NEIL3

Summary

NEIL3 (nei like DNA glycosylase 3, HGNC:24573) is a protein-coding gene on chromosome 4q34.3, encoding Endonuclease 8-like 3 (Q8TAT5). DNA glycosylase which prefers single-stranded DNA (ssDNA), or partially ssDNA structures such as bubble and fork structures, to double-stranded DNA (dsDNA).

NEIL3 belongs to a class of DNA glycosylases homologous to the bacterial Fpg/Nei family. These glycosylases initiate the first step in base excision repair by cleaving bases damaged by reactive oxygen species and introducing a DNA strand break via the associated lyase reaction (Bandaru et al., 2002 [PubMed 12509226]).

Source: NCBI Gene 55247 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autoimmune disease (Disputed, ClinGen)
• GWAS associations: 4
• Clinical variants (ClinVar): 88 total
• MANE Select transcript: NM_018248

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24573
Approved symbol	NEIL3
Name	nei like DNA glycosylase 3
Location	4q34.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10858, hFPG2, FPG2, hNEI3, ZGRF3
Ensembl gene	ENSG00000109674
Ensembl biotype	protein_coding
OMIM	608934
Entrez	55247

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 nonsense_mediated_decay

ENST00000264596, ENST00000513321, ENST00000905043, ENST00000939669

RefSeq mRNA: 1 — MANE Select: NM_018248 NM_018248

CCDS: CCDS3828

Canonical transcript exons

ENST00000264596 — 10 exons

Exon	Start	End
ENSE00000741192	177339783	177339857
ENSE00000741193	177341476	177341642
ENSE00000741201	177351380	177351549
ENSE00000741202	177353308	177353728
ENSE00000886403	177360503	177360677
ENSE00000886404	177362289	177362936
ENSE00000970645	177309874	177310109
ENSE00000970646	177322459	177322580
ENSE00003625202	177336108	177336321
ENSE00003639491	177335688	177335822

Expression profiles

Bgee: expression breadth ubiquitous, 127 present calls, max score 86.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.0737 / max 253.6790, expressed in 1157 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
50715	4.8896	1060
50713	0.7947	486
50716	0.7564	365
50714	0.3692	231
50717	0.2637	103

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.95	gold quality
ventricular zone	UBERON:0003053	84.67	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.76	gold quality
secondary oocyte	CL:0000655	81.28	gold quality
oocyte	CL:0000023	78.43	gold quality
ganglionic eminence	UBERON:0004023	77.79	gold quality
stromal cell of endometrium	CL:0002255	71.36	gold quality
bone marrow	UBERON:0002371	69.80	gold quality
pancreatic ductal cell	CL:0002079	68.80	gold quality
bone marrow cell	CL:0002092	67.57	gold quality
embryo	UBERON:0000922	66.37	gold quality
lower esophagus mucosa	UBERON:0035834	65.70	gold quality
rectum	UBERON:0001052	65.23	gold quality
mucosa of transverse colon	UBERON:0004991	64.56	gold quality
esophagus mucosa	UBERON:0002469	64.35	gold quality
thymus	UBERON:0002370	64.08	gold quality
vermiform appendix	UBERON:0001154	63.14	gold quality
lymph node	UBERON:0000029	63.05	gold quality
buccal mucosa cell	CL:0002336	61.82	gold quality
ileal mucosa	UBERON:0000331	61.40	gold quality
adrenal tissue	UBERON:0018303	61.36	gold quality
caecum	UBERON:0001153	59.62	gold quality
trabecular bone tissue	UBERON:0002483	59.62	gold quality
colonic epithelium	UBERON:0000397	58.71	silver quality
smooth muscle tissue	UBERON:0001135	57.17	gold quality
upper leg skin	UBERON:0004262	56.27	gold quality
tonsil	UBERON:0002372	55.43	gold quality
endometrium	UBERON:0001295	54.85	gold quality
cranial nerve II	UBERON:0000941	54.29	silver quality
skin of abdomen	UBERON:0001416	53.61	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.32

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting NEIL3, 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-656-3P	100.00	72.15	2788
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-5009-3P	99.45	69.43	1341
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-190B-3P	99.33	68.29	1382
HSA-MIR-183-5P	99.31	72.27	1164
HSA-MIR-3152-3P	99.10	66.35	678
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-4751	98.80	64.95	525
HSA-MIR-500A-5P	98.76	69.13	1241
HSA-MIR-4731-3P	98.56	68.60	1860
HSA-MIR-6516-5P	98.42	70.19	1551

Literature-anchored findings (GeneRIF, showing 28)

• hFPG1 and hFPG2 repair 8-oxoguanine and other DNA oxidation products. (hFPG1 and hFPG2) (PMID:12433996)
• NEIL3 partially rescues an E. coli nth nei mutant from hydrogen peroxide sensitivity. Taken together, repair of certain base damage including base loss in ssDNA may be mediated by NEIL3. (PMID:19170771)
• both the transcription and protein levels of hNEIL3 fluctuated during the cell cycle (PMID:22365498)
• Here we report the construction of bicistronic expression vectors for expressing in Escherichia coli the full-length mouse Neil3 (MmuNeil3), its glycosylase domain (MmuNeil3Delta324), as well as the glycosylase domain of human Neil3 (NEIL3Delta324). (PMID:22569481)
• Results show that the base excision and strand incision activities of NEIL3 exhibited a non-concerted action, indicating that NEIL3 mainly operates as a monofunctional DNA glycosylase. (PMID:23755964)
• one role for Neil3 and NEIL1 is to repair DNA base damages in telomeres in vivo and that Neil3 and Neil1 may function in quadruplex-mediated cellular events, such as gene regulation via removal of damaged bases from quadruplex DNA. (PMID:23926102)
• Polymorphisms within FLT3, EGFR, NEIL3, and ALOX5 may contribute to the occurrence of GBM. (PMID:24005813)
• NEIL3 rs12645561 SNP TT genotype was associated with increased risk of myocardial infarction. (PMID:25703835)
• The abnormal expressions of NEIL1, NEIL2, and NEIL3 are involved in cancer through their association with the somatic mutation load. (PMID:27042257)
• SNPs in NEIL3 are associated with impulsivity in Native American sample. (PMID:27167163)
• Results suggest a novel role for the DNA glycosylase Neil3 in atherogenesis in balancing lipid metabolism and macrophage function, potentially independently of genome-wide canonical base excision repair of oxidative DNA damage. (PMID:27328939)
• These findings demonstrate that deficiency in NEIL3 is associated with increased lymphocyte apoptosis, autoantibodies, and predisposition to autoimmunity. (PMID:27760045)
• Single nucleotide polymorphism (SNP) rs142310826 near the NEIL3 gene showed a genome-wide significant interaction with caffeine consumption .There was no gender difference for this interaction (P = 0.64 for heterogeneity). NEIL3, a gene belonging to the base excision DNA repair pathway, encodes a DNA glycosylase that recognizes and removes lesions produced by oxidative stress. (PMID:27797824)
• NEIL3-dependent modulation of DNA methylation regulates cardiac fibroblast proliferation and thereby affects extracellular matrix modulation after myocardial infarction. (PMID:28052262)
• Data indicate that DNA glycosylases MYH, UNG2, MPG, NTH1, NEIL1, 2 and 3 on nascent DNA. (PMID:28575236)
• NEIL3 protects genome stability through targeted repair of oxidative damage in telomeres during S/G2 phase. (PMID:28854357)
• NEIL3 cleaves psoralen-induced DNA-DNA cross-links in three-stranded and four-stranded DNA substrates to generate unhooked DNA fragments containing either an abasic site or a psoralen-thymine monoadduct. Nei and NEIL1 also cleave a psoralen-induced four-stranded DNA substrate to generate 2 unhooked DNA duplexes with a nick; NEIL3 targets both DNA strands in interstrand cross-links without generating single-strand breaks. (PMID:29234069)
• This study identifies the NEIL3 promoter possessing a G-rich element that can adopt a G4 fold, and when 8-oxo-7,8-dihydroguanine is incorporated, the sequence can lock into a more stable G4 fold via recruitment of the fifth track of Gs. (PMID:29718661)
• NEIL1 and NEIL3 may protect cells against cytotoxic and mutagenic effects of NM-Fapy-dG, but NEIL1 may have a unique role in initiation of base excision repair of AFB1-Fapy-dG (PMID:30448017)
• Results indicate that whilst specificity for 5-hydroxyuracil and thymine glycol was observed, NEIL3 preferentially excises oxidized bases from single stranded DNA and within open fork structures. (PMID:31018584)
• TRAIP is important for the recruitment of NEIL3 but not FANCD2, and knockdown of TRAIP promotes FA/BRCA pathway activation. Interestingly, TRAIP is non-epistatic with both NEIL3 and FA pathways in psoralen-ICL repair, suggesting that TRAIP may function upstream of the two pathways. (PMID:31980815)
• An autoinhibitory role for the GRF zinc finger domain of DNA glycosylase NEIL3. (PMID:32878989)
• DNA glycosylase Neil3 regulates vascular smooth muscle cell biology during atherosclerosis development. (PMID:33714552)
• CircNEIL3 regulatory loop promotes pancreatic ductal adenocarcinoma progression via miRNA sponging and A-to-I RNA-editing. (PMID:33750389)
• Deficiency of NEIL3 Enhances the Chemotherapy Resistance of Prostate Cancer. (PMID:33921035)
• EWSR1-induced circNEIL3 promotes glioma progression and exosome-mediated macrophage immunosuppressive polarization via stabilizing IGF2BP3. (PMID:35031058)
• [Overexpression of Nei endonuclease VIII-like protein 3 in hepatocellular carcinoma indicates increased levels of immune infiltration and an unfavorable prognosis]. (PMID:37872095)
• NEIL3 promotes cell proliferation of ccRCC via the cyclin D1-Rb-E2F1 feedback loop regulation. (PMID:37992567)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	neil3	ENSDARG00000020079
mus_musculus	Neil3	ENSMUSG00000039396
rattus_norvegicus	Neil3	ENSRNOG00000011688

Paralogs (2): NEIL1 (ENSG00000140398), NEIL2 (ENSG00000154328)

Protein

Protein identifiers

Endonuclease 8-like 3 — Q8TAT5 (reviewed: Q8TAT5)

Alternative names: DNA glycosylase FPG2, DNA glycosylase/AP lyase Neil3, Endonuclease VIII-like 3, Nei-like protein 3

All UniProt accessions (2): Q8TAT5, D6RAV1

UniProt curated annotations — full annotation on UniProt →

Function. DNA glycosylase which prefers single-stranded DNA (ssDNA), or partially ssDNA structures such as bubble and fork structures, to double-stranded DNA (dsDNA). Mediates interstrand cross-link repair in response to replication stress: acts by mediating DNA glycosylase activity, cleaving one of the two N-glycosyl bonds comprising the interstrand cross-link, which avoids the formation of a double-strand break but generates an abasic site that is bypassed by translesion synthesis polymerases. In vitro, displays strong glycosylase activity towards the hydantoin lesions spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh) in both ssDNA and dsDNA; also recognizes FapyA, FapyG, 5-OHU, 5-OHC, 5-OHMH, Tg and 8-oxoA lesions in ssDNA. No activity on 8-oxoG detected. Also shows weak DNA-(apurinic or apyrimidinic site) lyase activity. In vivo, appears to be the primary enzyme involved in removing Sp and Gh from ssDNA in neonatal tissues.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Expressed in keratinocytes and embryonic fibroblasts (at protein level). Also detected in thymus, testis and fetal lung primary fibroblasts.

Domain organisation. The N-terminal region (2-281) contains the glycosylase and lyase activities. The RanBP2-type zinc-finger, also named NZF zinc finger, recognizes and binds ubiquitinated CMG helicase complex. The GRF-type zinc-fingers recognize single-stranded DNA (ssDNA), possibly on the lagging strand template.

Similarity. Belongs to the FPG family.

RefSeq proteins (1): NP_060718* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000214	Znf_DNA_glyclase/AP_lyase	Domain
IPR001876	Znf_RanBP2	Domain
IPR010666	Znf_GRF	Domain
IPR010979	Ribosomal_uS13-like_H2TH	Homologous_superfamily
IPR012319	FPG_cat	Domain
IPR015886	H2TH_FPG	Domain
IPR015887	DNA_glyclase_Znf_dom_DNA_BS	Binding_site
IPR035937	FPG_N	Homologous_superfamily
IPR036443	Znf_RanBP2_sf	Homologous_superfamily

Pfam: PF00641, PF06831, PF06839

Catalyzed reactions (Rhea), 1 shown:

• 2’-deoxyribonucleotide-(2’-deoxyribose 5’-phosphate)-2’-deoxyribonucleotide-DNA = a 3’-end 2’-deoxyribonucleotide-(2,3-dehydro-2,3-deoxyribose 5’-phosphate)-DNA + a 5’-end 5’-phospho-2’-deoxyribonucleoside-DNA + H(+) (RHEA:66592)

UniProt features (53 total): sequence variant 12, binding site 10, strand 9, mutagenesis site 5, zinc finger region 4, turn 3, site 2, helix 2, initiator methionine 1, chain 1, modified residue 1, sequence conflict 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7TMY	X-RAY DIFFRACTION	2.21
7JL5	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TAT5-F1	70.11	0.37

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 (3): 2 (important for monofunctional glycosylase activity); 81 (required for glycosylase and lyase activities); 2 (schiff-base intermediate with dna; via amino nitrogen)

Ligand- & substrate-binding residues (10): 507; 510; 533; 541; 554; 556; 579; 587; 192; 271

Post-translational modifications (1): 450

Mutagenesis-validated functional residues (5):

Position	Phenotype
2	no effect on ap lyase activity. impairs monofunctional glycosylase activity.
3	no effect on ap lyase activity.
81	loss of glycosylase and lyase activities.
276	abolishes ap lyase activity.
279	abolishes ap lyase activity.

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-110328	Recognition and association of DNA glycosylase with site containing an affected pyrimidine
R-HSA-110329	Cleavage of the damaged pyrimidine
R-HSA-110330	Recognition and association of DNA glycosylase with site containing an affected purine
R-HSA-110331	Cleavage of the damaged purine
R-HSA-9629232	Defective Base Excision Repair Associated with NEIL3
R-HSA-9636003	NEIL3-mediated resolution of ICLs
R-HSA-1643685	Disease
R-HSA-73884	Base Excision Repair
R-HSA-73894	DNA Repair
R-HSA-73927	Depurination
R-HSA-73928	Depyrimidination
R-HSA-73929	Base-Excision Repair, AP Site Formation
R-HSA-9605308	Diseases of Base Excision Repair
R-HSA-9675135	Diseases of DNA repair

MSigDB gene sets: 194 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, GOMF_ENDONUCLEASE_ACTIVITY, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, HNF3ALPHA_Q6, GOMF_NUCLEASE_ACTIVITY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, chr4q34, KAUFFMANN_DNA_REPAIR_GENES, GOBP_DNA_MODIFICATION, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, FISCHER_G2_M_CELL_CYCLE, WTGAAAT_UNKNOWN, OCT1_07, GOBP_DNA_DAMAGE_RESPONSE, LIAO_METASTASIS

GO Biological Process (7): single strand break repair (GO:0000012), base-excision repair (GO:0006284), base-excision repair, AP site formation (GO:0006285), interstrand cross-link repair (GO:0036297), depurination (GO:0045007), DNA repair (GO:0006281), DNA damage response (GO:0006974)

GO Molecular Function (17): bubble DNA binding (GO:0000405), damaged DNA binding (GO:0003684), double-stranded DNA binding (GO:0003690), single-stranded DNA binding (GO:0003697), DNA-(apurinic or apyrimidinic site) endonuclease activity (GO:0003906), zinc ion binding (GO:0008270), DNA N-glycosylase activity (GO:0019104), class I DNA-(apurinic or apyrimidinic site) endonuclease activity (GO:0140078), MCM complex binding (GO:1904931), nucleic acid binding (GO:0003676), DNA binding (GO:0003677), catalytic activity (GO:0003824), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798), hydrolase activity, hydrolyzing N-glycosyl compounds (GO:0016799), lyase activity (GO:0016829), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Base-Excision Repair, AP Site Formation	3
Depyrimidination	2
Depurination	2
Diseases of Base Excision Repair	1
DNA Repair	1
Base Excision Repair	1
Diseases of DNA repair	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA repair	3
DNA binding	3
DNA metabolic process	2
catalytic activity	2
base-excision repair	1
base-excision repair, AP site formation	1
DNA modification	1
DNA damage response	1
cellular response to stress	1
DNA secondary structure binding	1
DNA endonuclease activity	1
transition metal ion binding	1
hydrolase activity, hydrolyzing N-glycosyl compounds	1
catalytic activity, acting on DNA	1
DNA-(apurinic or apyrimidinic site) endonuclease activity	1
carbon-oxygen lyase activity	1
protein-containing complex binding	1
binding	1
nucleic acid binding	1
molecular_function	1
hydrolase activity	1
hydrolase activity, acting on glycosyl bonds	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1828 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NEIL3	NEIL1	Q96FI4	989
NEIL3	OGG1	P78554	910
NEIL3	NTHL1	P78549	906
NEIL3	TOP2A	P11388	836
NEIL3	APEX1	P27695	760
NEIL3	MUTYH	Q9UIF7	715
NEIL3	TDG	Q13569	674
NEIL3	UNG	P13051	667
NEIL3	TRAIP	Q9BWF2	666
NEIL3	XRCC1	P18887	665
NEIL3	APEX2	Q9UBZ4	665
NEIL3	FEN1	P39748	664
NEIL3	MPG	P29372	647
NEIL3	NEIL2	Q969S2	626
NEIL3	SMUG1	Q53HV7	613

IntAct

19 interactions, top by confidence:

A	B	Type	Score
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
PTGES3	AIP	psi-mi:“MI:0914”(association)	0.530
TP53	NEIL3	psi-mi:“MI:0915”(physical association)	0.400
TWIST1	NEIL3	psi-mi:“MI:0915”(physical association)	0.400
Ect2	STX18	psi-mi:“MI:0914”(association)	0.350
NEIL3	SF3B2	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
FKBP5	IFT56	psi-mi:“MI:0914”(association)	0.350
PTGES3	KIFBP	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
PTGES3	SBNO1	psi-mi:“MI:0914”(association)	0.350
EDAR	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
KCNE3	PIK3R2	psi-mi:“MI:0914”(association)	0.350
CRYBG2	DDX3Y	psi-mi:“MI:0914”(association)	0.350
TNFRSF1B	MAP3K7	psi-mi:“MI:0914”(association)	0.350
CRYBG2	CORO1A	psi-mi:“MI:0914”(association)	0.350

BioGRID (110): NEIL3 (Reconstituted Complex), NEIL3 (Reconstituted Complex), ROCK1 (Affinity Capture-MS), SFSWAP (Affinity Capture-MS), SLC2A1 (Affinity Capture-MS), SMARCA4 (Affinity Capture-MS), BCL7C (Affinity Capture-MS), SLC25A13 (Affinity Capture-MS), SF3B2 (Affinity Capture-MS), NNT (Affinity Capture-MS), GLTSCR1 (Affinity Capture-MS), GPATCH4 (Affinity Capture-MS), CDKN2AIP (Affinity Capture-MS), PRPF40A (Affinity Capture-MS), HMCES (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8HU22, A1A5R8, A8K979, B8A5Y1, E1BB03, F6UH96, O75113, P62283, P62285, P62286, P62287, P62288, P62289, P62290, P62291, P62292, P62293, P62294, P62296, P62297, Q08AX9, Q3MHN7, Q3US16, Q5BKS4, Q5HZL1, Q5XKL5, Q5ZIX8, Q5ZLE9, Q64702, Q68FF0, Q6A037, Q6IE81, Q6NQ79, Q6NSI8, Q6NZP1, Q6PCM1, Q8BMI4, Q8BVE8, Q8BZ05, Q8CJ27

Diamond homologs: A0A1L8HU22, A0KEN2, A0L2N2, A1AV29, A1BAN2, A1JHR7, A1RE25, A2C0H4, A3CYP7, A3QJA8, A4J4X3, A4STD1, A4TSD4, A5D0T6, A5UDC3, A5UI87, A5UUN1, A5VG06, A6UFF8, A6WUE9, A7FCT7, A8HA27, A8LNK8, A9BDY5, A9KW47, A9R677, A9WDC2, B0TER7, B0TN04, B0UUX0, B1JQX0, B1WTF7, B1YKA0, B2JYN6, B3Q620, B7K1T1, B7N9V3, B8CVD1, B8EDQ9, B8G9X1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NEIL3	up-regulates	Base-excision_repair

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	5
Benign	11

Top pathogenic / likely-pathogenic (0)

SpliceAI

1606 predictions. Top by Δscore:

Variant	Effect	Δscore
4:177310108:AGGT:A	donor_loss	1.0000
4:177310109:GGT:G	donor_loss	1.0000
4:177310110:GTGA:G	donor_loss	1.0000
4:177310111:T:G	donor_loss	1.0000
4:177335682:TTTCA:T	acceptor_loss	1.0000
4:177335683:TTCAG:T	acceptor_loss	1.0000
4:177335684:TCAG:T	acceptor_loss	1.0000
4:177335685:CAG:C	acceptor_loss	1.0000
4:177335686:A:AG	acceptor_gain	1.0000
4:177335686:AG:A	acceptor_gain	1.0000
4:177335687:G:A	acceptor_loss	1.0000
4:177335687:G:GG	acceptor_gain	1.0000
4:177335687:GG:G	acceptor_gain	1.0000
4:177335687:GGATT:G	acceptor_gain	1.0000
4:177335767:G:GT	donor_gain	1.0000
4:177335819:TCAGG:T	donor_loss	1.0000
4:177335820:CAG:C	donor_loss	1.0000
4:177335821:AG:A	donor_loss	1.0000
4:177335822:GGTA:G	donor_loss	1.0000
4:177335823:G:GA	donor_loss	1.0000
4:177335824:T:A	donor_loss	1.0000
4:177336103:TATA:T	acceptor_loss	1.0000
4:177336105:T:G	acceptor_gain	1.0000
4:177336105:TA:T	acceptor_loss	1.0000
4:177336106:A:AG	acceptor_gain	1.0000
4:177336107:G:GT	acceptor_gain	1.0000
4:177336107:GA:G	acceptor_gain	1.0000
4:177336107:GAA:G	acceptor_gain	1.0000
4:177336107:GAAA:G	acceptor_gain	1.0000
4:177336107:GAAAC:G	acceptor_gain	1.0000

AlphaMissense

4034 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:177351477:T:C	C323R	0.986
4:177362291:G:C	W546C	0.986
4:177362291:G:T	W546C	0.986
4:177362289:T:A	W546R	0.985
4:177362289:T:C	W546R	0.985
4:177351486:T:C	C326R	0.984
4:177360630:T:C	F530L	0.984
4:177360632:T:A	F530L	0.984
4:177360632:T:G	F530L	0.984
4:177322541:G:T	G80V	0.983
4:177351479:T:G	C323W	0.978
4:177351519:T:C	C337R	0.978
4:177351488:T:G	C326W	0.977
4:177362388:T:C	C579R	0.977
4:177351486:T:A	C326S	0.976
4:177351487:G:C	C326S	0.976
4:177351528:T:C	C340R	0.976
4:177322580:G:C	R93P	0.975
4:177339840:A:C	S229R	0.975
4:177339842:C:A	S229R	0.975
4:177339842:C:G	S229R	0.975
4:177360626:G:C	R528S	0.975
4:177360626:G:T	R528S	0.975
4:177362429:G:C	W592C	0.974
4:177362429:G:T	W592C	0.974
4:177309963:G:A	G4R	0.973
4:177309963:G:C	G4R	0.973
4:177351471:T:A	W321R	0.972
4:177351471:T:C	W321R	0.972
4:177351473:G:C	W321C	0.972

dbSNP variants (sampled 300 via entrez): RS10000175 (4:177370862 C>G), RS1000024129 (4:177339993 T>C), RS10001041 (4:177351879 T>A,G), RS1000107506 (4:177315498 A>G), RS1000230188 (4:177315128 G>A), RS1000291363 (4:177308985 G>A), RS10003102 (4:177357741 T>C), RS1000322505 (4:177346654 A>G), RS1000323315 (4:177340022 C>T), RS1000343927 (4:177309295 T>C), RS1000369291 (4:177327496 C>T), RS1000387155 (4:177351841 A>G), RS1000438696 (4:177346353 G>A), RS1000507878 (4:177310591 T>A), RS1000540377 (4:177311003 C>T)

Disease associations

OMIM: gene MIM:608934 | disease phenotypes:

GenCC curated gene-disease

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
autoimmune disease	Disputed	AR

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000086_1	Heart rate variability traits	7.000000e-06
GCST005588_25	Idiopathic dilated cardiomyopathy	9.000000e-06
GCST009391_1931	Metabolite levels	1.000000e-10
GCST012017_1	Mastocytosis (KIT D816V positive)	2.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009094	idiopathic dilated cardiomyopathy
EFO:0009766	asparagine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, affects expression, decreases expression	4
sodium arsenite	affects methylation, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Testosterone	affects cotreatment, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
TAK-243	increases sumoylation	1
propionaldehyde	decreases expression	1
bisphenol A	decreases expression	1
N(4)-hydroxycytidine	increases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
diallyl trisulfide	decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
chromium hexavalent ion	decreases expression, increases abundance	1
deguelin	increases expression	1
2-palmitoylglycerol	increases expression	1
trans-10,cis-12-conjugated linoleic acid	decreases expression	1
abrine	decreases expression	1
pyrachlostrobin	increases expression	1
jinfukang	increases expression	1
incobotulinumtoxinA	decreases expression	1
picoxystrobin	increases expression	1
(+)-JQ1 compound	decreases expression	1

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2DL	HAP1 NEIL3 (-) 3	Cancer cell line	Male
CVCL_E2DM	HAP1 NEIL3 (-) 4	Cancer cell line	Male
CVCL_E2DN	HAP1 NEIL3 (-) 5	Cancer cell line	Male
CVCL_TA28	HAP1 NEIL3 (-) 1	Cancer cell line	Male
CVCL_TA29	HAP1 NEIL3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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