NEIL2

protein-coding

nei like DNA glycosylase 2, the group of DNA glycosylases

Gene summary

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]

MANE transcript

NM_145043.4

Inheritance

—

ClinVar variants

U:91B:15

Top phenotype

High myopia

gnomAD constraint

pLI —, LoF o/e 1.16

Max pathogenic AF

—

Genomic locus

chr8:11,769,639-11,787,345

External References & Databases

Ensembl (ENSG00000154328)

Transcript & Mutation Effects

hg38 • Region Span ~17.7 kb

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GenCC 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 NEIL2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 88

not providedTotal: 10

High myopiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_145043.4. 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				3 clinvar	3 clinvar	6
missense			87 clinvar	7 clinvar	2 clinvar	96
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	91	10	5	106

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 47 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_145043.4	RefSeq	NP_659480.1	4	MANE Select
ENST00000284503.7	Ensembl	ENSP00000284503.6	4	MANE Select
NM_001135746.3	RefSeq	NP_001129218.1	4	Standard
NM_001135747.3	RefSeq	NP_001129219.1	3	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
depyrimidination

Molecular Function

damaged DNA binding
DNA-(apurinic or apyrimidinic site) endonuclease activity
protein binding
microtubule binding
zinc ion binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
spindle microtubule
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000284503
Coding exons: 4
Length: 17708
Individuals with no LoFs: 125641
Homozygous LoFs: 0
Heterozygous LoFs: 107
Defined: 125748
p: 0.000426

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-2.09	264	184	1.43	0.0000100	2155
Missense (PolyPhen)		88	62.001	1.4193		828
Synonymous	-2.84	112	79.7	1.40	0.00000488	653
Loss of Function	-0.530	15	12.9	1.16	6.23e-7	147

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00064	0.00064	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00031	0.00031	rare
South Asian	0.0011	0.0011	notable
Other	0.00082	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Has DNA glycosylase activity towards 5-hydroxyuracil and other oxidized derivatives of cytosine with a preference for mismatched double-stranded DNA (DNA bubbles). Has low or no DNA glycosylase activity towards thymine glycol, 2-hydroxyadenine, hypoxanthine and 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. {ECO:0000269|PubMed:12097317, ECO:0000269|PubMed:14522990, ECO:0000269|PubMed:15175427, ECO:0000269|PubMed:15339932}.;

Recessive Scores

pRec: 0.0775

Intolerance Scores

LoFtool: 0.948
RVIS EVS: 0.13
RVIS percentile EVS: 63.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.794

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium