DNM2

Summary

DNM2 (dynamin 2, HGNC:2974) is a protein-coding gene on chromosome 19p13.2, encoding Dynamin-2 (P50570). 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. It is a selective cancer dependency (DepMap: 89.2% of cell lines).

Dynamins represent one of the subfamilies of GTP-binding proteins. These proteins share considerable sequence similarity over the N-terminal portion of the molecule, which contains the GTPase domain. Dynamins are associated with microtubules. They have been implicated in cell processes such as endocytosis and cell motility, and in alterations of the membrane that accompany certain activities such as bone resorption by osteoclasts. Dynamins bind many proteins that bind actin and other cytoskeletal proteins. Dynamins can also self-assemble, a process that stimulates GTPase activity. Five alternatively spliced transcripts encoding different proteins have been described. Additional alternatively spliced transcripts may exist, but their full-length nature has not been determined.

Source: NCBI Gene 1785 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Charcot-Marie-Tooth disease (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 1,371 total — 12 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 78
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 89.2% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001005361

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2974
Approved symbol	DNM2
Name	dynamin 2
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	DYNII, DYN2, CMTDIB, CMTDI1, DI-CMTB, CMT2M
Ensembl gene	ENSG00000079805
Ensembl biotype	protein_coding
OMIM	602378
Entrez	1785

Gene structure

Transcript identifiers

Ensembl transcripts: 58 — 41 protein_coding, 11 retained_intron, 6 protein_coding_CDS_not_defined

ENST00000355667, ENST00000359692, ENST00000389253, ENST00000408974, ENST00000585892, ENST00000586130, ENST00000586939, ENST00000587329, ENST00000587485, ENST00000587830, ENST00000587991, ENST00000588976, ENST00000589106, ENST00000590787, ENST00000590806, ENST00000591118, ENST00000591266, ENST00000591701, ENST00000591818, ENST00000591819, ENST00000593203, ENST00000593220, ENST00000681972, ENST00000682285, ENST00000682524, ENST00000683738, ENST00000908371, ENST00000908372, ENST00000908373, ENST00000908374, ENST00000908375, ENST00000908376, ENST00000908377, ENST00000908378, ENST00000908379, ENST00000908380, ENST00000908381, ENST00000908382, ENST00000908383, ENST00000916585, ENST00000957413, ENST00000957414, ENST00000957415, ENST00000957416, ENST00000957417, ENST00000957418, ENST00000957419, ENST00000957420, ENST00000957421, ENST00000957422, ENST00000957423, ENST00000957424, ENST00000957425, ENST00000957426, ENST00000957427, ENST00000957428, ENST00000957429, ENST00000957430

RefSeq mRNA: 5 — MANE Select: NM_001005361 NM_001005360, NM_001005361, NM_001005362, NM_001190716, NM_004945

CCDS: CCDS32907, CCDS32908, CCDS45968, CCDS45969, CCDS59351

Canonical transcript exons

ENST00000389253 — 21 exons

Exon	Start	End
ENSE00001117476	10798486	10798572
ENSE00001272899	10797380	10797518
ENSE00001632492	10805916	10805967
ENSE00001674034	10808569	10808580
ENSE00001688623	10795372	10795439
ENSE00001702118	10812264	10812377
ENSE00001737502	10777118	10777216
ENSE00001796741	10830978	10831903
ENSE00002686845	10802288	10802358
ENSE00003492581	10823788	10823899
ENSE00003513546	10819980	10820089
ENSE00003538147	10775703	10775906
ENSE00003546635	10793720	10793855
ENSE00003547050	10825057	10825221
ENSE00003561592	10772479	10772628
ENSE00003589576	10786564	10786706
ENSE00003603749	10830127	10830378
ENSE00003657975	10782960	10783120
ENSE00003677107	10829036	10829268
ENSE00003683640	10759738	10759811
ENSE00003902790	10718079	10718403

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 98.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 69.6478 / max 1100.7359, expressed in 1825 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173851	66.9958	1824
173852	1.1460	769
173850	1.0399	668
173857	0.3083	136
173855	0.1350	70
173856	0.0228	11

Top tissues by expression

274 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
metanephros cortex	UBERON:0010533	98.66	gold quality
granulocyte	CL:0000094	98.55	gold quality
mucosa of transverse colon	UBERON:0004991	98.35	gold quality
skin of leg	UBERON:0001511	98.29	gold quality
transverse colon	UBERON:0001157	98.26	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.19	gold quality
right lung	UBERON:0002167	98.14	gold quality
upper lobe of left lung	UBERON:0008952	98.09	gold quality
rectum	UBERON:0001052	98.07	gold quality
body of stomach	UBERON:0001161	97.98	gold quality
skin of abdomen	UBERON:0001416	97.98	gold quality
apex of heart	UBERON:0002098	97.68	gold quality
mucosa of stomach	UBERON:0001199	97.63	gold quality
lower esophagus mucosa	UBERON:0035834	97.63	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.44	gold quality
right atrium auricular region	UBERON:0006631	97.32	gold quality
colonic epithelium	UBERON:0000397	97.26	gold quality
right uterine tube	UBERON:0001302	97.20	gold quality
body of pancreas	UBERON:0001150	97.10	gold quality
right adrenal gland cortex	UBERON:0035827	97.09	gold quality
minor salivary gland	UBERON:0001830	97.04	gold quality
left adrenal gland cortex	UBERON:0035825	97.00	gold quality
monocyte	CL:0000576	96.99	gold quality
right adrenal gland	UBERON:0001233	96.99	gold quality
left adrenal gland	UBERON:0001234	96.91	gold quality
left lobe of thyroid gland	UBERON:0001120	96.80	gold quality
upper lobe of lung	UBERON:0008948	96.78	gold quality
right lobe of thyroid gland	UBERON:0001119	96.77	gold quality
tibial nerve	UBERON:0001323	96.75	gold quality
stomach	UBERON:0000945	96.70	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.34

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GDNF

miRNA regulators (miRDB)

36 targeting DNM2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-633	98.35	69.45	1167
HSA-MIR-6801-3P	98.04	64.64	805
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-6811-5P	97.98	64.96	848
HSA-MIR-6810-3P	97.96	64.57	1023
HSA-MIR-296-5P	97.61	64.02	851
HSA-MIR-4640-5P	97.42	66.33	1543
HSA-MIR-4726-5P	97.24	65.67	1299
HSA-MIR-203B-5P	97.24	68.54	543

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 89.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• These findings suggest that dynamin is part of a protein network that controls nucleation of actin from membranes. (PMID:11782545)
• dynamin2 and Rab5 have roles in endocytosis of lysophosphatidic acid-coupled LPA1/EDG-2 receptors (PMID:12668728)
• dynamin-2 membrane recruitment is mediated by sorting nexin 9 (PMID:15299020)
• Dynamin-2 at least partially regulated oxLDL-induced apoptosis of VSMC by participating in 2 independent pathways: the oxLDL endocytotic pathway and the p53 pathway. (PMID:15545517)
• Mutations in the PH domain of dynamin 2 is associated with dominant intermediate Charcot-Marie-Tooth neuropathy (DI-CMTB) (PMID:15731758)
• dynamin-2 regulates KDR expression and function and plays an important role in VPF/VEGF mediated angiogenesis (PMID:16049137)
• Missense mutations in dynamin 2 is associated with dominant centronuclear myopathy (PMID:16227997)
• Thus, syndapin-dynamin complexes are crucial and sufficient to promote vesicle formation from the trans-Golgi network. (PMID:16551695)
• dynamin has roles in the IL-5 signaling pathway and in receptor endocytosis and termination of the ERK1/2 signaling pathway (PMID:16556602)
• Dyn2 is a Nef-associated protein required for the infectivity enhancement of progeny virions by Nef. (PMID:17412836)
• DNM2 reglates riboflavin endocytosis in human placental trophoblasts. (PMID:17565002)
• HPV type 31 (HPV31) entry and initiation of early infection events require both caveolin 1 and dynamin 2 and occur independently of clathrin-mediated endocytosis. (PMID:17626097)
• DNM2 has an etiologic role in axonal Charcot-Marie-Tooth disease type 2 neuropathy. (PMID:17636067)
• myoferlin forms a complex with dynamin-2 and VEGFR-2, which prevents CBL-dependent VEGFR-2 polyubiquitination and proteasomal degradation. (PMID:17702744)
• CD44 is an important regulator of HGF/c-Met-mediated in vitro and in vivo barrier enhancement, a process with essential involvement of Tiam1, Rac1, dynamin 2, and cortactin. (PMID:17702746)
• This study suggests that the phenotypes of dynamin 2 related centronuclear myopathy and Charcot-Marie-Tooth disease overlap and that DNM2 mutations may alter cerebral function. (PMID:17825552)
• Four heterozygous dynamin 2 (DNM2) mutations in five centronuclear myopathy patients aged 1 to 15 years. (PMID:17932957)
• DNM2 mediates fluid-phase micropinocytosis in epithelial cells. (PMID:18003703)
• Dynamin 2 gene is a novel susceptibility gene for late-onset Alzheimer disease in non-APOE-epsilon4 carriers. (PMID:18236001)
• we report a novel DNM2 mutation in the Pleckstrin homology domain of DNM2 (p.K559del) in a patient with an axonal length-dependent sensorimotor polyneuropathy predominantly affecting the lower limbs. (PMID:18394888)
• MR imaging study accurately depicts lower limb muscle involvement in CMT2 caused by DNM2 mutation. (PMID:18560793)
• REVIEW : DNM2 mutations and centronuclear myopathy (PMID:18817572)
• These findings identify a novel role for Dynamin 2 in the exocytic events required for effective NK cell-mediated cytotoxicity. (PMID:18981119)
• report a novel DNM2 CNM mutation in the CMT region. Among the DNM2-related CNM, the phenotype appears intermediate, with an onset at the end of the first decade and a more rapid progression relative to the mild late-onset DNM2-CNM. (PMID:19122038)
• These data suggest that DNM2 expression is reduced in late-onset Alzheimer’s disease , which results in the accumulation of APP in lipid raft-rich plasma membranes. (PMID:19126407)
• formin-binding protein 17 (FBP17) recruits WASP, WASP-interacting protein (WIP), and dynamin-2 to the plasma membrane and that this recruitment is necessary for the formation of podosomes and phagocytic cups. (PMID:19155218)
• These results provide a first evidence for a regulated interaction of dynamin-2 with microtubules in cultured mammalian cells. (PMID:19331814)
• dynamin 2 mutations should be screened in the autosomal dominant Charcot-Marie-Tooth neuropathy families with intermediate or axonal NCV, and in patients with a classical mild to moderately severe Charcot-Marie-Tooth phenotype. (PMID:19502294)
• Results suggest that dynamin 2 regulates dynamic instability of microtubules, which is essential for organelle motility, and that this function may be impaired in Charcot-Marie-Tooth disease. (PMID:19528294)
• impairment of clathrin-mediated endocytosis may play a role in the pathophysiological mechanisms leading to DNM2-related diseases, but the tissue-specific impact of DNM2 mutations in both diseases remains unclear (PMID:19623537)
• These results suggest that hyperoxia induces caveolin-1-dependent, c-Abl-mediated dynamin 2 phosphorylation required for recruitment of p47(phox) to caveolin-enriched microdomains and subsequent ROS production in lung endothelium. (PMID:19833721)
• DNM2 mutation leading to neonatal onset of centronuclear myopathy follows a course similar to adult-onset cases (PMID:19932619)
• Internalization of coxsackievirus A9 is mediated by {beta}2-microglobulin, dynamin, and Arf6. (PMID:20089652)
• We report a series of 12 patients from eight families with CNM in whom we have identified a number of novel features that expand the reported clinicopathological phenotype. We identified two novel and five recurrent missense mutations in DNM2. (PMID:20227276)
• Data confirm that inhibition of dyamin-2 induces leakiness in the endothelial monolayer by increasing the load of peroxynitrite under hypoxia. (PMID:20397975)
• results suggest dynamin 2 might be involved in preventing tumor invasion and lymph node metastasis, possibly in relation with extracellular matrix degradation; may be a prognostic marker for these risk factors in early cervical squamous cell carcinoma (PMID:20574164)
• The authors conclude that the second extracellular loop of occludin dictates the Dynamin 2-dependent hepatitis C virus entry. (PMID:20822789)
• {alpha}V{beta}3-integrin routes herpes simplex virus to an entry pathway dependent on cholesterol-rich lipid rafts and dynamin2. (PMID:21135248)
• The deletion of PRD domain of dynamin 2 resulted in the impairment of both the localization and the abscission of daughter cells. (PMID:21150131)
• Phosphorylation of dynamin II primarily occurs on a single site that regulates cytokinesis downstream of calcineurin, rather than regulating endocytosis or centrosome function. (PMID:21195118)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnm3a	ENSDARG00000032238
danio_rerio	dnm2a	ENSDARG00000069937
danio_rerio	zmp:0000000625	ENSDARG00000100145
danio_rerio	dnm2b	ENSDARG00000103054
danio_rerio		ENSDARG00000113332
mus_musculus	Dnm2	ENSMUSG00000033335
rattus_norvegicus	Dnm2	ENSRNOG00000007649

Paralogs (6): DNM1L (ENSG00000087470), DNM1 (ENSG00000106976), MX1 (ENSG00000157601), MX2 (ENSG00000183486), DNM3 (ENSG00000197959), OPA1 (ENSG00000198836)

Protein

Protein identifiers

Dynamin-2 — P50570 (reviewed: P50570)

Alternative names: Dynamin 2, Dynamin II

All UniProt accessions (5): P50570, K7EMQ3, K7EMR9, K7ENE7, K7EPK9

UniProt curated annotations — full annotation on UniProt →

Function. 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. 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. Self-assembly increases GTPase activity and the GTP hydrolysis causes the rapid depolymerization of dynamin spiral polymers, and results in dispersion of actin bundles. 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. 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. Also plays a role in cytokinesis. May participate in centrosome cohesion through its interaction with TUBG1. Plays a role in the regulation of neuron morphology, axon growth and formation of neuronal growth cones. Involved in membrane tubulation.

Subunit / interactions. Oligomerizes into a helical polymer that self-assembles around the vesicle membrane, when associated to the menbrane through lipid binding. Interacts with SHANK1 and SHANK2. Interacts with SNX9. Interacts (via C-terminal proline-rich domain (PRD)) with SNX18 (via SH3 domain); this interaction regulates ATG9A and ATG16L1 trafficking from recycling endosomes to sites of autophagosome formation. Interacts with SNX33 (via SH3 domain). Interacts with MYO1E (via SH3 domain). Interacts with PSTPIP1 (via SH3 domain). Interacts with CTNND2. Interacts (via C-terminal proline-rich domain (PRD)) with BIN1 (via SH3 domain); this interaction allows the recruitment of DNM2 to the membrane tubules and inhibits self-assembly-stimulated GTPase activity on the membrane. Interacts with GABARAP, GABARAPL1 and GABARAPL2. Interacts with MAP1LC3B (the lipidate and non-lipidated LC3 form); this interaction mediates recycling endosome scission leading to autophagosome release. Interacts with ITSN1. Interacts (via C-terminal proline-rich domain (PRD)) with SH3BP4 (via SH3 domain); this interaction controls the GTPase activity and is prevented by EGFR-induced tyrosine phosphorylation of either DNM2 or SH3BP4. May interact with PIK3C3. May be a component of a complex composed of RAB5A (in GDP-bound form), DYN2 and PIK3C3. Interacts with SDC4; this interaction is markedly enhanced at focal ahesion site upon induction of focal adhesions and stress-fiber formation. Interacts with ACTN1. Interacts with CTTN; this interaction stimulates the intrinsic GTPase activity of DNM2 and stabilizes the association of DNM2 and actin filaments; in addition this interaction is stimulated by ligand binding to the receptor, leading to the recruitment of the DNM2-CTTN complex to the sequestered receptor-ligand complex to its internalization. Interacts with NOSTRIN (via SH3 domain); this interaction allows the recruitment of NOS3 to dynamin-positive structures. Interacts with TUBG1; this interaction may participate in centrosome cohesion.

Subcellular location. Cytoplasm. Cytoskeleton. Cytoplasmic vesicle. Clathrin-coated vesicle. Cell projection. Uropodium. Endosome. Microtubule organizing center. Centrosome. Centriole. Recycling endosome. Phagocytic cup. Phagosome membrane. Podosome. Cell junction. Postsynaptic density. Synapse. Synaptosome. Midbody. Membrane. Clathrin-coated pit.

Tissue specificity. Widely expressed. Expressed in skeletal muscle and the peripheral nerve.

Post-translational modifications. Phosphorylation at Ser-848 by GSK3-alpha relieves the inhibition of BIN1 and promotes endocytosis. Phosphorylation at Ser-764 by CDK1 is greatly increased upon mitotic entry. It regulates cytokinesis downstream of calcineurin, and does not affect clathrin-mediated endocytosis. Dephosphorylated by calcineurin/PP2 during cytokinesis in a Ca(2+)- and calmodulin-dependent manner. Phosphorylated on tyrosine residues by EGFR and after activation of SRC.

Disease relevance. Myopathy, centronuclear, 1 (CNM1) [MIM:160150] A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers. The disease is caused by variants affecting the gene represented in this entry. Lethal congenital contracture syndrome 5 (LCCS5) [MIM:615368] A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy and congenital non-progressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. The disease is caused by variants affecting the gene represented in this entry. Charcot-Marie-Tooth disease, dominant intermediate B (CMTDIB) [MIM:606482] A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. The dominant intermediate type B is characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec. The disease is caused by variants affecting the gene represented in this entry. Charcot-Marie-Tooth disease, axonal, type 2M (CMT2M) [MIM:606482] An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Overexpression of CNM- and CMT-related DNM2 mutants in COS7 cells, whatever the mutated domain, led to a reduction in clathrin-mediated receptor endocytosis associated with MAPK ERK-1 and ERK-2 impairment. The membrane trafficking impairment process may represent a common pathophysiological pathway in the autosomal forms of CNM DNM2-CMT neuropathy.

Similarity. Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family.

Isoforms (5)

UniProt ID	Names	Canonical?
P50570-1	1	yes
P50570-2	2
P50570-3	3
P50570-4	4
P50570-5	5

RefSeq proteins (5): NP_001005360, NP_001005361, NP_001005362, NP_001177645, NP_004936 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000375	Dynamin_stalk	Domain
IPR001401	Dynamin_GTPase	Domain
IPR001849	PH_domain	Domain
IPR003130	GED	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR019762	Dynamin_GTPase_CS	Conserved_site
IPR020850	GED_dom	Domain
IPR022812	Dynamin	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR030381	G_DYNAMIN_dom	Domain
IPR045063	Dynamin_N	Domain

Pfam: PF00169, PF00350, PF01031, PF02212

Enzyme classification (BRENDA):

• EC 3.6.5.5 — dynamin GTPase (BRENDA: 23 organisms, 104 substrates, 250 inhibitors, 42 Km, 26 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GTP	0.0034–2.115	37
ATP	0.2	1

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (83 total): sequence variant 26, binding site 13, strand 9, modified residue 7, region of interest 6, mutagenesis site 6, sequence conflict 5, domain 3, compositionally biased region 3, splice variant 3, chain 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2YS1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50570-F1	78.38	0.41

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (13): 41; 43; 44; 45; 46; 59; 60; 206; 208; 211; 236; 237 …

Post-translational modifications (7): 231, 299, 597, 598, 755, 764, 848

Mutagenesis-validated functional residues (6):

Position	Phenotype
44	inhibits receptor-mediated endocytosis. inhibits egf-induced mapk3 and mapk1 activation.
231	greatly reduces tyrosine phosphorylation; when associated with f-597.
525	abolishes interaction with map1lc3b. does not affect interaction with itsn1. affects nascent autophagosome membranes. do
597	greatly reduces tyrosine phosphorylation; when associated with f-231.
848	decreases receptor internalization.
848	decreases binding affinity to bin1. increases gtpase mediated-membrane fission activity by bin1. decreases cell surface

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade
R-HSA-177504	Retrograde neurotrophin signalling
R-HSA-190873	Gap junction degradation
R-HSA-196025	Formation of annular gap junctions
R-HSA-203641	NOSTRIN mediated eNOS trafficking
R-HSA-2132295	MHC class II antigen presentation
R-HSA-432720	Lysosome Vesicle Biogenesis
R-HSA-432722	Golgi Associated Vesicle Biogenesis
R-HSA-437239	Recycling pathway of L1
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-9031628	NGF-stimulated transcription
R-HSA-9766229	Degradation of CDH1

MSigDB gene sets: 502 (showing top): GGGACCA_MIR133A_MIR133B, REACTOME_RETROGRADE_NEUROTROPHIN_SIGNALLING, GOBP_SYNAPTIC_VESICLE_LOCALIZATION, MODULE_52, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_OR_POLYSACCHARIDE_ANTIGEN_VIA_MHC_CLASS_II, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_NEURON_PROJECTION_EXTENSION, CCAWYNNGAAR_UNKNOWN, GOBP_VESICLE_LOCALIZATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_TRANSITION_METAL_ION_TRANSPORT, GOBP_VESICLE_ORGANIZATION

GO Biological Process (25): G2/M transition of mitotic cell cycle (GO:0000086), regulation of DNA-templated transcription (GO:0006355), post-Golgi vesicle-mediated transport (GO:0006892), endocytosis (GO:0006897), receptor-mediated endocytosis (GO:0006898), phagocytosis (GO:0006909), autophagy (GO:0006914), centrosome cycle (GO:0007098), signal transduction (GO:0007165), synaptic vesicle budding from presynaptic endocytic zone membrane (GO:0016185), antigen processing and presentation of exogenous peptide antigen via MHC class II (GO:0019886), regulation of axon extension (GO:0030516), receptor internalization (GO:0031623), transferrin transport (GO:0033572), positive regulation of apoptotic process (GO:0043065), stress fiber assembly (GO:0043149), positive regulation of DNA-templated transcription (GO:0045893), synaptic vesicle transport (GO:0048489), neuron projection morphogenesis (GO:0048812), protein polymerization (GO:0051258), membrane organization (GO:0061024), actin filament bundle organization (GO:0061572), membrane tubulation (GO:0097749), vesicle scission (GO:0099050), negative regulation of membrane tubulation (GO:1903526)

GO Molecular Function (9): GTPase activity (GO:0003924), GTP binding (GO:0005525), phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), microtubule binding (GO:0008017), SH3 domain binding (GO:0017124), enzyme binding (GO:0019899), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (32): Golgi membrane (GO:0000139), phagocytic cup (GO:0001891), uropod (GO:0001931), podosome (GO:0002102), cytoplasm (GO:0005737), endosome (GO:0005768), Golgi apparatus (GO:0005794), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), microtubule (GO:0005874), plasma membrane (GO:0005886), clathrin-coated pit (GO:0005905), focal adhesion (GO:0005925), postsynaptic density (GO:0014069), clathrin-coated vesicle (GO:0030136), midbody (GO:0030496), endocytic vesicle membrane (GO:0030666), phagocytic vesicle membrane (GO:0030670), neuron projection (GO:0043005), synapse (GO:0045202), postsynaptic membrane (GO:0045211), recycling endosome (GO:0055037), extracellular exosome (GO:0070062), presynapse (GO:0098793), cytoskeleton (GO:0005856), endomembrane system (GO:0012505), membrane (GO:0016020), growth cone (GO:0030426), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
trans-Golgi Network Vesicle Budding	2
Toll-like Receptor Cascades	1
Signaling by NTRK1 (TRKA)	1
Gap junction trafficking	1
Gap junction degradation	1
Metabolism of nitric oxide: NOS3 activation and regulation	1
Adaptive Immune System	1
L1CAM interactions	1
Membrane Trafficking	1
Nuclear Events (kinase and transcription factor activation)	1
Regulation of CDH1 Function	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
endomembrane system	3
DNA-templated transcription	2
endocytosis	2
cellular process	2
bounding membrane of organelle	2
plasma membrane bounded cell projection	2
cytoplasm	2
microtubule organizing center	2
membrane	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G2/M phase transition	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
Golgi vesicle transport	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
cell cycle process	1
microtubule organizing center organization	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
synaptic vesicle endocytosis	1
synaptic vesicle budding	1
antigen processing and presentation of exogenous peptide antigen	1
antigen processing and presentation of peptide antigen via MHC class II	1
regulation of developmental growth	1
axon extension	1
regulation of extent of cell growth	1
receptor-mediated endocytosis	1
iron ion transport	1
protein transport	1
apoptotic process	1

Protein interactions and networks

STRING

4040 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNM2	HCLS1	P14317	983
DNM2	CTTN	Q14247	983
DNM2	BIN1	O00499	959
DNM2	MTM1	Q13496	926
DNM2	WASL	O00401	900
DNM2	MTMR14	Q8NCE2	900
DNM2	CAV1	Q03135	885
DNM2	ARC	Q7LC44	884
DNM2	SNX18	Q96RF0	881
DNM2	AMPH	P49418	875
DNM2	ITSN1	Q15811	815
DNM2	FIS1	Q9Y3D6	808
DNM2	PLEK2	Q9NYT0	794
DNM2	EPS15	P42566	791
DNM2	PLEK	P08567	788

IntAct

299 interactions, top by confidence:

A	B	Type	Score
HRAS	RAF1	psi-mi:“MI:0914”(association)	0.980
GRB2	DNM2	psi-mi:“MI:0915”(physical association)	0.930
DNM2	GRB2	psi-mi:“MI:0915”(physical association)	0.930
SNX9	DNM2	psi-mi:“MI:0915”(physical association)	0.920
DNM2	SNX9	psi-mi:“MI:0915”(physical association)	0.920
MED29	MED19	psi-mi:“MI:0914”(association)	0.890
SNX9	SYNJ1	psi-mi:“MI:0914”(association)	0.790
DNM1	DNM2	psi-mi:“MI:0914”(association)	0.740
DNM2	DNM1	psi-mi:“MI:0914”(association)	0.740
MED19	MED19	psi-mi:“MI:0914”(association)	0.730
GRB2	WIPF3	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
SCN2B	EXOC5	psi-mi:“MI:0914”(association)	0.640
KPNB1	ERBB2	psi-mi:“MI:0914”(association)	0.570
DNM2	UBASH3A	psi-mi:“MI:0915”(physical association)	0.560
	DNM2	psi-mi:“MI:0915”(physical association)	0.560
DNM2	SEC23A	psi-mi:“MI:0915”(physical association)	0.560
RNF8	DNM2	psi-mi:“MI:0915”(physical association)	0.560
BAG3	DNM2	psi-mi:“MI:0915”(physical association)	0.560
DNM2	TRAF4	psi-mi:“MI:0915”(physical association)	0.560
SDCBP	DNM2	psi-mi:“MI:0915”(physical association)	0.560
DNM2	PRKAA2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (376): DNM2 (Affinity Capture-MS), DNM2 (Affinity Capture-MS), DNM2 (Affinity Capture-MS), DNM2 (Affinity Capture-MS), DNM2 (Protein-peptide), GBE1 (Co-fractionation), GGA1 (Co-fractionation), PTPN13 (Co-fractionation), RPE (Co-fractionation), RTCB (Co-fractionation), SH3KBP1 (Co-fractionation), DNM2 (Affinity Capture-MS), DNM2 (Reconstituted Complex), DNM2 (Co-localization), DNM2 (Proximity Label-MS)

ESM2 similar proteins: A0A1D5P556, A6H7I5, B0DOB5, D3ZGS3, F1M386, F1MSG6, F1PBJ0, G5EGS5, H2KZZ6, O95466, P21575, P23678, P27619, P39052, P39053, P39054, P39055, P48608, P50570, P78344, P79398, Q01968, Q05193, Q08877, Q08DF4, Q15057, Q15172, Q24564, Q2KI89, Q5R629, Q5R7J9, Q5ZK62, Q62448, Q6IVG4, Q6NXC0, Q6ZQK5, Q7SIG6, Q7XPJ0, Q80U19, Q86T65

Diamond homologs: A0MWD1, A1E2I4, A1E2I5, A6H7I5, A7VK00, G0SGC7, O00429, O35303, O60313, P09922, P18588, P18589, P18590, P20591, P20592, P20593, P21575, P27594, P27619, P32266, P33237, P33238, P39052, P39053, P39054, P39055, P42697, P50570, P54861, P58281, P79135, P87320, Q000A9, Q05193, Q08877, Q08DF4, Q28379, Q2KIA5, Q2KTC2, Q3UD61

SIGNOR signaling

14 interactions.

A	Effect	B	Mechanism
SNX9	up-regulates	DNM2	binding
DNM2	up-regulates	MYO1C	binding
PSTPIP1	down-regulates	DNM2	binding
DNM2	down-regulates	GJB2	binding
DNM2	“up-regulates quantity by stabilization”	VAV1	binding
SRC	“up-regulates activity”	DNM2	phosphorylation
SRC	“down-regulates activity”	DNM2	phosphorylation
PPP3CB	unknown	DNM2	dephosphorylation
PPP3CC	unknown	DNM2	dephosphorylation
PPP3CA	unknown	DNM2	dephosphorylation
GDNF	“down-regulates quantity by repression”	DNM2	“transcriptional regulation”
Calcineurin	unknown	DNM2	dephosphorylation
PP2B	unknown	DNM2	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 179 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of signaling by CBL	5	21.2×	4e-04
DAP12 signaling	6	18.9×	2e-04
Signaling by CSF1 (M-CSF) in myeloid cells	6	17.8×	2e-04
FCERI mediated MAPK activation	5	14.8×	2e-03
Signaling by FGFR1 in disease	5	12.5×	3e-03
NCAM signaling for neurite out-growth	5	11.6×	3e-03
Signaling by SCF-KIT	5	10.6×	4e-03
FCGR3A-mediated phagocytosis	6	9.6×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
endocytosis	11	6.7×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1371 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	13
Uncertain significance	587
Likely benign	544
Benign	49

Top pathogenic / likely-pathogenic (25)

Variant ID	HGVS	Classification
1067936	NM_001005361.3(DNM2):c.1115T>C (p.Phe372Ser)	Pathogenic
158514	NM_001005361.3(DNM2):c.1565G>A (p.Arg522His)	Pathogenic
265656	NM_001005361.3(DNM2):c.1879C>G (p.Pro627Ala)	Pathogenic
449326	NM_001005361.3(DNM2):c.1852G>A (p.Ala618Thr)	Pathogenic
465283	NM_001005361.3(DNM2):c.1853C>A (p.Ala618Asp)	Pathogenic
637072	NM_001005361.3(DNM2):c.1739T>C (p.Met580Thr)	Pathogenic
7279	NM_001005361.3(DNM2):c.1106G>A (p.Arg369Gln)	Pathogenic
7280	NM_001005361.3(DNM2):c.1105C>T (p.Arg369Trp)	Pathogenic
7281	NM_001005361.3(DNM2):c.1393C>T (p.Arg465Trp)	Pathogenic
7282	NM_001005361.3(DNM2):c.1102G>A (p.Glu368Lys)	Pathogenic
7285	NM_001005361.3(DNM2):c.1856C>T (p.Ser619Leu)	Pathogenic
7286	NM_001005361.3(DNM2):c.1856C>G (p.Ser619Trp)	Pathogenic
157522	NM_001005361.3(DNM2):c.1241A>G (p.Lys414Arg)	Likely pathogenic
158513	NM_001005361.3(DNM2):c.1124T>A (p.Val375Glu)	Likely pathogenic
158515	NM_001005361.3(DNM2):c.1567A>G (p.Arg523Gly)	Likely pathogenic
1705621	NM_001005361.3(DNM2):c.1840G>A (p.Asp614Asn)	Likely pathogenic
218920	NM_001005361.3(DNM2):c.1021G>A (p.Glu341Lys)	Likely pathogenic
246082	NM_001005361.3(DNM2):c.1678G>A (p.Glu560Lys)	Likely pathogenic
2506371	NM_001005361.3(DNM2):c.1781G>A (p.Arg594Lys)	Likely pathogenic
373110	NM_001005361.3(DNM2):c.1565G>T (p.Arg522Leu)	Likely pathogenic
418164	NM_001005361.3(DNM2):c.1070C>T (p.Ser357Phe)	Likely pathogenic
580216	NM_001005361.3(DNM2):c.1463C>G (p.Thr488Arg)	Likely pathogenic
931135	NM_001005361.3(DNM2):c.1948G>A (p.Glu650Lys)	Likely pathogenic
982192	NM_001005361.3(DNM2):c.2204T>C (p.Ile735Thr)	Likely pathogenic
986927	NM_001005361.3(DNM2):c.1564C>T (p.Arg522Cys)	Likely pathogenic

SpliceAI

3457 predictions. Top by Δscore:

Variant	Effect	Δscore
19:10718400:GCCG:G	donor_gain	1.0000
19:10718402:CGG:C	donor_loss	1.0000
19:10718404:G:GG	donor_gain	1.0000
19:10759808:ACAGG:A	donor_loss	1.0000
19:10759809:CAGG:C	donor_loss	1.0000
19:10759810:AGG:A	donor_loss	1.0000
19:10759813:T:G	donor_loss	1.0000
19:10772474:TCTAG:T	acceptor_loss	1.0000
19:10772475:CTAGA:C	acceptor_loss	1.0000
19:10772476:TA:T	acceptor_loss	1.0000
19:10772477:A:AG	acceptor_gain	1.0000
19:10772478:G:GC	acceptor_gain	1.0000
19:10772478:GA:G	acceptor_gain	1.0000
19:10772478:GAA:G	acceptor_gain	1.0000
19:10772478:GAAC:G	acceptor_gain	1.0000
19:10772478:GAACA:G	acceptor_gain	1.0000
19:10772625:CACG:C	donor_loss	1.0000
19:10772627:CGG:C	donor_loss	1.0000
19:10772629:G:GA	donor_loss	1.0000
19:10772629:G:GG	donor_gain	1.0000
19:10772630:T:C	donor_loss	1.0000
19:10775688:T:A	acceptor_gain	1.0000
19:10775689:G:A	acceptor_gain	1.0000
19:10775701:A:AG	acceptor_gain	1.0000
19:10775701:AGT:A	acceptor_gain	1.0000
19:10775702:G:A	acceptor_loss	1.0000
19:10775702:G:GT	acceptor_gain	1.0000
19:10775702:GT:G	acceptor_gain	1.0000
19:10775702:GTG:G	acceptor_gain	1.0000
19:10775702:GTGT:G	acceptor_gain	1.0000

AlphaMissense

5730 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:10718354:G:C	G38R	1.000
19:10718355:G:A	G38D	1.000
19:10718362:G:C	Q40H	1.000
19:10718362:G:T	Q40H	1.000
19:10718369:G:C	G43R	1.000
19:10718370:G:A	G43D	1.000
19:10718372:A:C	K44Q	1.000
19:10718373:A:T	K44M	1.000
19:10718375:A:C	S45R	1.000
19:10718377:C:A	S45R	1.000
19:10718377:C:G	S45R	1.000
19:10759767:T:A	V64D	1.000
19:10759782:T:C	L69P	1.000
19:10759788:T:C	L71P	1.000
19:10772490:T:C	F83L	1.000
19:10772491:T:C	F83S	1.000
19:10772492:T:A	F83L	1.000
19:10772492:T:G	F83L	1.000
19:10772608:T:A	L122H	1.000
19:10772608:T:C	L122P	1.000
19:10775718:T:C	L134P	1.000
19:10775724:A:C	D136A	1.000
19:10775724:A:G	D136G	1.000
19:10775725:C:A	D136E	1.000
19:10775725:C:G	D136E	1.000
19:10775727:T:C	L137P	1.000
19:10775730:C:A	P138Q	1.000
19:10775732:G:C	G139R	1.000
19:10775733:G:A	G139D	1.000
19:10775832:T:C	L172P	1.000

dbSNP variants (sampled 300 via entrez): RS1000045407 (19:10806478 C>T), RS1000063359 (19:10730622 T>A), RS1000079692 (19:10729459 T>C), RS1000088653 (19:10803350 G>A), RS1000092441 (19:10768480 A>C), RS1000101949 (19:10797265 T>C), RS1000116383 (19:10762992 G>A), RS1000133472 (19:10763266 G>A), RS1000164861 (19:10731597 A>C), RS1000169505 (19:10803129 G>A), RS1000210739 (19:10771323 C>G,T), RS1000233471 (19:10811425 C>T), RS1000275803 (19:10726580 G>A,T), RS1000277477 (19:10739423 C>T), RS1000339124 (19:10731640 C>T)

Disease associations

OMIM: gene MIM:602378 | disease phenotypes: MIM:606482, MIM:160150, MIM:614408, MIM:118220, MIM:615368, MIM:601419, MIM:310400

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal dominant centronuclear myopathy	Strong	Autosomal dominant
Charcot-Marie-Tooth disease dominant intermediate B	Strong	Autosomal dominant
fetal akinesia-cerebral and retinal hemorrhage syndrome	Supportive	Autosomal recessive
autosomal dominant Charcot-Marie-Tooth disease type 2M	Supportive	Autosomal dominant
hereditary spastic paraplegia	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Charcot-Marie-Tooth disease	Definitive	AD
autosomal dominant centronuclear myopathy	Definitive	AD

Mondo (12): Charcot-Marie-Tooth disease dominant intermediate B (MONDO:0011674), autosomal dominant centronuclear myopathy (MONDO:0008048), centronuclear myopathy (MONDO:0018947), peripheral neuropathy (MONDO:0005244), Charcot-Marie-Tooth disease (MONDO:0015626), fetal akinesia-cerebral and retinal hemorrhage syndrome (MONDO:0014149), myofibrillar myopathy (MONDO:0018943), autosomal dominant Charcot-Marie-Tooth disease type 2M (MONDO:0016431), limb-girdle muscular dystrophy (MONDO:0016971), myopathy (MONDO:0005336), X-linked myotubular myopathy (MONDO:0010683), hereditary spastic paraplegia (MONDO:0019064)

Orphanet (10): Autosomal dominant intermediate Charcot-Marie-Tooth disease type B (Orphanet:100044), Autosomal dominant Charcot-Marie-Tooth disease type 2M (Orphanet:228179), Autosomal dominant centronuclear myopathy (Orphanet:169189), Centronuclear myopathy (Orphanet:595), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), Fetal akinesia-cerebral and retinal hemorrhage syndrome (Orphanet:363409), Myofibrillar myopathy (Orphanet:593), Limb-girdle muscular dystrophy (Orphanet:263), X-linked centronuclear myopathy (Orphanet:596), Moyamoya angiopathy (Orphanet:477768)

HPO phenotypes

78 total (30 of 78 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000020	Urinary incontinence
HP:0000028	Cryptorchidism
HP:0000467	Neck muscle weakness
HP:0000508	Ptosis
HP:0000544	External ophthalmoplegia
HP:0000573	Retinal hemorrhage
HP:0000597	Ophthalmoparesis
HP:0000762	Decreased nerve conduction velocity
HP:0000764	Peripheral axonal degeneration
HP:0000883	Thin ribs
HP:0001048	Cavernous hemangioma
HP:0001252	Hypotonia
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001371	Flexion contracture
HP:0001436	Abnormality of the foot musculature
HP:0001518	Small for gestational age
HP:0001520	Large for gestational age
HP:0001522	Death in infancy
HP:0001558	Decreased fetal movement
HP:0001561	Polyhydramnios
HP:0001761	Pes cavus
HP:0001771	Achilles tendon contracture
HP:0002021	Pyloric stenosis
HP:0002047	Malignant hyperthermia

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000975_6	LDL cholesterol	9.000000e-07
GCST002702_18	Height	5.000000e-11
GCST008103_119	Bipolar disorder	5.000000e-06
GCST010772_1	Hyperlipidemia (time to event)	5.000000e-08
GCST90020027_128	Waist-hip index	4.000000e-08
GCST90020028_1535	Hip circumference adjusted for BMI	3.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004918	age at diagnosis
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
D049288	Muscular Dystrophies, Limb-Girdle	C05.651.534.500.280; C10.668.491.175.500.149; C16.320.577.280
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820
C580316	Myofibrillar Myopathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5812 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

24 potent at pChembl≥5 of 40 total, top 24 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.54	IC50	290	nM	CHEMBL1094197
6.41	IC50	390	nM	CHEMBL1098764
6.36	IC50	440	nM	CHEMBL1094850
6.33	Kd	470.9	nM	CHEMBL5653589
6.33	ED50	470.9	nM	CHEMBL5653589
5.89	IC50	1300	nM	CHEMBL4073116
5.80	IC50	1600	nM	CHEMBL4098509
5.75	IC50	1800	nM	CHEMBL4083788
5.75	IC50	1800	nM	CHEMBL4064353
5.72	IC50	1900	nM	CHEMBL2312430
5.55	IC50	2800	nM	CHEMBL2312431
5.46	IC50	3500	nM	CHEMBL2312428
5.46	IC50	3500	nM	CHEMBL2312414
5.43	IC50	3700	nM	CHEMBL4073407
5.40	IC50	4000	nM	CHEMBL4060114
5.35	IC50	4500	nM	CHEMBL2312415
5.30	IC50	5000	nM	CHEMBL483059
5.29	IC50	5100	nM	CHEMBL4098509
5.22	IC50	6000	nM	CHEMBL4083788
5.21	IC50	6100	nM	CHEMBL4094056
5.17	IC50	6800	nM	CHEMBL2312432
5.08	IC50	8300	nM	CHEMBL4082410
5.07	IC50	8500	nM	CHEMBL4082410
5.06	IC50	8700	nM	CHEMBL4090457

PubChem BioAssay actives

23 with measured affinity, of 62 total; 20 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[3-[(6,7-dihydroxy-2-iminochromene-3-carbonyl)amino]propyl]-6,7-dihydroxy-2-iminochromene-3-carboxamide	480343: Inhibition of recombinant dynamin 2 expressed in Sf9 cells by malachite green GTPase assay	ic50	0.2900	uM
N-[3-[(7,8-dihydroxy-2-iminochromene-3-carbonyl)amino]propyl]-7,8-dihydroxy-2-iminochromene-3-carboxamide	480343: Inhibition of recombinant dynamin 2 expressed in Sf9 cells by malachite green GTPase assay	ic50	0.3900	uM
N-[2-[(7,8-dihydroxy-2-iminochromene-3-carbonyl)amino]ethyl]-7,8-dihydroxy-2-iminochromene-3-carboxamide	480343: Inhibition of recombinant dynamin 2 expressed in Sf9 cells by malachite green GTPase assay	ic50	0.4400	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148255: Binding affinity to human DNM2 incubated for 45 mins by Kinobead based pull down assay	kd	0.4709	uM
2-N-dodecyl-4-N,4-N,6-trimethylpyrimidine-2,4-diamine	1433928: Inhibition of phosphatidyl serine liposome-stimulated dynamin 2 GTPase activity (unknown origin) assessed as reduction orthophosphate release using GTP as substrate after 30 mins by malachite green reagent based colorimetric assay	ic50	1.3000	uM
4-N-decyl-2-N-[2-(dimethylamino)ethyl]-6-methylpyrimidine-2,4-diamine	1433928: Inhibition of phosphatidyl serine liposome-stimulated dynamin 2 GTPase activity (unknown origin) assessed as reduction orthophosphate release using GTP as substrate after 30 mins by malachite green reagent based colorimetric assay	ic50	1.6000	uM
2-N-cyclohexyl-4-N-[2-(dimethylamino)ethyl]-6-methylpyrimidine-2,4-diamine	1433928: Inhibition of phosphatidyl serine liposome-stimulated dynamin 2 GTPase activity (unknown origin) assessed as reduction orthophosphate release using GTP as substrate after 30 mins by malachite green reagent based colorimetric assay	ic50	1.8000	uM
6-N-decyl-4-N-[2-(dimethylamino)ethyl]pyrimidine-4,6-diamine	1433928: Inhibition of phosphatidyl serine liposome-stimulated dynamin 2 GTPase activity (unknown origin) assessed as reduction orthophosphate release using GTP as substrate after 30 mins by malachite green reagent based colorimetric assay	ic50	1.8000	uM
N-[[1-[3-(dimethylamino)propyl]indol-3-yl]methyl]decan-1-amine	722104: Inhibition of dyn2 in human U2OS cells assessed as clathrin-mediated endocytosis of Tfn after 30 mins	ic50	1.9000	uM
N-[[1-[3-(dimethylamino)propyl]indol-3-yl]methyl]dodecan-1-amine	722104: Inhibition of dyn2 in human U2OS cells assessed as clathrin-mediated endocytosis of Tfn after 30 mins	ic50	2.8000	uM
(E)-2-cyano-3-[1-[3-(dimethylamino)-2-hydroxypropyl]indol-3-yl]-N-octylprop-2-enamide	722104: Inhibition of dyn2 in human U2OS cells assessed as clathrin-mediated endocytosis of Tfn after 30 mins	ic50	3.5000	uM
N-[[1-[3-(dimethylamino)propyl]indol-3-yl]methyl]octan-1-amine	722104: Inhibition of dyn2 in human U2OS cells assessed as clathrin-mediated endocytosis of Tfn after 30 mins	ic50	3.5000	uM
4-N-decyl-2-N-[2-(dimethylamino)ethyl]pyrimidine-2,4-diamine	1433930: Inhibition of dynamin 2 in human U2OS cells assessed as reduction in clathrin-mediated endocytosis by measuring transferrin-A594 uptake preincubated for 30 mins followed by Tfn-A594 addition for 8 mins by DAPI staining based HTS assay	ic50	3.7000	uM
2-N-[2-(dimethylamino)ethyl]-4-N-hexyl-6-methylpyrimidine-2,4-diamine	1433928: Inhibition of phosphatidyl serine liposome-stimulated dynamin 2 GTPase activity (unknown origin) assessed as reduction orthophosphate release using GTP as substrate after 30 mins by malachite green reagent based colorimetric assay	ic50	4.0000	uM
(E)-2-cyano-3-[1-(2-hydroxy-3-pyrrolidin-1-ylpropyl)-2-methylindol-3-yl]-N-octylprop-2-enamide	722104: Inhibition of dyn2 in human U2OS cells assessed as clathrin-mediated endocytosis of Tfn after 30 mins	ic50	4.5000	uM
(E)-2-cyano-3-[1-[3-(dimethylamino)propyl]indol-3-yl]-N-octylprop-2-enamide	722104: Inhibition of dyn2 in human U2OS cells assessed as clathrin-mediated endocytosis of Tfn after 30 mins	ic50	5.0000	uM
2-N-[2-(dimethylamino)ethyl]-4-N-dodecylpyrimidine-2,4-diamine	1433930: Inhibition of dynamin 2 in human U2OS cells assessed as reduction in clathrin-mediated endocytosis by measuring transferrin-A594 uptake preincubated for 30 mins followed by Tfn-A594 addition for 8 mins by DAPI staining based HTS assay	ic50	6.1000	uM
N-[[1-[3-(dimethylamino)propyl]indol-3-yl]methyl]tetradecan-1-amine	722104: Inhibition of dyn2 in human U2OS cells assessed as clathrin-mediated endocytosis of Tfn after 30 mins	ic50	6.8000	uM
4-N-[2-(dimethylamino)ethyl]-6-N-dodecylpyrimidine-4,6-diamine	1433928: Inhibition of phosphatidyl serine liposome-stimulated dynamin 2 GTPase activity (unknown origin) assessed as reduction orthophosphate release using GTP as substrate after 30 mins by malachite green reagent based colorimetric assay	ic50	8.3000	uM
2-N-[2-(dimethylamino)ethyl]-6-methyl-4-N-octylpyrimidine-2,4-diamine	1433930: Inhibition of dynamin 2 in human U2OS cells assessed as reduction in clathrin-mediated endocytosis by measuring transferrin-A594 uptake preincubated for 30 mins followed by Tfn-A594 addition for 8 mins by DAPI staining based HTS assay	ic50	8.7000	uM

CTD chemical–gene interactions

55 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	4
Valproic Acid	affects cotreatment, increases expression, increases methylation	3
Air Pollutants	increases expression, affects cotreatment, decreases expression, increases abundance, increases oxidation	2
Smoke	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
bisphenol F	increases methylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
bisphenol A	affects cotreatment, increases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1
arsenite	increases reaction, affects binding	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
aflatoxin B2	decreases methylation	1
cupric chloride	increases expression	1
N-benzyloxycarbonylprolylprolinal	increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide	increases expression	1
CGP 52608	increases reaction, affects binding	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nilotinib	affects cotreatment, affects expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
bromovanin	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1

ChEMBL screening assays

15 unique, capped per target: 15 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1110055	Binding	Inhibition of recombinant dynamin 2 expressed in Sf9 cells by malachite green GTPase assay	Iminochromene inhibitors of dynamins I and II GTPase activity and endocytosis. — J Med Chem

Cellosaurus cell lines

3 cell lines: 2 transformed cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1335	KNS-62	Cancer cell line	Male
CVCL_AZ49	GM24268	Transformed cell line	Male
CVCL_D9DK	Ubigene HEK293 DNM2 KO	Transformed cell line	Female

Clinical trials (associated diseases)

350 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT00380965	PHASE4	COMPLETED	Evaluation of the Efficacy of Cesamet™ for the Treatment of Pain in Patients With Chemotherapy-Induced Neuropathy
NCT00487981	PHASE4	TERMINATED	Spinal Cord Stimulation for Painful Diabetic Neuropathy
NCT00904202	PHASE4	COMPLETED	A Study Of Lidocaine Patch 5% Alone, Gabapentin Alone, And Lidocaine Patch 5% And Gabapentin In Combination For The Relief Of Pain In Patients With Diverse Peripheral Neuropathic Pain Conditions
NCT01192113	PHASE4	COMPLETED	Safety and Efficacy of Mecobalamin Injection in Peripheral Neuropathies Patients (Study JGAZSY091109)
NCT01373983	PHASE4	COMPLETED	Intrathecal Bolus Doses of Ziconotide
NCT01458015	PHASE4	TERMINATED	Tapentadol Versus Oxycodone - a Mechanism-based Treatment Approach in Neuropathic Pain
NCT02074267	PHASE4	COMPLETED	Clinical Study for Assessment of the Efficacy of Gabapentin (Carbatin and Neurontin) in Patients With Neuropathy Pain
NCT02372149	PHASE4	UNKNOWN	IVIg for Demyelination in Diabetes Mellitus
NCT02670161	PHASE4	ENROLLING_BY_INVITATION	Quality Improvement and Practice Based Research in Neurology Using the EMR
NCT07022938	PHASE4	COMPLETED	Nutritional Supplement for Treating Chemotherapy Induced Neuropathy
NCT07025005	PHASE4	RECRUITING	Fenofibrate Role in the Prophylaxis From Peripheral Neuropathy Induced by Bortezomib, Lenalidomide and Dexamethasone (VRd) Protocol in the Treatment of Patients With Multiple Myeloma (MM)
NCT00058071	PHASE3	COMPLETED	Amifostine in Treating Peripheral Neuropathy in Patients Who Have Received Chemotherapy for Cancer
NCT00125268	PHASE3	TERMINATED	Near Infrared Light for the Treatment of Painful Peripheral Neuropathy
NCT00195013	PHASE3	COMPLETED	Randomized Placebo-Controlled Trial of Glutamine for Breast Cancer Patients With Peripheral Neuropathy
NCT00232141	PHASE3	COMPLETED	Study of Pregabalin Versus Placebo in the Treatment of Nerve Pain Associated With HIV Neuropathy
NCT00264875	PHASE3	COMPLETED	Open Label Safety And Efficacy Study Of Pregabalin In Subjects With Nerve Pain Asociated With Human Immunodeficiency Virus (HIV) Neuropathy
NCT00369564	PHASE3	COMPLETED	Glutamic Acid in Reducing Nerve Damage Caused by Vincristine in Young Patients With Cancer
NCT00471445	PHASE3	COMPLETED	Topical Amitriptyline and Ketamine Cream in Treating Peripheral Neuropathy Caused by Chemotherapy in Cancer Patients
NCT00489411	PHASE3	COMPLETED	Duloxetine in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer
NCT00710554	PHASE3	COMPLETED	A Study of Sativex® for Pain Relief of Peripheral Neuropathic Pain, Associated With Allodynia
NCT00711880	PHASE3	COMPLETED	A Study of Sativex® for Relief of Peripheral Neuropathic Pain Associated With Allodynia.
NCT00713323	PHASE3	COMPLETED	A Study to Compare the Safety and Tolerability of Sativex® in Patients With Neuropathic Pain.
NCT00713817	PHASE3	COMPLETED	A Study to Determine the Maintenance of Effect After Long-term Treatment of Sativex® in Subjects With Neuropathic Pain
NCT00775645	PHASE3	COMPLETED	S0715: Acetyl-L-Carnitine in Preventing Neuropathy in Women With Stage I, II, or IIIA Breast Cancer Undergoing Chemo
NCT00872352	PHASE3	UNKNOWN	Evaluation of Bortezomib Induced Peripheral Neuropathy of Multiple Myeloma (MM) Patients
NCT00998738	PHASE3	TERMINATED	Calcium and Magnesium in Preventing Peripheral Neuropathy Caused by Ixabepilone in Patients With Breast Cancer
NCT01049217	PHASE3	TERMINATED	Pregabalin Versus Placebo In The Treatment Of Neuropathic Pain Associated With HIV Neuropathy
NCT01099449	PHASE3	COMPLETED	Calcium Gluconate and Magnesium Sulfate in Preventing Neurotoxicity in Patients With Colon Cancer or Rectal Cancer Receiving Oxaliplatin-Based Combination Chemotherapy
NCT01288937	PHASE3	TERMINATED	A Placebo Controlled, Randomized, Double Blind Trial of Milnacipran for the Treatment of Idiopathic Neuropathy Pain
NCT01492920	PHASE3	WITHDRAWN	Acetyl-L-Carnitine Hydrochloride in Preventing Peripheral Neuropathy in Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer Undergoing Chemotherapy
NCT01775449	PHASE3	COMPLETED	Prevention of Oxaliplatin-induced Neuropathic Pain by a Specific Diet
NCT02024191	PHASE3	UNKNOWN	The Role of Glutamine for Preventing Oxaliplatin-Induced Peripheral Neuropathy
NCT02217267	PHASE3	COMPLETED	Long Term Outcome After Serial Lidocaine Infusion in Peripheral Neuropathic Pain
NCT02294149	PHASE3	UNKNOWN	Vit D3 and Omega 3 in Chemo Induced Neuropathy
NCT02311907	PHASE3	COMPLETED	Glutathione in Preventing Peripheral Neuropathy Caused by Paclitaxel and Carboplatin in Patients With Ovarian Cancer, Fallopian Tube Cancer, and/or Primary Peritoneal Cancer
NCT06071936	PHASE3	UNKNOWN	Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Traumatic or Post-operative Peripheral Neuropathy
NCT06071975	PHASE3	UNKNOWN	Long Term Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Diabetic Polyneuropathy
NCT06071988	PHASE3	UNKNOWN	Long Term Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Traumatic or Post-operative Peripheral Neuropathy
NCT06072573	PHASE3	UNKNOWN	Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Diabetic Polyneuropathy