NEIL1

Summary

NEIL1 (nei like DNA glycosylase 1, HGNC:18448) is a protein-coding gene on chromosome 15q24.2, encoding Endonuclease 8-like 1 (Q96FI4). Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents.

This gene is a member of the Nei endonuclease VIII-like gene family which encodes DNA glycosylases. The encoded enzyme participates in the DNA repair pathway by initiating base excision repair by removing damaged bases, primarily oxidized pyrimidines. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 79661 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 82 total — 1 pathogenic, 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_024608

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18448
Approved symbol	NEIL1
Name	nei like DNA glycosylase 1
Location	15q24.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22402, hFPG1, NEI1, FPG1
Ensembl gene	ENSG00000140398
Ensembl biotype	protein_coding
OMIM	608844
Entrez	79661

Gene structure

Transcript identifiers

Ensembl transcripts: 48 — 37 protein_coding, 7 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000355059, ENST00000561643, ENST00000564257, ENST00000564500, ENST00000564738, ENST00000564784, ENST00000564951, ENST00000565051, ENST00000565121, ENST00000566313, ENST00000566752, ENST00000567005, ENST00000567393, ENST00000567547, ENST00000567657, ENST00000567681, ENST00000567959, ENST00000568059, ENST00000568519, ENST00000568881, ENST00000569035, ENST00000569390, ENST00000569506, ENST00000569758, ENST00000866913, ENST00000866914, ENST00000866915, ENST00000866916, ENST00000866917, ENST00000866918, ENST00000866919, ENST00000866920, ENST00000866921, ENST00000866922, ENST00000866923, ENST00000866924, ENST00000866925, ENST00000866926, ENST00000866927, ENST00000866928, ENST00000928163, ENST00000954649, ENST00000954650, ENST00000954651, ENST00000954652, ENST00000954653, ENST00000954654, ENST00000954655

RefSeq mRNA: 3 — MANE Select: NM_024608 NM_001256552, NM_001352520, NM_024608

CCDS: CCDS10278

Canonical transcript exons

ENST00000355059 — 10 exons

Exon	Start	End
ENSE00001520211	75347039	75347473
ENSE00002480544	75353739	75353866
ENSE00003497076	75354431	75354492
ENSE00003506197	75352324	75352387
ENSE00003531036	75354250	75354277
ENSE00003561804	75354653	75354818
ENSE00003635419	75348884	75349339
ENSE00003741194	75354964	75357115
ENSE00003784464	75352602	75352701
ENSE00003788037	75352111	75352230

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 98.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.6140 / max 143.8326, expressed in 1016 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
147801	1.1471	482
147809	0.8602	400
147808	0.6134	320
147806	0.3862	107
147805	0.3598	100
147800	0.0942	43
147803	0.0658	29
147802	0.0414	23
147804	0.0267	11
147807	0.0193	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.69	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.11	gold quality
cerebellar hemisphere	UBERON:0002245	98.05	gold quality
cerebellar cortex	UBERON:0002129	97.92	gold quality
cerebellum	UBERON:0002037	96.42	gold quality
right adrenal gland cortex	UBERON:0035827	96.34	gold quality
right adrenal gland	UBERON:0001233	96.18	gold quality
right frontal lobe	UBERON:0002810	96.03	gold quality
metanephros cortex	UBERON:0010533	95.88	gold quality
minor salivary gland	UBERON:0001830	95.77	gold quality
left adrenal gland cortex	UBERON:0035825	95.53	gold quality
endocervix	UBERON:0000458	95.33	gold quality
left adrenal gland	UBERON:0001234	95.31	gold quality
right lobe of liver	UBERON:0001114	95.15	gold quality
right lobe of thyroid gland	UBERON:0001119	95.10	gold quality
adenohypophysis	UBERON:0002196	95.05	gold quality
left ovary	UBERON:0002119	94.78	gold quality
body of pancreas	UBERON:0001150	94.74	gold quality
adrenal cortex	UBERON:0001235	94.70	gold quality
left lobe of thyroid gland	UBERON:0001120	94.69	gold quality
mucosa of stomach	UBERON:0001199	94.68	gold quality
right ovary	UBERON:0002118	94.62	gold quality
transverse colon	UBERON:0001157	94.48	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.42	gold quality
body of stomach	UBERON:0001161	94.40	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.30	gold quality
left uterine tube	UBERON:0001303	94.25	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.17	gold quality
nucleus accumbens	UBERON:0001882	94.10	gold quality
cingulate cortex	UBERON:0003027	94.08	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	66.49
E-HCAD-6	yes	35.48
E-MTAB-9067	yes	14.54
E-CURD-122	yes	4.92
E-ANND-3	yes	4.81
E-CURD-112	no	1.96

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): JUN

miRNA regulators (miRDB)

22 targeting NEIL1, 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-150-5P	99.99	66.69	1976
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-3190-3P	97.61	66.95	1406
HSA-MIR-500A-3P	97.60	67.48	595
HSA-MIR-27B-5P	97.34	66.55	549
HSA-MIR-6859-3P	97.26	64.69	428
HSA-MIR-6894-3P	96.73	65.64	798
HSA-MIR-4491	96.53	66.20	935
HSA-MIR-4657	96.53	66.57	895
HSA-MIR-576-3P	96.14	65.63	773
HSA-MIR-217-3P	95.67	68.42	1000
HSA-MIR-6890-5P	92.89	65.83	442

Literature-anchored findings (GeneRIF, showing 40)

• hFPG1 and hFPG2 repair 8-oxoguanine and other DNA oxidation products. (hFPG1 and hFPG2) (PMID:12433996)
• Pyrimidine dimer repair enzyme located on the long arm of chromosome 15 that is frequently deleted in human cancers. (PMID:12509226)
• NEIL1 and NEIL2 are preferentially involved in repair of lesions in DNA bubbles generated during transcription and/or replication (PMID:14522990)
• hNEIL1 has a significant role in the repair of 5S-Tg in human cells. (PMID:14734554)
• Overproduction, crystallization and preliminary crystallographic analysis of NEIL1 (PMID:15159582)
• “zincless finger” appears to be required for NEIL1 activity, because mutating a very highly conserved arginine within this motif greatly reduces the glycosylase activity of the enzyme. (PMID:15232006)
• Reduced expression of NEIL1 is associated with the pathogenesis of gastric cancers (PMID:15319300)
• NEIL1 and OGG1, two DNA glycosylases which do not stably interact with each other, stimulate 8-oxoguanine repair by a collaboration that is possible because of higher abasic (AP) site affinity and stronger AP lyase activity of NEIL1 relative to OGG1. (PMID:15350146)
• NEIL1 is a DNA glycosylase that excise 5-formyluracil, 5-hydroxymethyluracil and Thymine glycol in human cells. (PMID:15533839)
• Oxidative stress-induced activation of NEIL1 appears to be involved in the feedback regulation of cellular repair activity needed to handle an increase in the level of oxidative base damage (PMID:16118226)
• Nth1 released 5R,6S 2’-deoxyribonucleoside diastereoisomer (Tg2) much more rapidly than cis 5S,6R-deoxyribonucleoside diastereoisomer (Tg1) regardless of the opposing purine. Neil1 released Thymine glycol non-stereoselectively. (PMID:16446124)
• A T434+2C mutation was found in familial colorectal cancer DNA suggesting a limited role for this gene in the devlopment of CRC. (PMID:17029639)
• The damage specificity of human homologues of Endo III (hNTHl) and Endo VIII (hNEIL1 and hNEIL2) is compared to elucidate the repair role in cells. (PMID:17150535)
• we found that although both SMUG1 and NEIL1 are able to excise 5-OHU lesions located in the proximity of the proximity of the 3’-end of a DNA SSB, NEIL1 is more efficient in the repair of these DNA lesions. (PMID:17348689)
• Human NEIL1 DNA glycosylase activity is significantly stimulated by hHus1, hRad1, hRad9 separately and by the 9-1-1 complex. (PMID:17395641)
• The ability of Neil1 to recognize a variety of pyrimidine lesions is connected to the flexible binding pocket of the enzyme and the common chemical features of lesions that contain a pyrimidine ring. (PMID:17432829)
• Centrosomal localization of hNEIL1 was observed when mitotic HeLa cells were immunostained with hNEIL1 antibodies (PMID:17556049)
• WRN participates in the same DNA repair pathway as NEIL1. (PMID:17611195)
• human DNA glycosylase NEIL1 interacts with proliferating cell nuclear antigen and may have a role in replication-associated repair of oxidized bases (PMID:18032376)
• These results indicate that the hydantoin lesions are the best substrates identified thus far for hNEIL1 and suggest that repair of these lesions may be a critical function of the hNEIL1 enzyme in vivo. (PMID:18543945)
• NEIL2, but not NEIL1, polymorphisms may have a role in risk and progression of squamous cell carcinomas of the oral cavity and oropharynx (PMID:18594018)
• NEIL1 could also participate in strand displacement repair synthesis (long patch repair (LP-BER)) mediated by FEN-1 and stimulated by PCNA. (PMID:18662981)
• Cockayne syndrome group B protein plays a role in repair of formamidopyrimidines, possibly by interacting with and stimulating NEIL1 (PMID:19179336)
• a model for the mechanism of ICL repair in mammalian cells that implicates the DNA glycosylase activity of NEIL1 downstream of XPF/ERCC1 and translesion DNA synthesis repair steps. (PMID:19258314)
• The NEIL1 G83D mutant was dysfunctional for the major oxidation products 7,8-dihydro-8-oxoguanine (8oxoG), thymine glycol and dihydrothymine in duplex DNA, and the ability to perform delta-elimination at abasic sites was significantly reduced. (PMID:19443904)
• enzymological activity in peripheral leukocytes is increased in children with asthma bronchiale (PMID:19840299)
• These results suggest that, in vivo, NEIL1 functions either at nucleosome-free regions (such as those near replication forks) or with cofactors that limit its non-specific binding to DNA. (PMID:20005182)
• The results indicate that NEIL1 does not require a base opposite to identify and remove hydantoin lesions. (PMID:20099873)
• Modulation of NEIL1’s activity on single-stranded DNA substrate by RPA and PCNA support NEIL1’s involvement in repairing the replicating genome. (PMID:20338831)
• WRN is the only human RecQ helicase that stimulates NEIL1 DNA glycosylase activity, and that this stimulation requires a double-stranded DNA substrate. (PMID:20346739)
• NEIL1 recoding site is a preferred editing site for the RNA editing adenosine deaminase ADAR1. (PMID:21068368)
• These data suggest Neil1 may be a critical mediator of base excision repair of incorporated dUMP following thymidylate synthetase pathway inhibition. (PMID:21131780)
• Homozygosity mapping and exome sequencing in a consanguineous kindred identified MYO1E and NEIL1 as novel candidate genes for human autosomal recessive steroid-resistant nephrotic syndrome. (PMID:21697813)
• NEIL1 gene mutation may have a causative role in the development of type 2 diabetes in the Turkish population. (PMID:21985917)
• Structural characterization of viral ortholog of human DNA glycosylase NEIL1 bound to thymine glycol or 5-hydroxyuracil-containing DNA. (PMID:22170059)
• aberrant promoter methylation of NEIL1 in head and neck squamous cell carcinoma (PMID:22286769)
• we demonstrated that hNEIL1 and hNTH1 cleave Oz sites as efficiently as 5-hydroxyuracil sites. Thus, hNEIL1 and hNTH1 can repair Oz lesions (PMID:22465744)
• the binding of these modified DNAs with the unedited and edited forms of human NEIL1 along with E. coli Endo III (PMID:22639086)
• Pro2 and Lys54 are involved in the AP lyase activity; Met81, Arg119 and Phe120 are essential for removal of 8-oxoG in duplex DNA (PMID:22858590)
• the hnRNP-U protection of cells after oxidative stress is largely due to enhancement of NEIL1-mediated repair. (PMID:22902625)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	neil1	ENSDARG00000018061
mus_musculus	Neil1	ENSMUSG00000032298
rattus_norvegicus	Neil1	ENSRNOG00000018577

Paralogs (2): NEIL3 (ENSG00000109674), NEIL2 (ENSG00000154328)

Protein

Protein identifiers

Endonuclease 8-like 1 — Q96FI4 (reviewed: Q96FI4)

Alternative names: DNA glycosylase/AP lyase Neil1, DNA-(apurinic or apyrimidinic site) lyase Neil1, Endonuclease VIII-like 1, FPG1, Nei homolog 1, Nei-like protein 1

All UniProt accessions (12): Q96FI4, H3BM98, H3BN83, H3BQE8, H3BQU8, H3BRZ2, H3BST2, H3BSZ5, H3BT75, H3BT94, H3BTX5, H3BU98

UniProt curated annotations — full annotation on UniProt →

Function. Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Acts as a DNA glycosylase that recognizes and removes damaged bases. Has a preference for oxidized pyrimidines, such as thymine glycol, formamidopyrimidine (Fapy) and 5-hydroxyuracil. Has marginal activity towards 8-oxoguanine. Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3’- and 5’-phosphates. Has DNA glycosylase/lyase activity towards mismatched uracil and thymine, in particular in U:C and T:C mismatches. Specifically binds 5-hydroxymethylcytosine (5hmC), suggesting that it acts as a specific reader of 5hmC.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Nucleus. Chromosome.

Tissue specificity. Ubiquitous.

Induction. Up-regulated during S-phase.

Similarity. Belongs to the FPG family.

RefSeq proteins (3): NP_001243481, NP_001339449, NP_078884* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010979	Ribosomal_uS13-like_H2TH	Homologous_superfamily
IPR012319	FPG_cat	Domain
IPR015371	Endonuclease-VIII_DNA-bd	Domain
IPR015886	H2TH_FPG	Domain
IPR035937	FPG_N	Homologous_superfamily

Pfam: PF01149, PF09292

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 (55 total): helix 12, strand 11, sequence variant 10, mutagenesis site 5, turn 5, active site 4, binding site 2, compositionally biased region 2, initiator methionine 1, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

27 structures.

PDB	Method	Resolution (Å)
5ITQ	X-RAY DIFFRACTION	1.48
1TDH	X-RAY DIFFRACTION	2.1
7TMX	X-RAY DIFFRACTION	2.3
8FTJ	X-RAY DIFFRACTION	2.3
5ITU	X-RAY DIFFRACTION	2.41
6LWD	X-RAY DIFFRACTION	2.41
5ITR	X-RAY DIFFRACTION	2.46
5ITY	X-RAY DIFFRACTION	2.48
6LWO	X-RAY DIFFRACTION	2.51
5ITT	X-RAY DIFFRACTION	2.53
6LWG	X-RAY DIFFRACTION	2.53
6LWB	X-RAY DIFFRACTION	2.55
6LWL	X-RAY DIFFRACTION	2.55
4NRV	X-RAY DIFFRACTION	2.6
6LWP	X-RAY DIFFRACTION	2.64
5ITX	X-RAY DIFFRACTION	2.65
6LWM	X-RAY DIFFRACTION	2.67
6LWI	X-RAY DIFFRACTION	2.72
6LWN	X-RAY DIFFRACTION	2.74
6LWA	X-RAY DIFFRACTION	2.76
6LWH	X-RAY DIFFRACTION	2.78
6LWF	X-RAY DIFFRACTION	2.79
6LWJ	X-RAY DIFFRACTION	2.83
6LWK	X-RAY DIFFRACTION	2.88
6LWQ	X-RAY DIFFRACTION	2.89
6LWR	X-RAY DIFFRACTION	2.9
6LWC	X-RAY DIFFRACTION	2.91

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96FI4-F1	81.01	0.65

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 (4): 2 (schiff-base intermediate with dna); 3 (proton donor); 54 (proton donor; for beta-elimination activity); 339 (proton donor; for delta-elimination activity)

Ligand- & substrate-binding residues (2): 339; 176

Mutagenesis-validated functional residues (5):

Position	Phenotype
2	loss of glycosylase and ap lyase activity.
2	loss of glycosylase activity.
3	loss of glycosylase and ap lyase activity.
54	loss of glycosylase activity.
277	strongly reduced glycosylase activity. has little effect on ap lyase activity.

Function

Pathways and Gene Ontology

Reactome pathways

12 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-5649702	APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway
R-HSA-9616334	Defective Base Excision Repair Associated with NEIL1
R-HSA-1643685	Disease
R-HSA-73884	Base Excision Repair
R-HSA-73894	DNA Repair
R-HSA-73928	Depyrimidination
R-HSA-73929	Base-Excision Repair, AP Site Formation
R-HSA-73933	Resolution of Abasic Sites (AP sites)
R-HSA-9605308	Diseases of Base Excision Repair
R-HSA-9675135	Diseases of DNA repair

MSigDB gene sets: 171 (showing top): GOMF_ENDONUCLEASE_ACTIVITY, MODULE_255, GOMF_NUCLEASE_ACTIVITY, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, MODULE_317, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, KAUFFMANN_DNA_REPAIR_GENES, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_PYRIMIDINE_CONTAINING_COMPOUND_CATABOLIC_PROCESS, GOBP_PYRIMIDINE_NUCLEOTIDE_METABOLIC_PROCESS, GOBP_DNA_MODIFICATION, GOBP_PYRIMIDINE_NUCLEOTIDE_CATABOLIC_PROCESS

GO Biological Process (7): base-excision repair (GO:0006284), base-excision repair, gap-filling (GO:0006287), response to oxidative stress (GO:0006979), obsolete negative regulation of nuclease activity (GO:0032074), depyrimidination (GO:0045008), DNA repair (GO:0006281), DNA damage response (GO:0006974)

GO Molecular Function (13): damaged DNA binding (GO:0003684), DNA-(apurinic or apyrimidinic site) endonuclease activity (GO:0003906), zinc ion binding (GO:0008270), hydrolase activity, acting on glycosyl bonds (GO:0016798), DNA N-glycosylase activity (GO:0019104), class I DNA-(apurinic or apyrimidinic site) endonuclease activity (GO:0140078), nucleic acid binding (GO:0003676), DNA binding (GO:0003677), catalytic activity (GO:0003824), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, hydrolyzing N-glycosyl compounds (GO:0016799), lyase activity (GO:0016829)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Depyrimidination	2
Base Excision Repair	2
Resolution of Abasic Sites (AP sites)	1
Diseases of Base Excision Repair	1
DNA Repair	1
Base-Excision Repair, AP Site Formation	1
Diseases of DNA repair	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
DNA metabolic process	2
binding	2
catalytic activity	2
intracellular membraneless organelle	2
DNA repair	1
base-excision repair	1
response to stress	1
base-excision repair, AP site formation	1
DNA modification	1
pyrimidine deoxyribonucleotide catabolic process	1
DNA damage response	1
cellular response to stress	1
DNA binding	1
DNA endonuclease activity	1
transition metal ion binding	1
hydrolase activity	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
nucleic acid binding	1
molecular_function	1
hydrolase activity, acting on glycosyl bonds	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
cytoplasm	1

Protein interactions and networks

STRING

1052 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NEIL1	NEIL3	Q8TAT5	989
NEIL1	NEIL2	Q969S2	989
NEIL1	NTHL1	P78549	984
NEIL1	OGG1	P78554	972
NEIL1	FEN1	P39748	962
NEIL1	XRCC1	P18887	956
NEIL1	MAF	O75444	946
NEIL1	POLB	P06746	826
NEIL1	PNKP	Q96T60	809
NEIL1	APEX1	P27695	793
NEIL1	SMUG1	Q53HV7	791
NEIL1	WRN	Q14191	770
NEIL1	PARP1	P09874	748
NEIL1	KEAP1	Q14145	743
NEIL1	TDG	Q13569	742

IntAct

9 interactions, top by confidence:

A	B	Type	Score
NEIL1	H3C13	psi-mi:“MI:0915”(physical association)	0.400
VASH2	NEIL1	psi-mi:“MI:0915”(physical association)	0.400
DUSP6	NEIL1	psi-mi:“MI:0915”(physical association)	0.400
NEIL1	U2SURP	psi-mi:“MI:0914”(association)	0.350
ARMC8	VWA8	psi-mi:“MI:0914”(association)	0.350
NEIL1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
SPRY4	ZDHHC13	psi-mi:“MI:0914”(association)	0.350
TAS2R8	NEIL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (285): NEIL1 (Reconstituted Complex), NEIL1 (Affinity Capture-RNA), LIG3 (Far Western), POLB (Far Western), NEIL1 (Reconstituted Complex), NEIL1 (Reconstituted Complex), LIG3 (Two-hybrid), NEIL1 (Reconstituted Complex), NEIL1 (Reconstituted Complex), NEIL1 (Reconstituted Complex), HUS1 (Reconstituted Complex), RAD1 (Reconstituted Complex), RAD9A (Reconstituted Complex), RAD9A (Affinity Capture-Western), HUS1 (Far Western)

ESM2 similar proteins: A2AI05, O00587, O08760, O15527, O55240, O70249, P21139, P49593, P50336, P56602, Q1JP61, Q1JPJ0, Q2TBI8, Q32PI0, Q3T0A0, Q501J2, Q5E9V4, Q5H879, Q5IS64, Q5SUV1, Q5T440, Q60HD5, Q6AYG0, Q6AYR8, Q6P9U1, Q8BNV1, Q8BZG5, Q8IZ69, Q8K4Q6, Q8N371, Q8N9H8, Q8R2H9, Q8VCA8, Q91W89, Q923W9, Q969S8, Q96AZ1, Q96FB5, Q96FI4, Q96FV2

Diamond homologs: A1A8X0, A4W871, A6T6E8, A7MQW6, A7ZJ95, A7ZXX5, A8AJA5, A9MJM8, A9MTR2, B1IY15, B1LLF1, B1X6P5, B2TU97, B4SZD3, B4TBC8, B4TQ44, B5BC82, B5EZF2, B5FNF0, B5QWF8, B5R679, B5XZD9, B6I7Y5, B7K1T1, B7LAC0, B7M5M8, B7MFX3, B7MPL0, B7N9V3, B7NMR0, B7ULJ5, C0PWD7, C4ZWI9, C6DCC8, E1W9M1, O86820, P0CL05, P50465, Q0T6V4, Q0TJX8

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
ERCC6	“up-regulates activity”	NEIL1	binding
MAPK8	“up-regulates activity”	NEIL1	phosphorylation
TRIM26	“down-regulates quantity”	NEIL1	ubiquitination
HUWE1	“down-regulates quantity by destabilization”	NEIL1	ubiquitination
NEIL1	up-regulates	Base-excision_repair

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	56
Likely benign	11
Benign	4

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
997817	Single allele	Pathogenic
1342929	NM_006715.4(MAN2C1):c.2733_2734del (p.His911fs)	Likely pathogenic

SpliceAI

2358 predictions. Top by Δscore:

Variant	Effect	Δscore
15:75347111:G:GG	donor_gain	1.0000
15:75349286:A:T	donor_gain	1.0000
15:75352686:G:GT	donor_gain	1.0000
15:75352686:G:T	donor_gain	1.0000
15:75352697:GTTGG:G	donor_gain	1.0000
15:75352698:T:G	donor_gain	1.0000
15:75352794:G:GT	donor_gain	1.0000
15:75353737:AGGG:A	acceptor_gain	1.0000
15:75353738:GGGG:G	acceptor_gain	1.0000
15:75356108:A:AC	donor_gain	1.0000
15:75356109:C:CC	donor_gain	1.0000
15:75356119:T:TA	donor_gain	1.0000
15:75356604:AC:A	donor_gain	1.0000
15:75356605:CC:C	donor_gain	1.0000
15:75356791:A:AC	donor_gain	1.0000
15:75356792:C:CC	donor_gain	1.0000
15:75356898:CACAC:C	acceptor_gain	1.0000
15:75356900:CAC:C	acceptor_gain	1.0000
15:75356904:T:C	acceptor_loss	1.0000
15:75349336:TCAG:T	donor_loss	0.9900
15:75349337:CAG:C	donor_loss	0.9900
15:75349338:AG:A	donor_loss	0.9900
15:75349339:GGTAG:G	donor_loss	0.9900
15:75349340:G:T	donor_loss	0.9900
15:75349341:T:A	donor_loss	0.9900
15:75352105:CTCCA:C	acceptor_loss	0.9900
15:75352106:TCCAG:T	acceptor_loss	0.9900
15:75352107:CCA:C	acceptor_loss	0.9900
15:75352109:A:AG	acceptor_gain	0.9900
15:75352110:G:GG	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000391570 (15:75349114 A>G), RS1000890518 (15:75355155 C>G), RS1001128493 (15:75354867 G>A), RS1001424088 (15:75353534 A>C), RS1001591308 (15:75348201 T>C), RS1002041360 (15:75348488 G>A,C), RS1002107833 (15:75349646 T>A), RS1002122012 (15:75354141 G>A), RS1002488659 (15:75352965 C>A,T), RS1002538131 (15:75348766 A>G), RS1003144374 (15:75356676 C>T), RS1003420307 (15:75351227 G>A,C), RS1003777238 (15:75351609 G>A,T), RS1003805692 (15:75347603 C>A,G,T), RS1003984270 (15:75355395 T>C)

Disease associations

OMIM: gene MIM:608844 | disease phenotypes: MIM:619775

GenCC curated gene-disease

Mondo (3): congenital disorder of deglycosylation 2 (MONDO:0030770), intellectual disability (MONDO:0001071), epilepsy (MONDO:0005027)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523426 (SINGLE PROTEIN)

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4462560	MAN2C1, MIR631, NEIL1		0.00	0
rs7402844	NEIL1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Vorinostat	affects cotreatment, decreases expression	2
Benzo(a)pyrene	decreases methylation, increases expression, affects methylation	2
Tobacco Smoke Pollution	decreases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sulforaphane	decreases expression	1
sodium arsenite	affects methylation	1
4,6-diamino-5-N-formamidopyrimidine	affects metabolic processing	1
di-n-butylphosphoric acid	affects expression	1
2,6-diamino-4-hydroxy-5-formamidopyrimidine	affects metabolic processing	1
benzo(a)pyrene diolepoxide I	increases expression	1
tris(2-carboxyethyl)phosphine	affects cotreatment, decreases activity, decreases reaction	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	decreases expression	1
Copper	affects binding, affects folding, decreases activity, decreases reaction, affects cotreatment	1
Curcumin	affects binding, decreases activity, decreases reaction	1
Doxorubicin	increases expression	1
Edetic Acid	decreases activity, decreases reaction, affects cotreatment, affects binding	1
Gallic Acid	decreases expression	1
Hydrogen Peroxide	decreases activity, decreases reaction	1
Iron	decreases reaction, affects folding, affects binding, decreases activity	1
Nickel	decreases expression	1
Smoke	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 5 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4422182	Binding	Inhibition of NEIL1 (unknown origin) assessed as remaining enzyme activity at 50 uM using Sp/Gh substrate incubated for 40 mins by TAMRA fluorescence-based assay	Small molecule inhibitors of 8-oxoguanine dna glycosylase-1 (ogg1)
CHEMBL5665447	Functional	Inhibition of NEIL1 by quantifying inhibition of NEIL1-mediated cleavage and dissociation of quenched duplex DNA oligonucleotides, measured as fluorescence at 594 nm.	Enzyme Inhibitor Single Concentration assay results for EUbOPEN Chemogenomics Library

Cellosaurus cell lines

7 cell lines: 5 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3C9	Abcam HEK293T NEIL1 KO 1	Transformed cell line	Female
CVCL_B3CA	Abcam HEK293T NEIL1 KO 2	Transformed cell line	Female
CVCL_E2DG	HAP1 NEIL1 (-) 2	Cancer cell line	Male
CVCL_E2DH	HAP1 NEIL1 (-) 3	Cancer cell line	Male
CVCL_E2DI	HAP1 NEIL1 (-) 4	Cancer cell line	Male
CVCL_KT81	HeLa SilenciX NEIL1	Cancer cell line	Female
CVCL_TA25	HAP1 NEIL1 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation