MASTL
Chr 10microtubule associated serine/threonine kinase like
Also known as: GREATWALL, GW, GWL, MAST-L, THC2
This gene encodes a serine/threonine kinase that regulates mitosis entry and maintenance by promoting protein phosphatase 2A inactivation during M phase, and may be involved in megakaryocyte differentiation. Mutations cause autosomal dominant thrombocytopenia-2, a bleeding disorder affecting platelet production. The gene shows minimal constraint against loss-of-function variants (pLI near zero), suggesting haploinsufficiency is unlikely to be lethal.
Limited evidence — not for standalone diagnostic reporting
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
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
254 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 11 | 0 | 11 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 2 | 118 | 14 | 6 | 140 |
Likely Benign | 0 | 17 | 7 | 13 | 37 |
Benign | 0 | 10 | 34 | 3 | 47 |
Conflicting | — | 3 | |||
| Total | 2 | 145 | 67 | 22 | 239 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MASTL · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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