PTTG1

Summary

PTTG1 (PTTG1 regulator of sister chromatid separation, securin, HGNC:9690) is a protein-coding gene on chromosome 5q33.3, encoding Securin (O95997). Regulatory protein, which plays a central role in chromosome stability, in the p53/TP53 pathway, and DNA repair. It is a selective cancer dependency (DepMap: 30.0% of cell lines).

The encoded protein is a homolog of yeast securin proteins, which prevent separins from promoting sister chromatid separation. It is an anaphase-promoting complex (APC) substrate that associates with a separin until activation of the APC. The gene product has transforming activity in vitro and tumorigenic activity in vivo, and the gene is highly expressed in various tumors. The gene product contains 2 PXXP motifs, which are required for its transforming and tumorigenic activities, as well as for its stimulation of basic fibroblast growth factor expression. It also contains a destruction box (D box) that is required for its degradation by the APC. The acidic C-terminal region of the encoded protein can act as a transactivation domain. The gene product is mainly a cytosolic protein, although it partially localizes in the nucleus. Three transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 9232 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 32 total
• Cancer dependency (DepMap): dependent in 30.0% of screened cell lines
• Transcription factor: yes — 16 downstream targets (CollecTRI)
• MANE Select transcript: NM_004219

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9690
Approved symbol	PTTG1
Name	PTTG1 regulator of sister chromatid separation, securin
Location	5q33.3
Locus type	gene with protein product
Status	Approved
Aliases	PTTG, HPTTG, EAP1, securin, ECRAR
Ensembl gene	ENSG00000164611
Ensembl biotype	protein_coding
OMIM	604147
Entrez	9232

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 17 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000352433, ENST00000393964, ENST00000517480, ENST00000519287, ENST00000520452, ENST00000523659, ENST00000524244, ENST00000922252, ENST00000922253, ENST00000922254, ENST00000922255, ENST00000922256, ENST00000922257, ENST00000922258, ENST00000922259, ENST00000922260, ENST00000922261, ENST00000922262, ENST00000922263, ENST00000922264

RefSeq mRNA: 3 — MANE Select: NM_004219 NM_001282382, NM_001282383, NM_004219

CCDS: CCDS4353

Canonical transcript exons

ENST00000352433 — 6 exons

Exon	Start	End
ENSE00001209726	160421855	160421891
ENSE00003458569	160422302	160422403
ENSE00003480460	160427715	160427873
ENSE00003492340	160422709	160422893
ENSE00003504727	160424237	160424330
ENSE00003674570	160428602	160428739

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 99.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 63.7525 / max 1587.5824, expressed in 1791 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59895	53.1109	1768
59894	10.4094	1566
59896	0.1390	56
59897	0.0931	38

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.97	gold quality
secondary oocyte	CL:0000655	99.97	gold quality
ventricular zone	UBERON:0003053	99.36	gold quality
left testis	UBERON:0004533	98.50	gold quality
ganglionic eminence	UBERON:0004023	98.44	gold quality
tongue squamous epithelium	UBERON:0006919	98.36	gold quality
embryo	UBERON:0000922	98.31	gold quality
right testis	UBERON:0004534	98.23	gold quality
sperm	CL:0000019	98.12	gold quality
male germ cell	CL:0000015	97.95	gold quality
gingival epithelium	UBERON:0001949	97.62	gold quality
adult organism	UBERON:0007023	97.27	gold quality
testis	UBERON:0000473	97.23	gold quality
trabecular bone tissue	UBERON:0002483	96.79	gold quality
gingiva	UBERON:0001828	96.77	gold quality
bone marrow	UBERON:0002371	95.38	gold quality
esophagus mucosa	UBERON:0002469	94.71	gold quality
lower esophagus mucosa	UBERON:0035834	94.50	gold quality
mucosa of transverse colon	UBERON:0004991	94.27	gold quality
hair follicle	UBERON:0002073	94.22	gold quality
endometrium epithelium	UBERON:0004811	94.15	gold quality
oral cavity	UBERON:0000167	93.77	gold quality
rectum	UBERON:0001052	93.73	gold quality
squamous epithelium	UBERON:0006914	93.67	gold quality
cervix squamous epithelium	UBERON:0006922	93.26	gold quality
cartilage tissue	UBERON:0002418	93.09	gold quality
ileal mucosa	UBERON:0000331	92.97	gold quality
left lobe of thyroid gland	UBERON:0001120	92.92	gold quality
thyroid gland	UBERON:0002046	92.85	gold quality
thymus	UBERON:0002370	92.85	gold quality

Single-cell (SCXA)

Detected in 47 experiment(s), a significant marker in 42.

Experiment	Marker?	Max mean expression
E-MTAB-10485	yes	3449.34
E-MTAB-8894	yes	2459.55
E-MTAB-9435	yes	2324.99
E-CURD-112	yes	2294.76
E-HCAD-56	yes	2229.56
E-HCAD-5	yes	2223.75
E-MTAB-11121	yes	1914.23
E-MTAB-10662	yes	1432.16
E-HCAD-10	yes	1401.54
E-GEOD-81383	yes	1392.38
E-GEOD-114530	yes	1388.79
E-MTAB-9906	yes	1283.12
E-MTAB-6505	yes	1262.00
E-HCAD-6	yes	1213.72
E-MTAB-6108	yes	1146.91

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

16 targets.

Target	Regulation
CCNB1	Activation
CDC42	Activation
CDK1	Activation
DOCK1	Activation
FGF2	Unknown
ID3	Activation
KDR	Activation
LGALS1	Activation
MYC	Activation
PTTG1	Repression
PTTG1IP	Activation
RAC1	Activation
RHOA	Activation
S100A4	Activation
TIMP2	Repression
VEGFA	Activation

Upstream regulators (CollecTRI, top): CTNNB1, CUX1, E2F1, FOXL2, KLF10, KLF6, NKX2-1, POU2F1, PTTG1, RUNX2, SP1, SP3, STAT3, STAT5A, TCF7L2, TFDP1, TP53, YY1

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 30.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Data suggest that separase is required for sister chromatid separation during mitosis in human cells, and that securin inhibits separase by blocking the access of substrates to the active site of separase. (PMID:12194817)
• findings implicate altered VEGF and KDR signaling in pituitary tumorigenesis; PTTG stimulation of FGF-2 and VEGF expression in the presence of up-regulated growth factor receptors may account for angiogenic growth and progression of human pituitary tumors (PMID:12213878)
• Tumor tissue expressed a significantly higher level of PTTG1 mRNA than the corresponding normal tissue. PTTG1 mRNA expression was significantly higher in tumors with higher pathological stage or more extensive lymph node metastasis (PMID:12324572)
• the oncogenic effect of increased expression of securin may result from modulation of p53 functions (PMID:12355087)
• Data suggest that securin is a p53 target gene and may play a role in p53-mediated cellular response to DNA damage. (PMID:12403781)
• the involvement of hpttg in lymphomagenesis (PMID:12444553)
• PTTG1-mediated signaling alters the hormonal phenotype in pituitary (PMID:12554778)
• The relationship between pituitary tumour transforming gene (PTTG) expression and in vitro growth hormone and vascular endothelial growth factor (VEGF) secretion from human pituitary adenomas. (PMID:12590639)
• pituitary tumor transforming gene and fibroblast growth factor-2 expression are potential prognostic markers (and perhaps therapeutic targets) for differentiated thyroid cancer (PMID:12727994)
• A potential role for PTTG in modulating cell proliferation and FGF-2 expression in the fetal brain. (PMID:12958169)
• Failure of PTTG degradation or enhanced PTTG accumulation, as a consequence of overexpression, inhibits mitosis progression and chromosome segregation but does not directly affect cytokinesis, resulting in aneuploidy. (PMID:12960092)
• Results do not support a major role of hSecurin in the development of aneuploidy in myeloid leukaemias. However, high expression of hSecurin may be of pathogenetic relevance in a subset of patients. (PMID:14671639)
• Overexpression of hPTTG inhibits the cell growth due to different mechanisms, which are p21WAF1/CIP1 -dependent and -independent. (PMID:14709851)
• PTTG1 expression is enhanced in metastatic lymph nodes in comparison to that in primary carcinomas and may contribute to lymph node metastases in gastric carcinoma (PMID:14966902)
• Results suggest that human securin has a novel role in cell cycle arrest after exposure to UV light or ionizing radiation. (PMID:15024062)
• higher PTTG expression in astrocytoma than normal astrocytes and PTTG is involved in glioma cell growth. (PMID:15178645)
• Clinical studies reveal that PTTG-binding factor, fibroblast growth factor 2, and vascular endothelial growth factor are elevated in pituitary tumors, and mostly correlate with PTTG levels, also confirming the PTTG role in angiogenesis. Review. (PMID:15281346)
• As a target gene of beta-catenin/TCF pathway, PTTG may play an important role in tumorigenesis of human esophageal squamous cell carcinoma. (PMID:15514942)
• PXXP structure and phosphorylation are likely to exert independent and critical influences upon PTTG’s diverse actions in vitro (PMID:15591026)
• Demonstration of the importance of PTTG1 in human tumorigenesis. (PMID:15649325)
• PTTG-1 is up-regulated in human uterine leiomyomas and that the positive feedback loop between PTTG-1 and basic fibroblast growth factor may be pivotal in the growth of leiomyoma cells. (PMID:15769981)
• Abundant cytoplasmic and nuclear securin expression was demonstrated in all 90 breast tumors. (PMID:15846392)
• density map at a resolution of 25 A of negatively stained separase-securin complex (PMID:15880121)
• PTTG may be an important gene in the mutator phenotype development in thyroid cancer (PMID:15897900)
• insulin and IGF-1 regulate the expression of PTTG in MCF-7 cells primarily through the activation of PI3K/AKT cascade (PMID:15922332)
• Securin degradation is not sufficient for centromere separation or anaphase onset in human cells; other targets of the proteasome must be degraded to allow anaphase onset. (PMID:16205121)
• data demonstrate that securin is dispensable for chromosomal stability in human cells (PMID:16292982)
• PTTG may promote angiogenesis by regulating the expression of multiple genes with both pro- and antiangiogenic properties and may thus be a key gene in triggering the angiogenic switch in thyroid tumorigenesis. (PMID:16394085)
• Data suggest that increased expression of PTTG1 contributes to the tumorigenicity of glioma cells. (PMID:16685397)
• Treatment of cells with okadaic acid, a potent inhibitor of PP2A, results in various hyperphosphorylated forms of hSecurin which are extremely unstable, due to the action of the Skp1/Cul1/F-box protein complex ubiquitin ligase. (PMID:16705156)
• High expression of beta-catenin and securin (hPTTG1) in colorectal adenomas and carcinomas; securin is a target of beta-catenin transcriptional activation. (PMID:16705313)
• PTTG1 is overexpressed in nodular melanoma, and contributes to tumor progression by causing aneuploidy or by modulating p53-function (PMID:16799481)
• PTTG participates in the pathogenesis of various tumors, including pituitary tumors, by inducing aneuploidy and upregulating FGF-2, a potent mitogenic and angiogenic factor. (PMID:16809406)
• PTTG has a role in lung tumor growth, and its suppression may inhibit tumor growth (PMID:16820881)
• Novel PTTG-mediated proliferative pathway that may be critical to thyroid cancer growth and progression. (PMID:16926250)
• securin may be a critical gene in the development of genetic instability in colorectal cancer. (PMID:17071631)
• overexpression of PTTG and PBF in differentiated thyroid cancer has profound implications for activity of the NIS gene, and hence significantly impacts upon the efficacy of radioiodine treatment. (PMID:17297475)
• Results show that PTTG1 exhibits properties of a global transcription factor, and specifically modulates the G1/S-phase transition by interacting with Sp1. (PMID:17353909)
• HCT116 cells devoid of PTTG1/securin (sec(-/-) HCT116) show a stabilized yet transcriptionally latent form of p53 protein in the absence of DNA damage. (PMID:17383977)
• Data show that overexpression of human pituitary tumor transforming gene cooperated with the HTLV-I Tax oncoprotein in cellular transformation. (PMID:17507465)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pttg1	ENSDARG00000075421
mus_musculus	Pttg1	ENSMUSG00000020415
rattus_norvegicus	Pttg1	ENSRNOG00000003802

Paralogs (1): PTTG2 (ENSG00000250254)

Protein

Protein identifiers

Securin — O95997 (reviewed: O95997)

Alternative names: Esp1-associated protein, Pituitary tumor-transforming gene 1 protein

All UniProt accessions (3): E5RJR4, O95997, Q6IAL9

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory protein, which plays a central role in chromosome stability, in the p53/TP53 pathway, and DNA repair. Probably acts by blocking the action of key proteins. During the mitosis, it blocks Separase/ESPL1 function, preventing the proteolysis of the cohesin complex and the subsequent segregation of the chromosomes. At the onset of anaphase, it is ubiquitinated, conducting to its destruction and to the liberation of ESPL1. Its function is however not limited to a blocking activity, since it is required to activate ESPL1. Negatively regulates the transcriptional activity and related apoptosis activity of TP53. The negative regulation of TP53 may explain the strong transforming capability of the protein when it is overexpressed. May also play a role in DNA repair via its interaction with Ku, possibly by connecting DNA damage-response pathways with sister chromatid separation.

Subunit / interactions. Interacts with RPS10 and DNAJA1. Interacts with the caspase-like ESPL1, and prevents its protease activity probably by covering its active site. Interacts with TP53 and blocks its activity probably by blocking its binding to DNA. Interacts with the Ku 70 kDa subunit of ds-DNA kinase. Interacts with PTTG1IP.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed at low level in most tissues, except in adult testis, where it is highly expressed. Overexpressed in many patients suffering from pituitary adenomas, primary epithelial neoplasias, and esophageal cancer.

Post-translational modifications. Phosphorylated at Ser-165 by CDK1 during mitosis. Phosphorylated in vitro by ds-DNA kinase. Ubiquitinated through ‘Lys-11’ linkage of ubiquitin moieties by the anaphase promoting complex (APC) at the onset of anaphase, conducting to its degradation. ‘Lys-11’-linked ubiquitination is mediated by the E2 ligase UBE2C/UBCH10.

Domain organisation. The N-terminal destruction box (D-box) acts as a recognition signal for degradation via the ubiquitin-proteasome pathway. The TEK-boxes are required for ‘Lys-11’-linked ubiquitination and facilitate the transfer of the first ubiquitin and ubiquitin chain nucleation. TEK-boxes may direct a catalytically competent orientation of the UBE2C/UBCH10-ubiquitin thioester with the acceptor lysine residue.

Similarity. Belongs to the securin family.

RefSeq proteins (3): NP_001269311, NP_001269312, NP_004210* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006940	Securin_separation_inhibitor	Family

Pfam: PF04856

UniProt features (16 total): mutagenesis site 5, short sequence motif 4, modified residue 2, initiator methionine 1, chain 1, helix 1, strand 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7NJ1	ELECTRON MICROSCOPY	2.9
7NJ0	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95997-F1	63.83	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 (2): 2, 165

Mutagenesis-validated functional residues (5):

Position	Phenotype
64	abolishes ubiquitination and subsequent degradation; when associated with a-61.
163	strongly reduces transforming capability; when associated with l-170; a-172 and l-173.
165	abolishes phosphorylation.
170–173	strongly reduces transforming capability; when associated with a-163.
61	abolishes ubiquitination and subsequent degradation; when associated with a-64.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-174154	APC/C:Cdc20 mediated degradation of Securin
R-HSA-174178	APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1
R-HSA-2467813	Separation of Sister Chromatids

MSigDB gene sets: 453 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, MODULE_52, HORIUCHI_WTAP_TARGETS_DN, REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1, GNF2_CENPF, CROONQUIST_NRAS_SIGNALING_DN, GNF2_H2AFX, MCBRYAN_PUBERTAL_TGFB1_TARGETS_DN, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_MALE_GAMETE_GENERATION, MODULE_16, KAUFFMANN_DNA_REPAIR_GENES, CROSBY_E2F4_TARGETS, WIELAND_UP_BY_HBV_INFECTION

GO Biological Process (7): DNA repair (GO:0006281), spermatogenesis (GO:0007283), homologous chromosome segregation (GO:0045143), chromosome organization (GO:0051276), cell division (GO:0051301), DNA damage response (GO:0006974), chromosome segregation (GO:0007059)

GO Molecular Function (4): cysteine-type endopeptidase inhibitor activity (GO:0004869), SH3 domain binding (GO:0017124), molecular function activator activity (GO:0140677), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
APC/C:Cdc20 mediated degradation of mitotic proteins	1
APC/C-mediated degradation of cell cycle proteins	1
Mitotic Anaphase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
DNA metabolic process	1
DNA damage response	1
developmental process involved in reproduction	1
male gamete generation	1
meiosis I	1
meiotic chromosome segregation	1
organelle organization	1
cellular process	1
cellular response to stress	1
cell cycle process	1
cysteine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
protein domain specific binding	1
molecular function regulator activity	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1976 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTTG1	ESPL1	Q14674	999
PTTG1	CDC20	Q12834	969
PTTG1	BUB1B	O60566	923
PTTG1	CDK1	P06493	902
PTTG1	CCNB1	P14635	900
PTTG1	PTTG1IP	P53801	855
PTTG1	BUB1	O43683	834
PTTG1	UBE2C	O00762	814
PTTG1	PLK1	P53350	809
PTTG1	BUB3	O43684	809
PTTG1	CCNB2	O95067	790
PTTG1	SGO1	Q5FBB7	789
PTTG1	RAD21	O60216	780
PTTG1	MAD2L1	Q13257	774
PTTG1	CDC27	P30260	765

IntAct

31 interactions, top by confidence:

A	B	Type	Score
ESPL1	PTTG1	psi-mi:“MI:0407”(direct interaction)	0.900
PTTG1	ESPL1	psi-mi:“MI:0914”(association)	0.900
PTTG1	ESPL1	psi-mi:“MI:0407”(direct interaction)	0.900
ESPL1	PTTG1	psi-mi:“MI:0914”(association)	0.900
ESPL1	PTTG1	psi-mi:“MI:0915”(physical association)	0.900
ESPL1	RAD21	psi-mi:“MI:0570”(protein cleavage)	0.620
Espl1	PTTG1	psi-mi:“MI:0915”(physical association)	0.560
PTTG1	PLCG2	psi-mi:“MI:0915”(physical association)	0.490
PLCG2	PTTG1	psi-mi:“MI:0915”(physical association)	0.490
CCNB1	PTTG1	psi-mi:“MI:0915”(physical association)	0.490
PTTG1	PTTG1	psi-mi:“MI:0915”(physical association)	0.400
KEAP1	PTTG1	psi-mi:“MI:0915”(physical association)	0.400
PTTG1	CRK	psi-mi:“MI:0915”(physical association)	0.370
PTTG1	CFTR	psi-mi:“MI:0915”(physical association)	0.370
PTTG1	PMS1	psi-mi:“MI:0914”(association)	0.350
Espl1	BDP1	psi-mi:“MI:0914”(association)	0.350
SYNCRIP	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
BAG6	CNOT1	psi-mi:“MI:0914”(association)	0.350
Tbc1d7	SLC25A20	psi-mi:“MI:0914”(association)	0.350
YEATS4	ING3	psi-mi:“MI:0914”(association)	0.350
MRPL1	MRPL43	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
CDC27	PTTG1	psi-mi:“MI:0914”(association)	0.350
PTTG1	ESPL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (218): PTTG1 (Biochemical Activity), PTTG1 (Biochemical Activity), PTTG1 (Reconstituted Complex), PTTG1 (Reconstituted Complex), PTTG1 (Reconstituted Complex), PTTG1 (Biochemical Activity), PTTG1 (Biochemical Activity), PTTG1 (Biochemical Activity), PTTG1 (Biochemical Activity), PTTG1 (Biochemical Activity), PTTG1 (Biochemical Activity), PTTG1 (Biochemical Activity), FZR1 (Affinity Capture-Western), PTTG1 (Biochemical Activity), PTTG1 (Biochemical Activity)

ESM2 similar proteins: A1YF19, A2T767, B0K035, F1RCE7, F7BHS0, O95997, P0DPK0, P23999, P97613, Q08B36, Q08BD8, Q09HN1, Q0VA20, Q14140, Q2KHM9, Q2QD14, Q2QD15, Q2T9X8, Q2WG80, Q3SZY3, Q3UHI0, Q3V1H1, Q5R7F8, Q5RBY6, Q5RKG1, Q5XG16, Q5ZJU5, Q6A000, Q6AYH4, Q6DF94, Q7SXC6, Q8BHE0, Q8BHZ5, Q8C804, Q8N0Z3, Q8QGU6, Q8R080, Q8WWK9, Q96C57, Q96FF9

Diamond homologs: A1YF19, A2T767, O95997, P97613, Q2QD14, Q2QD15, Q3SZY3, Q9BDP6, Q9CQJ7, Q9NZH4, Q9NZH5

SIGNOR signaling

23 interactions.

A	Effect	B	Mechanism
PTTG1	“up-regulates quantity by expression”	LGALS1	“transcriptional regulation”
PTTG1	“down-regulates quantity”	TIMP2
PTTG1	“up-regulates quantity by expression”	S100A4	“transcriptional regulation”
Gbeta	up-regulates	PTTG1	phosphorylation
ERK1/2	up-regulates	PTTG1	phosphorylation
UBE4B	“down-regulates quantity by destabilization”	PTTG1	polyubiquitination
PTTG1	“down-regulates activity”	ESPL1	binding
GSK3B	“down-regulates quantity by destabilization”	PTTG1	phosphorylation
PPP2CA	“up-regulates quantity by stabilization”	PTTG1	dephosphorylation
CAMK2A	“down-regulates quantity by destabilization”	PTTG1	phosphorylation
GSK3B	“down-regulates activity”	PTTG1	phosphorylation
CDK1	up-regulates	PTTG1	phosphorylation
MAPK1	up-regulates	PTTG1	phosphorylation
MAPK3	up-regulates	PTTG1	phosphorylation
PTTG1	“up-regulates activity”	Metastasis
APC-c	“down-regulates quantity by destabilization”	PTTG1	ubiquitination

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

771 predictions. Top by Δscore:

Variant	Effect	Δscore
5:160421877:GCTGT:G	donor_gain	1.0000
5:160421890:GC:G	donor_gain	1.0000
5:160421892:G:GG	donor_gain	1.0000
5:160422300:A:AG	acceptor_gain	1.0000
5:160422301:G:GG	acceptor_gain	1.0000
5:160422404:G:GG	donor_gain	1.0000
5:160421881:T:G	donor_gain	0.9900
5:160421887:CCTGC:C	donor_gain	0.9900
5:160421888:CTGC:C	donor_gain	0.9900
5:160421889:TGC:T	donor_gain	0.9900
5:160421890:GCG:G	donor_gain	0.9900
5:160421891:CG:C	donor_loss	0.9900
5:160421892:GT:G	donor_loss	0.9900
5:160421894:G:GG	donor_loss	0.9900
5:160421895:A:AC	donor_loss	0.9900
5:160422297:CTTA:C	acceptor_loss	0.9900
5:160422298:TTA:T	acceptor_loss	0.9900
5:160422300:A:AT	acceptor_loss	0.9900
5:160422301:G:GT	acceptor_loss	0.9900
5:160422301:GA:G	acceptor_gain	0.9900
5:160422301:GAAT:G	acceptor_gain	0.9900
5:160422301:GAATA:G	acceptor_gain	0.9900
5:160422400:CCTT:C	donor_gain	0.9900
5:160422401:CTT:C	donor_gain	0.9900
5:160422402:TT:T	donor_gain	0.9900
5:160422402:TTG:T	donor_loss	0.9900
5:160422403:TGT:T	donor_loss	0.9900
5:160422404:GTAAG:G	donor_loss	0.9900
5:160422405:TAA:T	donor_loss	0.9900
5:160422406:A:AG	donor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000033782 (5:160426388 C>T), RS1000289158 (5:160425846 T>C), RS1000928629 (5:160421366 C>A,T), RS1001035771 (5:160427858 C>T), RS1001151387 (5:160427490 T>C), RS1001699039 (5:160421676 T>C), RS1001731640 (5:160421894 G>A,C), RS1001829244 (5:160427368 C>T), RS1001945507 (5:160427079 T>G), RS1002495367 (5:160420115 T>C), RS1002601266 (5:160423912 C>T), RS1002605029 (5:160427047 A>G), RS1002692021 (5:160423154 T>C), RS1002723220 (5:160423374 G>T), RS1003638220 (5:160428943 T>C)

Disease associations

OMIM: gene MIM:604147 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000996_18	Systemic lupus erythematosus	2.000000e-06
GCST001604_3	Insulin-related traits	6.000000e-06
GCST003620_2	Systemic lupus erythematosus or rheumatoid arthritis	1.000000e-07
GCST004867_4	Systemic lupus erythematosus	2.000000e-06
GCST004878_13	Sjögren’s syndrome	2.000000e-07
GCST005752_145	Systemic lupus erythematosus	3.000000e-21
GCST005752_48	Systemic lupus erythematosus	1.000000e-12
GCST006053_3	Dermatomyositis or juvenile dermatomyositis	8.000000e-06
GCST007400_28	Systemic lupus erythematosus	4.000000e-14

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, increases stability, decreases reaction, decreases response to substance, affects expression (+2 more)	6
bisphenol A	affects expression, decreases expression, decreases methylation, affects cotreatment, increases expression	4
Fluorouracil	increases expression, affects reaction, decreases reaction, decreases expression	4
Particulate Matter	decreases expression, increases abundance, affects cotreatment	4
Cadmium	decreases expression, increases expression	3
Cisplatin	affects expression, affects cotreatment, increases expression, decreases expression	3
Cyclosporine	decreases expression	3
palbociclib	decreases expression	2
Arsenic Trioxide	increases expression, increases reaction	2
Fulvestrant	decreases expression, affects cotreatment	2
Acetaminophen	increases expression	2
Air Pollutants	increases abundance, decreases expression	2
Copper	decreases expression, affects binding	2
Dimethylnitrosamine	increases expression	2
Doxorubicin	decreases expression	2
Estradiol	increases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Quercetin	decreases expression	2
Tretinoin	decreases expression	2
Valproic Acid	decreases expression, decreases methylation, increases expression	2
Aflatoxin B1	affects expression, increases methylation	2
Okadaic Acid	affects expression, increases expression	2
abemaciclib	decreases expression	1
echimidine	decreases expression, increases metabolic processing	1
lasiocarpine	increases metabolic processing, decreases expression	1
naringenin	affects cotreatment, increases expression	1
propionaldehyde	decreases expression	1
geraniol	decreases expression	1
riddelliine	decreases expression, increases metabolic processing	1

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_AW39	K562 eGFP-PTTG1	Cancer cell line	Female
CVCL_B9W4	Abcam HEK293T PTTG1 KO	Transformed cell line	Female
CVCL_HD93	HCT 116 PTTG1(-/-)	Cancer cell line	Male

Clinical trials (associated diseases)

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