FEN1

flap structure-specific endonuclease 1

Basic information

Region (hg38): 11:61792910-61797238

Previous symbols: [ "RAD2" ]

Links

ENSG00000168496 ∙ NCBI:2237 ∙ OMIM:600393 ∙ HGNC:3650 ∙ Uniprot:P39748 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FEN1 gene.

• Inborn genetic diseases (7 variants)
• not provided (1 variants)
• Hereditary breast ovarian cancer syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FEN1 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			9			9
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	9	0	0

Variants in FEN1

This is a list of pathogenic ClinVar variants found in the FEN1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-61795501-G-A		not specified	Uncertain significance (Oct 05, 2022)
11-61795593-G-A		not specified	Uncertain significance (Feb 16, 2023)
11-61795654-C-T		not specified	Uncertain significance (Mar 17, 2023)
11-61795672-G-A		Hereditary breast ovarian cancer syndrome	Uncertain significance (Aug 01, 2020)
11-61795747-G-A		not specified	Uncertain significance (Jan 24, 2024)
11-61795930-T-C			Uncertain significance (Apr 08, 2021)
11-61796065-G-A		Non-immune hydrops fetalis	Uncertain significance (Apr 29, 2021)
11-61796077-G-A		not specified	Uncertain significance (Mar 11, 2024)
11-61796257-G-A		not specified	Uncertain significance (Apr 18, 2023)
11-61796308-T-A		not specified	Uncertain significance (Sep 07, 2022)
11-61796325-C-T		not specified	Uncertain significance (Mar 22, 2022)
11-61796356-G-A		not specified	Uncertain significance (Nov 13, 2023)
11-61796403-G-A		not specified	Uncertain significance (Feb 28, 2024)
11-61796463-G-A		not specified	Uncertain significance (Apr 07, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FEN1	protein_coding	protein_coding	ENST00000305885	1	4608

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000477	0.673	125730	0	17	125747	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.36	169	227	0.745	0.0000139	2500
Missense in Polyphen		34	67.984	0.50012		670
Synonymous	1.78	67	88.3	0.759	0.00000491	766
Loss of Function	0.905	8	11.3	0.709	7.51e-7	124

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.0000996	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000528	0.0000527
Middle Eastern	0.0000544	0.0000544
South Asian	0.000229	0.000229
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Structure-specific nuclease with 5'-flap endonuclease and 5'-3' exonuclease activities involved in DNA replication and repair. During DNA replication, cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. It enters the flap from the 5'-end and then tracks to cleave the flap base, leaving a nick for ligation. Also involved in the long patch base excision repair (LP-BER) pathway, by cleaving within the apurinic/apyrimidinic (AP) site-terminated flap. Acts as a genome stabilization factor that prevents flaps from equilibrating into structurs that lead to duplications and deletions. Also possesses 5'-3' exonuclease activity on nicked or gapped double- stranded DNA, and exhibits RNase H activity. Also involved in replication and repair of rDNA and in repairing mitochondrial DNA. {ECO:0000255|HAMAP-Rule:MF_03140, ECO:0000269|PubMed:10744741, ECO:0000269|PubMed:11986308, ECO:0000269|PubMed:18443037, ECO:0000269|PubMed:20729856, ECO:0000269|PubMed:7961795, ECO:0000269|PubMed:8621570}.
• Pathway: Base excision repair - Homo sapiens (human);DNA replication - Homo sapiens (human);Non-homologous end-joining - Homo sapiens (human);HDR through MMEJ (alt-NHEJ);DNA Repair;Disease;DNA Double-Strand Break Repair;HIV Life Cycle;HIV Infection;Homology Directed Repair;Infectious disease;DNA Replication;Removal of the Flap Intermediate;Processive synthesis on the lagging strand;Lagging Strand Synthesis;DNA strand elongation;Synthesis of DNA;POLB-Dependent Long Patch Base Excision Repair;S Phase;PCNA-Dependent Long Patch Base Excision Repair;Resolution of AP sites via the multiple-nucleotide patch replacement pathway;Resolution of Abasic Sites (AP sites);Base Excision Repair;Removal of the Flap Intermediate from the C-strand;Processive synthesis on the C-strand of the telomere;Telomere C-strand (Lagging Strand) Synthesis;Extension of Telomeres;Telomere Maintenance;Chromosome Maintenance;Cell Cycle;Cell Cycle, Mitotic;Early Phase of HIV Life Cycle (Consensus)

Recessive Scores

• pRec: 0.543

Intolerance Scores

• loftool: 0.701
• rvis_EVS: -0.12
• rvis_percentile_EVS: 44.89

Haploinsufficiency Scores

• pHI: 0.974
• hipred: Y
• hipred_score: 0.813
• ghis: 0.696

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.976

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Fen1
• Phenotype: neoplasm; hematopoietic system phenotype; reproductive system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); liver/biliary system phenotype; respiratory system phenotype; embryo phenotype; renal/urinary system phenotype; immune system phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: fen1
• Affected structure: anatomical system
• Phenotype tag: abnormal
• Phenotype quality: quality

Gene ontology

• Biological process: double-strand break repair via homologous recombination;DNA replication;base-excision repair;double-strand break repair;UV protection;telomere maintenance via semi-conservative replication;DNA replication, removal of RNA primer;positive regulation of sister chromatid cohesion;nucleic acid phosphodiester bond hydrolysis;RNA phosphodiester bond hydrolysis, endonucleolytic
• Cellular component: nuclear chromosome, telomeric region;nucleus;nucleoplasm;nucleolus;mitochondrion;membrane;protein-containing complex
• Molecular function: magnesium ion binding;DNA binding;damaged DNA binding;double-stranded DNA binding;endonuclease activity;RNA-DNA hybrid ribonuclease activity;exonuclease activity;protein binding;double-stranded DNA exodeoxyribonuclease activity;5'-3' exonuclease activity;5'-flap endonuclease activity;manganese ion binding;flap endonuclease activity