APEX1

apurinic/apyrimidinic endodeoxyribonuclease 1, the group of SET complex|Endoribonucleases

Basic information

Region (hg38): 14:20455190-20457772

Previous symbols: [ "APEX" ]

Links

ENSG00000100823 ∙ NCBI:328 ∙ OMIM:107748 ∙ HGNC:587 ∙ Uniprot:P27695 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• amyotrophic lateral sclerosis (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the APEX1 gene.

• not provided (13 variants)
• Inborn genetic diseases (7 variants)
• Head and neck cancer (1 variants)

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				4	1	5
missense			7	1	3	11
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1	2	3
Total	0	0	7	6	6

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 (Mar 16, 2022)
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 (Feb 23, 2022)
14-20457047-G-A		not specified	Uncertain significance (Apr 17, 2023)
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/Likely benign (Feb 18, 2019)
14-20457494-T-C		not specified	Uncertain significance (Feb 27, 2024)
14-20457496-C-T			Likely benign (May 02, 2018)
14-20457510-A-T			Likely benign (Jan 01, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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