DNM1

Summary

DNM1 (dynamin 1, HGNC:2972) is a protein-coding gene on chromosome 9q34.11, encoding Dynamin-1 (Q05193). Catalyzes the hydrolysis of GTP and utilizes this energy to mediate vesicle scission and participates in many forms of endocytosis, such as clathrin-mediated endocytosis or synaptic vesicle endocytosis as well as rapid endocytosis (RE).

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.

Source: NCBI Gene 1759 — RefSeq curated summary.

At a glance

• Gene–disease (curated): genetic developmental and epileptic encephalopathy (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 968 total — 26 pathogenic, 27 likely-pathogenic
• Phenotypes (HPO): 107
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_004408

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2972
Approved symbol	DNM1
Name	dynamin 1
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000106976
Ensembl biotype	protein_coding
OMIM	602377
Entrez	1759

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 14 protein_coding, 12 protein_coding_CDS_not_defined, 3 retained_intron, 3 nonsense_mediated_decay

ENST00000341179, ENST00000372923, ENST00000393594, ENST00000441149, ENST00000463998, ENST00000475805, ENST00000482638, ENST00000486160, ENST00000493925, ENST00000625457, ENST00000627061, ENST00000627543, ENST00000628346, ENST00000630850, ENST00000631179, ENST00000634267, ENST00000635766, ENST00000635859, ENST00000636103, ENST00000636201, ENST00000636220, ENST00000636280, ENST00000636760, ENST00000636874, ENST00000637094, ENST00000637317, ENST00000637999, ENST00000638030, ENST00000638061, ENST00000706053, ENST00000706054, ENST00000965157

RefSeq mRNA: 6 — MANE Select: NM_004408 NM_001005336, NM_001288737, NM_001288738, NM_001288739, NM_001374269, NM_004408

CCDS: CCDS43882, CCDS6895, CCDS75911, CCDS75912, CCDS94491

Canonical transcript exons

ENST00000372923 — 22 exons

Exon	Start	End
ENSE00001607425	128248583	128248753
ENSE00001674469	128218231	128218304
ENSE00001686999	128247924	128247935
ENSE00001728908	128250725	128250940
ENSE00003458973	128239445	128239515
ENSE00003470783	128242232	128242345
ENSE00003514879	128250115	128250356
ENSE00003533094	128219988	128220086
ENSE00003574406	128234021	128234107
ENSE00003585102	128222197	128222339
ENSE00003601246	128222793	128222860
ENSE00003615820	128224251	128224389
ENSE00003625707	128239985	128239996
ENSE00003631161	128219049	128219252
ENSE00003650115	128246394	128246503
ENSE00003656925	128220181	128220341
ENSE00003664090	128218582	128218731
ENSE00003666449	128222461	128222596
ENSE00003674513	128247375	128247486
ENSE00003687858	128239728	128239779
ENSE00003902110	128254654	128255244
ENSE00003902655	128203379	128203631

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 99.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.3550 / max 797.0974, expressed in 1438 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98735	11.8872	1194
98736	8.6629	1102
98741	3.2823	547
98734	2.3149	708
98742	0.1121	46
98738	0.0597	31
98739	0.0359	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	99.90	gold quality
cerebellar hemisphere	UBERON:0002245	99.88	gold quality
cerebellar cortex	UBERON:0002129	99.87	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.84	gold quality
cerebellum	UBERON:0002037	99.77	gold quality
middle temporal gyrus	UBERON:0002771	99.65	gold quality
superior frontal gyrus	UBERON:0002661	99.62	gold quality
right frontal lobe	UBERON:0002810	99.56	gold quality
frontal pole	UBERON:0002795	99.49	gold quality
paraflocculus	UBERON:0005351	99.49	gold quality
parietal lobe	UBERON:0001872	99.41	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.41	gold quality
postcentral gyrus	UBERON:0002581	99.37	gold quality
orbitofrontal cortex	UBERON:0004167	99.33	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.30	gold quality
frontal cortex	UBERON:0001870	99.29	gold quality
CA1 field of hippocampus	UBERON:0003881	99.27	gold quality
primary visual cortex	UBERON:0002436	99.26	gold quality
cerebellar vermis	UBERON:0004720	99.26	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.26	gold quality
occipital lobe	UBERON:0002021	99.23	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.22	gold quality
pons	UBERON:0000988	99.12	gold quality
prefrontal cortex	UBERON:0000451	99.11	gold quality
entorhinal cortex	UBERON:0002728	99.09	gold quality
neocortex	UBERON:0001950	98.93	gold quality
cingulate cortex	UBERON:0003027	98.92	gold quality
anterior cingulate cortex	UBERON:0009835	98.91	gold quality
temporal lobe	UBERON:0001871	98.89	gold quality
cerebral cortex	UBERON:0000956	98.81	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	42.23
E-ANND-3	yes	10.10
E-GEOD-137537	no	1180.57
E-MTAB-7381	no	254.41

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP3, YY1

miRNA regulators (miRDB)

43 targeting DNM1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-8064	99.45	66.92	875
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-140-3P	99.04	67.69	1324
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-1228-3P	99.00	66.53	857
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-496	98.66	69.80	931

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

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)
• dynamin-dependent endocytosis is inhibited by syntaphilin (PMID:12896979)
• serglycin-bound granzyme B in high-molecular-weight degranulate material from cytotoxic T lymphocytes predominantly followed a dynamin-dependent pathway to kill target cells (PMID:14739229)
• Point mutations were made in the GTPase effector/assembly domain (GED)of dynamin 1 and tested for their effects on self-assembly and clathrin-mediated endocytosis. (PMID:15004222)
• dynamin-1 interacts with Sumo-1, Ubc9, and PIAS-1, all of which are members of the sumoylation machinery (PMID:15123615)
• Dynamin GTPase domain is important for GTP binding, GTP hydrolysis, and clathrin-mediated endocytosis (PMID:15262989)
• dynamin, Cbl, and Src coordinately participate in signaling complexes that are important in the assembly and remodeling of the actin cytoskeleton, leading to changes in osteoclast adhesion, migration, and resorption (PMID:15872089)
• S-nitrosylation of dynamin regulates endocytosis through nitric oxide (PMID:16432212)
• PLD functions as a GTPase activating protein (GAP) through its phox homology domain (PX), which directly activates the GTPase domain of dynamin and increased epidermal growth factor receptor (EGFR) endocytosis at physiological EGF concentrations. (PMID:16622417)
• Data show that swapping the highly homologous GTPase domain of dynamin-2 into dynamin-1 is sufficient to confer caspase-3 activation. (PMID:16938290)
• Two mutations in middle domain, R361S and R399A, disrupt the tetrameric structure of dynamin in the unassembled state and impair its ability to stably bind to and nucleate higher-order self-assembly on membranes. (PMID:17170701)
• Pockets of short-range transient order and restricted topological heterogeneity in the guanidine-denatured state ensemble of GED of DNM1. (PMID:17910478)
• Data show that dynamin-1 is an inclusion body component in neuronal intranuclear inclusion disease identified by anti-SUMO-1-immunocapture. (PMID:18836734)
• our findings indicate that DNM1 is likely involved in the etiology of nicotine dependence and represents a plausible candidate for further investigation in independent samples (PMID:18987626)
• This protein has been found differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19110265)
• Data suggest that the components of the GTPase-GED interface act as an intramolecular signaling module, which we term the bundle signaling element, that can modulate dynamin function in vitro and in vivo. (PMID:19515832)
• The ability of dynamin to alter the local distribution of PtdIns(4,5)P(2) could be crucial for the role of this GTPase in promoting membrane scission during clathrin-mediated endocytosis. (PMID:19666604)
• Results demonstrate that, in concert with dynamin-1 self-assembly, pleckstrin homology domain membrane insertion is essential for fission and vesicle release in vitro and for clathrin-mediated endocytosis in vivo. (PMID:19776347)
• Endocytosis of FcalphaR is clathrin- and dynamin-dependent, but is not regulated by Rab5, and the endocytic motif is not located in the cytoplasmic domain of FcalphaR. (PMID:19859085)
• 2.0 A resolution crystal structure of a human dynamin 1-derived minimal GTPase-GED fusion protein, which was dimeric in the presence of the transition state mimic GDP.AlF(4)(-) (PMID:20428113)
• In conclusion, Clostridium botulinum C2 toxin is endocytosed by dynamin-dependent mechanisms and we provide evidence for involvement of clathrin and Rho. (PMID:20690924)
• The authors find that HIV-1 entry into macrophages is sensitive to inhibitors of Na(+)/H(+) exchange, actin rearrangement, dynamin, Rac1, and Pak1. (PMID:21056892)
• A new role for the dynamin-1 GTPase in the regulation of fusion pore expansion (PMID:21460182)
• crystal structure of human dynamin 1 in the nucleotide-free state with a four-domain architecture comprising the GTPase domain, the bundle signalling element, the stalk and the pleckstrin homology domain. (PMID:21927000)
• Study presents the GMPPCP-bound structures of the truncated human dynamin 1 helical polymer at 12.2 A and a fusion protein, GG, linking human dynamin 1’s catalytic G domain to its GTPase effector domain (GED) at 2.2 A. (PMID:21962517)
• Herpes simplex virus type 1 can enter human keratinocytes by alternative entry pathways that require dynamin and host cholesterol. (PMID:22022400)
• dyn1 affects amyloid generation through regulation of BACE-1 subcellular localization and therefore its enzymatic activities. (PMID:23024787)
• analysis of how the membrane interactions of disease-related dynorphin A variants cause differences in cell toxicity (PMID:23705820)
• The discovery that the pre-mRNA sequence of dnm1 in humans has sequence features similar to that of the alternative splicing patterns observed in insects greatly expands the applicability of the docking site-selector sequence pairing model to bilaterian animals. (PMID:23793749)
• activity-dependent acceleration is only prominent at physiological temperature and that the mechanism of this modulation is based on the dephosphorylation of dynamin 1 (PMID:23908769)
• Alternate pleckstrin homology domain orientations regulate dynamin-catalyzed membrane fission. (PMID:24478459)
• Dynamin1 is associated with both preserved cognition and regenerative responses in older people with cerebrovascular disease and may represent a novel treatment target. (PMID:24486840)
• Data suggest that dynorphin A (DynA) is ligand for opioid receptor kappa (KOR); upon DynA binding, only small chemical shifts observed in second extracellular loop of KOR; chemical shift changes of DynA show conclusively that DynA interacts with KOR. (PMID:24616919)
• Data show that the classical dynamin DNM1 and DNM3 genes reach their maximum expression levels (100% of maximal expression) in all normal central nervous system tissues studied. (PMID:24673776)
• findings show NDPKs (NM23-H1/H2/H4) interact with and provide GTP to dynamins, allowing these motor proteins to work with high thermodynamic efficiency for membrane remodeling (PMID:24970086)
• determined the alpha-synuclein-binding domain of beta-III tubulin and demonstrated that a short fragment containing this domain can suppress alpha-synuclein accumulation in the primary cultured cells (PMID:25031323)
• This study identified and confirmed DNM1 protein changes within the postsynaptic density in schizophrenia. (PMID:25048004)
• Dynamin 1 and dynamin 2 activity are not essential for Chlamydia trachomatis internalization but is required for normal development. (PMID:25116793)
• De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies. (PMID:25262651)
• The rare variants in DNM1 were significantly associated with smoking status. (PMID:25450229)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnm1b	ENSDARG00000009281
danio_rerio	dnm1a	ENSDARG00000010042
mus_musculus	Dnm1	ENSMUSG00000026825
rattus_norvegicus	Dnm1	ENSRNOG00000033835

Paralogs (6): DNM2 (ENSG00000079805), DNM1L (ENSG00000087470), MX1 (ENSG00000157601), MX2 (ENSG00000183486), DNM3 (ENSG00000197959), OPA1 (ENSG00000198836)

Protein

Protein identifiers

Dynamin-1 — Q05193 (reviewed: Q05193)

Alternative names: Dynamin, Dynamin I

All UniProt accessions (11): Q05193, A0A0D9SFB1, A0A0D9SFE4, A0A0D9SFP1, A0A0U1RQP1, A0A1B0GU67, A0A1B0GUX5, A0A1B0GVK6, A0A994J5P0, A0A994J7J4, H7C5U0

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolysis of GTP and utilizes this energy to mediate vesicle scission and participates in many forms of endocytosis, such as clathrin-mediated endocytosis or synaptic vesicle endocytosis as well as rapid endocytosis (RE). Associates to the membrane, through lipid binding, and self-assembles into rings and stacks of interconnected rings through oligomerization to form a helical polymer around the vesicle membrane leading to constriction of invaginated coated pits around their necks. Self-assembly of the helical polymer induces membrane tubules narrowing until the polymer reaches a length sufficient to trigger GTP hydrolysis. Depending on the curvature imposed on the tubules, membrane detachment from the helical polymer upon GTP hydrolysis can cause spontaneous hemifission followed by complete fission. May play a role in regulating early stages of clathrin-mediated endocytosis in non-neuronal cells through its activation by dephosphorylation via the signaling downstream of EGFR. Controls vesicle size at a step before fission, during formation of membrane pits, at hippocampal synapses. Controls plastic adaptation of the synaptic vesicle recycling machinery to high levels of activity. Mediates rapid endocytosis (RE), a Ca(2+)-dependent and clathrin- and K(+)-independent process in chromaffin cells. Microtubule-associated force-producing protein involved in producing microtubule bundles and able to bind and hydrolyze GTP. Through its interaction with DNAJC6, acts during the early steps of clathrin-coated vesicle (CCV) formation.

Subunit / interactions. Homodimer; homodimerization is mediated by the dynamin-type G domain which promotes assembly-stimulated GTPase activity. Homo-tetramer formed from two dimers in the absence of lipid. Oligomerizes into a helical polymer that self-assembles around the vesicle membrane, when associated to the menbrane through lipid binding. Interacts (via C-terminal proline-rich domain (PRD)) with SNX9 (via SH3 domain); this interaction allows regulation of DNM1 self-assembly during late stages of endocytic vesicle formation and supports DNM1’s early functions in accelerating clathrin-coated pits (CCPs) maturation in non neuronals cell. Interacts (via C-terminal proline-rich domain (PRD)) with MYO1E (via SH3 domain); this interaction regulates receptor-mediated endocytosis. Interacts with SNX33 (via SH3 domain); this interaction decreases DNM1-dependent endocytosis. Interacts with DIAPH1. Interacts with GRB2 (via SH3 domain); this interaction mediates disassembly of DNM1 polymers, therefore modulates self-assembly. Forms a complex with BIN1 (via SH3 domain) and SH3GL2 (via SH3 domain). Forms a complex with SH3GL2 (via SH3 domain) and AMPH (via SH3 domain). Forms a complex with SH3GL2 (via SH3 domain) and SYNJ1. Interacts with AMPH. Interacts (via C-terminal proline-rich domain (PRD)) with SYT1; this interaction facilitates vesicle fission during clathrin-mediated endocytosis (CME). Interacts (via C-terminal proline-rich domain (PRD)) with PLCG1 (via SH3 domain); this interaction stimulates the release of GDP from DNM1 and enhances DNM1-dependent endocytosis. Interacts with SNPH; this interaction inhibits the binding of DNM1 to AMPH and DNM1-receptor-mediated endocytosis. Interacts with CAV1. Interacts with SH3GLB1 (via SH3 domain). Interacts with PACSIN1 (via SH3 domain), PACSIN2 (via SH3 domain) and PACSIN3 (via SH3 domain). Interacts with UNC119; this interaction decreases DNM1’s GTPase activity and affects DNM1’s interaction with AMPH. Interacts (GTP-bound form) with DNAJC6; this interaction allows clathrin-coated vesicle (CCV) formation at the plasma membrane.

Subcellular location. Cell membrane. Membrane. Clathrin-coated pit. Cytoplasmic vesicle. Presynapse. Secretory vesicle. Chromaffin granule.

Post-translational modifications. Phosphorylation at Ser-774 by GSK3B/GSK3-beta leads to inactivation of receptor-mediated endocytosis in non-neuronal cells. Dephosphorylation at Ser-774, through the EGFR downstream signaling, leads to activation and regulates early stages of clathrin-mediated endocytosis (CME). Phosphorylated by CDK5 leading to synaptic vesicle endocytosis (SVE) activation.

Disease relevance. Developmental and epileptic encephalopathy 31A (DEE31A) [MIM:616346] An autosomal dominant epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. The disease is caused by variants affecting the gene represented in this entry. Developmental and epileptic encephalopathy 31B (DEE31B) [MIM:620352] A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE31B is an autosomal recessive form with onset in the first months of life. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. GTPase activity is activated by 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate. GTPase activity is inhibited by the heterodimer G protein formed by GNB1 and GNG2 with an IC(50)=400 nM when DNM1 concentration is 5 nM.

Domain organisation. The dynamin-type G mediates homodimerization and plays a role in self-assembly. The C-terminal proline-rich domain (PRD) mediates interaction with SH3-binding partners. Is required for DNM1 self-assembly. The PH domain binds phosphoinositides such as 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate, 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate and 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate, and mediates receptor-mediated endocytosis.

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q05193-1	1	yes
Q05193-2	2
Q05193-3	3
Q05193-5	4

RefSeq proteins (6): NP_001005336, NP_001275666, NP_001275667, NP_001275668, NP_001361198, NP_004399* (*=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 (122 total): helix 30, strand 19, mutagenesis site 19, binding site 13, modified residue 13, sequence variant 7, region of interest 6, turn 5, domain 3, sequence conflict 3, splice variant 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

22 structures.

PDB	Method	Resolution (Å)
5D3Q	X-RAY DIFFRACTION	1.7
6S9A	X-RAY DIFFRACTION	1.86
2X2E	X-RAY DIFFRACTION	2
2X2F	X-RAY DIFFRACTION	2
1DYN	X-RAY DIFFRACTION	2.2
3ZYC	X-RAY DIFFRACTION	2.2
2DYN	X-RAY DIFFRACTION	2.3
8SZ7	ELECTRON MICROSCOPY	2.84
8SZ4	ELECTRON MICROSCOPY	2.86
8SXZ	ELECTRON MICROSCOPY	3.26
8TYN	ELECTRON MICROSCOPY	3.26
8SZ8	ELECTRON MICROSCOPY	3.55
8T0K	ELECTRON MICROSCOPY	3.58
8TYM	ELECTRON MICROSCOPY	3.58
3SNH	X-RAY DIFFRACTION	3.7
7AX3	ELECTRON MICROSCOPY	3.74
6DLU	ELECTRON MICROSCOPY	3.75
8T0R	ELECTRON MICROSCOPY	3.97
6DLV	ELECTRON MICROSCOPY	10.1
3ZYS	ELECTRON MICROSCOPY	12.2
4UUD	ELECTRON MICROSCOPY	12.5
4UUK	ELECTRON MICROSCOPY	12.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q05193-F1	78.87	0.38

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 (13): 80, 125, 125, 306, 347, 354, 512, 774, 778, 796, 822, 851, 857

Mutagenesis-validated functional residues (19):

Position	Phenotype
40	impairs assembly-stimulated gtpase activity. does not affect basal gtpase activity. does not affect membrane binding. do
41	impairs assembly-stimulated gtpase activity. does not affect basal gtpase activity. does not affect membrane binding. do
44	inhibits receptor-mediated endocytosis. significantly decreases endocytosis. impairs receptor-mediated endocytosis. impa
180	inhibits assembly-stimulated gtpase activity. significantly increases basal gtpase activity does not affect membrane bin
290	does not significantly affect receptor-mediated endocytosis; when associated with a-291 and a-292.
291	does not significantly affect receptor-mediated endocytosis; when associated with a-290 and a-292.
292	does not significantly affect receptor-mediated endocytosis; when associated with a-290 and a-291.
292	substantially reduces receptor-mediated endocytosis; whena ssociated with a-293 and a-294.
293	substantially reduces receptor-mediated endocytosis; whena ssociated with a-292 and a-294.
294	does not significantly affect receptor-mediated endocytosis. substantially reduces receptor-mediated endocytosis; whena
330	significantly decreases receptor-mediated endocytosis; when associated with r-334 and r-702.
334	significantly decreases receptor-mediated endocytosis; when associated with r-330 and r-702.
406	significantly decreases receptor-mediated endocytosis; when associated with r-407 and w-488.
407	significantly decreases receptor-mediated endocytosis; when associated with r-406 and w-488.
488	significantly decreases receptor-mediated endocytosis; when associated with r-406 and w-407.
591–602	abolishes 1-phosphatidyl-1d-myo-inositol 4,5-bisphosphate binding. impairs receptor-mediated endocytosis. impairs recept
702	significantly decreases endocytosis; when associated with r-330 and r-334.
774	increases clathrin-mediated endocytosis (cme); when associated with a-778. increases interaction with snx9; when associa
778	increases clathrin-mediated endocytosis (cme); when associated with a-774. increases interaction with snx9; when associa

Function

Pathways and Gene Ontology

Reactome pathways

8 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-2132295	MHC class II antigen presentation
R-HSA-3928665	EPH-ephrin mediated repulsion of cells
R-HSA-437239	Recycling pathway of L1
R-HSA-8856828	Clathrin-mediated endocytosis

MSigDB gene sets: 409 (showing top): REACTOME_RETROGRADE_NEUROTROPHIN_SIGNALLING, GOBP_SYNAPTIC_VESICLE_LOCALIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, MODULE_274, PAX4_01, GOBP_ENDOSOME_ORGANIZATION, TGCGCANK_UNKNOWN, GOBP_PROTEIN_HOMOTETRAMERIZATION, GOBP_VESICLE_LOCALIZATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, BIOCARTA_BARRESTIN_SRC_PATHWAY

GO Biological Process (9): endocytosis (GO:0006897), receptor-mediated endocytosis (GO:0006898), endosome organization (GO:0007032), synaptic vesicle budding from presynaptic endocytic zone membrane (GO:0016185), protein homooligomerization (GO:0051260), protein homotetramerization (GO:0051289), regulation of vesicle size (GO:0097494), clathrin coat assembly involved in endocytosis (GO:0099049), vesicle scission (GO:0099050)

GO Molecular Function (13): RNA binding (GO:0003723), GTPase activity (GO:0003924), GTP binding (GO:0005525), phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), phosphatidylinositol-3,4,5-trisphosphate binding (GO:0005547), microtubule binding (GO:0008017), GDP binding (GO:0019003), protein kinase binding (GO:0019901), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (12): cytoplasm (GO:0005737), microtubule (GO:0005874), plasma membrane (GO:0005886), clathrin-coated pit (GO:0005905), endocytic vesicle (GO:0030139), chromaffin granule (GO:0042583), synapse (GO:0045202), extracellular exosome (GO:0070062), presynapse (GO:0098793), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Toll-like Receptor Cascades	1
Signaling by NTRK1 (TRKA)	1
Gap junction trafficking	1
Gap junction degradation	1
Adaptive Immune System	1
EPH-Ephrin signaling	1
L1CAM interactions	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
guanyl ribonucleotide binding	2
phosphatidylinositol phosphate binding	2
anion binding	2
membrane	2
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
endocytosis	1
endomembrane system organization	1
vesicle organization	1
synaptic vesicle endocytosis	1
synaptic vesicle budding	1
protein complex oligomerization	1
protein homooligomerization	1
protein tetramerization	1
regulation of cellular component size	1
clathrin coat assembly	1
clathrin-dependent endocytosis	1
membrane fission	1
nucleic acid binding	1
ribonucleoside triphosphate phosphatase activity	1
purine ribonucleoside triphosphate binding	1
phosphatidylinositol bisphosphate binding	1
tubulin binding	1
kinase binding	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
cell periphery	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

3254 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNM1	FIS1	Q9Y3D6	997
DNM1	BIN1	O00499	985
DNM1	AMPH	P49418	974
DNM1	ITSN1	Q15811	928
DNM1	SYNJ1	O43426	867
DNM1	CLTC	Q00610	845
DNM1	PFN1	P07737	814
DNM1	PEX11A	O75192	778
DNM1	MFN2	O95140	766
DNM1	PACSIN1	Q9BY11	753
DNM1	ITSN2	Q9NZM3	735
DNM1	CTTN	Q14247	725
DNM1	HCLS1	P14317	723
DNM1	SYN1	P17600	718
DNM1	EEA1	Q15075	711

IntAct

160 interactions, top by confidence:

A	B	Type	Score
DNM1	DNM1	psi-mi:“MI:0407”(direct interaction)	0.930
APP	APBB1	psi-mi:“MI:0914”(association)	0.910
GRB2	DNM1	psi-mi:“MI:0915”(physical association)	0.900
GRB2	DNM1	psi-mi:“MI:0407”(direct interaction)	0.900
DNM1	GRB2	psi-mi:“MI:0915”(physical association)	0.900
DNM1	SNX9	psi-mi:“MI:0915”(physical association)	0.870
DNM1	SNX9	psi-mi:“MI:0407”(direct interaction)	0.870
DNM1	AMPH	psi-mi:“MI:0407”(direct interaction)	0.820
AMPH	DNM1	psi-mi:“MI:0407”(direct interaction)	0.820
SNX9	SYNJ1	psi-mi:“MI:0914”(association)	0.790

BioGRID (200): BIN1 (Protein-peptide), SUMO1 (Co-crystal Structure), DNM1 (Affinity Capture-MS), DNM1 (Affinity Capture-MS), DNM1 (Affinity Capture-MS), DNM1 (Affinity Capture-MS), DNM1 (Affinity Capture-MS), DNM1 (Affinity Capture-MS), DNM1 (Affinity Capture-MS), RPE (Co-fractionation), DNM1 (Affinity Capture-MS), DNM1 (Co-localization), DNM1 (Affinity Capture-MS), DNM1 (Affinity Capture-MS), DNM1 (Affinity Capture-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

11 interactions.

A	Effect	B	Mechanism
DYRK1A	down-regulates	DNM1	phosphorylation
SNX9	up-regulates	DNM1	binding
SRC	“up-regulates activity”	DNM1	phosphorylation
DNM1	up-regulates	Synaptic_vesicle_recycling
DNM1	“up-regulates activity”	SYP	binding
DNM1	“up-regulates activity”	MYO1E	binding
PRKCA	unknown	DNM1	phosphorylation
CDK5	“up-regulates activity”	DNM1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 117 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
RHO GTPases Activate WASPs and WAVEs	5	21.4×	2e-04
FCGR3A-mediated phagocytosis	7	17.7×	1e-05
trans-Golgi Network Vesicle Budding	5	17.1×	6e-04
Golgi Associated Vesicle Biogenesis	6	16.2×	2e-04
Clathrin-mediated endocytosis	14	16.1×	6e-11
Recycling pathway of L1	5	15.1×	1e-03
Regulation of actin dynamics for phagocytic cup formation	5	12.4×	2e-03
Membrane Trafficking	14	7.0×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
synaptic vesicle endocytosis	5	22.1×	1e-03
ephrin receptor signaling pathway	5	17.6×	2e-03
positive regulation of actin filament polymerization	5	16.9×	2e-03
endocytosis	15	14.6×	1e-10
neuron projection morphogenesis	5	14.1×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	26
Likely pathogenic	27
Uncertain significance	359
Likely benign	400
Benign	71

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1011518	NM_004408.4(DNM1):c.2296C>T (p.Gln766Ter)	Pathogenic
1386547	NM_004408.4(DNM1):c.767del (p.Arg256fs)	Pathogenic
1443519	NM_004408.4(DNM1):c.2299dup (p.Ser767fs)	Pathogenic
1474244	NM_004408.4(DNM1):c.2434dup (p.Ala812fs)	Pathogenic
156557	NM_004408.4(DNM1):c.529G>C (p.Ala177Pro)	Pathogenic
156558	NM_004408.4(DNM1):c.618G>C (p.Lys206Asn)	Pathogenic
1705841	NM_004408.4(DNM1):c.590-2A>G	Pathogenic
190311	NM_004408.4(DNM1):c.865A>T (p.Ile289Phe)	Pathogenic
2094695	NM_004408.4(DNM1):c.1626del (p.Trp542fs)	Pathogenic
2500127	NM_004408.4(DNM1):c.850C>T (p.Gln284Ter)	Pathogenic
2500128	NM_004408.4(DNM1):c.350del (p.Pro117fs)	Pathogenic
2578048	NM_004408.4(DNM1):c.1181A>G (p.Asn394Ser)	Pathogenic
2729722	NM_004408.4(DNM1):c.416G>C (p.Gly139Ala)	Pathogenic
2755885	NM_004408.4(DNM1):c.197G>C (p.Arg66Pro)	Pathogenic
280148	NM_004408.4(DNM1):c.709C>T (p.Arg237Trp)	Pathogenic
3245261	NC_000009.11:g.(?130980490)(130996406_?)del	Pathogenic
3572927	NM_004408.4(DNM1):c.194C>A (p.Thr65Asn)	Pathogenic
3637806	NM_004408.4(DNM1):c.1321C>T (p.Gln441Ter)	Pathogenic
421089	NM_004408.4(DNM1):c.1037G>T (p.Gly346Val)	Pathogenic
4685075	NM_004408.4(DNM1):c.520G>A (p.Val174Met)	Pathogenic
4745019	NM_004408.4(DNM1):c.539A>C (p.Asp180Ala)	Pathogenic
520433	NM_004408.4(DNM1):c.1036G>A (p.Gly346Ser)	Pathogenic
520569	NM_004408.4(DNM1):c.1190G>A (p.Gly397Asp)	Pathogenic
520714	NM_004408.4(DNM1):c.713G>T (p.Ser238Ile)	Pathogenic
520737	NM_004408.4(DNM1):c.1075G>A (p.Gly359Arg)	Pathogenic
587399	NM_004408.4(DNM1):c.1090_1091insTTCCAC (p.Asn363_Arg364insLeuPro)	Pathogenic
1067855	NM_004408.4(DNM1):c.1726G>A (p.Glu576Lys)	Likely pathogenic
1802580	NM_004408.4(DNM1):c.2045C>G (p.Pro682Arg)	Likely pathogenic
1803020	NM_004408.4(DNM1):c.1943T>C (p.Met648Thr)	Likely pathogenic
1803021	NM_004408.4(DNM1):c.415_423del (p.Gly139_Thr141del)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

5690 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:128203574:C:A	A35D	1.000
9:128203582:G:C	G38R	1.000
9:128203583:G:A	G38D	1.000
9:128203590:G:C	Q40H	1.000
9:128203590:G:T	Q40H	1.000
9:128203591:A:C	S41R	1.000
9:128203593:C:A	S41R	1.000
9:128203593:C:G	S41R	1.000
9:128203595:C:A	A42D	1.000
9:128203597:G:C	G43R	1.000
9:128203597:G:T	G43C	1.000
9:128203598:G:A	G43D	1.000
9:128203598:G:T	G43V	1.000
9:128203600:A:C	K44Q	1.000
9:128203600:A:G	K44E	1.000
9:128203601:A:T	K44M	1.000
9:128203602:G:C	K44N	1.000
9:128203602:G:T	K44N	1.000
9:128203603:A:C	S45R	1.000
9:128203603:A:T	S45C	1.000
9:128203605:C:A	S45R	1.000
9:128203605:C:G	S45R	1.000
9:128203613:T:A	L48H	1.000
9:128203613:T:C	L48P	1.000
9:128203616:A:T	E49V	1.000
9:128218239:T:C	L57S	1.000
9:128218247:G:A	G60R	1.000
9:128218247:G:C	G60R	1.000
9:128218248:G:A	G60E	1.000
9:128218260:T:A	V64D	1.000

dbSNP variants (sampled 300 via entrez): RS1000022094 (9:128212095 C>T), RS1000033489 (9:128212452 G>GCAACA), RS1000046045 (9:128254083 A>G,T), RS1000102936 (9:128228044 T>G), RS1000145942 (9:128247233 G>A), RS1000155628 (9:128247632 G>T), RS1000167695 (9:128237842 T>A,C), RS1000200343 (9:128206636 G>A,T), RS1000214497 (9:128231578 G>T), RS1000309489 (9:128231899 G>A), RS1000380960 (9:128203908 C>T), RS1000398800 (9:128253872 GGCCTGTT>G), RS1000641942 (9:128233221 A>G), RS1000707046 (9:128226564 C>T), RS1000718859 (9:128223417 T>A)

Disease associations

OMIM: gene MIM:602377 | disease phenotypes: MIM:616346, MIM:606369, MIM:620352, MIM:308350

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 31A	Strong	Autosomal dominant
developmental and epileptic encephalopathy, 31B	Strong	Autosomal recessive
Lennox-Gastaut syndrome	Supportive	Autosomal dominant
undetermined early-onset epileptic encephalopathy	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
genetic developmental and epileptic encephalopathy	Moderate	AR
genetic developmental and epileptic encephalopathy	Definitive	AD

Mondo (9): developmental and epileptic encephalopathy, 31A (MONDO:0014598), Lennox-Gastaut syndrome (MONDO:0016532), infantile spasms (MONDO:0018097), developmental and epileptic encephalopathy (MONDO:0100620), developmental and epileptic encephalopathy, 31B (MONDO:0957248), epilepsy (MONDO:0005027), intellectual disability (MONDO:0001071), developmental and epileptic encephalopathy, 1 (MONDO:0010632), undetermined early-onset epileptic encephalopathy (MONDO:0018614)

Orphanet (4): Lennox-Gastaut syndrome (Orphanet:2382), West syndrome (Orphanet:3451), Infantile epileptic spasms syndrome (Orphanet:697160), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

107 total (30 of 107 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000212	Gingival overgrowth
HP:0000252	Microcephaly
HP:0000283	Broad face
HP:0000341	Narrow forehead
HP:0000348	High forehead
HP:0000369	Low-set ears
HP:0000494	Downslanted palpebral fissures
HP:0000504	Abnormality of vision
HP:0000508	Ptosis
HP:0000546	Retinal degeneration
HP:0000637	Long palpebral fissure
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000668	Hypodontia
HP:0000708	Atypical behavior
HP:0000709	Psychosis
HP:0000717	Autism
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000737	Irritability
HP:0000741	Apathy
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000246_22	Attention deficit hyperactivity disorder	2.000000e-06
GCST003523_13	Coenzyme Q10 levels	3.000000e-06
GCST005951_65	Body mass index	5.000000e-09
GCST90002401_494	Platelet distribution width	2.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007836	coenzyme Q10 measurement
EFO:0004340	body mass index
EFO:0007984	platelet component distribution width

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065768	Lennox Gastaut Syndrome	C10.228.140.490.493.750; C16.320.495

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4958 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 6,829 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL5219790	CETRIMIDE	4
CHEMBL589390	LATREPIRDINE	3	466
CHEMBL324665	CARAZOLOL	2	5,806
CHEMBL3544932	TAK-901	1	557

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

ChEMBL bioactivities

49 potent at pChembl≥5 of 108 total, top 49 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.00	IC50	1000	nM	CHEMBL5397838
6.00	IC50	1000	nM	CHEMBL5400843
5.82	IC50	1500	nM	CHEMBL1198288
5.77	IC50	1700	nM	CHEMBL198466
5.77	IC50	1700	nM	CHEMBL67535
5.77	IC50	1700	nM	CHEMBL199469
5.77	IC50	1700	nM	CHEMBL196854
5.68	IC50	2100	nM	CHEMBL358746
5.50	IC50	3200	nM	CHEMBL144589
5.50	IC50	3150	nM	CHEMBL109458
5.48	IC50	3300	nM	CHEMBL483059
5.44	IC50	3600	nM	CHEMBL1208927
5.36	IC50	4370	nM	CHEMBL5314343
5.30	IC50	5000	nM	CHEMBL197374
5.30	IC50	5000	nM	CHEMBL144842
5.30	IC50	5000	nM	CHEMBL483059
5.29	IC50	5100	nM	CHEMBL144908
5.29	IC50	5100	nM	CHEMBL198705
5.29	IC50	5100	nM	CHEMBL1208862
5.24	IC50	5790	nM	CETRIMIDE
5.23	IC50	5900	nM	CHEMBL2062753
5.22	IC50	6000	nM	CHEMBL197068
5.21	IC50	6200	nM	CHEMBL5404798
5.16	IC50	7000	nM	CHEMBL2062743
5.14	IC50	7200	nM	CHEMBL5414459
5.13	IC50	7400	nM	CHEMBL5423066
5.13	IC50	7370	nM	CHEMBL111027
5.12	IC50	7500	nM	CHEMBL5426248
5.11	IC50	7700	nM	WISKOSTATIN
5.11	IC50	7700	nM	CHEMBL5426975
5.11	IC50	7750	nM	CHEMBL112857
5.10	IC50	8000	nM	CHEMBL198573
5.10	IC50	8000	nM	CHEMBL197017
5.10	IC50	8000	nM	CHEMBL5421094
5.10	IC50	8020	nM	CHEMBL113172
5.09	IC50	8150	nM	CHEMBL325636
5.07	IC50	8450	nM	CHEMBL109914
5.06	IC50	8800	nM	CHEMBL5408331
5.06	IC50	8740	nM	CHEMBL325871
5.05	IC50	9000	nM	CHEMBL198915
5.05	IC50	9000	nM	CHEMBL5433864
5.05	IC50	8850	nM	CHEMBL321384
5.05	IC50	8850	nM	CHEMBL109566
5.04	IC50	9100	nM	CHEMBL3774960
5.04	IC50	9200	nM	CHEMBL5436624
5.03	IC50	9360	nM	CHEMBL112718
5.02	IC50	9620	nM	CHEMBL110737
5.01	IC50	9800	nM	CHEMBL5405495
5.01	IC50	9680	nM	CHEMBL109747

PubChem BioAssay actives

47 with measured affinity, of 253 total; 46 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
1-carbazol-9-yl-3-[(4-methylphenyl)methylamino]propan-2-ol	2002832: Inhibition of phosphotidylserine liposome-stimulated Dynamin 1 (unknown origin) GTPase activity by malachite green assay	ic50	1.0000	uM
1-carbazol-9-yl-3-[(4-chlorophenyl)methylamino]propan-2-ol	2002832: Inhibition of phosphotidylserine liposome-stimulated Dynamin 1 (unknown origin) GTPase activity by malachite green assay	ic50	1.0000	uM
1-(benzylamino)-3-carbazol-9-ylpropan-2-ol	2002832: Inhibition of phosphotidylserine liposome-stimulated Dynamin 1 (unknown origin) GTPase activity by malachite green assay	ic50	1.5000	uM
(E)-2-cyano-N-[2-[[(E)-2-cyano-3-(3,4,5-trihydroxyphenyl)prop-2-enoyl]amino]ethyl]-3-(3,4,5-trihydroxyphenyl)prop-2-enamide	257178: Inhibitory activity against dynamin1 GTPase expressed in sheep brain	ic50	1.7000	uM
(E)-2-cyano-N-[3-[[(E)-2-cyano-3-(3,4-dihydroxyphenyl)prop-2-enoyl]amino]propyl]-3-(3,4-dihydroxyphenyl)prop-2-enamide	257178: Inhibitory activity against dynamin1 GTPase expressed in sheep brain	ic50	1.7000	uM
(E)-2-cyano-N-[3-[[(E)-2-cyano-3-(3,4,5-trihydroxyphenyl)prop-2-enoyl]amino]propyl]-3-(3,4,5-trihydroxyphenyl)prop-2-enamide	257178: Inhibitory activity against dynamin1 GTPase expressed in sheep brain	ic50	1.7000	uM
(E)-2-cyano-N-[5-[[(E)-2-cyano-3-(3,4,5-trihydroxyphenyl)prop-2-enoyl]amino]pentyl]-3-(3,4,5-trihydroxyphenyl)prop-2-enamide	257178: Inhibitory activity against dynamin1 GTPase expressed in sheep brain	ic50	1.7000	uM
(E)-2-cyano-N-[4-[[(E)-2-cyano-3-(3,4,5-trihydroxyphenyl)prop-2-enoyl]amino]butyl]-3-(3,4,5-trihydroxyphenyl)prop-2-enamide	257178: Inhibitory activity against dynamin1 GTPase expressed in sheep brain	ic50	2.1000	uM
trimethyl(octadecyl)azanium bromide	63727: Concentration required against dynamin-1 GTPase activity of sheep brain.	ic50	3.1500	uM
(E)-2-cyano-N-[4-[[(E)-2-cyano-3-(3,4-dihydroxyphenyl)prop-2-enoyl]amino]butyl]-3-(3,4-dihydroxyphenyl)prop-2-enamide	257178: Inhibitory activity against dynamin1 GTPase expressed in sheep brain	ic50	3.2000	uM
(E)-2-cyano-3-[1-[3-(dimethylamino)propyl]indol-3-yl]-N-octylprop-2-enamide	2002832: Inhibition of phosphotidylserine liposome-stimulated Dynamin 1 (unknown origin) GTPase activity by malachite green assay	ic50	3.3000	uM
3-hydroxy-N-[(E)-(3-hydroxy-4-methoxyphenyl)methylideneamino]naphthalene-2-carboxamide	494094: Inhibition of GTPase activity of Dynamin 1	ic50	3.6000	uM
(E)-2-cyano-N-[3-[[(E)-2-cyano-3-(3,4-dihydroxy-5-methoxyphenyl)prop-2-enoyl]amino]propyl]-3-(3,4-dihydroxy-5-methoxyphenyl)prop-2-enamide	257178: Inhibitory activity against dynamin1 GTPase expressed in sheep brain	ic50	5.0000	uM
(E)-2-cyano-N-[5-[[(E)-2-cyano-3-(3,4-dihydroxyphenyl)prop-2-enoyl]amino]pentyl]-3-(3,4-dihydroxyphenyl)prop-2-enamide	257178: Inhibitory activity against dynamin1 GTPase expressed in sheep brain	ic50	5.0000	uM
(E)-2-cyano-N-[3-[[(E)-2-cyano-3-(3,4-dihydroxyphenyl)prop-2-enoyl]amino]-2-hydroxypropyl]-3-(3,4-dihydroxyphenyl)prop-2-enamide	257178: Inhibitory activity against dynamin1 GTPase expressed in sheep brain	ic50	5.1000	uM
N-[(E)-(3,4-dihydroxyphenyl)methylideneamino]naphthalene-2-carboxamide	494094: Inhibition of GTPase activity of Dynamin 1	ic50	5.1000	uM
(E)-2-cyano-N-[2-[[(E)-2-cyano-3-(3,4-dihydroxyphenyl)prop-2-enoyl]amino]ethyl]-3-(3,4-dihydroxyphenyl)prop-2-enamide	257178: Inhibitory activity against dynamin1 GTPase expressed in sheep brain	ic50	5.1000	uM
(5Z)-5-[[4-[3-(dimethylamino)propoxy]phenyl]methylidene]-3-prop-2-enyl-2-sulfanylidene-1,3-thiazolidin-4-one	673865: Inhibition of dynamin1-mediated endocytosis in human U2OS cells assessed as inhibition of Texas red-Tf uptake incubated for 30 mins prior to Texas red-Tf addition measured after 8 mins by receptor-mediated endocytosis assay	ic50	5.9000	uM
(E)-2-cyano-N-[6-[[(E)-2-cyano-3-(3,4,5-trihydroxyphenyl)prop-2-enoyl]amino]hexyl]-3-(3,4,5-trihydroxyphenyl)prop-2-enamide	257178: Inhibitory activity against dynamin1 GTPase expressed in sheep brain	ic50	6.0000	uM
1-[(4-aminophenyl)methylamino]-3-carbazol-9-ylpropan-2-ol	2002832: Inhibition of phosphotidylserine liposome-stimulated Dynamin 1 (unknown origin) GTPase activity by malachite green assay	ic50	6.2000	uM
(5Z)-5-[[4-[3-(dimethylamino)propoxy]phenyl]methylidene]-3-ethyl-2-sulfanylidene-1,3-thiazolidin-4-one	673865: Inhibition of dynamin1-mediated endocytosis in human U2OS cells assessed as inhibition of Texas red-Tf uptake incubated for 30 mins prior to Texas red-Tf addition measured after 8 mins by receptor-mediated endocytosis assay	ic50	7.0000	uM
1-carbazol-9-yl-3-[(4-phenylphenyl)methylamino]propan-2-ol	2002832: Inhibition of phosphotidylserine liposome-stimulated Dynamin 1 (unknown origin) GTPase activity by malachite green assay	ic50	7.2000	uM
2-tetradecoxypropane-1,3-diamine;dihydrochloride	63727: Concentration required against dynamin-1 GTPase activity of sheep brain.	ic50	7.3700	uM
1-(3,6-dibromocarbazol-9-yl)-3-[(4-methylphenyl)methylamino]propan-2-ol	2002832: Inhibition of phosphotidylserine liposome-stimulated Dynamin 1 (unknown origin) GTPase activity by malachite green assay	ic50	7.4000	uM
1-[(4-tert-butylphenyl)methylamino]-3-carbazol-9-ylpropan-2-ol	2002832: Inhibition of phosphotidylserine liposome-stimulated Dynamin 1 (unknown origin) GTPase activity by malachite green assay	ic50	7.5000	uM
1-carbazol-9-yl-3-[(3-methylphenyl)methylamino]propan-2-ol	2002832: Inhibition of phosphotidylserine liposome-stimulated Dynamin 1 (unknown origin) GTPase activity by malachite green assay	ic50	7.7000	uM
(2S)-1-(3,6-dibromocarbazol-9-yl)-3-(dimethylamino)propan-2-ol	2002832: Inhibition of phosphotidylserine liposome-stimulated Dynamin 1 (unknown origin) GTPase activity by malachite green assay	ic50	7.7000	uM
N-[3-(dimethylamino)propyl]tridecanamide	63727: Concentration required against dynamin-1 GTPase activity of sheep brain.	ic50	7.7500	uM
(E)-2-cyano-N-[5-[[(E)-2-cyano-3-(3,4-dihydroxy-5-methoxyphenyl)prop-2-enoyl]amino]pentyl]-3-(3,4-dihydroxy-5-methoxyphenyl)prop-2-enamide	257178: Inhibitory activity against dynamin1 GTPase expressed in sheep brain	ic50	8.0000	uM
(E)-2-cyano-N-[4-[[(E)-2-cyano-3-(3,4-dihydroxy-5-methoxyphenyl)prop-2-enoyl]amino]butyl]-3-(3,4-dihydroxy-5-methoxyphenyl)prop-2-enamide	257178: Inhibitory activity against dynamin1 GTPase expressed in sheep brain	ic50	8.0000	uM
1-[(4-bromophenyl)methylamino]-3-carbazol-9-ylpropan-2-ol	2002832: Inhibition of phosphotidylserine liposome-stimulated Dynamin 1 (unknown origin) GTPase activity by malachite green assay	ic50	8.0000	uM
butyl-dimethyl-tetradecylazanium bromide	63727: Concentration required against dynamin-1 GTPase activity of sheep brain.	ic50	8.0200	uM
trimethyl(tetradecyl)azanium iodide	63727: Concentration required against dynamin-1 GTPase activity of sheep brain.	ic50	8.1500	uM
triethyl(tetradecyl)azanium bromide	63727: Concentration required against dynamin-1 GTPase activity of sheep brain.	ic50	8.4500	uM
tetradecan-1-amine;hydrochloride	63727: Concentration required against dynamin-1 GTPase activity of sheep brain.	ic50	8.7400	uM
(2S)-1-carbazol-9-yl-3-[(4-methylphenyl)methylamino]propan-2-ol	2002832: Inhibition of phosphotidylserine liposome-stimulated Dynamin 1 (unknown origin) GTPase activity by malachite green assay	ic50	8.8000	uM
N-[2-(dimethylamino)ethyl]tridecanamide	63727: Concentration required against dynamin-1 GTPase activity of sheep brain.	ic50	8.8500	uM
dimethyl-propyl-tetradecylazanium bromide	63727: Concentration required against dynamin-1 GTPase activity of sheep brain.	ic50	8.8500	uM
(E)-2-cyano-N-[2-[[(E)-2-cyano-3-(3,4-dihydroxy-5-methoxyphenyl)prop-2-enoyl]amino]ethyl]-3-(3,4-dihydroxy-5-methoxyphenyl)prop-2-enamide	257178: Inhibitory activity against dynamin1 GTPase expressed in sheep brain	ic50	9.0000	uM
1-[(4-azidophenyl)methylamino]-3-carbazol-9-ylpropan-2-ol	2002832: Inhibition of phosphotidylserine liposome-stimulated Dynamin 1 (unknown origin) GTPase activity by malachite green assay	ic50	9.0000	uM
(2R)-1-(3,6-dibromocarbazol-9-yl)-3-(dimethylamino)propan-2-ol	2002832: Inhibition of phosphotidylserine liposome-stimulated Dynamin 1 (unknown origin) GTPase activity by malachite green assay	ic50	9.1000	uM
1-carbazol-9-yl-3-(pyridin-2-ylmethylamino)propan-2-ol	2002832: Inhibition of phosphotidylserine liposome-stimulated Dynamin 1 (unknown origin) GTPase activity by malachite green assay	ic50	9.2000	uM
2-hydroxyethyl-dimethyl-tetradecylazanium bromide	63727: Concentration required against dynamin-1 GTPase activity of sheep brain.	ic50	9.3600	uM
triethyl(hexadecyl)azanium bromide	63727: Concentration required against dynamin-1 GTPase activity of sheep brain.	ic50	9.6200	uM
trimethyl(tetradecyl)azanium chloride	63727: Concentration required against dynamin-1 GTPase activity of sheep brain.	ic50	9.6800	uM
1-[(4-chlorophenyl)methylamino]-3-(3,6-dibromocarbazol-9-yl)propan-2-ol	2002832: Inhibition of phosphotidylserine liposome-stimulated Dynamin 1 (unknown origin) GTPase activity by malachite green assay	ic50	9.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, increases methylation, affects cotreatment	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Valproic Acid	affects expression, decreases expression, increases expression	4
Air Pollutants	decreases expression, increases abundance, increases expression	2
Arsenic	increases abundance, increases expression, affects cotreatment, decreases expression	2
Gallic Acid	decreases reaction, affects cotreatment, affects reaction, decreases expression	2
Rotenone	decreases expression	2
Tretinoin	decreases expression, increases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
lasiocarpine	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
enilconazole	decreases expression	1
zinc chromate	increases abundance, increases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, affects reaction, decreases expression, decreases reaction	1
gallocatechol	affects cotreatment, affects reaction, decreases expression, decreases reaction	1
epicatechin gallate	decreases expression, decreases reaction, affects cotreatment, affects reaction	1
chromium hexavalent ion	increases abundance, increases expression	1
deguelin	decreases expression	1
entinostat	increases expression	1
thifluzamide	decreases expression	1
abrine	decreases expression	1
pyrachlostrobin	decreases expression	1
Sunitinib	decreases expression	1

ChEMBL screening assays

11 unique, capped per target: 11 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1212033	Binding	Inhibition of GTPase activity of Dynamin 1	Synthesis of potent chemical inhibitors of dynamin GTPase. — Bioorg Med Chem Lett

Cellosaurus cell lines

2 cell lines: 1 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A4NZ	U2OS DNM1 KO	Cancer cell line	Female
CVCL_B5IK	FDCHi007-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01370486	PHASE4	WITHDRAWN	Melatonin Versus Placebo in the Lennox-Gastaut Syndrome: Neurophysiological and Neuropsychological Effects
NCT02731300	PHASE4	COMPLETED	Transcranial Direct Current Stimulation, Treatment of Childhood Drug-Resistant Lennox-Gastaut Syndrome, A Pilot Study
NCT04133480	PHASE4	WITHDRAWN	Investigation of Cognitive Outcomes With Cannabidiol Oral Solution
NCT05044819	PHASE4	ACTIVE_NOT_RECRUITING	Assessment of Potential for Chronic Liver Injury in Participants Treated With Epidiolex (Cannabidiol) Oral Solution
NCT06924827	PHASE4	NOT_YET_RECRUITING	A Study to Investigate the Transition of Children From ‘Artisanal Cannabidiol (CBD) to Epidiolex
NCT01413711	PHASE4	WITHDRAWN	An Open-Label, Single and Multiple Oral Dose Pharmacokinetic Study of Vigabatrin in Infants With Infantile Spasms
NCT02092883	PHASE4	COMPLETED	Evaluation of Neuroinflammation in Children With Infantile Spasms
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients