KIF1A
kinesin family member 1A, the group of Pleckstrin homology domain containing|Kinesins
Basic information
Region (hg38): 2:240713761-240824293
Previous symbols: [ "ATSV", "C2orf20", "SPG30" ]
Links
Phenotypes
GenCC
Source:
- intellectual disability, autosomal dominant 9 (Definitive), mode of inheritance: AD
- neuropathy, hereditary sensory, type 2C (Definitive), mode of inheritance: AR
- intellectual disability, autosomal dominant 9 (Moderate), mode of inheritance: AD
- neuropathy, hereditary sensory, type 2C (Limited), mode of inheritance: AR
- hereditary spastic paraplegia 30 (Strong), mode of inheritance: AD
- hereditary spastic paraplegia 30 (Strong), mode of inheritance: AR
- hereditary sensory and autonomic neuropathy type 2 (Supportive), mode of inheritance: AR
- PEHO syndrome (Supportive), mode of inheritance: AD
- hereditary spastic paraplegia 30 (Supportive), mode of inheritance: AD
- autosomal dominant non-syndromic intellectual disability (Supportive), mode of inheritance: AD
- intellectual disability, autosomal dominant 9 (Strong), mode of inheritance: AD
- neuropathy, hereditary sensory, type 2C (Strong), mode of inheritance: AR
- hereditary spastic paraplegia 30 (Strong), mode of inheritance: AR
- hereditary spastic paraplegia 30 (Strong), mode of inheritance: AD
- syndromic intellectual disability (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| NESCAV syndrome; Neuropathy, hereditary sensory, type IIC; Spastic paraplegia 30A, autosomal dominant; Spastic paraplegia 30B, 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 | Neurologic | 21376300; 21487076; 21820098; 22258533 |
| Insensitivity to pain can result in injuries and infections |
ClinVar
This is a list of variants' phenotypes submitted to
- Hereditary_spastic_paraplegia_30 (2552 variants)
- Intellectual_disability,_autosomal_dominant_9 (2550 variants)
- Neuropathy,_hereditary_sensory,_type_2C (2497 variants)
- not_provided (797 variants)
- Inborn_genetic_diseases (382 variants)
- not_specified (191 variants)
- KIF1A-related_disorder (110 variants)
- Hereditary_spastic_paraplegia (91 variants)
- Neuropathy,_hereditary_sensory_and_autonomic,_type_2A (39 variants)
- History_of_neurodevelopmental_disorder (10 variants)
- Spastic_paraplegia (9 variants)
- Intellectual_disability (7 variants)
- Spastic_paraplegia_30b,_autosomal_recessive (6 variants)
- KIF1A_related_neurological_disorder (6 variants)
- See_cases (4 variants)
- PEHO_syndrome (3 variants)
- Spastic_Paraplegia,_Recessive (3 variants)
- Hereditary_sensory_and_autonomic_neuropathy_type_2 (3 variants)
- Intellectual_Disability,_Dominant (3 variants)
- Hereditary_ataxia (2 variants)
- Spastic_paraplegia,_autosomal_dominant (1 variants)
- Lower_limb_hyperreflexia (1 variants)
- Syndromic_intellectual_disability (1 variants)
- Hyperreflexia (1 variants)
- Charcot-Marie-Tooth_disease_type_2 (1 variants)
- Craniosynostosis_syndrome (1 variants)
- Neurodevelopmental_delay (1 variants)
- Autosomal_dominant_non-syndromic_intellectual_disability (1 variants)
- Spastic_ataxia (1 variants)
- Clonus (1 variants)
- Developmental_disorder (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the KIF1A gene is commonly pathogenic or not. These statistics are base on transcript: NM_001244008.2. 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 | 30 | 680 | 20 | 730 | ||
| missense | 33 | 117 | 959 | 242 | 1359 | |
| nonsense | 19 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 16 | 23 | ||||
| splice donor/acceptor (+/-2bp) | 19 | 28 | ||||
| Total | 65 | 146 | 999 | 922 | 28 |
Highest pathogenic variant AF is 0.00006258885
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| KIF1A | protein_coding | protein_coding | ENST00000498729 | 48 | 106545 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 4.09e-11 | 124789 | 0 | 8 | 124797 | 0.0000321 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 5.16 | 640 | 1.13e+3 | 0.568 | 0.0000774 | 11569 |
| Missense in Polyphen | 175 | 470.59 | 0.37188 | 4732 | ||
| Synonymous | 0.00569 | 485 | 485 | 1.00 | 0.0000364 | 3504 |
| Loss of Function | 8.44 | 7 | 96.4 | 0.0726 | 0.00000479 | 1117 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000873 | 0.0000873 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000391 | 0.0000354 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Motor for anterograde axonal transport of synaptic vesicle precursors. {ECO:0000250}.;
- Disease
- DISEASE: Neuropathy, hereditary sensory, 2C (HSN2C) [MIM:614213]: A neurodegenerative disorder characterized by onset in the first decade of progressive distal sensory loss leading to ulceration and amputation of the fingers and toes. Affected individuals also develop distal muscle weakness, primarily affecting the lower limbs. {ECO:0000269|PubMed:21820098}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Mental retardation, autosomal dominant 9 (MRD9) [MIM:614255]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:21376300, ECO:0000269|PubMed:25265257, ECO:0000269|PubMed:26125038, ECO:0000269|PubMed:26410750}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Defects in KIF1A are a cause autosomal dominant spastic paraplegia. Spastic paraplegia is a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. {ECO:0000269|PubMed:25585697, ECO:0000269|PubMed:26410750}.;
- Pathway
- Vesicle-mediated transport;Membrane Trafficking;Kinesins;Factors involved in megakaryocyte development and platelet production;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
- 0.152
Intolerance Scores
- loftool
- 0.438
- rvis_EVS
- -3.67
- rvis_percentile_EVS
- 0.27
Haploinsufficiency Scores
- pHI
- 0.502
- hipred
- Y
- hipred_score
- 0.733
- ghis
- 0.607
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.809
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Kif1a
- Phenotype
- behavior/neurological phenotype (the observable actions or reactions of mammalian organisms 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); 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); hearing/vestibular/ear phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype;
Gene ontology
- Biological process
- microtubule-based movement;anterograde axonal transport;vesicle-mediated transport;interkinetic nuclear migration;cytoskeleton-dependent intracellular transport;protein transport along microtubule;anterograde neuronal dense core vesicle transport;retrograde neuronal dense core vesicle transport
- Cellular component
- cytosol;kinesin complex;microtubule;synaptic vesicle;axon;dendrite;neuron projection;neuronal cell body;postsynapse;axon cytoplasm
- Molecular function
- motor activity;microtubule motor activity;ATP binding;microtubule binding;ATP-dependent microtubule motor activity, plus-end-directed;ATPase activity;identical protein binding;protein homodimerization activity