FAN1: FANCD2 and FANCI Associated Nuclease 1
A key DNA interstrand crosslink repair nuclease implicated in karyomegalic interstitial nephritis and cancer susceptibility
Gene Information Card
| Symbol | FAN1 |
|---|---|
| Full Name | FANCD2 and FANCI Associated Nuclease 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 15q13.3 |
| NCBI Gene ID | 22909 ncbi.nlm.nih.gov/gene/22909 |
| Ensembl ID | ENSG00000127990 |
| UniProt ID | Q9Y2M0 |
| OMIM ID | 613534 |
| HGNC ID | 29170 |
| Aliases | KIAA1018, MTMR15, FANCD2/FANCI-associated nuclease 1 |
Description
FAN1 encodes a structure-specific nuclease that is recruited to sites of DNA interstrand crosslinks (ICLs) via interaction with the Fanconi anemia core complex proteins FANCD2 and FANCI. It cleaves DNA near the ICL to facilitate repair. Loss-of-function mutations cause karyomegalic interstitial nephritis (KIN) and are associated with increased cancer risk, particularly colorectal and breast cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Karyomegalic interstitial nephritis (KIN) | Biallelic loss-of-function mutations impair ICL repair in renal tubular cells, leading to progressive kidney fibrosis. | OMIM #614817; PMID: 22267198 |
| Fanconi anemia (FA) complementation group? | FAN1 is not a classical FA gene; mutations do not cause FA but can phenocopy some FA features. | OMIM #613534; PMID: 20603074 |
| Colorectal cancer | Heterozygous loss-of-function variants increase susceptibility to colorectal cancer. | PMID: 24448499 |
| Breast cancer | Rare FAN1 variants may contribute to breast cancer risk. | PMID: 27601076 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Testis | 10.8 | Medium |
| Bone marrow | 8.2 | Medium |
| Liver | 6.1 | Low |
| Brain | 3.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | Embryonic kidney cell line |
| HeLa | 9.8 | Cervical carcinoma |
| HCT 116 | 11.5 | Colorectal carcinoma |
| K562 | 7.3 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense/start loss | <0.01% | Loss of protein expression; associated with KIN |
| c.1480C>T (p.Arg494*) | Nonsense | <0.01% | Truncation; loss of nuclease activity; KIN |
| c.2634+1G>A | Splice donor | <0.01% | Splicing defect; loss of function; KIN |
| p.Arg377Trp | Missense | 0.02% | Reduced nuclease activity; colorectal cancer risk |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations cause karyomegalic interstitial nephritis (KIN). Heterozygous loss-of-function increases cancer risk.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Fanconi anemia pathway (Reactome: R-HSA-6783310)
• DNA interstrand crosslink repair (KEGG: hsa03460)
Protein Summary
FAN1 is a 1017-amino acid protein containing a nuclease domain (PD-(D/E)XK) and a UBZ (ubiquitin-binding zinc finger) domain. It localizes to chromatin upon DNA damage and processes ICLs by making incisions 5' and 3' of the crosslink. The protein also interacts with PCNA and is involved in replication fork stability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FAN1 Knockout HEK293 Cell Line | EDJ-KQ7742 | Human | 22909 | Details Get a Quote |
| FAN1 Knockout A-549 Cell Line | EDJ-KQ33173 | Human | 22909 | Details Get a Quote |
| FAN1 Knockout HCT 116 Cell Line | EDJ-KQ33174 | Human | 22909 | Details Get a Quote |
| FAN1 Knockout HeLa Cell Line | EDJ-KQ33175 | Human | 22909 | Details Get a Quote |
