DNM1L

Chr 12ADAR

dynamin 1 like

The protein mediates mitochondrial and peroxisomal division through its GTPase activity and regulates developmentally programmed cell death. Mutations cause lethal encephalopathy due to defective mitochondrial and peroxisomal fission and optic atrophy 5, inherited in both autosomal dominant and autosomal recessive patterns. The pathogenic mechanism involves dominant-negative effects that disrupt normal organellar fission processes.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
DNmechanismAD/ARLOEUF 0.512 OMIM phenotypes
Clinical SummaryDNM1L
🧬
Gene-Disease Validity (ClinGen)
Leigh syndrome · ARLimited

Limited evidence — not for standalone diagnostic reporting

3 total gene-disease associations curated

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Missense constrained — critical functional residues
LoF Constraint
0.51LOEUF
pLI 0.001
Z-score 4.13
OE 0.32 (0.210.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
3.83Z-score
OE missense 0.46 (0.410.52)
187 obs / 403.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.32 (0.210.51)
00.351.4
Missense OE0.46 (0.410.52)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 14 / 43.3Missense obs/exp: 187 / 403.4Syn Z: 0.26
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongDNM1L-related developmental disorderOTHERAD
strongDNM1L-related optic atrophyDNAD
DN
0.77top 25%
GOF
0.6444th %ile
LOF
0.3259th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median · 1 literature citation
GOFprediction 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.

Literature Evidence

DNWe found a defect of the fission of both mitochondria and peroxisomes, as well as a heterozygous, dominant-negative mutation in the dynamin-like protein 1 gene (DLP1).PMID:17460227

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

DNM1L · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