MIS12
Chr 17MIS12 kinetochore complex component
Also known as: 2510025F08Rik, KNTC2AP, MTW1, hMis12
The MIS12 protein is essential for proper kinetochore formation and chromosome alignment during cell division, ensuring accurate chromosome segregation by facilitating spindle microtubule attachments to kinetochores. Mutations in MIS12 cause Mosaic variegated aneuploidy syndrome 4, an autosomal recessive disorder characterized by growth retardation, intellectual disability, microcephaly, and increased cancer risk due to chromosomal instability. This condition typically presents in early childhood with developmental delays and distinctive facial features.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
MIS12 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools