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 (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
• syndromic intellectual disability (Definitive), 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
• 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 (Definitive), mode of inheritance: AD
• neuropathy, hereditary sensory, type 2C (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the KIF1A gene.

• Intellectual_disability,_autosomal_dominant_9 (2712 variants)
• Hereditary_spastic_paraplegia_30 (2710 variants)
• Neuropathy,_hereditary_sensory,_type_2C (2658 variants)
• not_provided (844 variants)
• Inborn_genetic_diseases (388 variants)
• not_specified (206 variants)
• KIF1A-related_disorder (112 variants)
• Hereditary_spastic_paraplegia (91 variants)
• Neuropathy,_hereditary_sensory_and_autonomic,_type_2A (39 variants)
• KIF1A_related_neurological_disorder (10 variants)
• Spastic_paraplegia (9 variants)
• History_of_neurodevelopmental_disorder (8 variants)
• Intellectual_disability (7 variants)
• Spastic_paraplegia_30B,_autosomal_recessive (6 variants)
• See_cases (4 variants)
• PEHO_syndrome (3 variants)
• Spastic_Paraplegia,_Recessive (3 variants)
• Spastic_paraplegia_30A,_autosomal_dominant (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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			32	718	21	771
missense	36	122	1023	250	8	1439
nonsense	11	7	5			23
start loss			1			1
frameshift	18	4	5			27
splice donor/acceptor (+/-2bp)	8	22	5			35
Total	73	155	1071	968	29

Highest pathogenic variant AF is 0.00006258885

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
		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

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

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