gold quality
granulocyte	CL:0000094	93.61	gold quality
left testis	UBERON:0004533	92.12	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	91.94	gold quality
popliteal artery	UBERON:0002250	91.86	gold quality
tibial artery	UBERON:0007610	91.86	gold quality
skeletal muscle tissue	UBERON:0001134	91.74	gold quality
right testis	UBERON:0004534	91.70	gold quality
tendon	UBERON:0000043	91.65	gold quality
testis	UBERON:0000473	91.23	gold quality
heart left ventricle	UBERON:0002084	91.22	gold quality
cardiac ventricle	UBERON:0002082	91.05	gold quality
vastus lateralis	UBERON:0001379	90.97	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.96	gold quality
biceps brachii	UBERON:0001507	90.95	gold quality
quadriceps femoris	UBERON:0001377	90.55	gold quality
right lung	UBERON:0002167	90.42	gold quality
aorta	UBERON:0000947	90.41	gold quality
right atrium auricular region	UBERON:0006631	90.31	gold quality
left coronary artery	UBERON:0001626	90.23	gold quality
heart	UBERON:0000948	90.11	gold quality
deltoid	UBERON:0001476	89.97	gold quality
muscle tissue	UBERON:0002385	89.74	gold quality
tibial nerve	UBERON:0001323	89.61	gold quality
coronary artery	UBERON:0001621	89.54	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
IL6	Activation

miRNA regulators (miRDB)

38 targeting PPP3CC, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-501-3P	99.33	66.12	651
HSA-MIR-502-3P	99.33	66.12	651
HSA-MIR-1273H-3P	99.29	67.55	980
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-6804-3P	98.72	64.82	852
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-224-5P	98.33	70.12	1256

Literature-anchored findings (GeneRIF, showing 21)

• results identify PPP3CC, located at 8p21.3, as a potential schizophrenia susceptibility gene and support the proposal that alterations in calcineurin signaling contribute to schizophrenia pathogenesis (PMID:12851458)
• Decreased hippocampal expression of the susceptibility gene PPP3CC in schizophrenia. (PMID:15820226)
• PPP3CC may not play a major role in Japanese schizophrenia (PMID:15843870)
• The results suggest that PPP3CC gene may be a true susceptibility gene for schizophrenia. (PMID:17339875)
• The Polymorphism, Single Nucleotide of ppp3cc is assosciated with schizophrenia. (PMID:17895921)
• No significant differences in calcineurin A gamma expression was observed between patients with schizophrenia and normal controls (PMID:18343007)
• These data strongly support a recent proposal that a segment at 8p21.3 contains crucial prostate cancer tumor suppressors. (PMID:18460741)
• Data suggest that PPP3CC does not elevate the risk of methamphetamine-use disorder in the Japanese population. (PMID:18991849)
• Study demonstrates that all CaN isoforms display the same cytoplasmic subcellular distribution and are expressed in each tested cell line, differences in substrate specificities may determine specific physiological functions of the distinct isoforms. (PMID:19154138)
• This study demoistrated that PPP3CC are not genetic risk factors for schizophrenia in japanese. (PMID:20537399)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• study suggests that NMDA receptor-mediated signalling genes, DAO, PPP3CC, DTNBP1 might be involved in schizophrenia pathogenic mechanisms related to gender (PMID:23497497)
• protein level of PPP3CC negatively correlates with the cellular level of IP3, suggesting a regulatory role of PPP3CC in the IP3-Ca2+ signaling pathway (PMID:23747857)
• The PPP3CC involved in the regulation of immune system and synaptic plasticity, seems promising for further investigation. (PMID:24709691)
• Knockdown of CNAgamma leads to a disruption of synaptic vesicle cycling in hippocampal neurons. (PMID:26627835)
• The rs2443504 AA genotype was associated with the Glasgow coma score at 3, 6, and 12 months following severe brain injury. (PMID:27225880)
• PPP3CC rs7431 may alter miRNA binding ability of miR-212 and miR-132, and thus decrease bladder cancer risk. (PMID:29275364)
• These findings indicated that the down-regulation of PPP3CC by ZEB1 resulted in activation of NF-kappaB is a critical oncogenic event in gliomas. (PMID:29294030)
• Calcineurin A gamma and NFATc3/SRPX2 axis contribute to human embryonic stem cell differentiation. (PMID:33393109)
• Calcineurin Gamma Catalytic Subunit PPP3CC Inhibition by miR-200c-3p Affects Apoptosis in Epithelial Ovarian Cancer. (PMID:34573382)
• LINC-PINT suppresses breast cancer cell proliferation and migration via MEIS2/PPP3CC/NF-kappaB pathway by sponging miR-576-5p. (PMID:37660994)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppp3ccb	ENSDARG00000057456
mus_musculus	Ppp3cc	ENSMUSG00000022092
rattus_norvegicus	Ppp3cc	ENSRNOG00000009745
drosophila_melanogaster	CanA1	FBGN0010015
drosophila_melanogaster	Pp2B-14D	FBGN0011826
drosophila_melanogaster	CanA-14F	FBGN0267912
caenorhabditis_elegans		WBGENE00006527

Paralogs (12): PPP5C (ENSG00000011485), PPEF1 (ENSG00000086717), PPP2CB (ENSG00000104695), PPP3CB (ENSG00000107758), PPP2CA (ENSG00000113575), PPP6C (ENSG00000119414), PPP3CA (ENSG00000138814), PPP4C (ENSG00000149923), PPEF2 (ENSG00000156194), PPP1CA (ENSG00000172531), PPP1CC (ENSG00000186298), PPP1CB (ENSG00000213639)

Protein

Protein identifiers

Serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform — P48454 (reviewed: P48454)

Alternative names: CAM-PRP catalytic subunit, Calcineurin, testis-specific catalytic subunit, Calmodulin-dependent calcineurin A subunit gamma isoform

All UniProt accessions (6): E5RJH4, P48454, G3V111, H0YB02, H0YB04, H0YC26

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals. Dephosphorylates and activates transcription factor NFATC1. Dephosphorylates and inactivates transcription factor ELK1. Dephosphorylates DARPP32.

Subunit / interactions. Forms a complex composed of a calmodulin-dependent catalytic subunit (also known as calcineurin A) and a regulatory Ca(2+)-binding subunit (also known as calcineurin B). There are three catalytic subunits, each encoded by a separate gene (PPP3CA, PPP3CB, and PPP3CC) and two regulatory subunits which are also encoded by separate genes (PPP3R1 and PPP3R2). In response to an increase in Ca(2+) intracellular levels, forms a complex composed of PPP3CC/calcineurin A, calcineurin B and calmodulin. Interacts (via calmodulin-binding domain) with calmodulin; the interaction depends on calmodulin binding to Ca(2+). Interacts with UNC119. Interacts with SPATA33 (via PQIIIT motif). Interacts with VDAC2 in a SPATA33-dependent manner.

Subcellular location. Mitochondrion.

Tissue specificity. Testis.

Activity regulation. Activated by Ca(2+)-bound calmodulin following an increase in intracellular Ca(2+). At low Ca(2+) concentrations, the catalytic subunit (also known as calcineurin A) is inactive and is bound to the regulatory subunit (also known as calcineurin B) in which only two high-affinity binding sites are occupied by Ca(2+). In response to elevated calcium levels, the occupancy of the low-affinity sites on calcineurin B by Ca(2+) causes a conformational change of the C-terminal regulatory domain of calcineurin A, resulting in the exposure of the calmodulin-binding domain and in the partial activation of calcineurin A. The subsequent binding of Ca(2+)-bound calmodulin leads to the displacement of the autoinhibitory domain from the active site and possibly of the autoinhibitory segment from the substrate binding site which fully activates calcineurin A.

Cofactor. Binds 1 Fe(3+) ion per subunit. Binds 1 zinc ion per subunit.

Domain organisation. The autoinhibitory domain prevents access to the catalytic site. The autoinhibitory segment prevents access to the substrate binding site. Possible isomerization of Pro-305 within the SAPNY motif triggers a conformation switch which affects the organization and thus accessibility of the active site and the substrate binding region (PxIxIF motif). The trans- to cis-transition may favor calcineurin A activation and substrate binding. The reverse cis- to trans-transition may be enhanced by peptidyl-prolyl isomerases such as PPIA.

Similarity. Belongs to the PPP phosphatase family. PP-2B subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P48454-1	1	yes
P48454-2	2
P48454-3	3

RefSeq proteins (3): NP_001230903, NP_001230904, NP_005596* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004843	Calcineurin-like_PHP	Domain
IPR006186	Ser/Thr-sp_prot-phosphatase	Domain
IPR029052	Metallo-depent_PP-like	Homologous_superfamily
IPR041751	MPP_PP2B	Domain
IPR043360	PP2B	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 (25 total): binding site 7, region of interest 6, splice variant 2, helix 2, compositionally biased region 2, chain 1, active site 1, modified residue 1, sequence variant 1, sequence conflict 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7U0T	X-RAY DIFFRACTION	2.45

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48454-F1	86.07	0.61

Functional residue map

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

Catalytic / active sites (1): 147 (proton donor)

Ligand- & substrate-binding residues (7): 86; 88; 114; 114; 146; 195; 277

Post-translational modifications (1): 483

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-111447	Activation of BAD and translocation to mitochondria
R-HSA-180024	DARPP-32 events

MSigDB gene sets: 354 (showing top): PID_BCR_5PATHWAY, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, BIOCARTA_FMLP_PATHWAY, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, KEGG_MAPK_SIGNALING_PATHWAY, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, MODULE_45, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, TGACCTY_ERR1_Q2, GOBP_VESICLE_MEDIATED_TRANSPORT, MODULE_16, BIOCARTA_NOS1_PATHWAY, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP

GO Biological Process (8): protein dephosphorylation (GO:0006470), calcineurin-NFAT signaling cascade (GO:0033173), positive regulation of calcineurin-NFAT signaling cascade (GO:0070886), calcineurin-mediated signaling (GO:0097720), positive regulation of synaptic vesicle endocytosis (GO:1900244), positive regulation of calcium ion import across plasma membrane (GO:1905665), negative regulation of calcium ion import across plasma membrane (GO:1905949), regulation of synaptic vesicle endocytosis (GO:1900242)

GO Molecular Function (8): calcium-dependent protein serine/threonine phosphatase activity (GO:0004723), calmodulin binding (GO:0005516), calmodulin-dependent protein phosphatase activity (GO:0033192), metal ion binding (GO:0046872), phosphoprotein phosphatase activity (GO:0004721), protein serine/threonine phosphatase activity (GO:0004722), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (7): cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), calcineurin complex (GO:0005955), protein serine/threonine phosphatase complex (GO:0008287), presynapse (GO:0098793), glutamatergic synapse (GO:0098978)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Activation of BH3-only proteins	1
Opioid Signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
synaptic vesicle endocytosis	2
calcium ion import across plasma membrane	2
regulation of calcium ion import across plasma membrane	2
cytoplasm	2
synapse	2
dephosphorylation	1
protein modification process	1
calcineurin-mediated signaling	1
calcineurin-NFAT signaling cascade	1
regulation of calcineurin-NFAT signaling cascade	1
positive regulation of calcineurin-mediated signaling	1
calcium-mediated signaling	1
positive regulation of endocytosis	1
regulation of synaptic vesicle endocytosis	1
positive regulation of synaptic vesicle recycling	1
positive regulation of calcium ion import	1
positive regulation of calcium ion transmembrane transport	1
negative regulation of calcium ion import	1
negative regulation of calcium ion transmembrane transport	1
regulation of endocytosis	1
regulation of synaptic vesicle recycling	1
protein serine/threonine phosphatase activity	1
protein binding	1
calcium-dependent protein serine/threonine phosphatase activity	1
cation binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
phosphoprotein phosphatase activity	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1
protein serine/threonine phosphatase complex	1
intracellular protein-containing complex	1
phosphatase complex	1

Protein interactions and networks

STRING

3233 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPP3CC	PPP3R1	P06705	916
PPP3CC	PPP3R2	Q96LZ3	795
PPP3CC	DTNBP1	Q96EV8	705
PPP3CC	DAOA	P59103	687
PPP3CC	PPP3CB	P16298	685
PPP3CC	PPP3CA	Q08209	661
PPP3CC	PNOC	Q13519	654
PPP3CC	HTR2A	P28223	634
PPP3CC	TAAR6	Q96RI8	627
PPP3CC	ZNF804A	Q7Z570	613
PPP3CC	PRODH	O43272	592
PPP3CC	DAO	P14920	586
PPP3CC	ZDHHC8	Q9ULC8	586
PPP3CC	RGS4	P49798	581
PPP3CC	DISC1	Q9NRI5	580

IntAct

103 interactions, top by confidence:

A	B	Type	Score
PPP3CC	PPP3R1	psi-mi:“MI:0915”(physical association)	0.800
PPP3CC	SPATA33	psi-mi:“MI:0915”(physical association)	0.670
RCAN1	PPP3CB	psi-mi:“MI:0914”(association)	0.660
KSR2	MAP2K2	psi-mi:“MI:0914”(association)	0.640
CRTC2	PPP3CC	psi-mi:“MI:0914”(association)	0.640
ESS2	ACADS	psi-mi:“MI:0914”(association)	0.640
AMPH	PPP3CC	psi-mi:“MI:0915”(physical association)	0.560
PPP3CC	AMPH	psi-mi:“MI:0915”(physical association)	0.560
PPP3CC	UNC119	psi-mi:“MI:0915”(physical association)	0.560
APP	PPP3CC	psi-mi:“MI:0915”(physical association)	0.560
KLRG2	GXYLT2	psi-mi:“MI:0914”(association)	0.530
IGFBP6	TCAF2	psi-mi:“MI:0914”(association)	0.530
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
ARHGAP44	VPS26A	psi-mi:“MI:0914”(association)	0.530
ESS2	HSPA8	psi-mi:“MI:0914”(association)	0.530
CSN2	PPP3CC	psi-mi:“MI:0914”(association)	0.530
SRBD1	PPP3CC	psi-mi:“MI:0914”(association)	0.530
CDR2	IGSF3	psi-mi:“MI:0914”(association)	0.530
PPP3CC	NFATC1	psi-mi:“MI:0914”(association)	0.530
CSN2	CRYBB3	psi-mi:“MI:0914”(association)	0.530

BioGRID (125): PPP3CC (Two-hybrid), PPP3CC (Affinity Capture-MS), PPP3CC (Affinity Capture-MS), PPP3CB (Affinity Capture-MS), SIK3 (Affinity Capture-MS), NFATC1 (Affinity Capture-MS), PPP3R1 (Affinity Capture-MS), RCAN1 (Affinity Capture-MS), NFATC4 (Affinity Capture-MS), ARID3B (Affinity Capture-MS), GSK3B (Affinity Capture-MS), GSK3A (Affinity Capture-MS), LRRC41 (Affinity Capture-MS), PPP3CC (Affinity Capture-MS), C6orf211 (Co-fractionation)

ESM2 similar proteins: A0A1S4A695, A0CDD4, A2VE01, A8IU92, B0R0D7, D3ZRP6, O88958, O97556, P46926, P48454, P50397, P50399, P62495, P62496, P62497, P62498, Q0VCX5, Q1W377, Q24208, Q259G4, Q3SYW1, Q499T7, Q4R7R3, Q503E1, Q5PQL4, Q5R4C7, Q5R8T8, Q5U2Q7, Q5ZHP3, Q5ZJL4, Q61598, Q64422, Q6B857, Q6GL74, Q6GPY6, Q6PBJ2, Q6Q7J2, Q7XPW5, Q8BTU1, Q8BWY3

Diamond homologs: A0C1E4, A0CCD2, A0DJ90, G5EBX9, O04858, O14829, O14830, O35385, O35655, O74789, P14747, P16298, P20604, P20651, P23287, P26570, P32345, P32838, P32945, P33329, P34430, P36614, P40421, P48452, P48453, P48454, P48455, P48456, P48457, P48528, P48529, P49576, P53043, P63328, P63329, Q05681, Q08209, Q09496, Q0G819, Q10298

SIGNOR signaling

37 interactions.

A	Effect	B	Mechanism
CALM1	up-regulates	PPP3CC	binding
“cyclosporin A”	down-regulates	PPP3CC	“chemical inhibition”
“tacrolimus (anhydrous)”	down-regulates	PPP3CC	“chemical inhibition”
PPP3CC	up-regulates	NFATC1	relocalization
PPP3CC	up-regulates	NFATC2	dephosphorylation
PPP3CC	“up-regulates activity”	DNM1L	dephosphorylation
PPP3CC	“down-regulates quantity by destabilization”	FLNA	dephosphorylation
PPP3CC	“up-regulates activity”	NFATC2	dephosphorylation
PPP3CC	“up-regulates activity”	BAD	dephosphorylation
CALM2	up-regulates	PPP3CC	binding
CALM3	up-regulates	PPP3CC	binding
PPP3CC	up-regulates	MEF2C
PPP3CC	up-regulates	NFATC2	relocalization
IGF1	up-regulates	PPP3CC

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 99 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.

GO biological processes:

GO term	Partners	Fold	FDR
calcineurin-NFAT signaling cascade	5	48.4×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2932 predictions. Top by Δscore:

Variant	Effect	Δscore
8:22474949:TGTA:T	acceptor_loss	1.0000
8:22474950:GTAG:G	acceptor_loss	1.0000
8:22474952:A:AG	acceptor_gain	1.0000
8:22474952:AGCT:A	acceptor_gain	1.0000
8:22474953:G:GT	acceptor_gain	1.0000
8:22474953:GC:G	acceptor_gain	1.0000
8:22474953:GCT:G	acceptor_gain	1.0000
8:22474953:GCTG:G	acceptor_gain	1.0000
8:22474953:GCTGT:G	acceptor_gain	1.0000
8:22475067:G:GT	donor_gain	1.0000
8:22475130:G:GT	donor_gain	1.0000
8:22475148:ACAG:A	donor_loss	1.0000
8:22475151:GG:G	donor_loss	1.0000
8:22475152:GTAT:G	donor_loss	1.0000
8:22475494:TCCTA:T	acceptor_loss	1.0000
8:22475496:CTAGT:C	acceptor_loss	1.0000
8:22475497:TA:T	acceptor_loss	1.0000
8:22475498:A:AG	acceptor_gain	1.0000
8:22475498:AGTAT:A	acceptor_gain	1.0000
8:22475499:G:GT	acceptor_gain	1.0000
8:22475499:GT:G	acceptor_gain	1.0000
8:22475499:GTA:G	acceptor_gain	1.0000
8:22475499:GTAT:G	acceptor_gain	1.0000
8:22475499:GTATG:G	acceptor_gain	1.0000
8:22475594:C:G	donor_gain	1.0000
8:22475621:AGAG:A	donor_loss	1.0000
8:22475623:AG:A	donor_loss	1.0000
8:22475624:GGTA:G	donor_loss	1.0000
8:22475625:G:GA	donor_loss	1.0000
8:22475626:T:A	donor_loss	1.0000

AlphaMissense

3368 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:22475505:G:C	G85R	1.000
8:22475505:G:T	G85C	1.000
8:22475506:G:A	G85D	1.000
8:22475506:G:T	G85V	1.000
8:22475508:G:C	D86H	1.000
8:22475509:A:C	D86A	1.000
8:22475509:A:G	D86G	1.000
8:22475509:A:T	D86V	1.000
8:22475510:T:A	D86E	1.000
8:22475510:T:G	D86E	1.000
8:22475514:C:G	H88D	1.000
8:22475517:G:A	G89R	1.000
8:22475517:G:C	G89R	1.000
8:22475518:G:A	G89E	1.000
8:22475518:G:T	G89V	1.000
8:22475533:T:C	L94P	1.000
8:22475577:T:G	Y109D	1.000
8:22475581:T:A	L110H	1.000
8:22475581:T:C	L110P	1.000
8:22475584:T:C	F111S	1.000
8:22475589:G:C	G113R	1.000
8:22475589:G:T	G113C	1.000
8:22475590:G:A	G113D	1.000
8:22475590:G:T	G113V	1.000
8:22475592:G:C	D114H	1.000
8:22475593:A:C	D114A	1.000
8:22475593:A:G	D114G	1.000
8:22475593:A:T	D114V	1.000
8:22475594:C:A	D114E	1.000
8:22475594:C:G	D114E	1.000

dbSNP variants (sampled 300 via entrez): RS1000005555 (8:22448047 A>G), RS1000008614 (8:22508949 A>G), RS1000045710 (8:22455130 T>C,G), RS1000061864 (8:22475436 T>C), RS1000122709 (8:22470327 C>G), RS1000156548 (8:22441655 C>T), RS1000179488 (8:22523750 A>G), RS1000209146 (8:22489307 T>C), RS1000227218 (8:22440812 T>C,G), RS1000232659 (8:22439357 T>C), RS1000232826 (8:22518902 G>A,C), RS1000273385 (8:22520684 T>C), RS1000313358 (8:22527906 A>G), RS1000331215 (8:22505885 G>A,T), RS1000345291 (8:22439863 A>G,T)

Disease associations

OMIM: gene MIM:114107 | disease phenotypes: MIM:148300

GenCC curated gene-disease

Disease	Classification	Inheritance
schizophrenia	No Known Disease Relationship	Unknown

Mondo (2): keratoconus (MONDO:0015486), schizophrenia (MONDO:0005090)

Orphanet (2): OBSOLETE: Keratoconus (Orphanet:156071), NON RARE IN EUROPE: Isolated keratoconus (Orphanet:2335)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000563	Keratoconus

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000656_10	HIV-1 viral setpoint	9.000000e-06
GCST002701_20	Verbal declarative memory	2.000000e-06
GCST002701_21	Verbal declarative memory	2.000000e-06
GCST007325_179	General risk tolerance (MTAG)	1.000000e-08

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0000180	HIV-1 infection
EFO:0004874	memory performance
EFO:0006805	word list delayed recall measurement
EFO:0006806	paragraph delayed recall measurement
EFO:0008579	risk-taking behaviour

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D007640	Keratoconus	C11.204.627

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

Binding affinities (BindingDB)

37 measured of 37 human assays (38 total across all organisms); most potent 37 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-5-(5-methoxy-2-pyridinyl)-2-methylpentyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	0.72 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-5-(5-fluoro-2-pyridinyl)-1-hydroxy-2-methylpentyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	1.5 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-5-(2-methylpyrazol-3-yl)pentyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	2.1 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-5-pyrazin-2-ylpentyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	2.2 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-33-[(1R,2R)-3-(1H-benzimidazol-2-yl)-1-hydroxy-2-methylpropyl]-30-ethyl-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	2.3 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-5-pyridin-4-ylpentyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	2.5 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-5-pyridin-4-ylpentyl]-27-(methoxymethyl)-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	3.1 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-27-(hydroxymethyl)-33-[(1R,2R)-1-hydroxy-2-methyl-5-pyridin-2-ylpentyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	3.1 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-5-(2-methyl-1,3-thiazol-4-yl)pentyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	3.2 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-5-pyridazin-3-ylpentyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	3.2 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9R,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-5-pyrimidin-2-ylpentyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	3.2 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-5-(1,3-oxazol-2-yl)pentyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	3.5 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-5-pyridin-2-ylpentyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	3.8 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-5-(1-methylpyrazol-3-yl)pentyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	3.8 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-5-(2-methyl-4-pyridinyl)pentyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	3.9 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-6-pyridin-2-ylhexyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	3.9 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-3-[1-(pyridin-2-ylmethyl)imidazol-2-yl]propyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	4.1 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9R,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-5-pyridin-2-ylpentyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-27-methylsulfanyl-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	4.4 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-3-[1-(2-morpholin-4-ylethyl)imidazol-2-yl]propyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	4.6 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-33-[(1R,2R)-3-[1-[2-(dimethylamino)ethyl]imidazol-2-yl]-1-hydroxy-2-methylpropyl]-30-ethyl-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	5.1 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-3-[1-(3-hydroxypropyl)imidazol-2-yl]-2-methylpropyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	5.1 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9R,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-5-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-yl)pentyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	5.4 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9R,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-3-[1-(2-pyridin-3-ylethyl)imidazol-2-yl]propyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	5.6 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-5-pyridin-3-ylpentyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	5.6 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-4-(pyridin-4-ylmethoxy)butyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	5.6 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-5-(1-methylimidazol-4-yl)pentyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	5.7 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-5-(1-methylpyrazol-4-yl)pentyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	6.8 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,30S,33R)-33-[(1R,2R)-3-(1H-benzimidazol-2-yl)-1-hydroxy-2-methylpropyl]-30-ethyl-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	7.1 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-3-[1-(3,3,3-trifluoropropyl)imidazol-2-yl]propyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	7.4 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-4-pyrimidin-2-yloxybutyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	7.7 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-5-pyrimidin-2-ylpentyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	8.3 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-3-[1-(2-pyrrolidin-1-ylethyl)imidazol-2-yl]propyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	8.6 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-5-pyridin-3-ylpentyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	9.5 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-5-pyridin-2-ylpentyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	11 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-5-(1-methylimidazol-2-yl)pentyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	12.2 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-5-pyridin-4-ylpentyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	14 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methyl-3-(1-methylimidazol-2-yl)propyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	15 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Leflunomide	increases expression	2
Cannabidiol	decreases expression	2
Cisplatin	decreases expression, affects expression	2
Doxorubicin	affects expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	increases expression	2
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
ethyl-p-hydroxybenzoate	increases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases 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	increases expression, affects cotreatment	1
clothianidin	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Decitabine	affects expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	increases expression	1
Glyphosate	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7Y8	Ubigene A-549 PPP3CC KO	Cancer cell line	Male
CVCL_TG18	HAP1 PPP3CC (-) 1	Cancer cell line	Male
CVCL_TG19	HAP1 PPP3CC (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety