GeneBe

NTHL1

nth like DNA glycosylase 1, the group of DNA glycosylases

Basic information

Region (hg38): 16:2039815-2047866

Links

ENSG00000065057 ∙ NCBI:4913 ∙ OMIM:602656 ∙ HGNC:8028 ∙ Uniprot:P78549 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • familial adenomatous polyposis 3 (Strong), mode of inheritance: AR
  • familial adenomatous polyposis 3 (Strong), mode of inheritance: AR
  • familial adenomatous polyposis 3 (Supportive), mode of inheritance: AR
  • familial adenomatous polyposis 3 (Definitive), mode of inheritance: AR
  • NTHL1-deficiency tumor predisposition syndrome (Definitive), mode of inheritance: AR
  • breast cancer (Limited), mode of inheritance: AR
  • meningioma (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Familial adenomatous polyposis 3AROncologicIndividuals have been described as affected by multiple types of cancer, including colorectal cancer, endometrial cancer, and other neoplasms, and awareness may allow surveillance and early managementOncologic25938944; 26559593

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NTHL1 gene.

  • not_provided (1312 variants)
  • Hereditary_cancer-predisposing_syndrome (1027 variants)
  • Familial_adenomatous_polyposis_3 (282 variants)
  • not_specified (79 variants)
  • NTHL1-related_disorder (46 variants)
  • NTHL1-deficiency_tumor_predisposition_syndrome (6 variants)
  • Inherited_polyposis_and_early_onset_colorectal_cancer_-_germline_testing (2 variants)
  • Hereditary_cancer (2 variants)
  • Isolated_focal_cortical_dysplasia_type_II (1 variants)
  • Lymphangiomyomatosis (1 variants)
  • Tuberous_sclerosis_2 (1 variants)
  • Familial_adenomatous_polyposis_1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NTHL1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002528.7. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
8
clinvar
343
clinvar
 351
missense
3
clinvar
2
clinvar
796
clinvar
49
clinvar
 850
nonsense
23
clinvar
18
clinvar
2
clinvar
 43
start loss
7
 7
frameshift
66
clinvar
25
clinvar
7
clinvar
 98
splice donor/acceptor (+/-2bp)
22
clinvar
2
clinvar
 24
Total 92 67 822 392 0

Highest pathogenic variant AF is 0.0015918671

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
NTHL1protein_codingprotein_codingENST00000219066 68052
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
5.66e-100.066212532204091257310.00163
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.7972332011.160.00001251995
Missense in Polyphen5152.4140.97302546
Synonymous0.4098488.90.9450.00000615645
Loss of Function-0.09751413.61.036.68e-7146

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.001470.00146
Ashkenazi Jewish0.0006960.000695
East Asian0.0001090.000109
Finnish0.003860.00384
European (Non-Finnish)0.002220.00221
Middle Eastern0.0001090.000109
South Asian0.0003270.000327
Other0.001800.00179

dbNSFP

Source: dbNSFP

Function
FUNCTION: Bifunctional DNA N-glycosylase with associated apurinic/apyrimidinic (AP) lyase function that catalyzes the first step in base excision repair (BER), the primary repair pathway for the repair of oxidative DNA damage. The DNA N-glycosylase activity releases the damaged DNA base from DNA by cleaving the N- glycosidic bond, leaving an AP site. The AP-lyase activity cleaves the phosphodiester bond 3' to the AP site by a beta-elimination. Primarily recognizes and repairs oxidative base damage of pyrimidines. Has also 8-oxo-7,8-dihydroguanine (8-oxoG) DNA glycosylase activity. Acts preferentially on DNA damage opposite guanine residues in DNA. Is able to process lesions in nucleosomes without requiring or inducing nucleosome disruption. {ECO:0000255|HAMAP-Rule:MF_03183, ECO:0000269|PubMed:10882850, ECO:0000269|PubMed:11328882, ECO:0000269|PubMed:11380260, ECO:0000269|PubMed:11695910, ECO:0000269|PubMed:12140329, ECO:0000269|PubMed:12144783, ECO:0000269|PubMed:12519758, ECO:0000269|PubMed:14734554, ECO:0000269|PubMed:15533839, ECO:0000269|PubMed:17923696, ECO:0000269|PubMed:20005182, ECO:0000269|PubMed:20110254, ECO:0000269|PubMed:21930793, ECO:0000269|PubMed:8990169, ECO:0000269|PubMed:9045706, ECO:0000269|PubMed:9705289, ECO:0000269|PubMed:9890904}.;
Disease
DISEASE: Familial adenomatous polyposis 3 (FAP3) [MIM:616415]: A form of familial adenomatous polyposis, a condition characterized by the development of multiple colorectal adenomatous polyps, benign neoplasms derived from glandular epithelium. Some affected individuals may develop colorectal carcinoma. {ECO:0000269|PubMed:25938944}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
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;Base-Excision Repair, AP Site Formation;Resolution of Abasic Sites (AP sites);Base Excision Repair;Displacement of DNA glycosylase by APEX1 (Consensus)

Recessive Scores

pRec
0.216

Intolerance Scores

loftool
0.373
rvis_EVS
-0.58
rvis_percentile_EVS
18.59

Haploinsufficiency Scores

pHI
0.754
hipred
N
hipred_score
0.239
ghis
0.544

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.997

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Nthl1
Phenotype
cellular phenotype; homeostasis/metabolism phenotype;

Gene ontology

Biological process
base-excision repair, AP site formation;nucleotide-excision repair, DNA incision, 5'-to lesion;depyrimidination
Cellular component
nucleus;nucleoplasm;mitochondrion
Molecular function
oxidized pyrimidine nucleobase lesion DNA N-glycosylase activity;double-stranded DNA binding;DNA-(apurinic or apyrimidinic site) endonuclease activity;endonuclease activity;protein binding;oxidized purine nucleobase lesion DNA N-glycosylase activity;DNA N-glycosylase activity;metal ion binding;4 iron, 4 sulfur cluster binding;class I DNA-(apurinic or apyrimidinic site) endonuclease activity