FEN1

Chr 11

flap structure-specific endonuclease 1

Also known as: FEN-1, MF1, RAD2

NCBI Gene: 2237ENSG00000168496UniProt: P39748

The protein encoded by this gene removes 5' overhanging flaps in DNA repair and processes the 5' ends of Okazaki fragments in lagging strand DNA synthesis. Direct physical interaction between this protein and AP endonuclease 1 during long-patch base excision repair provides coordinated loading of the proteins onto the substrate, thus passing the substrate from one enzyme to another. The protein is a member of the XPG/RAD2 endonuclease family and is one of ten proteins essential for cell-free DNA replication. DNA secondary structure can inhibit flap processing at certain trinucleotide repeats in a length-dependent manner by concealing the 5' end of the flap that is necessary for both binding and cleavage by the protein encoded by this gene. Therefore, secondary structure can deter the protective function of this protein, leading to site-specific trinucleotide expansions. [provided by RefSeq, Jul 2008]

47
ClinVar variants
8
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— FEN1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 37 VUS of 47 total submissions

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.
1.28LOEUF
pLI 0.000
Z-score 0.91
OE 0.71 (0.41–1.28)
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.
1.36Z-score
OE missense 0.75 (0.66–0.85)
169 obs / 226.7 exp
Tolerant

Mild missense constraint

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.0.71 (0.41–1.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.66–0.85)
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.0.76
0≤1.21.6
LoF obs/exp: 8 / 11.3Missense obs/exp: 169 / 226.7Syn Z: 1.78

ClinVar Variant Classifications

47 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic3
VUS37
Likely Benign2
5
Pathogenic
3
Likely Pathogenic
37
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
3
0
3
VUS
0
35
2
0
37
Likely Benign
0
0
1
1
2
Benign
0
0
0
0
0
Total03511147

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

View in ClinVar →

Protein Context — Lollipop Plot

FEN1 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors.
Murai J et al.·Cancer Res
2012
Down-regulation of DNA key protein-FEN1 inhibits OSCC growth by affecting immunosuppressive phenotypes via IFN-γ/JAK/STAT-1.
Wang S et al.·Int J Oral Sci
2023
Inhibition of the FEN1-PBX1 axis elicits cellular senescence in breast cancer via the increased intracellular reactive oxygen species levels.
Wu M et al.·J Transl Med
2025
Application and development of biosensing strategies for the analysis of the activity of the tumour-associated enzyme FEN1.
Chen S et al.·Talanta
2025Review
Molecular autopsy in maternal-fetal medicine.
Shamseldin HE et al.·Genet Med
2018
Ultrasensitive Detection of FEN1 Activity for Cancer Diagnosis Using a CRISPR/Cas13a-Based Triple Cascade Amplification System.
Cheng X et al.·Adv Healthc Mater
2025
FEN1-assisted LAMP for specific and multiplex detection of pathogens associated with community-acquired pneumonia.
Teng G et al.·Analyst
2025
Correlation of senescence-related gene FEN1 on neuroblastoma progression and cisplatin chemotherapy sensitivity.
Hu Y et al.·Oncol Res
2025
The endonuclease FEN1 mediates activation of STAT3 and facilitates proliferation and metastasis in breast cancer.
Wu M et al.·Mol Biol Rep
2024
Discovery of new inhibitors of nuclease MRE11.
Nikulenkov F et al.·Eur J Med Chem
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
A FEN1-EDCR dual-amplification strategy for ultrasensitive detection of CHCHD10 c.176C>T mutation.
Pan H et al.·Biosens Bioelectron
2026
An ultrasensitive FEN1-aided LCR-electrochemical biosensor enables detection of BCR/ABL1 fusion transcripts in clinical samples for early diagnosis and minimal residual monitoring of CML.
Yang LY et al.·Biosens Bioelectron
2026
DNA Flap-Controlled CRISPR/Cas12a Trans-Cleavage Enables Mix-and-Read FEN1 Activity Detection.
Ding S et al.·Anal Chem
2026
Giardia duodenalis: Base excision repair pathway enzyme FEN1 carries out catalytic activities pertaining to NER pathway.
García-Lepe UO et al.·Biochimie
2026
N-α-Acetyltransferase 40 promotes oral squamous cell carcinoma progression by enhancing FEN1 transcription and suppressing CD8+ T cell antitumor immunity.
Jiao K et al.·Cell Signal
2026
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools