NEIL1
protein-codingnei like DNA glycosylase 1, the group of DNA glycosylases
Gene summary
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. [provided by RefSeq, Feb 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~10.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NEIL1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_024608.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 3 | 4 | |||
| missense | 54 | 7 | 2 | 63 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 55 | 12 | 2 | 69 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_078884.2 | 9 | MANE Select | |
| Ensembl | ENSP00000347170.4 | 9 | MANE Select | |
| RefSeq | NP_001243481.1 | 10 | Standard | |
| RefSeq | NP_001339448.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Base excision repair - Homo sapiens (human)
- DNA Repair
- Recognition and association of DNA glycosylase with site containing an affected pyrimidine
- Cleavage of the damaged pyrimidine
- Depyrimidination
Biological Process
- base-excision repair
- nucleotide-excision repair
- response to oxidative stress
- negative regulation of nuclease activity
- depyrimidination
Molecular Function
- damaged DNA binding
- DNA-(apurinic or apyrimidinic site) endonuclease activity
- protein C-terminus binding
- zinc ion binding
- hydrolase activity, acting on glycosyl bonds
Cellular Component
- nucleus
- nucleoplasm
- chromosome
- cytoplasm
- microtubule organizing center
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000564784
- Coding exons
- 9
- Length
- 8297
- Individuals with no LoFs
- 123446
- Homozygous LoFs
- 18
- Heterozygous LoFs
- 2284
- Defined
- 125748
- p
- 0.00920
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.259 | 259 | 248 | 1.05 | 0.0000161 | 2461 |
| Missense (PolyPhen) | 87 | 85.14 | 1.0218 | 870 | ||
| Synonymous | -1.56 | 120 | 100 | 1.20 | 0.00000570 | 824 |
| Loss of Function | 1.53 | 13 | 20.5 | 0.635 | 0.00000114 | 206 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0018 | 0.0017 | notable |
| Latino/Admixed American | 0.0078 | 0.0076 | notable |
| Ashkenazi Jewish | 0.0084 | 0.0082 | notable |
| East Asian | 0.00049 | 0.00049 | rare |
| Finnish | 0.0068 | 0.0058 | notable |
| European (Non-Finnish) | 0.016 | 0.015 | notable |
| South Asian | 0.0019 | 0.0018 | notable |
| Other | 0.013 | 0.013 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Acts as 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. {ECO:0000269|PubMed:11904416, ECO:0000269|PubMed:12200441, ECO:0000269|PubMed:12509226, ECO:0000269|PubMed:14522990}.;
Recessive Scores
- pRec
- 0.184
Intolerance Scores
- LoFtool
- 0.862
- RVIS EVS
- 0.8
- RVIS percentile EVS
- 87.54
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.910
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |