OGG1

Chr 3

8-oxoguanine DNA glycosylase

Also known as: HMMH, HOGG1, MUTM, OGH1

NCBI Gene: 4968ENSG00000114026UniProt: O15527

This gene encodes the enzyme responsible for the excision of 8-oxoguanine, a mutagenic base byproduct which occurs as a result of exposure to reactive oxygen. The action of this enzyme includes lyase activity for chain cleavage. Alternative splicing of the C-terminal region of this gene classifies splice variants into two major groups, type 1 and type 2, depending on the last exon of the sequence. Type 1 alternative splice variants end with exon 7 and type 2 end with exon 8. All variants share the N-terminal region in common, which contains a mitochondrial targeting signal that is essential for mitochondrial localization. Many alternative splice variants for this gene have been described, but the full-length nature for every variant has not been determined. [provided by RefSeq, Aug 2008]

Primary Disease Associations & Inheritance

Renal cell carcinoma, clear cell, somaticMIM #144700
218
ClinVar variants
47
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— OGG1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
47 Pathogenic / Likely Pathogenic· 152 VUS of 218 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.30LOEUF
pLI 0.000
Z-score 0.49
OE 0.89 (0.62–1.30)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.57Z-score
OE missense 1.10 (1.00–1.22)
271 obs / 245.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.89 (0.62–1.30)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.10 (1.00–1.22)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.15
0≤1.21.6
LoF obs/exp: 19 / 21.5Missense obs/exp: 271 / 245.8Syn Z: -1.21

ClinVar Variant Classifications

218 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic44
Likely Pathogenic3
VUS152
Likely Benign15
Benign4
44
Pathogenic
3
Likely Pathogenic
152
VUS
15
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
44
0
44
Likely Pathogenic
0
0
3
0
3
VUS
0
134
18
0
152
Likely Benign
0
8
2
5
15
Benign
0
2
0
2
4
Total0144677218

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

View in ClinVar →

Protein Context — Lollipop Plot

OGG1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Renal cell carcinoma, clear cell, somatic

MIM #144700

Molecular basis of disorder known

📖
GeneReview available — OGG1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Base Excision Repair: Mechanisms and Impact in Biology, Disease, and Medicine.
Gohil D et al.·Int J Mol Sci
2023Review
Inhibition of OGG1 ameliorates pulmonary fibrosis via preventing M2 macrophage polarization and activating PINK1-mediated mitophagy.
Wu W et al.·Mol Med
2024
The Neuroprotective Potential of Vitamin D(3).
Pietruszkiewicz J et al.·Nutrients
2025Review
OGG1: An emerging multifunctional therapeutic target for the treatment of diseases caused by oxidative DNA damage.
Zhong Y et al.·Med Res Rev
2024Review
Current concept of photocarcinogenesis.
Nishisgori C·Photochem Photobiol Sci
2015Review
OGG1 Mutations and Risk of Female Breast Cancer: Meta-Analysis and Experimental Data.
Ali K et al.·Dis Markers
2015Meta-analysis
OGG1-driven pathogenesis in Kawasaki disease: Identification and pharmacological regulation of a molecular marker validated in transgenic mice and clinical models.
Yun X et al.·Pharmacol Res
2025Functional
OGG1 augments the transcriptional activation of Foxp3 to promote iTreg differentiation for IBD alleviation.
Tian M et al.·Proc Natl Acad Sci U S A
2025
Molecular basis of asbestos-induced lung disease.
Liu G et al.·Annu Rev Pathol
2013Review
Modulation of OGG1 enzymatic activities by small molecules, promising tools and current challenges.
Renaudin X et al.·DNA Repair (Amst)
2025Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
OGG1 and MUTYH DNA Glycosylases, the Dynamic Duo Against 8-Oxoguanine DNA Lesion: Structure, Regulation, and Novel Emerging Roles.
Gómez-Ramírez AP et al.·Biomolecules
2026
African swine fever virus DEAD-box helicase D1133L promotes OGG1-driven incision of genomic 8-oxoG via HDAC5 deacetylation.
Fan J et al.·J Mol Cell Biol
2026🔓 Open Access
A coordinated haptic mechanism ensures efficient DNA sampling by the 8-oxoguanine glycosylase OGG1.
Martinez M et al.·Cell Rep
2026Functional
Investigating the Extent of mRNAs of the Genes Associated with Apoptosis and OGG1 in the Gingival Connective Tissue of Patients Suffering from Chronic Periodontitis and Diabetes Mellitus.
Kalbassi S et al.·Asian Pac J Cancer Prev
2026Cohort
miR-103a regulates DNA repair capacity in human astrocytes under oxidative stress through direct OGG1 targeting.
Nwokwu CDO et al.·Mol Biol Rep
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Colorectal Cancer

Diet Modulation of Bacterial Sulfur and Bile Acid Metabolism and Colon Cancer Risk

ENROLLING BY INVITATION
NCT03550885Phase NAUniversity of Illinois at ChicagoStarted 2018-08-01
High taurine and saturated fat dietLow in taurine and saturated fat diet

External Resources

Links to major genomics databases and tools