MAST2

Chr 1

microtubule associated serine/threonine kinase 2

Also known as: MAST205, MTSSK

NCBI Gene: 23139ENSG00000086015UniProt: Q6P0Q8

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]

295
ClinVar variants
6
Pathogenic / LP
0.00
pLI score
0
Active trials
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
6 Pathogenic / Likely Pathogenic· 260 VUS of 295 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.71LOEUF
pLI 0.000
Z-score 3.73
OE 0.55 (0.43–0.71)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.55 (0.43–0.71)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.78–0.87)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.05
0≤1.21.6
LoF obs/exp: 44 / 80.0Missense obs/exp: 845 / 1029.1Syn Z: -0.84

ClinVar Variant Classifications

295 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic2
VUS260
Likely Benign23
Benign6
4
Pathogenic
2
Likely Pathogenic
260
VUS
23
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
2
0
2
VUS
0
239
21
0
260
Likely Benign
0
14
4
5
23
Benign
0
2
2
2
6
Total0255337295

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

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Mutations in MAST1 Cause Mega-Corpus-Callosum Syndrome with Cerebellar Hypoplasia and Cortical Malformations.
Tripathy R et al.·Neuron
2018
Identification of fusions with potential clinical significance in melanoma.
Moran JMT et al.·Mod Pathol
2022
High MAST2 mRNA expression and its role in diagnosis and prognosis of liver cancer.
Jiao Y et al.·Sci Rep
2019
A rare coding mutation in the MAST2 gene causes venous thrombosis in a French family with unexplained thrombophilia: The Breizh MAST2 Arg89Gln variant.
Morange PE et al.·PLoS Genet
2021
Rare-variant association analysis reveals known and new age-related hearing loss genes.
Cornejo-Sanchez DM et al.·Eur J Hum Genet
2023
Whole-genome sequencing of phenotypically distinct inflammatory breast cancers reveals similar genomic alterations to non-inflammatory breast cancers.
Li X et al.·Genome Med
2021
Functionally recurrent rearrangements of the MAST kinase and Notch gene families in breast cancer.
Robinson DR et al.·Nat Med
2011Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Novel SZT2::MAST2 Fusion Detected in Salivary Duct Carcinoma.
Bedeir A et al.·Case Rep Pathol
2025🔓 Open Access
Characterization of Mast2 kinase defines structural features, regulation, and substrates.
Lemke MC et al.·J Biol Chem
2025🔓 Open Access
Cellular phospho-signaling map of the enigmatic serine/threonine kinase MAST2.
Fathima I et al.·Biochem Biophys Rep
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools