APEX2

Summary

APEX2 (apurinic/apyrimidinic endodeoxyribonuclease 2, HGNC:17889) is a protein-coding gene on chromosome Xp11.21, encoding DNA-(apurinic or apyrimidinic site) endonuclease 2 (Q9UBZ4). Functions as a weak apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents. It is a selective cancer dependency (DepMap: 14.2% of cell lines).

Apurinic/apyrimidinic (AP) sites occur frequently in DNA molecules by spontaneous hydrolysis, by DNA damaging agents or by DNA glycosylases that remove specific abnormal bases. AP sites are pre-mutagenic lesions that can prevent normal DNA replication so the cell contains systems to identify and repair such sites. Class II AP endonucleases cleave the phosphodiester backbone 5’ to the AP site. This gene encodes a protein shown to have a weak class II AP endonuclease activity. Most of the encoded protein is located in the nucleus but some is also present in mitochondria. This protein may play an important role in both nuclear and mitochondrial base excision repair. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 27301 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 93 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 14.2% of screened cell lines
• MANE Select transcript: NM_014481

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17889
Approved symbol	APEX2
Name	apurinic/apyrimidinic endodeoxyribonuclease 2
Location	Xp11.21
Locus type	gene with protein product
Status	Approved
Aliases	APEXL2, APE2, XTH2, ZGRF2
Ensembl gene	ENSG00000169188
Ensembl biotype	protein_coding
OMIM	300773
Entrez	27301

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000374987, ENST00000471758, ENST00000886736, ENST00000919357, ENST00000919358

RefSeq mRNA: 2 — MANE Select: NM_014481 NM_001271748, NM_014481

CCDS: CCDS14365

Canonical transcript exons

ENST00000374987 — 6 exons

Exon	Start	End
ENSE00001138120	55002251	55002431
ENSE00001465324	55006518	55009057
ENSE00001465326	55000363	55000579
ENSE00003549934	55002962	55003108
ENSE00003657186	55003799	55003868
ENSE00003669711	55001546	55001629

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 88.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.0170 / max 139.6549, expressed in 1808 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196450	17.8667	1804
196451	2.1503	1151

Top tissues by expression

282 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	88.82	silver quality
oocyte	CL:0000023	87.09	gold quality
mucosa of transverse colon	UBERON:0004991	86.77	gold quality
secondary oocyte	CL:0000655	84.60	gold quality
granulocyte	CL:0000094	84.39	gold quality
esophagus mucosa	UBERON:0002469	83.86	gold quality
lower esophagus mucosa	UBERON:0035834	83.76	gold quality
stromal cell of endometrium	CL:0002255	83.36	gold quality
esophagus squamous epithelium	UBERON:0006920	83.26	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.22	gold quality
rectum	UBERON:0001052	82.50	gold quality
epithelium of esophagus	UBERON:0001976	82.47	gold quality
apex of heart	UBERON:0002098	81.87	gold quality
islet of Langerhans	UBERON:0000006	81.77	gold quality
squamous epithelium	UBERON:0006914	81.42	gold quality
buccal mucosa cell	CL:0002336	81.41	silver quality
skin of leg	UBERON:0001511	81.22	gold quality
right adrenal gland cortex	UBERON:0035827	80.99	gold quality
skin of abdomen	UBERON:0001416	80.81	gold quality
right adrenal gland	UBERON:0001233	80.77	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.67	gold quality
leukocyte	CL:0000738	80.55	gold quality
monocyte	CL:0000576	80.53	gold quality
esophagus	UBERON:0001043	80.49	gold quality
type B pancreatic cell	CL:0000169	80.42	gold quality
transverse colon	UBERON:0001157	80.40	gold quality
left adrenal gland	UBERON:0001234	80.26	gold quality
mononuclear cell	CL:0000842	80.24	gold quality
tongue squamous epithelium	UBERON:0006919	80.24	silver quality
smooth muscle tissue	UBERON:0001135	80.01	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.17
E-GEOD-99795	no	156.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting APEX2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-491-3P	98.88	68.86	1224
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-12114	98.70	63.45	730
HSA-MIR-3928-5P	98.50	67.48	980
HSA-MIR-6806-3P	98.50	67.31	980
HSA-MIR-3158-3P	98.45	64.25	560
HSA-MIR-27A-5P	97.01	65.63	528
HSA-MIR-345-5P	96.40	66.43	663
HSA-MIR-6834-5P	96.25	64.88	823

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 14.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 10)

• Determinants in nuclease specificity of Ape1 and Ape2, human homologues of Escherichia coli exonuclease III (PMID:11866537)
• Ape2 exhibits strong 3’-5’ exonuclease and 3’-phosphodiesterase activities and has only a very weak AP-endonuclease activity. (PMID:16687656)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• Ape2 may be involved in repair of oxidative DNA damage and PCNA-dependent repair synthesis. (PMID:19443450)
• Single-Strand Break End Resection in Genome Integrity: Mechanism and Regulation by APE2. (PMID:30110897)
• Identified APEX2 and FEN1 as synthetic lethal genes with both BRCA1 and BRCA2 loss of function in tumor cell lines. (PMID:30686591)
• we describe the use of Clustered Regularly Interspaced Short Palindromic Repeats and an engineered ascorbate peroxidase 2 (APEX2) system to investigate local chromatin interactions (CAPLOCUS). We showed that with specific small-guide RNA targets, CAPLOCUS could efficiently identify both repetitive genomic regions and single-copy genomic locus with high resolution. (PMID:30805613)
• Authors now show by immunoelectron microscopy that VAPB also localizes to the inner nuclear membrane (INM). Using a modified enhanced ascorbate peroxidase 2 (APEX2) approach with rapamycin-dependent targeting of the peroxidase to a protein of interest, we searched for proteins that are in close proximity to VAPB, particularly at the INM. (PMID:31519755)
• we propose a two-step APE1/APE2-mediated mechanism for DNA single-strand breaks (SSBs) end resection that couples DNA damage response with SSB repair in a eukaryotic system. (PMID:31828326)
• Genomic alterations and abnormal expression of APE2 in multiple cancers. (PMID:32111912)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	apex2	ENSDARG00000008472
mus_musculus	Apex2	ENSMUSG00000025269
rattus_norvegicus	Apex2	ENSRNOG00000000166
rattus_norvegicus	Apex2l1	ENSRNOG00000083941

Paralogs (1): APEX1 (ENSG00000100823)

Protein

Protein identifiers

DNA-(apurinic or apyrimidinic site) endonuclease 2 — Q9UBZ4 (reviewed: Q9UBZ4)

Alternative names: AP endonuclease XTH2, APEX nuclease 2, APEX nuclease-like 2, Apurinic-apyrimidinic endonuclease 2

All UniProt accessions (2): Q9UBZ4, E5KN95

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a weak 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. Also displays double-stranded DNA 3’-5’ exonuclease, 3’-phosphodiesterase activities. Shows robust 3’-5’ exonuclease activity on 3’-recessed heteroduplex DNA and is able to remove mismatched nucleotides preferentially. Also exhibits 3’-5’ exonuclease activity on a single nucleotide gap containing heteroduplex DNA and on blunt-ended substrates. Shows fairly strong 3’-phosphodiesterase activity involved in the removal of 3’-damaged termini formed in DNA by oxidative agents. In the nucleus functions in the PCNA-dependent BER pathway. Plays a role in reversing blocked 3’ DNA ends, problematic lesions that preclude DNA synthesis. Required for somatic hypermutation (SHM) and DNA cleavage step of class switch recombination (CSR) of immunoglobulin genes. Required for proper cell cycle progression during proliferation of peripheral lymphocytes.

Subunit / interactions. Interacts with PCNA; this interaction is triggered by reactive oxygen species and increased by misincorporation of uracil in nuclear DNA.

Subcellular location. Nucleus. Cytoplasm. Mitochondrion.

Tissue specificity. Highly expressed in brain and kidney. Weakly expressed in the fetal brain.

Post-translational modifications. Ubiquitinated by the CUL9-RBX1 complex. Ubiquitinated by MKRN3 at Lys-371 leading to proteasomal degradation.

Activity regulation. 3’-5’ exonuclease activity is activated by sodium and manganese. 3’-5’ exonuclease and 3’-phosphodiesterase activities are stimulated in presence of PCNA.

Cofactor. Probably binds two magnesium or manganese ions per subunit.

Domain organisation. The PCNA interacting protein (PIP) box mediates interaction with PCNA and recruitment to DNA single-strand breaks.

Similarity. Belongs to the DNA repair enzymes AP/ExoA family.

RefSeq proteins (2): NP_001258677, NP_055296* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004808	AP_endonuc_1	Family
IPR005135	Endo/exonuclease/phosphatase	Domain
IPR010666	Znf_GRF	Domain
IPR020847	AP_endonuclease_F1_BS	Binding_site
IPR036691	Endo/exonu/phosph_ase_sf	Homologous_superfamily

Pfam: PF03372, PF06839

Enzyme classification (BRENDA):

• EC 4.2.99.18 — DNA-(apurinic or apyrimidinic site) lyase (BRENDA: 46 organisms, 543 substrates, 374 inhibitors, 166 Km, 138 kcat entries)

Substrate kinetics (BRENDA)

68 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
5’-CTCTCCCTTC-5,6-DIHYDROURACIL-CTCCTTTCCTCT-3'	—	13
DNA CONTAINING AN ABASIC SITE	100–413	9
5’-GACAAGCGCAG-(5R,6S)-2’-DEOXY-5,6-DIHYDROXYURI	—	8
DNA CONTAINING 5-OH-C/A	—	6
5’-GACAAGCGCAG-(5S,6R)-2’-DEOXY-5,6-DIHYDROXYURI	—	5
DNA CONTAINING 5-OH-C/G	—	5
OLIGOMER WITH G/U PAIR	0.0001–0.0013	5
43-MER OLIGONUCLEOTIDE CONTAINING APURINIC/APYRI	—	4
5’-CTCTCCCTTC-8-OXO-7,8-DIHYDROGUANINE-CTCCTTTCC	0.0006–0.0013	4
AP-DNA	0.0001–0.011	4
DNA	0.0009–0.0017	4
DNA CONTAINING APURINIC/APYRIMIDINIC SITES	—	4
THF-CONTAINING OLIGONUCLEOTIDE	0.0001–0.0002	4
12-MER OLIGODEOXYRIBONUCLEOTIDE CONTAINING A NAT	0.0001–0.0002	2
18-MER CONTAINING P33-LABELED TETRAHYDROFURAN	—	2

UniProt features (34 total): binding site 10, mutagenesis site 7, sequence variant 4, site 3, active site 3, region of interest 2, chain 1, zinc finger region 1, cross-link 1, sequence conflict 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBZ4-F1	78.87	0.57

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (6): 199 (transition state stabilizer); 277 (important for catalytic activity); 304 (interaction with dna substrate); 156; 197 (proton donor/acceptor); 304 (proton acceptor)

Ligand- & substrate-binding residues (10): 197; 199; 303; 304; 469; 472; 495; 509; 8; 48

Post-translational modifications (1): 371

Mutagenesis-validated functional residues (7):

Position	Phenotype
48	abolished 3’-5’ exonuclease activity; when associated with asn-197. synthetic lethality in a brca1 or brca2 mutant cell
197	abolished 3’-5’ exonuclease activity; when associated with gln-48. synthetic lethality in a brca1 or brca2 mutant cell l
269	abolishes ap endodeoxyribonuclease, 3’-5’ exonuclease activity and 3’-phosphodiesterase activities.
277	abolishes ap endodeoxyribonuclease, 3’-5’ exonuclease activity and 3’-phosphodiesterase activities.
396–397	loss of interaction with pcna.
396	reduces 3’-5’ exonuclease activity in presence of pcna. does not abolish the 3’-5’ exonuclease activity. does only parti
397	reduces 3’-5’ exonuclease activity in presence of pcna. does not abolish the 3’-5’ exonuclease activity. does only parti

