MAST2

Chr 1

microtubule associated serine/threonine kinase 2

Also known as: MAST205, MTSSK

The MAST2 protein kinase links the dystrophin/utrophin network to microtubule filaments and regulates inflammatory signaling pathways, including IL-12 synthesis in immune cells. Biallelic mutations cause a rare neurodevelopmental disorder characterized by intellectual disability, developmental delay, and behavioral abnormalities with autosomal recessive inheritance. This gene is moderately constrained against loss-of-function variants, suggesting haploinsufficiency is tolerated but complete loss of function causes disease.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.71
Clinical SummaryMAST2
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Gene-Disease Validity (ClinGen)
thrombotic disease · ADLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.71LOEUF
pLI 0.000
Z-score 3.73
OE 0.55 (0.430.71)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
2.04Z-score
OE missense 0.82 (0.780.87)
845 obs / 1029.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.55 (0.430.71)
00.351.4
Missense OE0.82 (0.780.87)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 44 / 80.0Missense obs/exp: 845 / 1029.1Syn Z: -0.84
DN
0.7228th %ile
GOF
0.6931th %ile
LOF
0.4429th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

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

MAST2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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