MAD1L1: Mitotic Arrest Deficient 1 Like 1
Key regulator of the spindle assembly checkpoint and chromosome stability
Gene Information Card
| Symbol | MAD1L1 |
|---|---|
| Full Name | Mitotic Arrest Deficient 1 Like 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 7p22.3 |
| NCBI Gene ID | 8379 ncbi.nlm.nih.gov/gene/8379 |
| Ensembl ID | ENSG00000156970 |
| UniProt ID | Q9Y6D9 |
| OMIM ID | 602686 |
| HGNC ID | 6762 |
| Aliases | MAD1, TP53I9, PIG9, HSMAD1 |
Description
MAD1L1 encodes a component of the mitotic spindle assembly checkpoint (SAC) that prevents anaphase onset until all chromosomes are properly attached to the spindle. It forms a complex with MAD2L1 to inhibit the anaphase-promoting complex/cyclosome (APC/C). Loss of MAD1L1 function leads to chromosome missegregation, aneuploidy, and genomic instability, contributing to tumorigenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | MAD1L1 haploinsufficiency leads to SAC weakening and aneuploidy | PMID: 17681175 |
| Breast cancer | Reduced MAD1L1 expression correlates with chromosomal instability and poor prognosis | PMID: 20010854 |
| Lung cancer | MAD1L1 mutations impair SAC function, promoting tumor progression | PMID: 21901158 |
| Hepatocellular carcinoma | MAD1L1 downregulation associated with aneuploidy and metastasis | PMID: 23034409 |
| Prostate cancer | MAD1L1 loss contributes to genomic instability and aggressive disease | PMID: 25691885 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | Medium |
| Bone marrow | 12.8 | Medium |
| Lymph node | 11.5 | Medium |
| Brain | 8.3 | Low |
| Liver | 6.1 | Low |
| Heart | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 18.7 | Cervical cancer cell line |
| A549 | 14.2 | Lung cancer cell line |
| MCF7 | 12.1 | Breast cancer cell line |
| HEK293 | 10.5 | Embryonic kidney cell line |
| HepG2 | 9.8 | Liver cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.205C>T (p.Arg69Trp) | Missense | 0.02% (gnomAD) | Potential loss of SAC function |
| c.433G>A (p.Gly145Ser) | Missense | 0.01% (gnomAD) | Unknown significance |
| c.1045_1046del (p.Leu349fs) | Frameshift | <0.01% | Loss of function |
| c.1234C>T (p.Arg412*) | Nonsense | <0.01% | Premature truncation, loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations lead to truncated or absent MAD1L1 protein, impairing SAC function and promoting aneuploidy.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
Missense mutations (e.g., p.Arg69Trp) may disrupt MAD1-MAD2 interaction, acting in a dominant-negative manner to weaken SAC.
View complete mutation data：
Gene Ontology (GO)
| • chromosome (GO:0000775) | • condensed chromosome kinetochore (GO:0000777) |
| • condensed nuclear chromosome kinetochore (GO:0000778) | • protein binding (GO:0005515) |
| • nucleus (GO:0005634) | • cytoplasm (GO:0005737) |
| • spindle (GO:0005819) | • cytosol (GO:0005829) |
| • chromosome segregation (GO:0007059) | • mitotic spindle assembly checkpoint (GO:0007094) |
| • spindle checkpoint (GO:0031577) | • cell division (GO:0051301) |
Pathways
• Cell Cycle
• Mitotic (Reactome: R-HSA-69278)
• Mitotic Spindle Checkpoint (Reactome: R-HSA-69618)
• APC/C-mediated degradation of cell cycle proteins (Reactome: R-HSA-174143)
Protein Summary
MAD1L1 is a 718-amino acid protein (UniProt Q9Y6D9) that localizes to unattached kinetochores during mitosis. It recruits and activates MAD2L1, forming the mitotic checkpoint complex (MCC) that inhibits APC/C. The protein contains a coiled-coil domain and a MAD2-binding motif. Post-translational modifications include phosphorylation by Aurora B kinase, which regulates its localization and function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MAD1L1 Knockout HEK293 Cell Line | EDJ-KQ2044 | Human | 8379 | Details Get a Quote |
| MAD1L1 Knockout A-549 Cell Line | EDJ-KQ22092 | Human | 8379 | Details Get a Quote |
| MAD1L1 Knockout HCT 116 Cell Line | EDJ-KQ22093 | Human | 8379 | Details Get a Quote |
| MAD1L1 Knockout HeLa Cell Line | EDJ-KQ22094 | Human | 8379 | Details Get a Quote |
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