MAST2

Chr 1

microtubule associated serine/threonine kinase 2

Also known as: MAST205, MTSSK

NCBI Gene: 23139 ENSG00000086015 UniProt: Q6P0Q8

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.

ResearchSummary from RefSeq, UniProt

Enables phosphatase binding activity. Predicted to be involved in several processes, including protein phosphorylation; regulation of interleukin-12 production; and spermatid differentiation. Predicted to be located in cytoplasm; cytoskeleton; and plasma membrane. Predicted to be active in microtubule cytoskeleton. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.71

Clinical Summary— MAST2

🧬

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.

📋

ClinVar Variants

241 VUS of 305 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.71LOEUF

pLI 0.000

Z-score 3.73

OE 0.55 (0.43–0.71)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.04Z-score

OE missense 0.82 (0.78–0.87)

845 obs / 1029.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.55 (0.43–0.71)

0≤0.351.4

Missense OE?0.82 (0.78–0.87)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 44 / 80.0Missense obs/exp: 845 / 1029.1Syn Z: -0.84

This gene — mechanism propensity

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

305 submitted variants in ClinVar

ClinVar

Classification Summary

VUS241

Likely Benign20

Benign5

241

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	241	0	0	241
Likely Benign	15	0	5	20
Benign	2	1	2	5
Total	258	1	7	266

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

6 pathogenic / likely-pathogenic (of 32) ClinVar copy-number / structural variants overlap MAST2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →