NTHL1 Gene
Nth Like DNA Glycosylase 1
Gene Information Card
| Symbol | NTHL1 |
|---|---|
| Full Name | Nth Like DNA Glycosylase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 16p13.3 |
| NCBI Gene ID | 4913 ncbi.nlm.nih.gov/gene/4913 |
| Ensembl ID | ENSG00000103197 |
| UniProt ID | P78549 |
| OMIM ID | 602656 |
| HGNC ID | 8009 |
| Aliases | NTH1, OCTS3, hNTH1 |
Description
NTHL1 encodes a DNA N-glycosylase that initiates base excision repair (BER) by removing oxidized pyrimidines, such as thymine glycol and 5-hydroxycytosine, from damaged DNA. It is a bifunctional enzyme with both DNA glycosylase and AP lyase activities. Biallelic loss-of-function mutations in NTHL1 cause NTHL1-associated polyposis (NAP), a hereditary colorectal cancer syndrome characterized by multiple adenomatous polyps and increased risk of colorectal and other cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| NTHL1-associated polyposis (NAP) | Biallelic loss-of-function mutations impair BER, leading to accumulation of somatic mutations in tumor suppressor genes (e.g., APC, TP53). | ClinVar, OMIM |
| Colorectal cancer | Heterozygous carriers may have moderately increased risk; biallelic mutations cause high risk. | ClinVar, NCBI |
| Breast cancer | Some studies suggest increased risk in NTHL1 mutation carriers, but evidence is limited. | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 10.2 | Medium |
| Colon | 8.5 | Medium |
| Small intestine | 7.9 | Medium |
| Kidney | 6.8 | Low |
| Heart | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 12.3 | Cervical cancer cell line |
| HCT116 | 9.8 | Colorectal carcinoma cell line |
| HEK293 | 8.4 | Embryonic kidney cell line |
| MCF7 | 7.2 | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.268C>T (p.Gln90*) | Nonsense | Rare (founder in Dutch population) | Loss of function; truncates protein |
| c.529G>A (p.Gly177Arg) | Missense | Rare | Likely loss of function; reduced glycosylase activity |
| c.796C>T (p.Arg266*) | Nonsense | Rare | Loss of function; truncates protein |
Mutation functional classification
Loss of Function (LOF)
Most NTHL1 pathogenic variants are loss-of-function, leading to impaired BER and genomic instability.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative effects described.
View complete mutation data：
Gene Ontology (GO)
| • DNA glycosylase activity (GO:0019104) | • AP lyase activity (GO:0003906) |
| • Base-excision repair (GO:0006284) | • Oxidation-dependent DNA damage response (GO:0033683) |
| • Nucleus (GO:0005634) |
Pathways
• Base excision repair (BER) - KEGG hsa03410
• Oxidative stress response - Reactome R-HSA-73894
Protein Summary
NTHL1 is a 312-amino acid bifunctional DNA glycosylase/AP lyase that localizes to the nucleus. It recognizes and excises oxidized pyrimidine bases, creating an apurinic/apyrimidinic (AP) site and then cleaving the DNA backbone via beta-elimination. The protein contains a helix-hairpin-helix (HhH) motif essential for DNA binding and catalytic activity. Loss of NTHL1 function leads to accumulation of oxidative DNA damage and contributes to tumorigenesis, particularly in the colorectum.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NTHL1 Knockout HEK293 Cell Line | EDJ-KQ5364 | Human | 4913 | Details Get a Quote |
| NTHL1 Knockout A-549 Cell Line | EDJ-KQ28481 | Human | 4913 | Details Get a Quote |
| NTHL1 Knockout HCT 116 Cell Line | EDJ-KQ28482 | Human | 4913 | Details Get a Quote |
| NTHL1 Knockout HeLa Cell Line | EDC90489 | Human | 4913 | Details Get a Quote |
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