PTTG1

PTTG1 regulator of sister chromatid separation, securin

Basic information

Region (hg38): 5:160421854-160428739

Previous symbols: [ "TUTR1" ]

Links

ENSG00000164611 ∙ NCBI:9232 ∙ OMIM:604147 ∙ HGNC:9690 ∙ Uniprot:O95997 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PTTG1 gene.

• Inborn genetic diseases (5 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PTTG1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense			5			5
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	5	0	1

Variants in PTTG1

This is a list of pathogenic ClinVar variants found in the PTTG1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-160422317-C-T		not specified	Uncertain significance (Nov 30, 2021)
5-160422371-C-T		not specified	Uncertain significance (Sep 17, 2021)
5-160422713-C-G		not specified	Uncertain significance (Jan 04, 2024)
5-160424311-C-A		not specified	Uncertain significance (Dec 28, 2023)
5-160424322-A-G		not specified	Uncertain significance (Aug 02, 2023)
5-160427719-T-A		not specified	Uncertain significance (Sep 26, 2023)
5-160427783-A-G		not specified	Uncertain significance (Jan 24, 2024)
5-160427815-G-T		not specified	Uncertain significance (Apr 11, 2023)
5-160428632-C-T		not specified	Uncertain significance (Mar 06, 2023)
5-160428637-C-T			Benign (Jul 23, 2018)
5-160428674-A-C		not specified	Uncertain significance (Jun 29, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PTTG1	protein_coding	protein_coding	ENST00000393964	5	6920

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000422	0.662	125733	0	15	125748	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.961	78	106	0.737	0.00000503	1300
Missense in Polyphen		11	27.791	0.39582		387
Synonymous	-0.0264	41	40.8	1.01	0.00000214	409
Loss of Function	0.748	6	8.33	0.720	3.48e-7	118

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000440	0.0000439
Middle Eastern	0.000109	0.000109
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:10411507, ECO:0000269|PubMed:11238996, ECO:0000269|PubMed:11371342, ECO:0000269|PubMed:12355087}.
• Pathway: Cell cycle - Homo sapiens (human);Oocyte meiosis - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Cell Cycle;Regulation of sister chromatid separation at the metaphase-anaphase transition;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;M Phase;APC/C:Cdc20 mediated degradation of Securin;APC/C:Cdc20 mediated degradation of mitotic proteins;Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins;APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1;APC/C-mediated degradation of cell cycle proteins;Regulation of mitotic cell cycle;Cell Cycle;Cell Cycle, Mitotic (Consensus)

Recessive Scores

• pRec: 0.317

Intolerance Scores

• loftool: 0.533
• rvis_EVS: -0.14
• rvis_percentile_EVS: 42.88

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.707
• ghis: 0.703

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.968

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Low	Low	Low
Cancer	Low	Low	Low

Mouse Genome Informatics

• Gene name: Pttg1
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; growth/size/body region phenotype; embryo phenotype; renal/urinary system phenotype; immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: DNA repair;regulation of transcription by RNA polymerase II;transcription by RNA polymerase II;spermatogenesis;negative regulation of endopeptidase activity;anaphase-promoting complex-dependent catabolic process;homologous chromosome segregation;chromosome organization;cell division;negative regulation of mitotic sister chromatid separation
• Cellular component: nucleus;cytoplasm;cytosol
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;cysteine-type endopeptidase inhibitor activity;protein binding;SH3 domain binding