DNM1

Chr 9ADAR

dynamin 1

Also known as: DEE31, DEE31A, DEE31B, DNM, EIEE31

NCBI Gene: 1759ENSG00000106976UniProt: Q05193

This gene encodes a member of the dynamin subfamily of GTP-binding proteins. The encoded protein possesses unique mechanochemical properties used to tubulate and sever membranes, and is involved in clathrin-mediated endocytosis and other vesicular trafficking processes. Actin and other cytoskeletal proteins act as binding partners for the encoded protein, which can also self-assemble leading to stimulation of GTPase activity. More than sixty highly conserved copies of the 3' region of this gene are found elsewhere in the genome, particularly on chromosomes Y and 15. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 31A, autosomal dominantMIM #616346
AD
Developmental and epileptic encephalopathy 31B, autosomal recessiveMIM #620352
AR
585
ClinVar variants
35
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— DNM1
🧬
Gene-Disease Validity (ClinGen)
developmental and epileptic encephalopathy · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

⚡
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
35 Pathogenic / Likely Pathogenic· 281 VUS of 585 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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.
0.25LOEUF
pLI 0.999
Z-score 5.54
OE 0.13 (0.07–0.25)
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.
5.18Z-score
OE missense 0.35 (0.31–0.40)
181 obs / 510.2 exp
Constrained

Extremely missense-constrained (top ~0.01%)

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.0.13 (0.07–0.25)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.35 (0.31–0.40)
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.0.85
0≤1.21.6
LoF obs/exp: 6 / 47.0Missense obs/exp: 181 / 510.2Syn Z: 1.67

ClinVar Variant Classifications

585 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic15
VUS281
Likely Benign231
Benign23
Conflicting15
20
Pathogenic
15
Likely Pathogenic
281
VUS
231
Likely Benign
23
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
5
11
0
20
Likely Pathogenic
4
10
1
0
15
VUS
4
226
43
8
281
Likely Benign
2
6
108
115
231
Benign
0
5
17
1
23
Conflicting
—15
Total14252180124585

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

View in ClinVar →

Protein Context — Lollipop Plot

DNM1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

DNM1-related microcephaly, developmental and epileptic encephalopathy (biallelic)

moderate
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗
stop gained NMD triggering

DNM1-related microcephaly, developmental and epileptic encephalopathy (monoallelic)

strong
ADDominant NegativeAltered Gene Product Structure
Dev. Disorders
G2P ↗
splice region variantmissense variantintron variant

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
DYNAMIN 1; DNM1
MIM #602377 · *

Developmental and epileptic encephalopathy 31A, autosomal dominant

MIM #616346

Molecular basis of disorder known

Autosomal dominant

Developmental and epileptic encephalopathy 31B, autosomal recessive

MIM #620352

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — DNM1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
AP2M1 as the potential biomarker for prediction of the response of atopic dermatitis to Dupilumab therapy: Multi-omics analysis and evidence.
Peng S et al.·Int J Biol Macromol
2025
Abnormal axonal development and severe epileptic phenotype in Dynamin-1 (DNM1) encephalopathy.
Matsubara K et al.·Epileptic Disord
2024Review
Whole exome sequencing of 491 individuals with inherited retinal diseases reveals a large spectrum of variants and identification of novel candidate genes.
Hayman T et al.·J Med Genet
2024
Effective knockdown-replace gene therapy in a novel mouse model of DNM1 developmental and epileptic encephalopathy.
Jones DJ et al.·Mol Ther
2024Functional
The neurodevelopmental spectrum of synaptic vesicle cycling disorders.
John A et al.·J Neurochem
2021Review
A deep intronic variant in DNM1 in a patient with developmental and epileptic encephalopathy creates a splice acceptor site and affects only transcript variants including exon 10a.
Harms FL et al.·Neurogenetics
2023
Clinical, Radiological, and Genetic Characterization of a Patient with a Novel Homoallelic Loss-of-Function Variant in DNM1.
AlTassan R et al.·Genes (Basel)
2022Case report
Expanding the phenotypic spectrum of DNM1-related disorders: novel GTPase domain variants and their diverse neurological outcomes.
Liu J et al.·Neurol Sci
2025
A recurrent de novo splice site variant involving DNM1 exon 10a causes developmental and epileptic encephalopathy through a dominant-negative mechanism.
Parthasarathy S et al.·Am J Hum Genet
2022Functional
Progressive Cone-Rod Synaptic Dysfunction in Dynamin-1 ( DNM1 ) Related Developmental and Epileptic Encephalopathy: A Distinct Retinal Phenotype in Human.
Marmoy OR et al.·Clin Genet
2025Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
MDA5 regulates BCR signaling and B-cell function via NF-κB-mediated DNM1.
Luo L et al.·Cell Mol Immunol
2026
Long-Read Genome Sequencing Establishes Biallelic Pathogenic Variants in DNM1 With Distinct Functional Effects as the Cause of Early Infantile Developmental and Epileptic Encephalopathy.
Drackley A et al.·Am J Med Genet A
2026Functional
Dnm1 Is Required for the Focal Clustering of Fis1 on the Mitochondrial Outer Membrane.
Sasahara M et al.·MicroPubl Biol
2025🔓 Open Access
The Yeast Parkinson's Disease Model Exhibits An Increase in Peroxisome Number Independent of the Division Proteins Vps1 and Dnm1.
Sarhadi TR et al.·Mol Neurobiol
2025Functional
Deep Brain Stimulation in Leigh-Like Syndrome Due to DNM1 Pathogenic Variant.
Villa-Villegas L et al.·Tremor Other Hyperkinet Mov (N Y)
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Rare DisordersUndiagnosed DisordersDisorders of Unknown Prevalence

Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford

RECRUITING
NCT01793168Sanford HealthStarted 2010-07

External Resources

Links to major genomics databases and tools