DNM3

Chr 1

dynamin 3

Also known as: Dyna III

NCBI Gene: 26052 ENSG00000197959 UniProt: Q9UQ16 OMIM: 611445

DNM3 encodes a GTP-binding protein that associates with microtubules and functions in vesicular trafficking processes, particularly endocytosis, and plays a role in megakaryocyte development. Mutations cause autosomal dominant developmental and epileptic encephalopathy with movement abnormalities, typically presenting in infancy with seizures, developmental delay, and dystonia. The gene is highly constrained against loss-of-function variants, indicating intolerance to protein-disrupting mutations.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of a family of guanosine triphosphate (GTP)-binding proteins that associate with microtubules and are involved in vesicular transport. The encoded protein functions in the development of megakaryocytes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.48

Clinical Summary— DNM3

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

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ClinVar Variants

86 VUS of 119 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.48LOEUF

pLI 0.002

Z-score 4.22

OE 0.30 (0.20–0.48)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.70Z-score

OE missense 0.65 (0.59–0.72)

314 obs / 480.2 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.30 (0.20–0.48)

0≤0.351.4

Missense OE?0.65 (0.59–0.72)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 13 / 42.8Missense obs/exp: 314 / 480.2Syn Z: -0.14

This gene — mechanism propensity

0.77top 25%

GOF

0.5367th %ile

LOF

0.3647th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

119 submitted variants in ClinVar

ClinVar

Classification Summary

VUS86

Likely Benign10

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	86	0	0	86
Likely Benign	3	3	4	10
Benign	0	0	2	2
Total	89	3	6	98

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

View in ClinVar →

29 pathogenic / likely-pathogenic (of 41) ClinVar copy-number / structural variants overlap DNM3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →