DYNC1H1
dynein cytoplasmic 1 heavy chain 1, the group of Dynein 1 complex subunits
Basic information
Region (hg38): 14:101964573-102056443
Previous symbols: [ "DNECL", "DNCL", "DNCH1" ]
Links
Phenotypes
GenCC
Source:
- autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures (Definitive), mode of inheritance: AD
- autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures (Strong), mode of inheritance: AD
- intellectual disability, autosomal dominant 13 (Strong), mode of inheritance: AD
- intellectual disability, autosomal dominant 13 (Definitive), mode of inheritance: AD
- autosomal dominant non-syndromic intellectual disability (Supportive), mode of inheritance: AD
- autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures (Supportive), mode of inheritance: AD
- Charcot-Marie-Tooth disease axonal type 2O (Supportive), mode of inheritance: AD
- intellectual disability, autosomal dominant 13 (Strong), mode of inheritance: AD
- Charcot-Marie-Tooth disease axonal type 2O (Strong), mode of inheritance: AD
- neuronopathy, distal hereditary motor (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Charcot-Marie-Tooth disease, axonal, type 2O; Intellectual developmental disorder, autosomal dominant 13; Cortical dysplasia, complex, with other brain malformations 13; Spinal muscular atrophy, lower extremity-predominant 1, autosomal dominant | AD | 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; Musculoskeletal; Neurologic | 20697106; 21076407; 21820100; 22459677; 22368300; 25140959 |
ClinVar
This is a list of variants' phenotypes submitted to
- Charcot-Marie-Tooth_disease_axonal_type_2O (4142 variants)
- not_provided (1282 variants)
- Inborn_genetic_diseases (648 variants)
- not_specified (346 variants)
- Intellectual_disability,_autosomal_dominant_13 (210 variants)
- DYNC1H1-related_disorder (197 variants)
- Charcot-Marie-Tooth_disease (173 variants)
- Autosomal_dominant_cerebellar_ataxia (161 variants)
- Autosomal_dominant_childhood-onset_proximal_spinal_muscular_atrophy_without_contractures (103 variants)
- Intellectual_disability (21 variants)
- Lissencephaly (18 variants)
- Neuronopathy,_distal_hereditary_motor,_autosomal_dominant (12 variants)
- Autism_spectrum_disorder (7 variants)
- See_cases (7 variants)
- Asphyxiating_thoracic_dystrophy_3 (6 variants)
- DYNC1H1-related_neurodevelopmental_disorders (6 variants)
- Spinal_muscular_atrophy_with_lower_extremity_predominance (5 variants)
- Distal_spinal_muscular_atrophy (5 variants)
- Global_developmental_delay (4 variants)
- Charcot-Marie-Tooth_disease,_type_I (4 variants)
- Microcephaly (3 variants)
- Seizure (3 variants)
- DYNC1H1-related_neuronopathy (3 variants)
- Neurodevelopmental_abnormality (3 variants)
- Distal_myopathy (2 variants)
- Neurodevelopmental_delay (2 variants)
- Intellectual_Disability,_Dominant (2 variants)
- Arthrogryposis_multiplex_congenita (2 variants)
- Charcot-Marie-Tooth_disease_type_2 (2 variants)
- Fetal_akinesia_deformation_sequence_1 (2 variants)
- Myopathy (2 variants)
- Progressive_muscle_weakness (1 variants)
- Motor_delay (1 variants)
- Peripheral_neuropathy (1 variants)
- DYNC1H1-related_neurological_disorders (1 variants)
- Corpus_callosum,_agenesis_of (1 variants)
- Polyneuropathy (1 variants)
- Delayed_speech_and_language_development (1 variants)
- Vertigo (1 variants)
- Distal_lower_limb_muscle_weakness (1 variants)
- Abnormal_cortical_gyration (1 variants)
- Pes_cavus (1 variants)
- Dyneinopathy (1 variants)
- Neurodevelopmental_disorder (1 variants)
- Delayed_gross_motor_development (1 variants)
- Hypoplasia_of_the_corpus_callosum (1 variants)
- Abnormality_of_the_nervous_system (1 variants)
- Muscle_spasm (1 variants)
- Impaired_vibration_sensation_in_the_lower_limbs (1 variants)
- Hereditary_motor_and_sensory_neuropathy (1 variants)
- High_palate (1 variants)
- Hypoglycemic_encephalopathy (1 variants)
- Cerebellar_atrophy (1 variants)
- Macrogyria (1 variants)
- Headache (1 variants)
- Periventricular_cysts (1 variants)
- Delayed_puberty (1 variants)
- Abnormal_cerebral_morphology (1 variants)
- Partial_agenesis_of_the_corpus_callosum (1 variants)
- Infantile_spasms (1 variants)
- Amyotrophic_lateral_sclerosis (1 variants)
- Small_for_gestational_age (1 variants)
- Hypotonia (1 variants)
- Abnormality_of_neuronal_migration (1 variants)
- Rhizomelic_chondrodysplasia_punctata_type_5 (1 variants)
- Muscle_weakness (1 variants)
- Multiple_congenital_anomalies/dysmorphic_syndrome (1 variants)
- Lower_limb_muscle_weakness (1 variants)
- Charcot-Marie-Tooth_disease_type_4 (1 variants)
- Spinal_muscular_atrophy (1 variants)
- Polymicrogyria (1 variants)
- Hereditary_motor_neuron_disease (1 variants)
- Epilepsy_with_generalized_tonic-clonic_seizures (1 variants)
- Charcot-Marie-Tooth_disease_type_5 (1 variants)
- Focal-onset_seizure (1 variants)
- Cerebellar_ataxia (1 variants)
- Ectopic_tissue (1 variants)
- Distal_lower_limb_amyotrophy (1 variants)
- Congenital_cerebellar_hypoplasia (1 variants)
- Hammertoe (1 variants)
- Gait_ataxia (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the DYNC1H1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001376.5. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 37 | 1496 | 22 | 1555 | ||
| missense | 33 | 149 | 1668 | 423 | 11 | 2284 |
| nonsense | 39 | 43 | ||||
| start loss | 0 | |||||
| frameshift | 59 | 69 | ||||
| splice donor/acceptor (+/-2bp) | 23 | 30 | ||||
| Total | 35 | 165 | 1826 | 1922 | 33 |
Highest pathogenic variant AF is 0.0000216941
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| DYNC1H1 | protein_coding | protein_coding | ENST00000360184 | 78 | 86265 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 1.23e-29 | 125723 | 0 | 25 | 125748 | 0.0000994 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 11.0 | 1022 | 2.59e+3 | 0.394 | 0.000172 | 30630 |
| Missense in Polyphen | 187 | 1008.9 | 0.18534 | 12005 | ||
| Synonymous | -1.72 | 1111 | 1.04e+3 | 1.07 | 0.0000735 | 8991 |
| Loss of Function | 13.3 | 11 | 228 | 0.0482 | 0.0000126 | 2670 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000239 | 0.000239 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000163 | 0.000163 |
| Finnish | 0.000141 | 0.000139 |
| European (Non-Finnish) | 0.000106 | 0.000105 |
| Middle Eastern | 0.000163 | 0.000163 |
| South Asian | 0.0000653 | 0.0000653 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Plays a role in mitotic spindle assembly and metaphase plate congression (PubMed:27462074). {ECO:0000269|PubMed:27462074}.;
- Disease
- DISEASE: Charcot-Marie-Tooth disease 2O (CMT2O) [MIM:614228]: 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. {ECO:0000269|PubMed:21820100, ECO:0000269|PubMed:24307404, ECO:0000269|PubMed:25512093}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Mental retardation, autosomal dominant 13 (MRD13) [MIM:614563]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD13 is associated with variable neuronal migration defects and mild dysmorphic features. Some patients may also show signs of peripheral neuropathy, such as abnormal gait and hyporeflexia. {ECO:0000269|PubMed:21076407, ECO:0000269|PubMed:22368300, ECO:0000269|PubMed:23033978, ECO:0000269|PubMed:23603762, ECO:0000269|PubMed:28193117}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Spinal muscular atrophy, lower extremity-predominant 1, autosomal dominant (SMALED1) [MIM:158600]: A form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMALED1 is characterized by muscle weakness predominantly affecting the proximal lower extremities. {ECO:0000269|PubMed:22459677, ECO:0000269|PubMed:22847149, ECO:0000269|PubMed:25484024, ECO:0000269|PubMed:25512093, ECO:0000269|PubMed:26846447, ECO:0000269|PubMed:28193117}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Salmonella infection - Homo sapiens (human);Phagosome - Homo sapiens (human);Vasopressin-regulated water reabsorption - Homo sapiens (human);Neutrophil degranulation;Signal Transduction;Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;Amplification of signal from the kinetochores;Mitotic Spindle Checkpoint;Cell Cycle Checkpoints;Innate Immune System;Immune System;RHO GTPases Activate Formins;RHO GTPase Effectors;Signaling by Rho GTPases;Regulation of PLK1 Activity at G2/M Transition;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;Recruitment of mitotic centrosome proteins and complexes;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;Centrosome maturation;AURKA Activation by TPX2;G2/M Transition;Mitotic G2-G2/M phases;COPI-independent Golgi-to-ER retrograde traffic;Golgi-to-ER retrograde transport;Recruitment of NuMA to mitotic centrosomes;Mitotic Prometaphase;COPI-mediated anterograde transport;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;M Phase;Cell Cycle;Resolution of Sister Chromatid Cohesion;ER to Golgi Anterograde Transport;Cell Cycle, Mitotic;Anchoring of the basal body to the plasma membrane;Lissencephaly gene (LIS1) in neuronal migration and development;Intra-Golgi and retrograde Golgi-to-ER traffic;Cilium Assembly;Organelle biogenesis and maintenance
(Consensus)
Recessive Scores
- pRec
- 0.375
Intolerance Scores
- loftool
- 0.0192
- rvis_EVS
- -6.01
- rvis_percentile_EVS
- 0.04
Haploinsufficiency Scores
- pHI
- 0.468
- hipred
- Y
- hipred_score
- 0.696
- ghis
- 0.676
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.849
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Dync1h1
- Phenotype
- muscle phenotype; growth/size/body region phenotype; reproductive system 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); 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);
Zebrafish Information Network
- Gene name
- dync1h1
- Affected structure
- retinal rod cell
- Phenotype tag
- abnormal
- Phenotype quality
- malformed
Gene ontology
- Biological process
- G2/M transition of mitotic cell cycle;endoplasmic reticulum to Golgi vesicle-mediated transport;microtubule-based movement;mitotic spindle organization;regulation of G2/M transition of mitotic cell cycle;antigen processing and presentation of exogenous peptide antigen via MHC class II;cytoplasmic microtubule organization;positive regulation of intracellular transport;cytoplasmic mRNA processing body assembly;stress granule assembly;neutrophil degranulation;establishment of spindle localization;cell division;regulation of mitotic spindle organization;minus-end-directed vesicle transport along microtubule;regulation of metaphase plate congression;ciliary basal body-plasma membrane docking;positive regulation of cold-induced thermogenesis;positive regulation of spindle assembly
- Cellular component
- extracellular region;centrosome;cytosol;cytoplasmic dynein complex;microtubule;membrane;filopodium;dynein complex;azurophil granule lumen;extracellular exosome
- Molecular function
- RNA binding;protein binding;ATP binding;ATP-dependent microtubule motor activity, minus-end-directed;dynein light chain binding;dynein intermediate chain binding;dynein light intermediate chain binding