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 112 (showing top): GOMF_ENDONUCLEASE_ACTIVITY, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOMF_NUCLEASE_ACTIVITY, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, TGACCTY_ERR1_Q2, KAUFFMANN_DNA_REPAIR_GENES, BROWNE_HCMV_INFECTION_24HR_UP, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, WTGAAAT_UNKNOWN, GOBP_DNA_DAMAGE_RESPONSE, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, MODULE_88, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP, GOMF_EXONUCLEASE_ACTIVITY, HOXA4_Q2

GO Biological Process (4): base-excision repair (GO:0006284), DNA recombination (GO:0006310), DNA repair (GO:0006281), DNA damage response (GO:0006974)

GO Molecular Function (13): DNA binding (GO:0003677), DNA-(apurinic or apyrimidinic site) endonuclease activity (GO:0003906), phosphoric diester hydrolase activity (GO:0008081), zinc ion binding (GO:0008270), double-stranded DNA 3’-5’ DNA exonuclease activity (GO:0008311), catalytic activity (GO:0003824), nuclease activity (GO:0004518), endonuclease activity (GO:0004519), exonuclease activity (GO:0004527), protein binding (GO:0005515), hydrolase activity (GO:0016787), lyase activity (GO:0016829), metal ion binding (GO:0046872)

GO Cellular Component (5): fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
DNA metabolic process	2
nuclease activity	2
catalytic activity	2
intracellular membrane-bounded organelle	2
DNA repair	1
DNA damage response	1
cellular response to stress	1
nucleic acid binding	1
DNA endonuclease activity	1
phosphoric ester hydrolase activity	1
transition metal ion binding	1
3’-5’-DNA exonuclease activity	1
double-stranded DNA exodeoxyribonuclease activity	1
molecular_function	1
catalytic activity, acting on a nucleic acid	1
hydrolase activity, acting on ester bonds	1
binding	1
cation binding	1
nucleolus	1
nuclear lumen	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1612 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APEX2	TOP3A	Q13472	829
APEX2	UNG	P13051	724
APEX2	TDP1	Q9NUW8	674
APEX2	NEIL3	Q8TAT5	665
APEX2	OGG1	P78554	665
APEX2	FEN1	P39748	645
APEX2	ATRIP	Q8WXE1	616
APEX2	APTX	Q7Z2E3	609
APEX2	NTHL1	P78549	587
APEX2	TOPBP1	Q92547	576
APEX2	EXO1	Q9UQ84	570
APEX2	XRCC1	P18887	566
APEX2	LIG3	P49916	557
APEX2	PNKP	Q96T60	552
APEX2	PARP1	P09874	546

IntAct

31 interactions, top by confidence:

A	B	Type	Score
COMMD4	VPS26C	psi-mi:“MI:0914”(association)	0.730
MKRN3	APEX2	psi-mi:“MI:0915”(physical association)	0.560
TSHZ3	APEX2	psi-mi:“MI:0915”(physical association)	0.560
RETN	GLI4	psi-mi:“MI:0914”(association)	0.530
MAD2L1	PPIP5K2	psi-mi:“MI:0914”(association)	0.530
APEX2	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.440
APEX2	DAPK1	psi-mi:“MI:0407”(direct interaction)	0.440
APEX2	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
Ogn	APEX2	psi-mi:“MI:0407”(direct interaction)	0.440
APEX2	ERLIN1	psi-mi:“MI:0915”(physical association)	0.400
APEX2	PCNA	psi-mi:“MI:0915”(physical association)	0.370
TRIM37	APEX2	psi-mi:“MI:0915”(physical association)	0.370
TRAF2	APEX2	psi-mi:“MI:0915”(physical association)	0.370
APEX2	HOOK2	psi-mi:“MI:0915”(physical association)	0.370
APEX2	EFEMP2	psi-mi:“MI:0915”(physical association)	0.370
NINL	APEX2	psi-mi:“MI:0915”(physical association)	0.370
CCDC85B	APEX2	psi-mi:“MI:0915”(physical association)	0.370
CALCOCO2	APEX2	psi-mi:“MI:0915”(physical association)	0.370
Pcna	SIVA1	psi-mi:“MI:0914”(association)	0.350
APEX2	CUL7	psi-mi:“MI:0914”(association)	0.350
MAD2L1	MED19	psi-mi:“MI:0914”(association)	0.350
S100P	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
APEX2	CUL9	psi-mi:“MI:0914”(association)	0.350
APBA2	APEX2	psi-mi:“MI:0915”(physical association)	0.000
APEX2	MKRN3	psi-mi:“MI:0915”(physical association)	0.000
TSHZ3	APEX2	psi-mi:“MI:0915”(physical association)	0.000
APEX2	UBA1	psi-mi:“MI:0220”(ubiquitination reaction)	0.000

BioGRID (50): APEX2 (Biochemical Activity), APEX2 (Two-hybrid), APEX2 (Two-hybrid), HOOK2 (Two-hybrid), EFEMP2 (Two-hybrid), APEX2 (Two-hybrid), APEX2 (Two-hybrid), APEX2 (Two-hybrid), APEX2 (Affinity Capture-MS), CUL9 (Affinity Capture-MS), APEX2 (Affinity Capture-MS), APBA2 (Affinity Capture-MS), SIRT1 (Affinity Capture-MS), WDR54 (Affinity Capture-MS), DDB2 (Affinity Capture-MS)

ESM2 similar proteins: A0JPH4, A6H7I3, A8MS41, A9JRL3, B2RYM0, E1C3P4, F1ND48, O35710, O81916, P55265, P55266, P57097, P79942, P97573, Q09M05, Q0WKY2, Q149N8, Q1RMU2, Q2TBA3, Q4U2V3, Q5E9N9, Q5R6Z9, Q5RED8, Q5RGT6, Q5VTE6, Q5XIX3, Q60805, Q66H62, Q6DD21, Q6P549, Q7TPQ3, Q80TQ2, Q8K1C0, Q8K2I9, Q8K4J0, Q8NFZ0, Q8VCU0, Q96MI9, Q99MU3, Q99MV5

Diamond homologs: F4JNY0, Q6DDT4, Q9UBZ4, A0MTA1, A1YES6, A1YFZ3, A2T6Y4, A2T7I6, O26314, P09030, P0A2X3, P0A2X4, P23196, P27695, P27864, P28352, P37454, P43138, P44318, P45951, P51173, P87175, Q5E9N9, Q68G58, A0A0L0P6P7, C7J0A2, F4ISQ7, O60126, O61660, O70157, O73954, O95985, O96651, P13099, Q0J0S6, Q0VGT4, Q13472, Q5HZL1, Q86YA3, Q8K203

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

93 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	52
Likely benign	11
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
154689	GRCh38/hg38 Xp11.22-q11.2(chrX:52809123-65305544)x3	Pathogenic

SpliceAI

694 predictions. Top by Δscore:

Variant	Effect	Δscore
X:55000564:G:GT	donor_gain	1.0000
X:55000565:A:T	donor_gain	1.0000
X:55000575:GACCA:G	donor_gain	1.0000
X:55000580:G:GG	donor_gain	1.0000
X:55000600:G:GT	donor_gain	1.0000
X:55001540:TTCCA:T	acceptor_loss	1.0000
X:55001542:CCA:C	acceptor_loss	1.0000
X:55001544:A:AG	acceptor_gain	1.0000
X:55001544:A:T	acceptor_loss	1.0000
X:55001544:AG:A	acceptor_gain	1.0000
X:55001544:AGG:A	acceptor_gain	1.0000
X:55001544:AGGG:A	acceptor_gain	1.0000
X:55001545:G:GG	acceptor_gain	1.0000
X:55001545:GG:G	acceptor_gain	1.0000
X:55001545:GGG:G	acceptor_gain	1.0000
X:55001545:GGGG:G	acceptor_gain	1.0000
X:55001630:G:GG	donor_gain	1.0000
X:55001630:GT:G	donor_loss	1.0000
X:55001631:T:A	donor_loss	1.0000
X:55002358:GA:G	donor_gain	1.0000
X:55002359:A:G	donor_gain	1.0000
X:55002960:A:AG	acceptor_gain	1.0000
X:55002961:G:GA	acceptor_gain	1.0000
X:55002961:GC:G	acceptor_gain	1.0000
X:55002961:GCA:G	acceptor_gain	1.0000
X:55002961:GCACA:G	acceptor_gain	1.0000
X:55003793:TTTCA:T	acceptor_loss	1.0000
X:55003794:TTCA:T	acceptor_loss	1.0000
X:55003795:TCA:T	acceptor_loss	1.0000
X:55003796:CA:C	acceptor_loss	1.0000

AlphaMissense

3393 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:55007352:T:C	F492L	0.990
X:55007354:C:A	F492L	0.990
X:55007354:C:G	F492L	0.990
X:55003081:G:C	R181P	0.987
X:55000441:T:A	W7R	0.986
X:55000441:T:C	W7R	0.986
X:55003072:T:C	L178P	0.986
X:55003083:G:C	A182P	0.984
X:55007412:T:C	F512L	0.982
X:55007414:C:A	F512L	0.982
X:55007414:C:G	F512L	0.982
X:55003059:T:C	F174L	0.980
X:55003061:C:A	F174L	0.980
X:55003061:C:G	F174L	0.980
X:55000438:A:C	S6R	0.979
X:55000440:C:A	S6R	0.979
X:55000440:C:G	S6R	0.979
X:55002257:C:A	A83D	0.979
X:55000565:A:T	E48V	0.978
X:55007418:T:A	W514R	0.978
X:55007418:T:C	W514R	0.978
X:55001599:A:C	S71R	0.977
X:55001601:C:A	S71R	0.977
X:55001601:C:G	S71R	0.977
X:55002293:C:A	A95D	0.977
X:55003001:C:A	N154K	0.977
X:55003001:C:G	N154K	0.977
X:55006614:A:C	S246R	0.977
X:55006616:C:A	S246R	0.977
X:55006616:C:G	S246R	0.977

dbSNP variants (sampled 300 via entrez): RS1000470371 (X:55008593 A>G), RS1000994387 (X:55001028 A>G), RS1002177796 (X:55002695 T>C), RS1002242249 (X:55001515 T>A), RS1002478846 (X:55004307 G>C), RS1002514685 (X:55004697 C>T), RS1002908572 (X:55005875 A>G), RS1003281502 (X:55004095 C>T), RS1004036133 (X:55004894 C>T), RS1005854446 (X:55000274 C>T), RS1006439569 (X:55009390 T>A,C), RS1006459827 (X:55001372 C>G), RS1006803572 (X:55001086 A>G,T), RS1006970434 (X:55008213 C>T), RS1007076948 (X:54998613 A>G)

Disease associations

OMIM: gene MIM:300773 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Arsenic	affects expression, affects cotreatment, decreases expression, increases abundance, increases expression	3
Acetaminophen	increases expression	2
dicrotophos	increases expression	1
bisphenol A	decreases expression	1
cobaltous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
CPG-oligonucleotide	decreases expression	1
abrine	decreases expression	1
riccardin D	decreases expression	1
Temozolomide	increases expression	1
Troglitazone	decreases expression	1
Glyphosate	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Demecolcine	decreases expression	1
Doxorubicin	decreases expression	1
Gasoline	increases abundance, increases expression, affects cotreatment	1
Methyl Methanesulfonate	increases expression	1
Nickel	increases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Smoke	decreases expression	1
Tamoxifen	increases expression	1
Tetradecanoylphorbol Acetate	increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tunicamycin	decreases expression	1
Vincristine	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Antirheumatic Agents	decreases expression	1

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2RU	Abcam HEK293T APEX2 KO	Transformed cell line	Female
CVCL_D7K8	Ubigene A-549 APEX2 KO	Cancer cell line	Male
CVCL_D9XN	Ubigene HeLa APEX2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.