PML

PML nuclear body scaffold, the group of Tripartite motif family|Ring finger proteins

Basic information

Region (hg38): 15:73994672-74047827

Links

ENSG00000140464 ∙ NCBI:5371 ∙ OMIM:102578 ∙ HGNC:9113 ∙ Uniprot:P29590 ∙ 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 PML gene.

• Inborn genetic diseases (25 variants)
• not provided (13 variants)
• not specified (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PML 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				2	3	5
missense			25	1	7	33
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	26	3	11

Variants in PML

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

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

Position	Type	Phenotype	Significance	ClinVar
15-73994832-G-T		not specified	Uncertain significance (Feb 10, 2022)
15-73994894-A-C			Benign (Jul 06, 2018)
15-73994933-C-T		not specified	Uncertain significance (Jan 23, 2023)
15-73998124-T-G		not specified	Uncertain significance (Dec 18, 2023)
15-73998239-T-C		not specified	Uncertain significance (Dec 28, 2023)
15-73998411-C-T		PML-related disorder	Likely benign (Feb 14, 2020)
15-73998461-C-A		not specified	Uncertain significance (Feb 10, 2023)
15-74022857-T-A		not specified	Uncertain significance (Apr 06, 2022)
15-74023001-C-T		not specified	Uncertain significance (Jun 27, 2023)
15-74023007-T-C		not specified	Uncertain significance (Mar 01, 2023)
15-74023017-C-T			Benign (Jul 07, 2018)
15-74023127-T-C		not specified	Uncertain significance (Apr 05, 2023)
15-74023130-A-T		not specified	Uncertain significance (Jan 26, 2022)
15-74023144-C-T			Uncertain significance (Sep 25, 2019)
15-74023152-C-CGAGGAGATGGCCA			Uncertain significance (Dec 02, 2021)
15-74023169-G-A		not specified	Likely benign (Oct 05, 2023)
15-74023196-A-G		not specified	Uncertain significance (Apr 19, 2023)
15-74023299-C-G			Likely benign (May 30, 2018)
15-74023374-G-A		PML-related disorder	Likely benign (Feb 20, 2019)
15-74023399-C-A		not specified	Uncertain significance (Dec 23, 2023)
15-74024893-C-T		not specified	Uncertain significance (Jan 10, 2023)
15-74024918-C-T			Likely benign (Feb 01, 2024)
15-74032596-G-A		not specified	Uncertain significance (May 27, 2022)
15-74032663-C-T		not specified	Uncertain significance (Dec 15, 2022)
15-74033264-C-T		not specified	Uncertain significance (Jun 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PML	protein_coding	protein_coding	ENST00000268058	9	53140

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.213	0.787	125723	0	25	125748	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.74	462	580	0.797	0.0000419	5692
Missense in Polyphen		106	162.21	0.65347		1824
Synonymous	1.19	231	255	0.905	0.0000191	1839
Loss of Function	4.07	8	33.3	0.240	0.00000181	333

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000127	0.000120
Ashkenazi Jewish	0.00	0.00
East Asian	0.000224	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000108	0.000105
Middle Eastern	0.000224	0.000217
South Asian	0.000164	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Functions via its association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, including tumor suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. Acts as the scaffold of PML-NBs allowing other proteins to shuttle in and out, a process which is regulated by SUMO-mediated modifications and interactions. Isoform PML-4 has a multifaceted role in the regulation of apoptosis and growth suppression: activates RB1 and inhibits AKT1 via interactions with PP1 and PP2A phosphatases respectively, negatively affects the PI3K pathway by inhibiting MTOR and activating PTEN, and positively regulates p53/TP53 by acting at different levels (by promoting its acetylation and phosphorylation and by inhibiting its MDM2-dependent degradation). Isoform PML-4 also: acts as a transcriptional repressor of TBX2 during cellular senescence and the repression is dependent on a functional RBL2/E2F4 repressor complex, regulates double-strand break repair in gamma- irradiation-induced DNA damage responses via its interaction with WRN, acts as a negative regulator of telomerase by interacting with TERT, and regulates PER2 nuclear localization and circadian function. Isoform PML-6 inhibits specifically the activity of the tetrameric form of PKM. The nuclear isoforms (isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4 and isoform PML-5) in concert with SATB1 are involved in local chromatin-loop remodeling and gene expression regulation at the MHC-I locus. Isoform PML-2 is required for efficient IFN-gamma induced MHC II gene transcription via regulation of CIITA. Cytoplasmic PML is involved in the regulation of the TGF-beta signaling pathway. PML also regulates transcription activity of ELF4 and can act as an important mediator for TNF-alpha- and IFN-alpha-mediated inhibition of endothelial cell network formation and migration.
• Disease: DISEASE: Note=A chromosomal aberration involving PML may be a cause of acute promyelocytic leukemia (APL). Translocation t(15;17)(q21;q21) with RARA. The PML breakpoints (type A and type B) lie on either side of an alternatively spliced exon. {ECO:0000269|PubMed:1652369, ECO:0000269|PubMed:1720570}.
• Pathway: Endocytosis - Homo sapiens (human);Influenza A - Homo sapiens (human);Acute myeloid leukemia - Homo sapiens (human);Ubiquitin mediated proteolysis - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);TGF-Ncore;miRNA Regulation of DNA Damage Response;Wnt-beta-catenin Signaling Pathway in Leukemia;TGF-beta Signaling Pathway;DNA Damage Response;Signal Transduction;Gene expression (Transcription);Regulation of PTEN localization;Generic Transcription Pathway;Cytokine Signaling in Immune system;SUMOylation of DNA damage response and repair proteins;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;RNA Polymerase II Transcription;Immune System;p73 transcription factor network;SUMOylation;regulation of transcriptional activity by pml;TGF_beta_Receptor;Validated transcriptional targets of TAp63 isoforms;PTEN Regulation;PIP3 activates AKT signaling;C-MYC pathway;Regulation of TP53 Activity through Acetylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Interferon gamma signaling;Direct p53 effectors;Regulation of RUNX1 Expression and Activity;TNFalpha;Intracellular signaling by second messengers;Transcriptional regulation by RUNX1;mTOR signaling pathway;Interferon Signaling;TGF-beta receptor signaling (Consensus)

Recessive Scores

• pRec: 0.572

Intolerance Scores

• loftool: 0.0112
• rvis_EVS: 0.15
• rvis_percentile_EVS: 64.12

Haploinsufficiency Scores

• pHI: 0.136
• hipred: Y
• hipred_score: 0.694
• ghis: 0.602

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.994

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pml
• Phenotype: endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; neoplasm; 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); normal phenotype; hematopoietic system phenotype; immune system phenotype

Gene ontology

• Biological process: response to hypoxia;regulation of protein phosphorylation;regulation of transcription, DNA-templated;protein import into nucleus;activation of cysteine-type endopeptidase activity involved in apoptotic process;DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest;cell cycle arrest;transforming growth factor beta receptor signaling pathway;common-partner SMAD protein phosphorylation;negative regulation of cell population proliferation;intrinsic apoptotic signaling pathway in response to DNA damage;intrinsic apoptotic signaling pathway in response to oxidative stress;response to UV;response to gamma radiation;regulation of calcium ion transport into cytosol;fibroblast migration;viral process;negative regulation of angiogenesis;protein sumoylation;myeloid cell differentiation;regulation of cell adhesion;negative regulation of cell growth;PML body organization;positive regulation of telomere maintenance;endoplasmic reticulum calcium ion homeostasis;circadian regulation of gene expression;response to cytokine;regulation of circadian rhythm;intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator;entrainment of circadian clock by photoperiod;proteasome-mediated ubiquitin-dependent protein catabolic process;innate immune response;cell fate commitment;negative regulation of transcription, DNA-templated;positive regulation of fibroblast proliferation;retinoic acid receptor signaling pathway;negative regulation of interleukin-1 beta secretion;maintenance of protein location in nucleus;defense response to virus;interferon-gamma-mediated signaling pathway;branching involved in mammary gland duct morphogenesis;protein-containing complex assembly;intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress;cellular response to interleukin-4;cellular senescence;extrinsic apoptotic signaling pathway;regulation of signal transduction by p53 class mediator;negative regulation of viral release from host cell;positive regulation of nucleic acid-templated transcription;cellular response to leukemia inhibitory factor;negative regulation of ubiquitin-dependent protein catabolic process;regulation of double-strand break repair;positive regulation of extrinsic apoptotic signaling pathway
• Cellular component: nuclear chromosome, telomeric region;heterochromatin;nucleus;nucleoplasm;nucleolus;cytoplasm;cytosol;nuclear matrix;PML body;early endosome membrane;extrinsic component of endoplasmic reticulum membrane
• Molecular function: DNA binding;transcription coactivator activity;protein binding;zinc ion binding;SUMO transferase activity;ubiquitin protein ligase binding;SUMO binding;protein homodimerization activity;SMAD binding