MAST3

Chr 19AD

microtubule associated serine/threonine kinase 3

Also known as: DEE108

NCBI Gene: 23031ENSG00000099308UniProt: O60307OMIM: 612258

This gene encodes a serine/threonine kinase that regulates cytoskeleton organization and intracellular signal transduction. Mutations cause developmental and epileptic encephalopathy 108, inherited in an autosomal dominant pattern, predominantly through loss-of-function mechanisms. The gene shows extreme intolerance to loss-of-function variants, consistent with haploinsufficiency being pathogenic.

OMIMResearchSummary from RefSeq, OMIM, Mechanism
GOFmechanismADLOEUF 0.221 OMIM phenotype
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 unique Pathogenic / Likely Pathogenic· 209 VUS of 334 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
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
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
LoF OE0.11 (0.06–0.22)
0≤0.351.4
Missense OE0.60 (0.56–0.65)
0≤0.61.4
Synonymous OE0.94
0≤1.21.6
LoF obs/exp: 6 / 52.8Missense obs/exp: 510 / 849.2Syn Z: 0.86
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateMAST3-related developmental and epileptic encephalopathyGOFAD
DN
0.5180th %ile
GOF
0.5954th %ile
LOF
0.70top 10%

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

LOFprediction above median · LOEUF 0.22
GOF1 literature citation

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.

Literature Evidence

GOFThese findings suggest the patient-specific variants may confer MAST3 gain-of-function.PMID:34185323

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

334 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic3
VUS209
Likely Benign54
Benign8
Conflicting2
13
Pathogenic
3
Likely Pathogenic
209
VUS
54
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
12
189
7
1
209
Likely Benign
0
37
3
14
54
Benign
0
3
2
3
8
Conflicting
—2
Total122372018289

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
The Role of Microtubule Associated Serine/Threonine Kinase 3 Variants in Neurodevelopmental Diseases: Genotype-Phenotype Association
Shu L et al.·Front Mol Neurosci
2022
PSMA4 as a Druggable Target in Hidradenitis Suppurativa: Evidence From Mendelian Randomization and Single-Cell Transcriptomics.
Guo S et al.·Mediators Inflamm
2026
New Insights on Nucleotide Sequence Variants and mRNA Levels of Candidate Genes Assessing Resistance/Susceptibility to Mastitis in Holstein and Montbeliarde Dairy Cows
Essa B et al.·Vet Sci
2023
Dynamic genetic regulation of CD4+ T cells in obstructive sleep apnea: integrating context-specific eQTL, Mendelian randomization, single-cell sequencing, and experimental validation.
Zhang X et al.·Front Immunol
2025
Deep multilayer brain omics identifies the potential involvement of menopause molecular networks in Gliomas' disease progression.
Liu C et al.·FASEB J
2022
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients