Developmental and epileptic encephalopathy 108

Summary

Developmental and epileptic encephalopathy 108 (MONDO:0859314) is a disease caused by MAST3 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: MAST3 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 22

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy 108
Mondo ID	MONDO:0859314
OMIM	620115
DOID	DOID:0070394
UMLS	C5774253
MedGen	1824026
GARD	0026692
Is cancer (heuristic)	no

Data availability: 22 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neurological disease › Mendelian neurodevelopmental disorder › genetic developmental and epileptic encephalopathy › developmental and epileptic encephalopathy 108

Related subtypes (104): developmental and epileptic encephalopathy, 9, developmental and epileptic encephalopathy, 8, developmental and epileptic encephalopathy, 2, multiple congenital anomalies-hypotonia-seizures syndrome 2, developmental and epileptic encephalopathy, 36, developmental and epileptic encephalopathy, 1, developmental and epileptic encephalopathy, 3, developmental and epileptic encephalopathy, 4, microcephaly, seizures, and developmental delay, developmental and epileptic encephalopathy, 5, developmental and epileptic encephalopathy, 7, developmental and epileptic encephalopathy, 11, neonatal-onset encephalopathy with rigidity and seizures, developmental and epileptic encephalopathy, 14, developmental and epileptic encephalopathy, 15, developmental and epileptic encephalopathy, 17, developmental and epileptic encephalopathy, 18, developmental and epileptic encephalopathy, 19, developmental and epileptic encephalopathy, 23, developmental and epileptic encephalopathy, 27, developmental and epileptic encephalopathy, 30, developmental and epileptic encephalopathy, 50, developmental and epileptic encephalopathy, 35, developmental and epileptic encephalopathy, 37, developmental and epileptic encephalopathy, 38, developmental and epileptic encephalopathy, 40, developmental and epileptic encephalopathy, 48, developmental and epileptic encephalopathy, 49, developmental and epileptic encephalopathy, 51, Lennox-Gastaut syndrome, developmental and epileptic encephalopathy 91, developmental and epileptic encephalopathy 92, developmental and epileptic encephalopathy 93, developmental and epileptic encephalopathy 96, developmental and epileptic encephalopathy, 90, developmental and epileptic encephalopathy, 85, with or without midline brain defects, developmental and epileptic encephalopathy, 67, developmental and epileptic encephalopathy, 86, developmental and epileptic encephalopathy, 87, developmental and epileptic encephalopathy, 88, developmental and epileptic encephalopathy 6B, developmental and epileptic encephalopathy 97, developmental and epileptic encephalopathy 98, developmental and epileptic encephalopathy 99, developmental and epileptic encephalopathy 100, developmental and epileptic encephalopathy 101, developmental and epileptic encephalopathy 89, developmental and epileptic encephalopathy 102, developmental and epileptic encephalopathy 103, developmental and epileptic encephalopathy 104, developmental and epileptic encephalopathy 105 with hypopituitarism, developmental and epileptic encephalopathy 106, developmental and epileptic encephalopathy 107, developmental and epileptic encephalopathy, 68, developmental and epileptic encephalopathy, 69, developmental and epileptic encephalopathy, 70, developmental and epileptic encephalopathy, 71, developmental and epileptic encephalopathy, 72, developmental and epileptic encephalopathy, 74, developmental and epileptic encephalopathy, 75, developmental and epileptic encephalopathy, 76, developmental and epileptic encephalopathy, 77, developmental and epileptic encephalopathy, 78, developmental and epileptic encephalopathy, 79, developmental and epileptic encephalopathy, 80, developmental and epileptic encephalopathy, 81, developmental and epileptic encephalopathy, 82, developmental and epileptic encephalopathy, 83, developmental and epileptic encephalopathy, 84, developmental and epileptic encephalopathy, 52, developmental and epileptic encephalopathy, 53, developmental and epileptic encephalopathy, 54, developmental and epileptic encephalopathy, 55, developmental and epileptic encephalopathy, 56, developmental and epileptic encephalopathy, 57, developmental and epileptic encephalopathy, 58, developmental and epileptic encephalopathy, 59, developmental and epileptic encephalopathy, 60, developmental and epileptic encephalopathy, 61, developmental and epileptic encephalopathy, 62, developmental and epileptic encephalopathy, 63, developmental and epileptic encephalopathy, 64, developmental and epileptic encephalopathy, 65, developmental and epileptic encephalopathy, 73, developmental and epileptic encephalopathy, 66, developmental and epileptic encephalopathy, 6A, non-neonatal early infantile epileptic encephalopathy, Dravet syndrome, neonatal-onset developmental and epileptic encephalopathy, hemiplegic migraine-developmental and epileptic encephalopathy spectrum, DNM1-encephalopathy and neurodevelopmental disorder, TMEM63B-related developmental and epileptic encephalopathy with anemia, developmental and epileptic encephalopathy 109, developmental and epileptic encephalopathy 110, developmental and epileptic encephalopathy 111, developmental and epileptic encephalopathy 112, developmental and epileptic encephalopathy 113, developmental and epileptic encephalopathy 114, developmental and epileptic encephalopathy 115, developmental and epileptic encephalopathy 116, developmental and epileptic encephalopathy 118, developmental and epileptic encephalopathy 120, developmental and epileptic encephalopathy 121, developmental and epileptic encephalopathy 119

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

22 retrieved; paginated sample, class counts are floors:

15 uncertain significance, 4 pathogenic, 1 conflicting classifications of pathogenicity, 1 likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1723192	NM_001393504.1(MAST3):c.1630G>A (p.Gly544Ser)	MAST3	Pathogenic	criteria provided, multiple submitters, no conflicts
1723193	NM_001393504.1(MAST3):c.1634T>C (p.Leu545Pro)	MAST3	Pathogenic	no assertion criteria provided
1723194	NM_001393504.1(MAST3):c.1738G>T (p.Val580Leu)	MAST3	Pathogenic	no assertion criteria provided
1723195	NM_001393504.1(MAST3):c.1304G>C (p.Arg435Pro)	MAST3	Pathogenic	no assertion criteria provided
3370513	NM_001393504.1(MAST3):c.3895G>T (p.Asp1299Tyr)	MAST3	Likely pathogenic	criteria provided, single submitter
1172537	NM_001393504.1(MAST3):c.1615G>A (p.Gly539Ser)	MAST3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4056605	NM_001393504.1(MAST3):c.422G>A (p.Arg141His)	LOC126862876	Uncertain significance	criteria provided, single submitter
2215710	NM_001393504.1(MAST3):c.2338C>T (p.Arg780Trp)	MAST3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2472151	NM_001393504.1(MAST3):c.2137G>A (p.Glu713Lys)	MAST3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2692301	NM_001393504.1(MAST3):c.1304G>A (p.Arg435His)	MAST3	Uncertain significance	criteria provided, single submitter
3065978	NM_001393504.1(MAST3):c.1747C>T (p.Arg583Cys)	MAST3	Uncertain significance	criteria provided, single submitter
3068155	NM_001393504.1(MAST3):c.2612G>A (p.Arg871His)	MAST3	Uncertain significance	criteria provided, single submitter
3254810	NM_001393504.1(MAST3):c.913A>G (p.Ile305Val)	MAST3	Uncertain significance	criteria provided, single submitter
3362297	NM_001393504.1(MAST3):c.1102G>A (p.Glu368Lys)	MAST3	Uncertain significance	criteria provided, multiple submitters, no conflicts
3391077	NM_001393504.1(MAST3):c.2680C>T (p.Arg894Cys)	MAST3	Uncertain significance	criteria provided, single submitter
3731476	NM_001393504.1(MAST3):c.1876A>G (p.Ile626Val)	MAST3	Uncertain significance	criteria provided, single submitter
3731496	NM_001393504.1(MAST3):c.1350T>G (p.Phe450Leu)	MAST3	Uncertain significance	criteria provided, single submitter
3766700	NM_001393504.1(MAST3):c.2884G>C (p.Asp962His)	MAST3	Uncertain significance	criteria provided, single submitter
3773722	NM_001393504.1(MAST3):c.905T>C (p.Leu302Pro)	MAST3	Uncertain significance	criteria provided, single submitter
4079245	NM_001393504.1(MAST3):c.3109G>A (p.Gly1037Arg)	MAST3	Uncertain significance	criteria provided, single submitter
4533268	NM_001393504.1(MAST3):c.3298C>T (p.Arg1100Trp)	MAST3	Uncertain significance	criteria provided, single submitter
4819561	NM_001393504.1(MAST3):c.2510C>T (p.Pro837Leu)	MAST3	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
MAST3	Strong	Autosomal dominant	developmental and epileptic encephalopathy 108	2

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MAST3	HGNC:19036	ENSG00000099308	O60307	Microtubule-associated serine/threonine-protein kinase 3	gencc,clinvar

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MAST3	Kinase	yes		Prot_kinase_dom, AGC-kinase_C, PDZ

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 10	1
frontal pole	1
middle frontal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MAST3	256	ubiquitous	marker	frontal pole, Brodmann (1909) area 10, middle frontal gyrus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAST3	968

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MAST3	O60307	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cytoskeleton organization	1	132.7×	0.015	MAST3
intracellular signal transduction	1	38.1×	0.026	MAST3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MAST3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
MAST3	38	Binding:38

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	MAST3
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
MAST3	38	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.