NEIL2

Chr 8

nei like DNA glycosylase 2

Also known as: NEH2, NEI2

NCBI Gene: 252969 ENSG00000154328 UniProt: Q969S2

The encoded DNA glycosylase removes oxidatively damaged cytosine bases from DNA and introduces strand breaks as part of the base excision repair pathway. NEIL2 mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability and seizures. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the Fpg/Nei family of DNA glycosylases. These glycosylases initiate the first step in base excision repair by cleaving oxidatively damaged bases and introducing a DNA strand break via their abasic site lyase activity. This enzyme is primarily associated with DNA repair during transcription and acts prefentially on cytosine-derived lesions, particularly 5-hydroxyuracil and 5-hydroxycytosine. It contains an N-terminal catalytic domain, a hinge region, and a C-terminal DNA-binding domain with helix-two-turn-helix and zinc finger motifs. This enzyme interacts with the X-ray cross complementing factor 1 scaffold protein as part of a multi-protein DNA repair complex. A pseudogene of this gene has been identified. [provided by RefSeq, Mar 2017]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.74

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.74LOEUF

pLI 0.000

Z-score -0.53

OE 1.16 (0.77–1.74)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.09Z-score

OE missense 1.43 (1.29–1.59)

264 obs / 184.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.16 (0.77–1.74)

0≤0.351.4

Missense OE?1.43 (1.29–1.59)

0≤0.61.4

Synonymous OE?1.40

0≤1.21.6

LoF obs/exp: 15 / 12.9Missense obs/exp: 264 / 184.2Syn Z: -2.84

Background carrier burden — how many people carry a rare variant somewhere in NEIL2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 75

624 rare PASS variants

Rare truncating (LoF)

1 in 930

101 rare PASS variants

Rare synonymous (reference)

1 in 190

241 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NEIL2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 95	1 in 1,200
South Asian	~43k	1 in 75	1 in 420
Remaining (unassigned)	~30k	1 in 63	1 in 1,200
European (Finnish)	~27k	1 in 160	1 in 3,300
Admixed American	~22k	1 in 70	1 in 490
African / African American	~21k	1 in 69	1 in 1,100
East Asian	~20k	1 in 120	1 in 830
Ashkenazi Jewish	~13k	1 in 170	none seen
Middle Eastern	~2,884	1 in 74	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