NEIL3
Chr 4nei like DNA glycosylase 3
Also known as: FGP2, FPG2, NEI3, ZGRF3, hFPG2, hNEI3
NEIL3 encodes a DNA glycosylase that repairs oxidative DNA damage by cleaving damaged bases and introducing strand breaks to initiate base excision repair, with particular activity on single-stranded DNA and specialized lesions like spiroiminodihydantoin and guanidinohydantoin. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability, developmental delay, and seizures. The gene shows minimal constraint against loss-of-function variants (LOEUF 1.081), which is consistent with recessive inheritance patterns.
Disputed — evidence questions this relationship
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
191 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 75 | 0 | 75 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 61 | 7 | 0 | 68 |
Likely Benign | 0 | 5 | 4 | 3 | 12 |
Benign | 0 | 4 | 6 | 4 | 14 |
| Total | 0 | 70 | 95 | 7 | 172 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NEIL3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools