CIP2A

Summary

CIP2A (cellular inhibitor of PP2A, HGNC:29302) is a protein-coding gene on chromosome 3q13.13, encoding Protein CIP2A (Q8TCG1). Acts as an inhibitor of protein phosphatase PP2A. In precision oncology, CIP2A Underexpression confers sensitivity to Gemcitabine in Pancreatic Ductal Adenocarcinoma (CIViC Level D). It is a selective cancer dependency (DepMap: 16.6% of cell lines).

Enables protein homodimerization activity and protein phosphatase inhibitor activity. Involved in broken chromosome clustering. Located in several cellular components, including cytosol; microtubule organizing center; and plasma membrane. Is active in chromosome.

Source: NCBI Gene 57650 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 165 total
• Druggable target: yes
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Cancer dependency (DepMap): dependent in 16.6% of screened cell lines
• MANE Select transcript: NM_020890

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29302
Approved symbol	CIP2A
Name	cellular inhibitor of PP2A
Location	3q13.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000163507
Ensembl biotype	protein_coding
OMIM	610643
Entrez	57650

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000295746, ENST00000461666, ENST00000468953, ENST00000481530, ENST00000487834, ENST00000491772, ENST00000625495, ENST00000923233

RefSeq mRNA: 1 — MANE Select: NM_020890 NM_020890

CCDS: CCDS33812

Canonical transcript exons

ENST00000295746 — 21 exons

Exon	Start	End
ENSE00001822100	108549864	108551319
ENSE00003462653	108559757	108559867
ENSE00003474369	108560649	108560841
ENSE00003482478	108568155	108568314
ENSE00003483003	108554376	108554489
ENSE00003490610	108557218	108557414
ENSE00003491293	108582977	108583083
ENSE00003505799	108582108	108582202
ENSE00003505942	108566497	108566638
ENSE00003506638	108569389	108569607
ENSE00003546569	108576271	108576346
ENSE00003557811	108579281	108579426
ENSE00003576233	108581415	108581511
ENSE00003580591	108552234	108552373
ENSE00003581014	108563126	108563244
ENSE00003584803	108579566	108579688
ENSE00003595116	108565355	108565454
ENSE00003608612	108559954	108560028
ENSE00003639722	108585065	108585212
ENSE00003660344	108553648	108553730
ENSE00003850523	108589274	108589438

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 91.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.2501 / max 117.1167, expressed in 1561 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
43673	6.5552	1204
43674	1.4341	943
43675	0.2609	122

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	91.12	gold quality
secondary oocyte	CL:0000655	85.90	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.42	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.99	gold quality
embryo	UBERON:0000922	84.96	gold quality
ganglionic eminence	UBERON:0004023	84.96	gold quality
buccal mucosa cell	CL:0002336	83.96	silver quality
bone marrow cell	CL:0002092	80.03	gold quality
adrenal tissue	UBERON:0018303	78.94	gold quality
vermiform appendix	UBERON:0001154	77.11	gold quality
stromal cell of endometrium	CL:0002255	76.52	gold quality
rectum	UBERON:0001052	75.45	gold quality
bone marrow	UBERON:0002371	75.01	gold quality
calcaneal tendon	UBERON:0003701	74.50	gold quality
cortical plate	UBERON:0005343	73.88	gold quality
lymph node	UBERON:0000029	73.39	gold quality
testis	UBERON:0000473	73.24	gold quality
smooth muscle tissue	UBERON:0001135	73.18	gold quality
left testis	UBERON:0004533	72.42	gold quality
monocyte	CL:0000576	72.37	gold quality
right testis	UBERON:0004534	72.36	gold quality
leukocyte	CL:0000738	72.08	gold quality
islet of Langerhans	UBERON:0000006	71.18	gold quality
ileal mucosa	UBERON:0000331	69.85	gold quality
esophagus mucosa	UBERON:0002469	69.21	gold quality
caecum	UBERON:0001153	69.20	gold quality
colonic epithelium	UBERON:0000397	69.11	silver quality
gall bladder	UBERON:0002110	68.57	gold quality
right adrenal gland cortex	UBERON:0035827	67.91	gold quality
right hemisphere of cerebellum	UBERON:0014890	67.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-124858	yes	214.40
E-ANND-3	yes	4.51
E-CURD-112	no	3.71

