DNM1

Chr 9ADAR

dynamin 1

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

NCBI Gene: 1759 ENSG00000106976 UniProt: Q05193 OMIM: 602377

The protein tubulates and severs membranes through its mechanochemical GTPase activity and is essential for clathrin-mediated endocytosis and vesicular trafficking processes. Mutations cause developmental and epileptic encephalopathy 31A (autosomal dominant) and 31B (autosomal recessive), with the gene being highly intolerant to loss-of-function variants. Disease can result from different mechanisms depending on the specific variant, with some mutations likely causing haploinsufficiency while others may act through dominant-negative or gain-of-function effects.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 31A, autosomal dominantMIM #616346

Developmental and epileptic encephalopathy 31B, autosomal recessiveMIM #620352

Clinical highlights

Gene–disease validity (ClinGen · GenCC)

Definitive · genetic developmental and epileptic encephalopathy · AD · ClinGen 2024
Strong · developmental and epileptic encephalopathy, 31B · AR · Ambry Genetics
Strong · developmental and epileptic encephalopathy, 31A · AD · Labcorp Genetics (formerly Invitae)
Supportive · Lennox-Gastaut syndrome · AD · Orphanet

+1 more curated pair

Interpreting a novel variant

The dominant disease is caused by dominant-negative changes and the recessive disease by loss of function (Gene2Phenotype). A single heterozygous truncating variant therefore fits the recessive disease and does not by itself explain a dominant presentation; a novel missense has to be read against the dominant mechanism.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.25

LOEUF· LoF intol.

Multiple*

Mechanism· G2P

📖

GeneReview available — DNM1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

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?

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?

LoF OE?0.13 (0.07–0.25)

0≤0.351.4

Missense OE?0.35 (0.31–0.40)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 6 / 47.0Missense obs/exp: 181 / 510.2Syn Z: 1.67

Background carrier burden — how many people carry a rare variant somewhere in DNM1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

778 rare PASS variants

Rare truncating (LoF)

1 in 820

86 rare PASS variants

Rare synonymous (reference)

1 in 120

514 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DNM1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 150	1 in 800
South Asian	~43k	1 in 130	1 in 400
Remaining (unassigned)	~30k	1 in 130	1 in 890
European (Finnish)	~27k	1 in 400	1 in 480
Admixed American	~22k	1 in 140	1 in 1,600
African / African American	~21k	1 in 140	1 in 1,300
East Asian	~20k	1 in 96	1 in 1,600
Ashkenazi Jewish	~13k	1 in 380	≈ 1 in 2,800
Middle Eastern	~2,884	1 in 150	≈ 1 in 770

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 19 of 22 coding exons well covered in gnomAD exomes; exons 1, 15, 21 marginal. Genomes: all 22.? see exons ↓