KIF5A
kinesin family member 5A, the group of Kinesins
Basic information
Region (hg38): 12:57546026-57586633
Previous symbols: [ "SPG10" ]
Links
Phenotypes
GenCC
Source:
- hereditary spastic paraplegia 10 (Strong), mode of inheritance: AD
- myoclonus, intractable, neonatal (Limited), mode of inheritance: AD
- hereditary spastic paraplegia 10 (Strong), mode of inheritance: AD
- hereditary spastic paraplegia 10 (Supportive), mode of inheritance: AD
- autosomal dominant Charcot-Marie-Tooth disease type 2 due to KIF5A mutation (Supportive), mode of inheritance: AD
- amyotrophic lateral sclerosis, susceptibility to, 25 (Definitive), mode of inheritance: AD
- myoclonus, intractable, neonatal (Moderate), mode of inheritance: AD
- myoclonus, intractable, neonatal (Definitive), mode of inheritance: AD
- hereditary spastic paraplegia 10 (Strong), mode of inheritance: AD
- myoclonus, intractable, neonatal (Strong), mode of inheritance: AD
- amyotrophic lateral sclerosis, susceptibility to, 25 (Strong), mode of inheritance: AD
- amyotrophic lateral sclerosis, susceptibility to, 25 (Definitive), mode of inheritance: AD
- inherited neurodegenerative disorder (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Neonatal intractable myoclonus (NEIMY); Spastic paraplegia 10, autosomal dominant; Amyotrophic lateral sclerosis, susceptibility to, 25 | 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 | Biochemical; Neurologic; Ophthalmologic | 10441583; 12355402; 15452312; 16489470; 16476820; 18245137; 18853458; 21107874; 21623771; 22788249; 25008398; 27414745; 27463701; 29342275; 29566793 |
ClinVar
This is a list of variants' phenotypes submitted to
- Spastic_paraplegia (1147 variants)
- not_provided (272 variants)
- Hereditary_spastic_paraplegia_10 (121 variants)
- KIF5A-related_disorder (68 variants)
- Inborn_genetic_diseases (59 variants)
- not_specified (54 variants)
- Hereditary_spastic_paraplegia (44 variants)
- Myoclonus,_intractable,_neonatal (25 variants)
- Amyotrophic_lateral_sclerosis,_susceptibility_to,_25 (13 variants)
- Amyotrophic_lateral_sclerosis (3 variants)
- Spastic_Paraglegia_10 (2 variants)
- Demyelinating_peripheral_neuropathy (2 variants)
- Peripheral_neuropathy (1 variants)
- Schizophrenia (1 variants)
- Distal_myopathy (1 variants)
- Intellectual_disability (1 variants)
- Prostate_cancer (1 variants)
- Inherited_neurodegenerative_disorder (1 variants)
- Frontotemporal_dementia_and/or_amyotrophic_lateral_sclerosis_4 (1 variants)
- Charcot-Marie-Tooth_disease (1 variants)
- Charcot-Marie-Tooth_disease_type_2 (1 variants)
- KIF5A-related_intractable_neonatal_myoclonus (1 variants)
- Paroxysmal_dyskinesia (1 variants)
- KIF5A-related_amyotrophic_lateral_sclerosis (1 variants)
- Auditory_neuropathy (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the KIF5A gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004984.4. 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 | 13 | 284 | 302 | |||
| missense | 12 | 37 | 462 | 101 | 617 | |
| nonsense | 10 | 10 | 21 | |||
| start loss | 2 | 2 | ||||
| frameshift | 13 | 25 | ||||
| splice donor/acceptor (+/-2bp) | 11 | 14 | ||||
| Total | 36 | 63 | 487 | 385 | 10 |
Highest pathogenic variant AF is 0.0000111552
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| KIF5A | protein_coding | protein_coding | ENST00000455537 | 28 | 36635 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.0000494 | 125738 | 0 | 10 | 125748 | 0.0000398 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.60 | 341 | 586 | 0.582 | 0.0000378 | 6792 |
| Missense in Polyphen | 74 | 201.85 | 0.36661 | 2385 | ||
| Synonymous | 0.850 | 217 | 234 | 0.929 | 0.0000150 | 1932 |
| Loss of Function | 6.44 | 8 | 63.3 | 0.126 | 0.00000371 | 734 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000163 | 0.000163 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.0000440 | 0.0000439 |
| Middle Eastern | 0.000163 | 0.000163 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Microtubule-dependent motor required for slow axonal transport of neurofilament proteins (NFH, NFM and NFL). Can induce formation of neurite-like membrane protrusions in non-neuronal cells in a ZFYVE27-dependent manner. The ZFYVE27-KIF5A complex contributes to the vesicular transport of VAPA, VAPB, SURF4, RAB11A, RAB11B and RTN3 proteins in neurons. Required for anterograde axonal transportation of MAPK8IP3/JIP3 which is essential for MAPK8IP3/JIP3 function in axon elongation. {ECO:0000250|UniProtKB:P33175, ECO:0000250|UniProtKB:Q6QLM7}.;
- Disease
- DISEASE: Spastic paraplegia 10, autosomal dominant (SPG10) [MIM:604187]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. {ECO:0000269|PubMed:12355402, ECO:0000269|PubMed:15452312, ECO:0000269|PubMed:16476820, ECO:0000269|PubMed:16489470, ECO:0000269|PubMed:18203753, ECO:0000269|PubMed:18245137, ECO:0000269|PubMed:18853458, ECO:0000269|PubMed:21107874}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Myoclonus, intractable, neonatal (NEIMY) [MIM:617235]: An autosomal dominant neurologic disorder characterized by severe, infantile-onset myoclonic seizures, hypotonia, optic nerve abnormalities, dysphagia, apnea, and early developmental arrest. Brain imaging shows a progressive leukoencephalopathy. Some patients may die in infancy. {ECO:0000269|PubMed:24215330, ECO:0000269|PubMed:27414745, ECO:0000269|PubMed:27463701}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Amyotrophic lateral sclerosis 25 (ALS25) [MIM:617921]: A form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. ALS25 is an autosomal dominant form with variable adult onset and incomplete penetrance. {ECO:0000269|PubMed:29342275, ECO:0000269|PubMed:29566793}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. The mutation NM_004984.2:c.33019A>G encoding the predicted missence variant p.Arg1007Gly, may also affect splicing and induce the skipping of exon 27, resulting in a frameshift and a premature stop codon producing a truncated protein p.Asn999Valfs*39. {ECO:0000269|PubMed:29342275}.;
- Pathway
- Dopaminergic synapse - Homo sapiens (human);Endocytosis - Homo sapiens (human);Signal Transduction;Vesicle-mediated transport;Membrane Trafficking;RHO GTPases activate KTN1;Kinesins;Factors involved in megakaryocyte development and platelet production;RHO GTPase Effectors;Signaling by Rho GTPases;Hemostasis;COPI-dependent Golgi-to-ER retrograde traffic;Golgi-to-ER retrograde transport;Intra-Golgi and retrograde Golgi-to-ER traffic
(Consensus)
Recessive Scores
- pRec
- 0.171
Intolerance Scores
- loftool
- 0.0960
- rvis_EVS
- -1.31
- rvis_percentile_EVS
- 4.88
Haploinsufficiency Scores
- pHI
- 0.409
- hipred
- Y
- hipred_score
- 0.685
- ghis
- 0.603
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.668
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Kif5a
- Phenotype
- homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region 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); 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); normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype;
Zebrafish Information Network
- Gene name
- kif5aa
- Affected structure
- retinal ganglion cell
- Phenotype tag
- abnormal
- Phenotype quality
- decreased occurrence
Gene ontology
- Biological process
- retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum;microtubule-based movement;chemical synaptic transmission;axon guidance;vesicle-mediated transport;antigen processing and presentation of exogenous peptide antigen via MHC class II;synaptic vesicle transport;anterograde dendritic transport of neurotransmitter receptor complex;anterograde axonal protein transport;retrograde neuronal dense core vesicle transport
- Cellular component
- cytosol;kinesin complex;microtubule;membrane;dendrite cytoplasm;ciliary rootlet;neuronal cell body;synapse;perinuclear region of cytoplasm;axon cytoplasm
- Molecular function
- motor activity;microtubule motor activity;protein binding;ATP binding;microtubule binding;ATP-dependent microtubule motor activity, plus-end-directed;ATPase activity;kinesin binding