APEX1
apurinic/apyrimidinic endodeoxyribonuclease 1, the group of SET complex|Endoribonucleases
Basic information
Region (hg38): 14:20455191-20457772
Previous symbols: [ "APEX" ]
Links
Phenotypes
GenCC
Source:
- amyotrophic lateral sclerosis (Limited), mode of inheritance: AD
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 APEX1 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 | 5 | |||||
| missense | 12 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 3 | |||||
| Total | 0 | 0 | 8 | 7 | 5 |
Variants in APEX1
This is a list of pathogenic ClinVar variants found in the APEX1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 14-20455682-G-A | not specified | Uncertain significance (Jan 26, 2022) | ||
| 14-20455692-A-C | not specified | Uncertain significance (Mar 31, 2023) | ||
| 14-20455989-A-C | not specified | Uncertain significance (Aug 24, 2023) | ||
| 14-20456045-A-G | Benign (Jun 09, 2021) | |||
| 14-20456275-T-C | Benign (Jun 18, 2021) | |||
| 14-20456290-T-A | Benign (Jun 19, 2021) | |||
| 14-20456680-G-C | Head and neck cancer | not provided (Oct 12, 2017) | ||
| 14-20456724-G-A | Likely benign (Dec 31, 2019) | |||
| 14-20456789-C-T | not specified | Uncertain significance (Aug 16, 2021) | ||
| 14-20456812-G-A | not specified | Uncertain significance (Sep 30, 2024) | ||
| 14-20456847-T-G | Likely benign (May 16, 2018) | |||
| 14-20456854-G-A | not specified | Uncertain significance (Feb 03, 2022) | ||
| 14-20456992-C-T | not provided (-) | |||
| 14-20456995-T-G | APEX1-related disorder | Benign (Jun 09, 2021) | ||
| 14-20456996-G-A | APEX1-related disorder | Likely benign (Jun 06, 2018) | ||
| 14-20457017-C-T | not specified | Uncertain significance (Aug 04, 2024) | ||
| 14-20457047-G-A | not specified | Uncertain significance (Apr 17, 2023) | ||
| 14-20457251-C-T | not specified | Uncertain significance (May 23, 2024) | ||
| 14-20457272-G-A | APEX1-related disorder | Benign (Dec 31, 2019) | ||
| 14-20457337-T-C | Likely benign (Jul 02, 2018) | |||
| 14-20457358-T-C | APEX1-related disorder | Benign (Aug 16, 2018) | ||
| 14-20457452-C-T | not specified | Uncertain significance (May 13, 2024) | ||
| 14-20457491-C-G | not specified | Uncertain significance (Nov 20, 2024) | ||
| 14-20457494-T-C | not specified | Uncertain significance (Feb 27, 2024) | ||
| 14-20457496-C-T | Likely benign (May 02, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| APEX1 | protein_coding | protein_coding | ENST00000216714 | 4 | 2578 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.92e-7 | 0.446 | 125660 | 0 | 88 | 125748 | 0.000350 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.121 | 172 | 177 | 0.974 | 0.0000102 | 2038 |
| Missense in Polyphen | 62 | 74.319 | 0.83425 | 862 | ||
| Synonymous | -1.64 | 89 | 71.4 | 1.25 | 0.00000380 | 651 |
| Loss of Function | 0.775 | 12 | 15.3 | 0.786 | 9.08e-7 | 167 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000481 | 0.000481 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000163 | 0.000163 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000563 | 0.000563 |
| Middle Eastern | 0.000163 | 0.000163 |
| South Asian | 0.000261 | 0.000261 |
| Other | 0.000326 | 0.000326 |
dbNSFP
Source:
- Function
- FUNCTION: Multifunctional protein that plays a central role in the cellular response to oxidative stress. The two major activities of APEX1 are DNA repair and redox regulation of transcriptional factors. Functions as a apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents. Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends. Does also incise at AP sites in the DNA strand of DNA/RNA hybrids, single-stranded DNA regions of R-loop structures, and single-stranded RNA molecules. Has a 3'-5' exoribonuclease activity on mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules during short-patch BER. Possesses a DNA 3' phosphodiesterase activity capable of removing lesions (such as phosphoglycolate) blocking the 3' side of DNA strand breaks. May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation. Acts as a loading factor for POLB onto non-incised AP sites in DNA and stimulates the 5'-terminal deoxyribose 5'- phosphate (dRp) excision activity of POLB. Plays a role in the protection from granzymes-mediated cellular repair leading to cell death. Also involved in the DNA cleavage step of class switch recombination (CSR). On the other hand, APEX1 also exerts reversible nuclear redox activity to regulate DNA binding affinity and transcriptional activity of transcriptional factors by controlling the redox status of their DNA-binding domain, such as the FOS/JUN AP-1 complex after exposure to IR. Involved in calcium-dependent down-regulation of parathyroid hormone (PTH) expression by binding to negative calcium response elements (nCaREs). Together with HNRNPL or the dimer XRCC5/XRCC6, associates with nCaRE, acting as an activator of transcriptional repression. Stimulates the YBX1-mediated MDR1 promoter activity, when acetylated at Lys-6 and Lys-7, leading to drug resistance. Acts also as an endoribonuclease involved in the control of single-stranded RNA metabolism. Plays a role in regulating MYC mRNA turnover by preferentially cleaving in between UA and CA dinucleotides of the MYC coding region determinant (CRD). In association with NMD1, plays a role in the rRNA quality control process during cell cycle progression. Associates, together with YBX1, on the MDR1 promoter. Together with NPM1, associates with rRNA. Binds DNA and RNA. {ECO:0000269|PubMed:10023679, ECO:0000269|PubMed:11118054, ECO:0000269|PubMed:11452037, ECO:0000269|PubMed:11809897, ECO:0000269|PubMed:11832948, ECO:0000269|PubMed:12524539, ECO:0000269|PubMed:16617147, ECO:0000269|PubMed:1719477, ECO:0000269|PubMed:18179823, ECO:0000269|PubMed:18439621, ECO:0000269|PubMed:18579163, ECO:0000269|PubMed:18809583, ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:19401441, ECO:0000269|PubMed:19934257, ECO:0000269|PubMed:20699270, ECO:0000269|PubMed:21496894, ECO:0000269|PubMed:21762700, ECO:0000269|PubMed:8355688, ECO:0000269|PubMed:8621488, ECO:0000269|PubMed:8932375, ECO:0000269|PubMed:9108029, ECO:0000269|PubMed:9207062, ECO:0000269|PubMed:9560228, ECO:0000269|PubMed:9804799}.;
- Pathway
- Base excision repair - Homo sapiens (human);Busulfan Pathway, Pharmacodynamics;Human Thyroid Stimulating Hormone (TSH) signaling pathway;Spinal Cord Injury;DNA Repair;granzyme a mediated apoptosis pathway;HIF-2-alpha transcription factor network;POLB-Dependent Long Patch Base Excision Repair;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;Displacement of DNA glycosylase by APEX1;Abasic sugar-phosphate removal via the single-nucleotide replacement pathway;Resolution of AP sites via the single-nucleotide replacement pathway
(Consensus)
Recessive Scores
- pRec
- 0.760
Intolerance Scores
- loftool
- 0.885
- rvis_EVS
- 0.08
- rvis_percentile_EVS
- 60.31
Haploinsufficiency Scores
- pHI
- 0.900
- hipred
- Y
- hipred_score
- 0.698
- ghis
- 0.619
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.964
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Apex1
- Phenotype
- endocrine/exocrine gland phenotype; growth/size/body region phenotype; muscle phenotype; immune system phenotype; homeostasis/metabolism phenotype; cellular phenotype; liver/biliary system phenotype; embryo phenotype; neoplasm; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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; reproductive system phenotype;
Zebrafish Information Network
- Gene name
- apex1
- Affected structure
- nucleate erythrocyte
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- telomere maintenance;DNA repair;base-excision repair;base-excision repair, base-free sugar-phosphate removal;DNA recombination;aging;negative regulation of smooth muscle cell migration;regulation of apoptotic process;regulation of mRNA stability;cell redox homeostasis;oxidation-reduction process;cellular response to hydrogen peroxide;cellular response to cAMP;cellular response to peptide hormone stimulus;DNA demethylation;RNA phosphodiester bond hydrolysis, endonucleolytic;telomere maintenance via base-excision repair;positive regulation of G1/S transition of mitotic cell cycle;negative regulation of nucleic acid-templated transcription;positive regulation of nucleic acid-templated transcription
- Cellular component
- nuclear chromosome, telomeric region;nucleus;nucleoplasm;transcription factor complex;nucleolus;cytoplasm;mitochondrion;endoplasmic reticulum;centrosome;ribosome;nuclear speck;perinuclear region of cytoplasm
- Molecular function
- DNA binding;damaged DNA binding;double-stranded telomeric DNA binding;transcription coactivator activity;transcription corepressor activity;RNA binding;DNA-(apurinic or apyrimidinic site) endonuclease activity;endonuclease activity;endodeoxyribonuclease activity;RNA-DNA hybrid ribonuclease activity;phosphodiesterase I activity;uracil DNA N-glycosylase activity;protein binding;phosphoric diester hydrolase activity;double-stranded DNA exodeoxyribonuclease activity;double-stranded DNA 3'-5' exodeoxyribonuclease activity;3'-5' exonuclease activity;oxidoreductase activity;site-specific endodeoxyribonuclease activity, specific for altered base;chromatin DNA binding;protein-containing complex binding;metal ion binding;NF-kappaB binding;class I DNA-(apurinic or apyrimidinic site) endonuclease activity