PCNA
proliferating cell nuclear antigen
Basic information
Region (hg38): 20:5114953-5126626
Links
Phenotypes
GenCC
Source:
- ataxia-telangiectasia-like disorder 2 (Supportive), mode of inheritance: AR
- ataxia-telangiectasia-like disorder 2 (Limited), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Ataxia-telangiectasia-like disorder 2 | AR | Oncologic | An individual has been described with evidence of predisposition to malignancy related to sun exposure, and preventive measures and surveillance may allow prevent oncologic disease and allow early diagnosis and management | Dermatologic; Neurologic; Oncologic; Ophthalmologic | 24911150 |
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PCNA 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 | 8 | |||||
| missense | 5 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 0 | |||||
| Total | 0 | 1 | 4 | 6 | 2 |
Variants in PCNA
This is a list of pathogenic ClinVar variants found in the PCNA region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 20-5115343-C-T | Benign (Dec 31, 2019) | |||
| 20-5115453-G-C | PCNA-related disorder | Benign (Dec 31, 2019) | ||
| 20-5115472-C-A | Ataxia-telangiectasia-like disorder 2 | Uncertain significance (Apr 03, 2018) | ||
| 20-5115510-A-G | Likely benign (Jun 06, 2018) | |||
| 20-5115543-T-C | Likely benign (Jun 22, 2018) | |||
| 20-5117506-C-A | not specified | Uncertain significance (Aug 02, 2023) | ||
| 20-5117507-A-C | not specified | Uncertain significance (Jun 29, 2023) | ||
| 20-5117609-C-G | Ataxia-telangiectasia-like disorder 2 | Likely pathogenic (May 28, 2019) | ||
| 20-5117637-T-C | Uncertain significance (Aug 08, 2023) | |||
| 20-5118827-G-T | Likely benign (Jan 01, 2019) | |||
| 20-5118853-G-A | Likely benign (Jan 02, 2019) | |||
| 20-5118870-G-A | PCNA-related disorder | Benign (Oct 21, 2019) | ||
| 20-5119633-C-T | not specified | Uncertain significance (Nov 22, 2022) | ||
| 20-5119641-C-T | not specified | Uncertain significance (Jul 14, 2024) | ||
| 20-5119646-G-C | PCNA-related disorder | Likely benign (May 01, 2019) | ||
| 20-5119674-G-A | not specified | Uncertain significance (May 26, 2024) | ||
| 20-5119757-C-T | Likely benign (Oct 23, 2018) | |||
| 20-5119766-G-A | Likely benign (Apr 23, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PCNA | protein_coding | protein_coding | ENST00000379160 | 6 | 11674 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.976 | 0.0239 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.47 | 62 | 146 | 0.424 | 0.00000689 | 1715 |
| Missense in Polyphen | 7 | 34.729 | 0.20156 | 439 | ||
| Synonymous | 0.450 | 51 | 55.3 | 0.923 | 0.00000286 | 486 |
| Loss of Function | 3.14 | 0 | 11.5 | 0.00 | 5.68e-7 | 138 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'- 5' exonuclease and 3'-phosphodiesterase, but not apurinic- apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways (PubMed:24939902). Acts as a loading platform to recruit DDR proteins that allow completion of DNA replication after DNA damage and promote postreplication repair: Monoubiquitinated PCNA leads to recruitment of translesion (TLS) polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is involved in error-free pathway and employs recombination mechanisms to synthesize across the lesion. {ECO:0000269|PubMed:18719106, ECO:0000269|PubMed:19443450, ECO:0000269|PubMed:24939902}.;
- Disease
- DISEASE: Ataxia-telangiectasia-like disorder 2 (ATLD2) [MIM:615919]: A neurodegenerative disorder due to defects in DNA excision repair. ATLD2 is characterized by developmental delay, ataxia, sensorineural hearing loss, short stature, cutaneous and ocular telangiectasia, and photosensitivity. {ECO:0000269|PubMed:24911150}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Nucleotide excision repair - Homo sapiens (human);Cell cycle - Homo sapiens (human);Tight junction - Homo sapiens (human);Base excision repair - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Mismatch repair - Homo sapiens (human);DNA replication - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Nucleotide Excision Repair ;Cell Cycle;Mitotic G1-G1-S phases;Retinoblastoma (RB) in Cancer;Primary Focal Segmental Glomerulosclerosis FSGS;Nifedipine Activity;Oxidative Damage;EGF-EGFR Signaling Pathway;G1 to S cell cycle control;DNA Replication;Mismatch repair;Senescence and Autophagy in Cancer;Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta);Mismatch Repair;HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;Gene expression (Transcription);DNA Double-Strand Break Repair;il-2 receptor beta chain in t cell activation;Generic Transcription Pathway;Homology Directed Repair;Post-translational protein modification;SUMOylation of DNA replication proteins;SUMO E3 ligases SUMOylate target proteins;Polymerase switching on the C-strand of the telomere;Metabolism of proteins;RNA Polymerase II Transcription;Transcription of E2F targets under negative control by DREAM complex;G0 and Early G1;Activation of E2F1 target genes at G1/S;G1/S-Specific Transcription;Mitotic G1-G1/S phases;DNA Replication;Polymerase switching;Leading Strand Synthesis;Removal of the Flap Intermediate;Processive synthesis on the lagging strand;Lagging Strand Synthesis;DNA strand elongation;Synthesis of DNA;SUMOylation;S Phase;PCNA-Dependent Long Patch Base Excision Repair;Resolution of AP sites via the multiple-nucleotide patch replacement pathway;Resolution of Abasic Sites (AP sites);Base Excision Repair;Removal of the Flap Intermediate from the C-strand;Processive synthesis on the C-strand of the telomere;Telomere C-strand (Lagging Strand) Synthesis;Extension of Telomeres;Telomere Maintenance;Chromosome Maintenance;p53 signaling pathway;TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest;TP53 Regulates Transcription of Cell Cycle Genes;G1/S Transition;Transcriptional Regulation by TP53;Recognition of DNA damage by PCNA-containing replication complex;Translesion synthesis by REV1;Direct p53 effectors;Translesion Synthesis by POLH;Translesion synthesis by POLK;Protein ubiquitination;Translesion synthesis by POLI;Termination of translesion DNA synthesis;Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template;DNA Damage Bypass;Cell Cycle;Dual Incision in GG-NER;Gap-filling DNA repair synthesis and ligation in GG-NER;Global Genome Nucleotide Excision Repair (GG-NER);Cell Cycle, Mitotic;Validated nuclear estrogen receptor alpha network;BARD1 signaling events;E3 ubiquitin ligases ubiquitinate target proteins;Dual incision in TC-NER;Gap-filling DNA repair synthesis and ligation in TC-NER;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Nucleotide Excision Repair;Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha);HDR through Homologous Recombination (HRR)
(Consensus)
Recessive Scores
- pRec
- 0.966
Intolerance Scores
- loftool
- rvis_EVS
- -0.21
- rvis_percentile_EVS
- 38.28
Haploinsufficiency Scores
- pHI
- 1.00
- hipred
- Y
- hipred_score
- 0.802
- ghis
- 0.736
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.984
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Pcna
- Phenotype
- reproductive 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); hematopoietic system phenotype; immune system phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan);
Gene ontology
- Biological process
- regulation of transcription involved in G1/S transition of mitotic cell cycle;telomere maintenance;leading strand elongation;transcription-coupled nucleotide-excision repair;nucleotide-excision repair, DNA incision, 5'-to lesion;nucleotide-excision repair, DNA gap filling;mismatch repair;DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest;heart development;cell population proliferation;viral process;protein ubiquitination;translesion synthesis;epithelial cell differentiation;replication fork processing;positive regulation of deoxyribonuclease activity;telomere maintenance via semi-conservative replication;response to estradiol;nucleotide-excision repair, DNA incision;cellular response to UV;error-prone translesion synthesis;DNA damage response, detection of DNA damage;estrous cycle;positive regulation of DNA repair;positive regulation of DNA replication;response to cadmium ion;cellular response to hydrogen peroxide;error-free translesion synthesis;response to dexamethasone;liver regeneration;response to L-glutamate;mitotic telomere maintenance via semi-conservative replication
- Cellular component
- nuclear chromosome, telomeric region;chromatin;nucleus;nucleoplasm;replication fork;DNA replication factor C complex;centrosome;nuclear body;replisome;nuclear replication fork;PCNA complex;extracellular exosome;PCNA-p21 complex
- Molecular function
- purine-specific mismatch base pair DNA N-glycosylase activity;chromatin binding;damaged DNA binding;protein binding;enzyme binding;estrogen receptor binding;DNA polymerase processivity factor activity;receptor tyrosine kinase binding;dinucleotide insertion or deletion binding;MutLalpha complex binding;histone acetyltransferase binding;identical protein binding;DNA polymerase binding