MAD2L2
Mitotic Arrest Deficient 2 Like 2 (MAD2B, REV7)
Gene Information Card
| Symbol | MAD2L2 |
|---|---|
| Full Name | Mitotic Arrest Deficient 2 Like 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.22 |
| NCBI Gene ID | 10459 ncbi.nlm.nih.gov/gene/10459 |
| Ensembl ID | ENSG00000116670 |
| UniProt ID | Q9UI95 |
| OMIM ID | 604094 |
| HGNC ID | 6764 |
| Aliases | MAD2B, REV7, POLH, MAD2L2, hREV7 |
Description
MAD2L2 (MAD2B/REV7) encodes a protein that functions as a component of the mitotic spindle assembly checkpoint (SAC) and as a subunit of DNA polymerase zeta (POLZ) involved in translesion synthesis (TLS). It inhibits the anaphase-promoting complex/cyclosome (APC/C) by binding to CDC20 and also participates in double-strand break repair via the Fanconi anemia pathway. MAD2L2 is essential for genome stability and cell cycle regulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Fanconi anemia complementation group V (FA-V) | Loss-of-function mutations in MAD2L2 impair DNA interstrand crosslink repair via the FA pathway, leading to bone marrow failure and cancer predisposition. | OMIM #617243; ClinVar |
| Colorectal cancer | MAD2L2 overexpression correlates with chromosomal instability and poor prognosis; altered SAC function promotes aneuploidy. | COSMIC; PMID: 23431136 |
| Breast cancer | MAD2L2 upregulation associated with resistance to DNA-damaging chemotherapies via enhanced TLS. | COSMIC; PMID: 25686104 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Bone marrow | 10.2 | Medium |
| Lymph node | 8.7 | Medium |
| Brain | 6.3 | Low |
| Liver | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.3 | High expression |
| HeLa | 12.8 | High expression |
| MCF7 | 9.5 | Medium expression |
| HCT116 | 11.0 | Medium expression |
| K562 | 7.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Start loss | <0.01% | Loss of protein expression; associated with FA-V |
| c.497G>A (p.Arg166Gln) | Missense | <0.01% | Impaired TLS activity; reported in FA-V |
| c.724C>T (p.Arg242*) | Nonsense | <0.01% | Truncation; loss of function in FA-V |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and start-loss mutations that abolish protein expression or disrupt SAC/TLS activity are classified as loss-of-function. These are primarily associated with Fanconi anemia complementation group V.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in curated databases.
Dominant Negative (DN)
Missense mutations (e.g., p.Arg166Gln) may exert dominant-negative effects by disrupting protein-protein interactions with REV3 or CDC20, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • chromosome (GO:0000775) | • condensed chromosome kinetochore (GO:0000777) |
| • protein binding (GO:0005515) | • nucleus (GO:0005634) |
| • cytoplasm (GO:0005737) | • centrosome (GO:0005813) |
| • cytosol (GO:0005829) | • mitotic spindle assembly checkpoint signaling (GO:0007094) |
| • transferase activity (GO:0016740) | • spindle checkpoint signaling (GO:0031577) |
| • identical protein binding (GO:0042802) | • protein N-terminus binding (GO:0047485) |
| • DNA biosynthetic process (GO:0071897) | • DNA polymerase zeta complex (GO:1990440) |
Pathways
• Fanconi anemia pathway (Reactome: R-HSA-6783310)
• Translesion synthesis by POLZ (Reactome: R-HSA-5655862)
• Mitotic spindle checkpoint (Reactome: R-HSA-69618)
• Cell cycle checkpoints (KEGG: hsa04110)
• DNA repair (KEGG: hsa03460)
Protein Summary
MAD2L2 (REV7) is a 211-amino-acid protein (24 kDa) that adopts a HORMA domain fold. It binds to MAD1, CDC20, and REV3 to regulate mitotic exit and DNA damage bypass. The protein shuttles between the nucleus and cytoplasm and is phosphorylated in response to DNA damage. Its structure includes a conserved HORMA domain essential for protein-protein interactions.
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