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF1A, NKX2-1, NR2F1, PAX9, TCF3

miRNA regulators (miRDB)

95 targeting CIP2A, 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-5692A	100.00	74.40	6850
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 16.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Data show that CIP2A/KIAA1524 is a human oncoprotein that inhibits protein phosphatase 2A and stabilizes c-Myc in human malignancies. (PMID:17632056)
• CIP2A in tumor cells is required for sustained proliferation by preventing cell growth arrest, senescence, or differentiation. (PMID:18559589)
• CIP2A and MYC appear to be regulated in a positive feedback loop, wherein they promote each other’s expression and gastric cancer cell proliferation. (PMID:19470954)
• CIP2A is associated with clinical aggressivity in human breast cancer and promotes the malignant growth of breast cancer cells. (PMID:19671842)
• CagA upregulated CIP2A expression and this upregulation effect was dependent on Src and Ras/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways. (PMID:19959630)
• Overexpression of CIP2A is associated with non-small cell lung cancer. (PMID:20842459)
• Expression of the CIP2A protein is increased in prostate cancer specimens and its expression is associated with poorly differentiated and high-risk tumors. (PMID:20964854)
• Data suggest that CIP2A may play a significant role in oral malignant transformation and therefore, it may be a potential target for chemotherapy of OSCC. (PMID:21068540)
• CIP2A is significantly overexpressed in human esophageal tumors (PMID:21140243)
• The high expression of CIP2A in HL60 cells may be related to active cell proliferation and arrest of cell differentiation. (PMID:21219591)
• results also suggest that in addition to its established role in invasion and angiogenesis, ETS1 may support malignant cellular growth via regulation of CIP2A expression and protein phosphatase 2A inhibition (PMID:21445343)
• The data demonstrated that CIP2A expression is closely associated with the histopathological score of synovitis and invasive function of fibroblast-like synoviocytes in rheumatoid arthritis. (PMID:21479604)
• CIP2A is biologically and clinically important in chronic myeloid leukemia and may be a novel therapeutic target. (PMID:21490338)
• CIP2A plays an important role in carcinogenisis of cervical cancer and shows promise for the diagnosis and treatment of cervical cancer. (PMID:21575984)
• Silencing CIP2A by siRNA inhibited the proliferation and clonogenic activity of lung cancer cells. (PMID:21655278)
• CIP2A expression in Chinese non-small-cell lung cancer patients may be a useful biomarker of biological malignancy (PMID:21874565)
• High Cancerous inhibitor of protein phosphatase 2A is associated with serous ovarian cancer. (PMID:21897396)
• CIP2A expression is elevated in cervical cancer. (PMID:22072119)
• Higher-CIP2A expression positively correlates with the aggressive phenotype of RCCs, and predicts poor prognosis for patients (PMID:22075943)
• Bortezomib sensitized solid tumor cells to radiation-induced apoptosis through the inhibition of CIP2A. (PMID:22085493)
• The results both validated CIP2A’s role in regulating MYC-mediated gene expression and provided a plausible novel explanation for the high MYC activity in basal-like and HER2thorn breast cancers. (PMID:22249265)
• Overexpression of CIP2A in colorectal cancer patients may be an important step in colorectal carcinogenesis. Based on findings, CIP2A shows no association with patient prognosis in colorectal cancer, but is associated with nuclear c-Myc. (PMID:22310977)
• Data suggest that nontumoral cancerous inhibitor of protein phosphatase 2A (CIP2A)mRNA expression might serve as a novel biomarker for HCC patients undergoing resection. (PMID:22537152)
• CIP2A is a major determinant mediating bortezomib-induced apoptosis in triple negative breast cancer cells. (PMID:22537901)
• CIP2A overexpression may be useful as an independent prognostic biomarker for overall survival and disease-free survival of hepatocellular carcinoma. (PMID:22847158)
• CIP2A overexpression is associated with ovarian cancer. (PMID:22923389)
• The binding of Ets1 and Elk1 together to the proximal CIP2A promoter is absolutely required for CIP2A expression in cervical, endometrial and liver carcinoma cell lines (PMID:23117818)
• CIP2A may be useful as a therapeutic biomarker for predicting clinical response to erlotinib in hepatocellular carcinoma treatment. (PMID:23178652)
• Our findings suggest that CIP2A is an independent predictor of poor prognosis of bladder urothelial cell carcinoma patients (PMID:23275123)
• Data show that E2F1 overexpression, due to p53 or p21 inactivation, promotes expression of human oncoprotein CIP2A. (PMID:23306062)
• CIP2A is an oncogene involved in bladder cancer as it is specifically expressed in bladder tumor tissue and not normal tissue. (PMID:23342256)
• Cancerous inhibitor of protein phosphatase 2A mediates bortezomib-induced autophagy in hepatocellular carcinoma independent of proteasome. (PMID:23383345)
• show that CIP2A expression in rheumatoid arthritis FLS is an important mediator of dysfunctional apoptosis independent of c-Myc stabilization (PMID:23455633)
• These results validate the role of CIP2A as a clinically relevant oncoprotein and establish CIP2A as a promising therapeutic target of astrocytoma. (PMID:23467938)
• CIP2A expression may be a potential biomarker for chemotherapeutic sensitivity and prognosis of breast cancer. (PMID:23471718)
• Tumor suppressor miR-375 regulates MYC expression via repression of CIP2A coding sequence through multiple miRNA-mRNA interactions. (PMID:23552692)
• results indicate that CIP2A expressioncorrelates with altered expression of epithelial-mesenchymal transition markers, increased lymph node metastasis, and poorer survival in pancreatic ductal adenocarcinoma (PMID:23568706)
• Cox-regression analysis showed that IL-10 and CIP2A mRNA levels may independently predict survival in patients with lung adenocarcinoma, especially in patients with E6-positive tumors (PMID:23743567)
• CIP2A immunoreactivity was usually weak or absent in indolent B-cell lymphomas, but moderately positive or strongly positive in almost all aggressive lymphomas, such as DLBCL, BL, and BCLU. (PMID:23802697)
• A novel function for CIP2A in facilitating the stability and activity of the pivotal mitotic kinase Plk1 in cell-cycle progression and tumor development. (PMID:23983103)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cip2a	ENSDARG00000058260
mus_musculus	Cip2a	ENSMUSG00000033031
rattus_norvegicus	Cip2a	ENSRNOG00000039183
caenorhabditis_elegans		WBGENE00015188

Paralogs (2): CCDC57 (ENSG00000176155), CCHCR1 (ENSG00000204536)

Protein

Protein identifiers

Protein CIP2A — Q8TCG1 (reviewed: Q8TCG1)

Alternative names: Cancerous inhibitor of PP2A, p90 autoantigen

All UniProt accessions (3): Q8TCG1, F8WAX6, F8WF26

UniProt curated annotations — full annotation on UniProt →

Function. Acts as an inhibitor of protein phosphatase PP2A. Promotes anchorage-independent cell growth and tumor formation by preventing dephosphorylation of MYC, thereby stabilizing MYC in human malignancies. Together with TOPBP1, plays an essential role in the response to genome instability generated by the presence of acentric chromosome fragments derived from shattered chromosomes within micronuclei. Micronuclei, which are frequently found in cancer cells, consist of chromatin surrounded by their own nuclear membrane: following breakdown of the micronuclear envelope, a process associated with chromothripsis, the CIP2A-TOPBP1 complex tethers chromosome fragments during mitosis to ensure clustered segregation of the fragments to a single daughter cell nucleus, facilitating re-ligation with limited chromosome scattering and loss.

Subunit / interactions. Homodimer. Interacts with MYC. Interacts with PPP2R5C; this interaction stabilizes CIP2A. Interacts with PPP2R1A; this interaction stabilizes CIP2A. Interacts with TOPBP1; forming the CIP2A-TOPBP1 complex.

Subcellular location. Cytoplasm. Chromosome.

Tissue specificity. Expressed at low levels in most of the tissues. Overexpressed in head-and-neck squamous cell carcinomas (HNSCC). Present in liver cancer cells (at protein level).

Miscellaneous. Antibodies against CIP2A are present in sera from many patients with gastric or prostate cancer, suggesting that it may act as a marker for such cancers.

Similarity. Belongs to the CIP2A family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TCG1-1	1	yes
Q8TCG1-2	2

RefSeq proteins (1): NP_065941* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR042510	CIP2A	Family
IPR048701	CIP2A_N	Domain

Pfam: PF21044

UniProt features (61 total): helix 34, sequence variant 8, mutagenesis site 3, turn 3, modified residue 3, region of interest 2, sequence conflict 2, strand 2, chain 1, coiled-coil region 1, short sequence motif 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5UFL	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TCG1-F1	84.09	0.56

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 (3): 1, 573, 904

Mutagenesis-validated functional residues (3):

Position	Phenotype
230	reduces binding to ppp2r5c.
522	decreases homodimerization. reduces binding to ppp2r5c. decreases protein level.
533	decreases homodimerization. reduces binding to ppp2r5c. decreases protein level.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 166 (showing top): GOBP_CHROMOSOME_ORGANIZATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MODULE_255, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MODULE_317, GGGTGGRR_PAX4_03, GOLDRATH_ANTIGEN_RESPONSE, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_DN, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, LE_EGR2_TARGETS_UP, GOBP_DNA_DAMAGE_RESPONSE, DODD_NASOPHARYNGEAL_CARCINOMA_UP

GO Biological Process (3): DNA damage response (GO:0006974), chromosome organization (GO:0051276), broken chromosome clustering (GO:0141112)

GO Molecular Function (4): protein phosphatase inhibitor activity (GO:0004864), protein homodimerization activity (GO:0042803), cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (6): chromosome (GO:0005694), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), ciliary basal body (GO:0036064)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
microtubule organizing center	2
cellular response to stress	1
organelle organization	1
DNA damage response	1
chromosome organization	1
phosphoprotein phosphatase activity	1
phosphatase inhibitor activity	1
protein phosphatase regulator activity	1
identical protein binding	1
protein dimerization activity	1
cell adhesion molecule binding	1
binding	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
centriole	1
cytoplasm	1
membrane	1
cell periphery	1
cilium	1

Protein interactions and networks

STRING

1856 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CIP2A	MYC	P01106	811
CIP2A	PPP2R1A	P30153	725
CIP2A	PPME1	Q9Y570	673
CIP2A	MINK1	Q8N4C8	659
CIP2A	SET	Q01105	632
CIP2A	E2F1	Q01094	628
CIP2A	PPP2CA	P05323	601
CIP2A	PLK1	P53350	565
CIP2A	ENSA	O43768	517
CIP2A	PPP2R5A	Q15172	507
CIP2A	YWHAZ	P29213	494
CIP2A	AKT1	P31749	483
CIP2A	ANP32A	P39687	454
CIP2A	PPP2R2A	P50409	451
CIP2A	PPP2R5C	Q13362	447

IntAct

161 interactions, top by confidence:

A	B	Type	Score
PPP2R1A	PPP2R2A	psi-mi:“MI:0914”(association)	0.970
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
SCN2B	EXOC5	psi-mi:“MI:0914”(association)	0.640
CIP2A	PPP2R1A	psi-mi:“MI:0915”(physical association)	0.610
PPP2R1A	CIP2A	psi-mi:“MI:0915”(physical association)	0.610
PDGFRB	PIK3R2	psi-mi:“MI:0914”(association)	0.610
CEP104	CCDC66	psi-mi:“MI:2364”(proximity)	0.540
MYC	CIP2A	psi-mi:“MI:0407”(direct interaction)	0.540
MYC	CIP2A	psi-mi:“MI:0915”(physical association)	0.540
HTR2C	KLRG2	psi-mi:“MI:0914”(association)	0.530
LRFN4	RIMOC1	psi-mi:“MI:0914”(association)	0.530
NPY2R	RTL8C	psi-mi:“MI:0914”(association)	0.530
COMTD1	IFRD1	psi-mi:“MI:0914”(association)	0.530
VASN	AP3B1	psi-mi:“MI:0914”(association)	0.530
FZD10	NRP1	psi-mi:“MI:0914”(association)	0.530
CD83	BTAF1	psi-mi:“MI:0914”(association)	0.530
VSIG2	TTI1	psi-mi:“MI:0914”(association)	0.530
CD274	TTI1	psi-mi:“MI:0914”(association)	0.530
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530

BioGRID (270): KIAA1524 (Affinity Capture-RNA), KIAA1524 (Affinity Capture-Western), KIAA1524 (Affinity Capture-MS), KIAA1524 (Affinity Capture-MS), KIAA1524 (Affinity Capture-MS), KIAA1524 (Affinity Capture-MS), KIAA1524 (Affinity Capture-MS), KIAA1524 (Affinity Capture-MS), KIAA1524 (Affinity Capture-MS), KIAA1524 (Affinity Capture-MS), KIAA1524 (Affinity Capture-MS), KIAA1524 (Affinity Capture-MS), KIAA1524 (Affinity Capture-MS), KIAA1524 (Affinity Capture-MS), KIAA1524 (Proximity Label-MS)

ESM2 similar proteins: A0A8M2BID5, A2AL36, A2CG49, A6PWD2, D3ZEY0, D3ZHV2, E9Q1U1, E9Q557, E9Q8Q6, F1LMV6, F1M0Z1, G3V7L1, O15068, O60229, O60437, O75962, O97592, P10911, P11530, P11531, P11532, P11533, P15924, P46939, P97924, Q0KL02, Q1LUA6, Q4FZC9, Q5GN48, Q5XK92, Q63406, Q64096, Q6TFL3, Q6UWE0, Q6ZMZ3, Q6ZP82, Q6ZWQ0, Q6ZWR6, Q80ZI6, Q86YR7

Diamond homologs: Q5XK92, Q5ZMJ7, Q8BWY9, Q8TCG1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
STUB1	“down-regulates quantity by destabilization”	CIP2A	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 178 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
positive regulation of cytosolic calcium ion concentration	9	6.8×	5e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	125
Likely benign	6
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3104 predictions. Top by Δscore:

Variant	Effect	Δscore
3:108551320:CT:C	acceptor_loss	1.0000
3:108552228:TCTTA:T	donor_loss	1.0000
3:108552229:CTTA:C	donor_loss	1.0000
3:108552230:TTACC:T	donor_loss	1.0000
3:108552231:TACC:T	donor_loss	1.0000
3:108552232:A:AC	donor_gain	1.0000
3:108552233:C:CC	donor_gain	1.0000
3:108552304:T:TA	donor_gain	1.0000
3:108552369:CAAAT:C	acceptor_gain	1.0000
3:108552370:AAAT:A	acceptor_gain	1.0000
3:108552371:AAT:A	acceptor_gain	1.0000
3:108552372:AT:A	acceptor_gain	1.0000
3:108552373:TCT:T	acceptor_loss	1.0000
3:108552374:C:CC	acceptor_gain	1.0000
3:108552375:T:C	acceptor_gain	1.0000
3:108552375:T:TC	acceptor_gain	1.0000
3:108553641:CACTT:C	donor_loss	1.0000
3:108553642:ACTTA:A	donor_loss	1.0000
3:108553643:CTTA:C	donor_loss	1.0000
3:108553644:TTA:T	donor_loss	1.0000
3:108553645:TA:T	donor_loss	1.0000
3:108553646:A:AC	donor_gain	1.0000
3:108553647:C:CA	donor_gain	1.0000
3:108553647:CTTG:C	donor_gain	1.0000
3:108553726:TACTT:T	acceptor_gain	1.0000
3:108553737:T:C	acceptor_gain	1.0000
3:108553737:T:TC	acceptor_gain	1.0000
3:108553739:A:C	acceptor_gain	1.0000
3:108553740:T:C	acceptor_gain	1.0000
3:108553740:T:TC	acceptor_gain	1.0000

AlphaMissense

5948 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:108551204:A:C	I888S	0.999
3:108551204:A:G	I888T	0.999
3:108551204:A:T	I888N	0.999
3:108579317:A:G	L261P	0.999
3:108579329:A:G	L257P	0.999
3:108579389:A:G	L237P	0.999
3:108551195:A:G	L891S	0.998
3:108551211:C:G	A886P	0.998
3:108581458:A:G	L169P	0.998
3:108579409:G:C	N230K	0.997
3:108579409:G:T	N230K	0.997
3:108579612:A:G	L209P	0.997
3:108559810:C:G	A654P	0.996
3:108559842:A:G	L643P	0.996
3:108579422:A:G	F226S	0.996
3:108579660:A:G	L193P	0.996
3:108582189:A:G	L124P	0.996
3:108551309:A:G	L853P	0.995
3:108557299:A:G	L710P	0.995
3:108559851:A:G	L640P	0.995
3:108579287:A:G	L271P	0.995
3:108579421:G:C	F226L	0.995
3:108579421:G:T	F226L	0.995
3:108579423:A:G	F226L	0.995
3:108579574:C:A	G222W	0.995
3:108579606:A:T	I211K	0.995
3:108581425:A:T	I180K	0.995
3:108581456:A:G	C170R	0.995
3:108579326:A:G	L258P	0.994
3:108579389:A:T	L237Q	0.994

dbSNP variants (sampled 300 via entrez): RS1000014939 (3:108558595 T>C), RS1000088108 (3:108584464 T>G), RS1000196779 (3:108551504 A>G), RS1000383855 (3:108572163 G>A), RS1000391123 (3:108576981 G>A), RS1000401962 (3:108581306 C>T), RS1000441749 (3:108577240 A>T), RS1000444669 (3:108558761 T>C), RS1000448018 (3:108569777 G>A), RS1000463563 (3:108587618 CTGTA>C), RS1000601040 (3:108564447 ATAT>A), RS1000683734 (3:108583492 A>G), RS1000754025 (3:108589301 G>A), RS1000791394 (3:108557930 G>A,C), RS1000804910 (3:108589513 C>T)

Disease associations

OMIM: gene MIM:610643 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007932_96	Medication use (thyroid preparations)	5.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009933	Thyroid preparation use measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2146355 (SINGLE PROTEIN)

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items; also 1 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
CIP2A Underexpression	Gemcitabine	Pancreatic Ductal Adenocarcinoma	Sensitivity/Response	CIViC D	EID1118

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
sodium arsenite	decreases expression	2
Resveratrol	increases expression, affects cotreatment	2
Acetaminophen	decreases expression, increases expression	2
Testosterone	decreases expression, affects cotreatment	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
bisphenol A	decreases expression	1
butyraldehyde	decreases expression	1
leupeptin	decreases expression, decreases reaction	1
polyhexamethyleneguanidine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
temsirolimus	decreases expression, decreases reaction, affects cotreatment, decreases response to substance, affects binding (+1 more)	1
Dasatinib	decreases expression	1
Antineoplastic Agents, Immunological	decreases response to substance, affects cotreatment	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	increases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Chloroquine	decreases reaction, decreases expression	1
Cisplatin	decreases expression	1
Coumestrol	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression	1
Ivermectin	decreases expression	1

ChEMBL screening assays

17 unique, capped per target: 17 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2150601	Binding	Inhibition of CIP2A in human SKHEP1 cells at 5 uM after 30 hrs by Western blot analysis	Development of erlotinib derivatives as CIP2A-ablating agents independent of EGFR activity. — Bioorg Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SU65	HAP1 KIAA1524 (-) 1	Cancer cell line	Male
CVCL_XQ01	HAP1 KIAA1524 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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