MAST3

Chr 19AD

microtubule associated serine/threonine kinase 3

Also known as: DEE108

NCBI Gene: 23031ENSG00000099308UniProt: O60307

Predicted to enable protein serine/threonine kinase activity. Predicted to be involved in cytoskeleton organization and intracellular signal transduction. Predicted to be located in cytoplasm. Implicated in developmental and epileptic encephalopathy 108. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 108MIM #620115
AD
282
ClinVar variants
16
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— MAST3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 207 VUS of 282 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.22LOEUF
pLI 1.000
Z-score 5.97
OE 0.11 (0.06–0.22)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
4.14Z-score
OE missense 0.60 (0.56–0.65)
510 obs / 849.2 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.11 (0.06–0.22)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.60 (0.56–0.65)
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.0.94
0≤1.21.6
LoF obs/exp: 6 / 52.8Missense obs/exp: 510 / 849.2Syn Z: 0.86

ClinVar Variant Classifications

282 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic3
VUS207
Likely Benign49
Benign8
Conflicting2
13
Pathogenic
3
Likely Pathogenic
207
VUS
49
Likely Benign
8
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
5
8
0
13
Likely Pathogenic
0
3
0
0
3
VUS
9
187
10
1
207
Likely Benign
0
34
3
12
49
Benign
0
3
2
3
8
Conflicting
—2
Total92322316282

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

View in ClinVar →

Protein Context — Lollipop Plot

MAST3 · protein map & ClinVar variants

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

Gene2Phenotype Curations

MAST3-related developmental and epileptic encephalopathy

moderate
ADGain Of FunctionAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variant

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Developmental and epileptic encephalopathy 108

MIM #620115

Molecular basis of disorder known

Autosomal dominant
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
Pathogenic MAST3 Variants in the STK Domain Are Associated with Epilepsy.
Spinelli E et al.·Ann Neurol
2021
Microtubule associated serine/threonine kinase-3 inhibits the malignant phenotype of breast cancer by promoting phosphorylation-mediated ubiquitination degradation of yes-associated protein.
Deng N et al.·Breast Cancer Res
2025
Genetic landscape of Rett syndrome-like phenotypes revealed by whole exome sequencing.
Iwama K et al.·J Med Genet
2019
MAST3: a novel IBD risk factor that modulates TLR4 signaling.
Labbé C et al.·Genes Immun
2008
Epigenome-Wide Study Identified Methylation Sites Associated with the Risk of Obesity.
Nikpay M et al.·Nutrients
2021
Integration of global spectral karyotyping, CGH arrays, and expression arrays reveals important genes in the pathogenesis of glioblastoma multiforme.
Leone PE et al.·Ann Surg Oncol
2012
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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