FANCM Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the FANCM gene, its role in DNA repair, associated diseases, and expression patterns.
Gene Information Card
| Symbol | FANCM |
|---|---|
| Full Name | FA complementation group M |
| Gene Type | protein-coding |
| Chromosomal Location | 14q21.2 |
| NCBI Gene ID | 57697 ncbi.nlm.nih.gov/gene/57697 |
| Ensembl ID | ENSG00000187790 |
| UniProt ID | Q8IYD8 |
| OMIM ID | 609644 |
| HGNC ID | 23168 |
| Aliases | KIAA1596, FAAP250, hMM2 |
Description
The FANCM gene encodes a protein that is a core component of the Fanconi anemia (FA) core complex. This protein possesses DNA helicase and ATPase activities and plays a critical role in the repair of DNA interstrand crosslinks (ICLs) and the maintenance of genomic stability. FANCM is involved in the activation of the FA/BRCA pathway, which coordinates DNA repair, cell cycle checkpoints, and replication fork stability. Mutations in FANCM have been associated with Fanconi anemia complementation group M and increased susceptibility to breast cancer and other cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Fanconi anemia complementation group M | Loss-of-function mutations impair DNA interstrand crosslink repair, leading to chromosomal instability and bone marrow failure. | OMIM: 609644; ClinVar |
| Breast cancer | Truncating variants (e.g., p.R1931*) increase breast cancer risk, likely due to defective DNA repair and genomic instability. | ClinVar; COSMIC; multiple case-control studies |
| Ovarian cancer | FANCM mutations may contribute to ovarian cancer susceptibility, though evidence is less robust than for breast cancer. | ClinVar; COSMIC |
| Spermatogenic failure | Biallelic mutations can cause male infertility due to meiotic defects. | OMIM; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.4 | Medium |
| Bone Marrow | 8.2 | Low |
| Lymph Node | 7.5 | Low |
| Spleen | 6.9 | Low |
| Brain | 3.1 | Low |
| Liver | 2.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 | 9.5 | Leukemia cell line; moderate expression |
| HeLa | 7.8 | Cervical cancer; moderate expression |
| MCF7 | 6.2 | Breast cancer; moderate expression |
| A549 | 5.4 | Lung cancer; low expression |
| HepG2 | 4.1 | Liver cancer; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.5791C>T (p.R1931*) | Nonsense | ~0.2% in European populations | Truncated protein; loss of function; associated with breast cancer risk |
| c.1972C>T (p.R658*) | Nonsense | Rare | Loss of function; Fanconi anemia |
| c.5101C>T (p.R1701*) | Nonsense | Rare | Loss of function; breast cancer susceptibility |
| c.3205C>T (p.R1069*) | Nonsense | Rare | Loss of function; Fanconi anemia |
| c.1A>G (p.M1V) | Missense | Rare | Potential loss of function; uncertain significance |
Mutation functional classification
Loss of Function (LOF)
Most FANCM mutations are loss-of-function, leading to impaired DNA crosslink repair and genomic instability.
Gain of Function (GOF)
No gain-of-function mutations have been reported for FANCM.
Dominant Negative (DN)
Some missense variants may exert dominant-negative effects by disrupting the FA core complex, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • DNA helicase activity | • ATPase activity |
| • DNA binding | • protein binding |
| • Fanconi anemia nuclear complex | • nucleus |
| • DNA repair | • interstrand cross-link repair |
| • cell cycle checkpoint | • response to DNA damage stimulus |
Pathways
• Fanconi anemia pathway
• Homologous recombination
• DNA damage response
• Replication fork protection
Protein Summary
The FANCM protein is a 2048-amino-acid helicase that anchors the FA core complex to chromatin. It contains an N-terminal DEAH-box helicase domain and a C-terminal translocase domain. FANCM recognizes stalled replication forks and ICLs, recruits the FA core complex, and promotes FANCD2 ubiquitination, which is essential for downstream repair. It also has a role in meiotic recombination and telomere maintenance.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FANCM Knockout HEK293 Cell Line | EDJ-KQ11356 | Human | 57697 | Details Get a Quote |
| FANCM Knockout A-549 Cell Line | EDJ-KQ40786 | Human | 57697 | Details Get a Quote |
| FANCM Knockout HCT 116 Cell Line | EDJ-KQ40788 | Human | 57697 | Details Get a Quote |
| FANCM Knockout HeLa Cell Line | EDJ-KQ40789 | Human | 57697 | Details Get a Quote |
| FANCM (p.T1339=) Point Mutation in HAP1 Cell Line | EDC03481 | Human | 57697 | Details Get a Quote |
| FANCM (c.1396+26G>A )Point Mutation in HAP1 Cell Line | EDC03480 | Human | 57697 | Details Get a Quote |
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