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

ENSG00000130294 ∙ NCBI:547 ∙ OMIM:601255 ∙ HGNC:888 ∙ Uniprot:Q12756 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
NESCAV syndrome; Neuropathy, hereditary sensory, type IIC; Spastic paraplegia 30, autosomal dominant; Spastic paraplegia 30, 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 ClinVar and linked to the KIF1A gene.

• Hereditary spastic paraplegia 30;Neuropathy, hereditary sensory, type 2C;Intellectual disability, autosomal dominant 9 (15 variants)
• not provided (13 variants)
• Hereditary spastic paraplegia 30 (13 variants)
• Neuropathy, hereditary sensory, type 2C;Intellectual disability, autosomal dominant 9;Hereditary spastic paraplegia 30 (11 variants)
• Intellectual disability, autosomal dominant 9 (8 variants)
• Hereditary spastic paraplegia 30;Intellectual disability, autosomal dominant 9;Neuropathy, hereditary sensory, type 2C (3 variants)
• Neuropathy, hereditary sensory and autonomic, type 2A (2 variants)
• Neuropathy, hereditary sensory, type 2C;Hereditary spastic paraplegia 30;Intellectual disability, autosomal dominant 9 (2 variants)
• Spastic paraplegia (2 variants)
• KIF1A-related disorder (2 variants)
• Hereditary spastic paraplegia 30;Neuropathy, hereditary sensory and autonomic, type 2A;Neuropathy, hereditary sensory, type 2C;Intellectual disability, autosomal dominant 9 (1 variants)
• Inborn genetic diseases (1 variants)
• Neuropathy, hereditary sensory, type 2C (1 variants)
• PEHO syndrome (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.

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			18	543	13	574
missense	31	78	790	87	6	992
nonsense	9	6	2			17
start loss			1			1
frameshift	13		2			15
inframe indel	2		18	3	1	24
splice donor/acceptor (+/-2bp)	7	13	1			21
splice region			100	115	3	218
non coding		2	85	495	147	729
Total	62	99	917	1128	167

Highest pathogenic variant AF is 0.00000657

Variants in KIF1A

This is a list of pathogenic ClinVar variants found in the KIF1A region.

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

Position	Type	Phenotype	Significance	ClinVar
2-240713768-G-A		Hereditary spastic paraplegia 30	Likely benign (Jan 13, 2018)
2-240713850-C-T		Hereditary spastic paraplegia 30	Uncertain significance (Mar 16, 2018)
2-240713865-G-A		Hereditary spastic paraplegia 30	Uncertain significance (Jan 13, 2018)
2-240713870-A-G		Hereditary spastic paraplegia 30	Benign (Jan 12, 2018)
2-240713876-C-T		Hereditary spastic paraplegia 30	Uncertain significance (Jan 12, 2018)
2-240713881-C-T		Hereditary spastic paraplegia 30	Uncertain significance (Jan 12, 2018)
2-240713954-G-A		Hereditary spastic paraplegia 30	Uncertain significance (Jan 12, 2018)
2-240713991-C-G		Hereditary spastic paraplegia 30	Uncertain significance (Jan 13, 2018)
2-240714019-C-T		Hereditary spastic paraplegia 30	Uncertain significance (Jan 13, 2018)
2-240714055-G-A		Hereditary spastic paraplegia 30	Uncertain significance (Jan 13, 2018)
2-240714058-C-T		Hereditary spastic paraplegia 30	Uncertain significance (Jan 13, 2018)
2-240714064-G-A		Hereditary spastic paraplegia 30	Uncertain significance (Jan 13, 2018)
2-240714077-A-G		Hereditary spastic paraplegia 30	Uncertain significance (Jan 12, 2018)
2-240714326-A-T		Hereditary spastic paraplegia 30	Benign (Jan 13, 2018)
2-240714329-C-G		Hereditary spastic paraplegia 30	Uncertain significance (Jan 12, 2018)
2-240714410-C-T		Hereditary spastic paraplegia 30	Uncertain significance (Jan 12, 2018)
2-240714467-C-A		Hereditary spastic paraplegia 30	Uncertain significance (Jan 13, 2018)
2-240714513-C-T		Hereditary spastic paraplegia 30	Uncertain significance (Jan 13, 2018)
2-240714524-A-T		Hereditary spastic paraplegia 30	Uncertain significance (Jan 13, 2018)
2-240714568-G-A		Hereditary spastic paraplegia 30	Uncertain significance (Jan 13, 2018)
2-240714570-G-A		Hereditary spastic paraplegia 30	Uncertain significance (Jan 13, 2018)
2-240714626-C-G		Hereditary spastic paraplegia 30	Uncertain significance (Jan 13, 2018)
2-240714644-G-A		Hereditary spastic paraplegia 30	Uncertain significance (Jan 13, 2018)
2-240714732-C-T		Hereditary spastic paraplegia 30	Uncertain significance (Jan 13, 2018)
2-240714788-T-C		Hereditary spastic paraplegia 30	Benign (Jan 13, 2018)

GnomAD

Source: gnomAD

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: dbNSFP

• 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