developmental and epileptic encephalopathy, 31A

Summary

developmental and epileptic encephalopathy, 31A (MONDO:0014598) is a disease caused by DNM1 (GenCC Strong), with 5 cohort genes and 1 clinical trial.

At a glance

• Causal gene: DNM1 (GenCC Strong)
• Cohort genes: 5
• ClinVar variants: 795
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy, 31A
Mondo ID	MONDO:0014598
OMIM	616346
DOID	DOID:0080437
UMLS	C4225357
MedGen	894942
GARD	0016094
Is cancer (heuristic)	no

Also known as: DEE31 · DEE31A · developmental and epileptic encephalopathy 31 · developmental and epileptic encephalopathy 31A, autosomal dominant · DNM1 early infantile epileptic encephalopathy · DNM1-encephalopathy and neurodevelopmental disorder · DNM1-related epilepsy and neurodevelopmental disorder · early infantile epileptic encephalopathy caused by mutation in DNM1 · EIEE31 · epileptic encephalopathy, early infantile, 31 · epileptic encephalopathy, early infantile, type 31

Data availability: 795 ClinVar variants · 3 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Lennox-Gastaut syndrome › developmental and epileptic encephalopathy, 31A

Related subtypes (2): developmental and epileptic encephalopathy 94, developmental and epileptic encephalopathy, 43

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

600 retrieved; paginated sample, class counts are floors:

289 likely benign, 219 uncertain significance, 23 conflicting classifications of pathogenicity, 21 benign, 17 pathogenic, 14 benign/likely benign, 12 likely pathogenic, 5 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3245119	NC_000009.11:g.(?130374683)(131329276_?)del	AK1	Pathogenic	criteria provided, single submitter
1056169	NC_000009.11:g.(?129376729)(131016993_?)del	CIZ1	Pathogenic	criteria provided, single submitter
224142	NM_004408.4(DNM1):c.139G>A (p.Val47Met)	CIZ1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1011518	NM_004408.4(DNM1):c.2296C>T (p.Gln766Ter)	DNM1	Pathogenic	criteria provided, single submitter
1386547	NM_004408.4(DNM1):c.767del (p.Arg256fs)	DNM1	Pathogenic	criteria provided, single submitter
1443519	NM_004408.4(DNM1):c.2299dup (p.Ser767fs)	DNM1	Pathogenic	criteria provided, single submitter
1472715	NM_004408.4(DNM1):c.1195A>T (p.Arg399Ter)	DNM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1474244	NM_004408.4(DNM1):c.2434dup (p.Ala812fs)	DNM1	Pathogenic	criteria provided, single submitter
156557	NM_004408.4(DNM1):c.529G>C (p.Ala177Pro)	DNM1	Pathogenic	no assertion criteria provided
156558	NM_004408.4(DNM1):c.618G>C (p.Lys206Asn)	DNM1	Pathogenic	criteria provided, single submitter
156559	NM_004408.4(DNM1):c.1076G>C (p.Gly359Ala)	DNM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1803022	NM_004408.4(DNM1):c.632A>T (p.Asp211Val)	DNM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
190311	NM_004408.4(DNM1):c.865A>T (p.Ile289Phe)	DNM1	Pathogenic	no assertion criteria provided
2094695	NM_004408.4(DNM1):c.1626del (p.Trp542fs)	DNM1	Pathogenic	criteria provided, single submitter
2729722	NM_004408.4(DNM1):c.416G>C (p.Gly139Ala)	DNM1	Pathogenic	criteria provided, single submitter
2755885	NM_004408.4(DNM1):c.197G>C (p.Arg66Pro)	DNM1	Pathogenic	criteria provided, single submitter
280148	NM_004408.4(DNM1):c.709C>T (p.Arg237Trp)	DNM1	Pathogenic	criteria provided, multiple submitters, no conflicts
3245261	NC_000009.11:g.(?130980490)(130996406_?)del	DNM1	Pathogenic	criteria provided, single submitter
3637806	NM_004408.4(DNM1):c.1321C>T (p.Gln441Ter)	DNM1	Pathogenic	criteria provided, single submitter
429529	NM_004408.4(DNM1):c.1335+1638G>A	DNM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3698462	NM_004408.4(DNM1):c.375C>G (p.Tyr125Ter)	LOC113839516	Pathogenic	criteria provided, single submitter
3775929	NM_004408.4(DNM1):c.416G>T (p.Gly139Val)	LOC113839516	Pathogenic	criteria provided, multiple submitters, no conflicts
1067855	NM_004408.4(DNM1):c.1726G>A (p.Glu576Lys)	DNM1	Likely pathogenic	criteria provided, single submitter
1802580	NM_004408.4(DNM1):c.2045C>G (p.Pro682Arg)	DNM1	Likely pathogenic	criteria provided, single submitter
1803020	NM_004408.4(DNM1):c.1943T>C (p.Met648Thr)	DNM1	Likely pathogenic	criteria provided, single submitter
1803021	NM_004408.4(DNM1):c.415_423del (p.Gly139_Thr141del)	DNM1	Likely pathogenic	criteria provided, single submitter
2431369	NM_004408.4(DNM1):c.1076G>A (p.Gly359Glu)	DNM1	Likely pathogenic	criteria provided, single submitter
2585186	NM_004408.4(DNM1):c.2369del (p.Pro790fs)	DNM1	Likely pathogenic	criteria provided, single submitter
2854004	NM_004408.4(DNM1):c.236-2A>C	DNM1	Likely pathogenic	criteria provided, single submitter
3393120	NM_004408.4(DNM1):c.206del (p.Leu69fs)	DNM1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 6 · 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
DNM1	Strong	Autosomal recessive	developmental and epileptic encephalopathy, 31B	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DNM1	Orphanet:2382	Lennox-Gastaut syndrome
DNM1	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
CIZ1	Orphanet:420492	Adult-onset cervical dystonia, DYT23 type
MBD5	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
MBD5	Orphanet:228402	2q23.1 microdeletion syndrome
AK1	Orphanet:86817	Hemolytic anemia due to adenylate kinase deficiency

Cohort genes → proteins

5 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DNM1	HGNC:2972	ENSG00000106976	Q05193	Dynamin-1	gencc,clinvar
CIZ1	HGNC:16744	ENSG00000148337	Q9ULV3	Cip1-interacting zinc finger protein	clinvar
MBD5	HGNC:20444	ENSG00000204406	Q9P267	Methyl-CpG-binding domain protein 5	clinvar
MIR199B	HGNC:31573	ENSG00000207581		microRNA 199b	clinvar
AK1	HGNC:361	ENSG00000106992	P00568	Adenylate kinase isoenzyme 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DNM1	Dynamin-1	Catalyzes the hydrolysis of GTP and utilizes this energy to mediate vesicle scission and participates in many forms of endocytosis, such as clathrin-mediated endocytosis or synaptic vesicle endocytosis as well as rapid endocytosis (RE).
CIZ1	Cip1-interacting zinc finger protein	May regulate the subcellular localization of CIP/WAF1.
MBD5	Methyl-CpG-binding domain protein 5	Non-catalytic component of the polycomb repressive deubiquitinase (PR-DUB) complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at ‘Lys-120’ (H2AK119ub1).
AK1	Adenylate kinase isoenzyme 1	Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP.

Protein-family classification

Druggable: 1 · Difficult: 2 · Unknown: 2 · Druggable fraction: 0.2

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	5.5×	0.515
Scaffold/PPI	1	3.5×	0.515
Transcription factor	1	1.6×	0.634
Other/Unknown	2	0.7×	0.877

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DNM1	Scaffold/PPI	no	3.6.5.5	Dynamin_stalk, Dynamin_GTPase, PH_domain
CIZ1	Transcription factor	no		Matrin/U1-C_Znf_C2H2, Matrin/U1-like-C_Znf_C2H2, Znf_C2H2_type
MBD5	Other/Unknown	no		PWWP_dom, Methyl_CpG_DNA-bd, DNA-bd_dom_sf
MIR199B	Other/Unknown	no
AK1	Kinase	yes	2.7.4.3	Adenylat/UMP-CMP_kin, AK1/5, P-loop_NTPase

Expression context

Cohort genes with no expression data: 0.

4 cohort genes 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar hemisphere	3
right hemisphere of cerebellum	3
cerebellar cortex	1
right ovary	1
adrenal tissue	1
calcaneal tendon	1
sural nerve	1
olfactory segment of nasal mucosa	1
apex of heart	1
gastrocnemius	1
hindlimb stylopod muscle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DNM1	257	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
CIZ1	281	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, right ovary
MBD5	243	ubiquitous	marker	calcaneal tendon, adrenal tissue, sural nerve
MIR199B	87		yes	olfactory segment of nasal mucosa, right hemisphere of cerebellum, cerebellar hemisphere
AK1	144	ubiquitous	marker	apex of heart, hindlimb stylopod muscle, gastrocnemius

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DNM1	3,614
AK1	3,526
CIZ1	2,160
MBD5	1,640
MIR199B	0

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DNM1	Q05193	22
AK1	P00568	5
CIZ1	Q9ULV3	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MBD5	Q9P267	43.20

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. Enrichment computed across 5 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of annular gap junctions	1	346.1×	0.018	DNM1
Gap junction degradation	1	317.2×	0.018	DNM1
Retrograde neurotrophin signalling	1	271.9×	0.018	DNM1
Interconversion of nucleotide di- and triphosphates	1	119.0×	0.029	AK1
Metabolism of nucleotides	1	100.2×	0.029	AK1
Recycling pathway of L1	1	74.6×	0.029	DNM1
EPH-ephrin mediated repulsion of cells	1	73.2×	0.029	DNM1
Toll Like Receptor 4 (TLR4) Cascade	1	43.8×	0.036	DNM1
Deubiquitination	1	41.4×	0.036	MBD5
UCH proteinases	1	41.4×	0.036	MBD5
MHC class II antigen presentation	1	29.7×	0.043	DNM1
Clathrin-mediated endocytosis	1	28.4×	0.043	DNM1
Post-translational protein modification	1	6.4×	0.171	MBD5
Metabolism of proteins	1	4.1×	0.237	MBD5
Metabolism	1	3.9×	0.237	AK1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
clathrin coat assembly involved in endocytosis	1	4213.0×	0.003	DNM1
positive regulation of DNA-templated DNA replication initiation	1	2106.5×	0.003	CIZ1
vesicle scission	1	2106.5×	0.003	DNM1
positive regulation of growth hormone receptor signaling pathway	1	1404.3×	0.004	MBD5
synaptic vesicle budding from presynaptic endocytic zone membrane	1	842.6×	0.005	DNM1
ADP biosynthetic process	1	601.9×	0.005	AK1
regulation of vesicle size	1	601.9×	0.005	DNM1
nucleoside triphosphate biosynthetic process	1	526.6×	0.005	AK1
AMP metabolic process	1	468.1×	0.005	AK1
nucleobase-containing small molecule interconversion	1	421.3×	0.005	AK1
regulation of behavior	1	351.1×	0.006	MBD5
maintenance of protein location in nucleus	1	280.9×	0.007	CIZ1
random inactivation of X chromosome	1	234.1×	0.007	CIZ1
regulation of multicellular organism growth	1	162.0×	0.010	MBD5
ATP metabolic process	1	117.0×	0.012	AK1
endosome organization	1	93.6×	0.015	DNM1
protein homotetramerization	1	59.3×	0.022	DNM1
receptor-mediated endocytosis	1	55.4×	0.022	DNM1
glucose homeostasis	1	32.7×	0.035	MBD5
protein homooligomerization	1	30.5×	0.036	DNM1
endocytosis	1	23.8×	0.043	DNM1
nervous system development	1	11.5×	0.084	MBD5

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 5 evidence-associated genes (40%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
DNM1	CETRIMIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DNM1	4	4
CIZ1	0	0
MBD5	0	0
MIR199B	0	0
AK1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CETRIMIDE	4	DNM1
LATREPIRDINE	3	DNM1
CARAZOLOL	2	DNM1
TAK-901	1	DNM1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
DNM1	11	Binding:11
AK1	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DNM1	3.6.5.5	dynamin GTPase
AK1	2.7.4.3	adenylate kinase

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

4 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.

Compound	Max phase	Cohort target (bioactivity)
CETRIMIDE	4	DNM1
LATREPIRDINE	3	DNM1
CARAZOLOL	2	DNM1
TAK-901	1	DNM1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	DNM1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	AK1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	CIZ1, MBD5, MIR199B

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CIZ1	0	—
MBD5	0	—
MIR199B	0	—
AK1	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford