Relationship to CMT

CMT2CMTDI AD 2 subtypes 19p13.2

First described 2005

Subtypes2

Subtype	Inheritance	Class	OMIM	Sentinel Publication
SubtypeCMTDIB	Inheritanceautosomal dominant	ClassCMTDI	OMIM606482	Sentinel Publication Mutations in the Pleckstrin Homology Domain of Dynamin 2 Cause Dominant Intermediate Charcot-Marie-Tooth Disease 2005 · 10.1038/ng1514
SubtypeCMT2M	Inheritanceautosomal dominant	ClassCMT2	OMIM606482	Sentinel Publication Two Novel Mutations in Dynamin-2 Cause Axonal Charcot-Marie-Tooth Disease 2007 · 10.1212/01.wnl.0000265820.51075.61

ClinVar Variants

Pathogenic and likely pathogenic variants in DNM2, as classified in ClinVar, are read live from NCBI.

Reported in CMT

Reported in Other Diseases

Reported in a disease other than CMT. Listed apart rather than counted as CMT variants.

Variants w/o a Recorded Disease

Pathogenic or likely pathogenic in ClinVar, submitted without a disease recorded.

What the review stars mean

Review stars are ClinVar’s measure of how well a classification is supported: four for a practice guideline, three for an expert panel review, two for agreement among multiple submitters, and one for a single submitter with criteria provided. A record with no criteria provided earns no stars and is not indexed.

Only aggregate germline records are indexed. Uncertain and conflicting classifications are not. Experts in CMT makes no claim to the accuracy of ClinVar data. This index is provided for informational purposes only.

View all DNM2 ClinVar Records

Gene Function

DNM2 catalyzes the hydrolysis of GTP and utilizes this energy to mediate vesicle scission at plasma membrane during endocytosis and filament remodeling at many actin structures during organization of the actin cytoskeleton. Plays an important role in vesicular trafficking processes, namely clathrin-mediated endocytosis (CME), exocytic and clathrin-coated vesicle from the trans-Golgi network, and PDGF stimulated macropinocytosis. During vesicular trafficking process, associates to the membrane, through lipid binding, and self-assembles into ring-like structure through oligomerization to form a helical polymer around the vesicle membrane and leading to vesicle scission. Plays a role in organization of the actin cytoskeleton by mediating arrangement of stress fibers and actin bundles in podocytes (By similarity). During organization of the actin cytoskeleton, self-assembles into ring-like structure that directly bundles actin filaments to form typical membrane tubules decorated with dynamin spiral polymers (By similarity). Self-assembly increases GTPase activity and the GTP hydrolysis causes the rapid depolymerization of dynamin spiral polymers, and results in dispersion of actin bundles (By similarity). Remodels, through its interaction with CTTN, bundled actin filaments in a GTPase-dependent manner and plays a role in orchestrating the global actomyosin cytoskeleton. The interaction with CTTN stabilizes the interaction of DNM2 and actin filaments and stimulates the intrinsic GTPase activity that results in actin filament-barbed ends and increases the sensitivity of filaments in bundles to the actin depolymerizing factor, CFL1 (By similarity). Plays a role in the autophagy process, by participating in the formation of ATG9A vesicles destined for the autophagosomes through its interaction with SNX18, by mediating recycling endosome scission leading to autophagosome release through MAP1LC3B interaction. Also regulates maturation of apoptotic cell corpse-containing phagosomes by recruiting PIK3C3 to the phagosome membrane (By similarity). Also plays a role in cytokinesis (By similarity). May participate in centrosome cohesion through its interaction with TUBG1 (By similarity). Plays a role in the regulation of neuron morphology, axon growth and formation of neuronal growth cones (By similarity). Involved in membrane tubulation Source: UniProt

Indexed Identifiers

HGNC Aliases: DYNII, DYN2

hgnc_idHGNC:2974

ensembl_gene_idENSG00000079805

coords_grch38chr19:10717967-10834209

coords_grch37chr19:10828755-10944164

entrez_id1785

omim_gene602378

uniprot_idsP50570

refseq_accessionNM_004945

mane_refseqNM_001005361.3

mane_ensemblENST00000389253.9

External recordsHGNC:2974OMIM 602378gnomADUniProt P50570ClinGenClinVar P/LPOrphanetMANE NM_001005361.3

EvidenceClinGen Definitive Charcot-Marie-Tooth diseasePanelApp Green

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