MAD2L1
protein-codingmitotic arrest deficient 2 like 1
Gene summary
MAD2L1 is a component of the mitotic spindle assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. MAD2L1 is related to the MAD2L2 gene located on chromosome 1. A MAD2 pseudogene has been mapped to chromosome 14. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MAD2L1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002358.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 4 | ||||
| missense | 13 | 1 | 14 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 13 | 4 | 1 | 18 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002349.1 | 5 | MANE Select | |
| Ensembl | ENSP00000296509.5 | 5 | MANE Select | |
| Ensembl | ENSP00000332295.5 | 3 | Standard | |
| Ensembl | ENSP00000425702.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cell cycle - Homo sapiens (human)
- Oocyte meiosis - Homo sapiens (human)
- HTLV-I infection - Homo sapiens (human)
- Progesterone-mediated oocyte maturation - Homo sapiens (human)
- Cell Cycle
Biological Process
- mitotic sister chromatid segregation
- mitotic cell cycle checkpoint
- mitotic spindle assembly checkpoint
- anaphase-promoting complex-dependent catabolic process
- negative regulation of protein catabolic process
Molecular Function
- protein binding
- protein C-terminus binding
- identical protein binding
- protein homodimerization activity
Cellular Component
- kinetochore
- condensed chromosome kinetochore
- spindle pole
- nucleus
- nucleoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000296509
- Coding exons
- 5
- Length
- 11467
- Individuals with no LoFs
- 125735
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 125745
- p
- 0.0000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.06 | 79 | 110 | 0.717 | 0.00000571 | 1317 |
| Missense (PolyPhen) | 12 | 29.84 | 0.40215 | 379 | ||
| Synonymous | 0.569 | 37 | 41.7 | 0.888 | 0.00000213 | 399 |
| Loss of Function | 1.73 | 5 | 11.2 | 0.445 | 5.20e-7 | 135 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0.00017 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. Required for the execution of the mitotic checkpoint which monitors the process of kinetochore- spindle attachment and inhibits the activity of the anaphase promoting complex by sequestering CDC20 until all chromosomes are aligned at the metaphase plate. {ECO:0000269|PubMed:10700282, ECO:0000269|PubMed:11804586, ECO:0000269|PubMed:15024386}.;
Recessive Scores
- pRec
- 0.156
Intolerance Scores
- LoFtool
- 0.304
- RVIS EVS
- 0.04
- RVIS percentile EVS
- 56.64
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.989
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |