DNM1

dynamin 1, the group of Pleckstrin homology domain containing

Basic information

Region (hg38): 9:128191654-128255248

Previous symbols: [ "DNM" ]

Links

ENSG00000106976 ∙ NCBI:1759 ∙ OMIM:602377 ∙ HGNC:2972 ∙ Uniprot:Q05193 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 31 (Moderate), mode of inheritance: AD
• Lennox-Gastaut syndrome (Supportive), mode of inheritance: AD
• undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD
• developmental and epileptic encephalopathy, 31 (Strong), mode of inheritance: AD
• developmental and epileptic encephalopathy 31B (Strong), mode of inheritance: AR
• developmental and epileptic encephalopathy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 31A, autosomal dominant; Developmental and epileptic encephalopathy 31B, autosomal recessive	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic; Ophthalmologic	25262651; 25533962; 34172529; 36553519
As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DNM1 gene.

• Developmental and epileptic encephalopathy, 31 (540 variants)
• not provided (213 variants)
• Inborn genetic diseases (80 variants)
• not specified (68 variants)
• DNM1-related condition (5 variants)
• See cases (2 variants)
• 6 conditions (1 variants)
• Developmental disorder (1 variants)
• Developmental and epileptic encephalopathy, 1 (1 variants)
• Lennox-Gastaut syndrome;West syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNM1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			9	165	10	184
missense	7	31	184	24	15	261
nonsense	3		2	1		6
start loss				1		1
frameshift	4	1	5	1		11
inframe indel	1	1	9			11
splice donor/acceptor (+/-2bp)	1		4	1		6
splice region			17	38	5	60
non coding		1	4	114	46	165
Total	16	34	217	307	71

Highest pathogenic variant AF is 0.0000263

Variants in DNM1

This is a list of pathogenic ClinVar variants found in the DNM1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-128191895-C-A		CIZ1-related disorder	Benign (Oct 01, 2019)
9-128192366-C-CA			Benign (Oct 05, 2019)
9-128203260-A-G			Benign (Jun 25, 2018)
9-128203436-C-T		not specified	Likely benign (Mar 11, 2016)
9-128203438-G-A		not specified	Likely benign (Apr 07, 2016)
9-128203444-T-G		not specified	Likely benign (Sep 19, 2017)
9-128203454-C-A		not specified	Benign (Mar 29, 2016)
9-128203456-G-T		not specified	Likely benign (Nov 08, 2017)
9-128203458-G-A		not specified	Likely benign (Feb 02, 2018)
9-128203472-T-C		Developmental and epileptic encephalopathy, 31	Uncertain significance (Aug 04, 2023)
9-128203473-G-T		Developmental and epileptic encephalopathy, 31	Likely benign (Oct 16, 2023)
9-128203476-C-T		Developmental and epileptic encephalopathy, 31	Benign (Feb 03, 2022)
9-128203481-G-A		Developmental and epileptic encephalopathy, 31	Uncertain significance (Sep 21, 2023)
9-128203483-G-A		Developmental and epileptic encephalopathy, 31	Uncertain significance (Oct 07, 2021)
9-128203484-G-T		Inborn genetic diseases	Uncertain significance (Jul 05, 2022)
9-128203498-ATCCCGC-A			Uncertain significance (Jan 17, 2022)
9-128203503-G-A		Inborn genetic diseases	Likely benign (Feb 01, 2018)
9-128203503-GC-AA		Developmental and epileptic encephalopathy, 31	Uncertain significance (Oct 28, 2022)
9-128203504-C-A		Inborn genetic diseases	Uncertain significance (Feb 01, 2018)
9-128203508-T-C		Developmental and epileptic encephalopathy, 31	Uncertain significance (Dec 02, 2022)
9-128203513-C-G		Developmental and epileptic encephalopathy, 31	Uncertain significance (Jun 20, 2022)
9-128203514-G-A		Developmental and epileptic encephalopathy, 31	Conflicting classifications of pathogenicity (Jan 10, 2024)
9-128203516-C-A		not specified • Developmental and epileptic encephalopathy, 31 • Inborn genetic diseases	Benign (Feb 01, 2024)
9-128203524-C-T		Developmental and epileptic encephalopathy, 31	Likely benign (Oct 17, 2022)
9-128203525-G-T			Uncertain significance (Mar 23, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DNM1	protein_coding	protein_coding	ENST00000372923	22	51870

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000828	125725	0	23	125748	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.18	181	510	0.355	0.0000311	5622
Missense in Polyphen		54	207.6	0.26011		2199
Synonymous	1.67	177	208	0.853	0.0000132	1685
Loss of Function	5.54	6	47.0	0.128	0.00000267	506

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000232	0.000232
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.0000888	0.0000879
Middle Eastern	0.000163	0.000163
South Asian	0.00	0.00
Other	0.000168	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Microtubule-associated force-producing protein involved in producing microtubule bundles and able to bind and hydrolyze GTP. Most probably involved in vesicular trafficking processes. Involved in receptor-mediated endocytosis.
• Disease: DISEASE: Epileptic encephalopathy, early infantile, 31 (EIEE31) [MIM:616346]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood 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. {ECO:0000269|PubMed:25262651, ECO:0000269|PubMed:25533962, ECO:0000269|PubMed:27476654}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Synaptic vesicle cycle - Homo sapiens (human);Endocytosis - Homo sapiens (human);Endocrine and other factor-regulated calcium reabsorption - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Bacterial invasion of epithelial cells - Homo sapiens (human);Synaptic Vesicle Pathway;Primary Focal Segmental Glomerulosclerosis FSGS;One carbon metabolism and related pathways;EGF-EGFR Signaling Pathway;Developmental Biology;Signal Transduction;Recycling pathway of L1;Vesicle-mediated transport;endocytotic role of ndk phosphins and dynamin;gamma-aminobutyric acid receptor life cycle pathway;role of -arrestins in the activation and targeting of map kinases;Membrane Trafficking;Toll-Like Receptors Cascades;MHC class II antigen presentation;Purine metabolism;Innate Immune System;Immune System;Adaptive Immune System;Retrograde neurotrophin signalling;roles of arrestin dependent recruitment of src kinases in gpcr signaling;Clathrin-mediated endocytosis;Signaling by NTRK1 (TRKA);Signaling by NTRKs;EGFR1;CXCR4-mediated signaling events;-arrestins in gpcr desensitization;Thromboxane A2 receptor signaling;Ephrin B reverse signaling;L1CAM interactions;Notch signaling pathway;Axon guidance;Toll Like Receptor 4 (TLR4) Cascade;Signaling by Receptor Tyrosine Kinases;Formation of annular gap junctions;Gap junction degradation;Gap junction trafficking;Gap junction trafficking and regulation;PAR1-mediated thrombin signaling events;Neurotrophic factor-mediated Trk receptor signaling;IL8- and CXCR1-mediated signaling events;Internalization of ErbB1;CXCR3-mediated signaling events;IL8- and CXCR2-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.679

Intolerance Scores

• loftool: 0.0630
• rvis_EVS: -0.56
• rvis_percentile_EVS: 19.54

Haploinsufficiency Scores

• pHI: 0.218
• hipred: Y
• hipred_score: 0.864
• ghis: 0.714

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.947

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Dnm1
• Phenotype: vision/eye phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: G protein-coupled receptor internalization;endocytosis;receptor-mediated endocytosis;endosome organization;synaptic vesicle budding from presynaptic endocytic zone membrane;receptor internalization;ephrin receptor signaling pathway;regulation of synapse structure or activity;modulation of chemical synaptic transmission;clathrin-dependent endocytosis;postsynaptic neurotransmitter receptor internalization;positive regulation of synaptic vesicle endocytosis;toxin transport;response to amyloid-beta
• Cellular component: photoreceptor inner segment;nucleus;nucleoplasm;cytoplasm;Golgi apparatus;microtubule;plasma membrane;synaptic vesicle;postsynaptic density;membrane;membrane coat;axon;cytoplasmic vesicle;varicosity;dendritic spine;myelin sheath;dendritic spine head;synapse;postsynaptic membrane;extracellular exosome;photoreceptor ribbon synapse;presynaptic endocytic zone membrane;postsynaptic endocytic zone membrane;glutamatergic synapse
• Molecular function: RNA binding;GTPase activity;protein binding;GTP binding;microtubule binding;protein C-terminus binding;SH3 domain binding;protein kinase binding;D2 dopamine receptor binding;identical protein binding;protein-containing complex binding;nitric-oxide synthase binding