NTHL1

Chr 16AR

nth like DNA glycosylase 1

Also known as: FAP3, NTH1, OCTS3, hNTH1

NCBI Gene: 4913ENSG00000065057UniProt: P78549OMIM: 602656

NTHL1 encodes a bifunctional DNA N-glycosylase that catalyzes the first step in base excision repair, the primary pathway for repairing oxidative DNA damage, by cleaving damaged pyrimidine bases and associated phosphodiester bonds. Biallelic mutations cause familial adenomatous polyposis 3, characterized by the development of multiple colorectal adenomas that can progress to colorectal cancer. This condition follows autosomal recessive inheritance.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.591 OMIM phenotype
Clinical Summary— NTHL1
🧬
Gene-Disease Validity (ClinGen)
NTHL1-deficiency tumor predisposition syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
14 unique Pathogenic / Likely Pathogenic· 63 VUS of 100 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — NTHL1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.59LOEUF
pLI 0.000
Z-score -0.10
OE 1.03 (0.68–1.59)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.80Z-score
OE missense 1.16 (1.04–1.29)
233 obs / 201.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.03 (0.68–1.59)
0≤0.351.4
Missense OE1.16 (1.04–1.29)
0≤0.61.4
Synonymous OE0.94
0≤1.21.6
LoF obs/exp: 14 / 13.6Missense obs/exp: 233 / 201.2Syn Z: 0.41

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic2
VUS63
Likely Benign23
12
Pathogenic
2
Likely Pathogenic
63
VUS
23
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
7
0
12
Likely Pathogenic
2
0
0
0
2
VUS
0
50
13
0
63
Likely Benign
0
2
11
10
23
Benign
0
0
0
0
0
Total7523110100

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NTHL1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients