developmental and epileptic encephalopathy, 31B

Summary

developmental and epileptic encephalopathy, 31B (MONDO:0957248) is a disease caused by DNM1 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: DNM1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy, 31B
Mondo ID	MONDO:0957248
OMIM	620352
DOID	DOID:0070376
UMLS	C5830459
MedGen	1841095
GARD	0026796
Is cancer (heuristic)	no

Also known as: DEE31B · developmental and epileptic encephalopathy 31B, autosomal recessive · DNM1-encephalopathy and neurodevelopmental disorder

Data availability: 6 ClinVar variants · 5 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 › DNM1-encephalopathy and neurodevelopmental disorder › developmental and epileptic encephalopathy, 31B

Related subtypes (1): developmental and epileptic encephalopathy, 31A

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

6 retrieved; paginated sample, class counts are floors:

3 pathogenic, 2 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
2500126	NM_004408.4(DNM1):c.97C>T (p.Gln33Ter)	CIZ1	Pathogenic	no assertion criteria provided
2500127	NM_004408.4(DNM1):c.850C>T (p.Gln284Ter)	DNM1	Pathogenic	criteria provided, multiple submitters, no conflicts
2500128	NM_004408.4(DNM1):c.350del (p.Pro117fs)	DNM1	Pathogenic	no assertion criteria provided
3596459	NM_004408.4(DNM1):c.1402G>A (p.Glu468Lys)	DNM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3359141	NM_004408.4(DNM1):c.2257C>T (p.Pro753Ser)	DNM1	Uncertain significance	criteria provided, single submitter
3359142	NM_004408.4(DNM1):c.2266C>A (p.Pro756Thr)	DNM1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 3 · 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

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

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

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.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 0 · Druggable fraction: 0.0

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
Scaffold/PPI	1	8.6×	0.225
Transcription factor	1	4.1×	0.228

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

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar hemisphere	2
right hemisphere of cerebellum	2
cerebellar cortex	1
right ovary	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DNM1	3,614
CIZ1	2,160

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DNM1	Q05193	22
CIZ1	Q9ULV3	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 2 evidence-associated genes (1 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 1 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	1038.2×	0.003	DNM1
Gap junction degradation	1	951.7×	0.003	DNM1
Retrograde neurotrophin signalling	1	815.7×	0.003	DNM1
Recycling pathway of L1	1	223.9×	0.007	DNM1
EPH-ephrin mediated repulsion of cells	1	219.6×	0.007	DNM1
Toll Like Receptor 4 (TLR4) Cascade	1	131.3×	0.010	DNM1
MHC class II antigen presentation	1	89.2×	0.012	DNM1
Clathrin-mediated endocytosis	1	85.2×	0.012	DNM1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 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	8426.0×	9e-04	DNM1
positive regulation of DNA-templated DNA replication initiation	1	4213.0×	9e-04	CIZ1
vesicle scission	1	4213.0×	9e-04	DNM1
synaptic vesicle budding from presynaptic endocytic zone membrane	1	1685.2×	0.002	DNM1
regulation of vesicle size	1	1203.7×	0.002	DNM1
maintenance of protein location in nucleus	1	561.7×	0.004	CIZ1
random inactivation of X chromosome	1	468.1×	0.004	CIZ1
endosome organization	1	187.2×	0.008	DNM1
protein homotetramerization	1	118.7×	0.011	DNM1
receptor-mediated endocytosis	1	110.9×	0.011	DNM1
protein homooligomerization	1	61.1×	0.018	DNM1
endocytosis	1	47.6×	0.021	DNM1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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

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): 1.

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

Symbol	Assays	Type breakdown
DNM1	11	Binding:11

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DNM1	3.6.5.5	dynamin GTPase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	CIZ1

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)
CIZ1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.