KIF1A |
- 0
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- KIF1A (HGNC:888) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- kinesin family member 1A
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- ATSV, C2orf20, SPG30
- Alias symbols
- UNC104
- %HI
- 50.62(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 1(Read more about gnomAD pLI score)
- LOEUF
- 0.14(Read more about gnomAD LOEUF score)
- Cytoband
- 2q37.3
- Genomic Coordinates
-
GRCh37/hg19: chr2:241653184-241760820 NCBI Ensembl UCSC GRCh38/hg38: chr2:240713767-240821403 NCBI Ensembl UCSC - MANE Select Transcript
- NM_001244008.2 ENST00000498729.9 (Read more about MANE Select)
- Function
- Motor for anterograde axonal transport of synaptic vesicle precursors (PubMed:33880452). Also required for neuronal dense core vesicles (DCVs) transport to the dendritic spines and axons. The interaction calcium-dependent with CALM1 increases vesicle motility and interaction with the scaffolding proteins PPFIA2 and TANC2 recruits DCVs to synaptic sites. {ECO:0000250|UniProtKB:F1M4A4, ECO:0000269|PubMed:33880452}. (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Dosage ID:
ISCA-17742
Curation Status:
Complete
Issue Type:
Dosage Curation -
Gene
Haploinsufficiency:
No Evidence for Haploinsufficiency
(0)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Last Evaluated:
08/08/2013
Haploinsufficiency (HI) Score Details
HI Score:
0
HI Evidence Strength:
No Evidence for Haploinsufficiency
(Disclaimer)
HI Evidence Comments:
In a single report (Hamdan et al., 2011 PMID: 21376300) identified a de novo heterozygous missense mutation (p.T99M) in a female patient with moderate intellectual disability. The mutation was located in a highly conserved p loop consensus ATP-binding site for the KIF1A motor domain. Primary rat hippocampal neurons transfected with eGFP fusion constructs containing the identified Thr99Met mutation displayed altered protein subcellular localization. Given that there are multiple entries in the Database for Genomic Variants (DGV) and that all previously identified missense and nonsense mutations affecting KIF1A have been associated with autosomal recessive disorders , the mutation identified by Hamdan et al, if responsible for the observed phenotype in this single individual, may result in a gain-of-function/dominant negative gene product. This gene has been given a haploinsufficiency score of 0 based on this phenotype.
Of note, mutations in the KIF1A gene (OMIM: 601255) have also been described in two different clinically and genetically heterogeneous groups of autosomal recessive neurodegenerative diseases: hereditary sensory neuropathy type IIC (HSN2C, OMIM: 614213) and spastic paraplegia-30 (SPG30, OMIM: 610357).
In HSN2C, all patients from four families of different origins were carriers of homozygous or compound heterozygous nonsense mutations of KIF1A. Rivière et al., 2011 (PMID: 21820098) identified homozygous 1 bp deletion resulting in a truncating mutation, in three affected members of an Afghan family as well as four patients from two unrelated families from Turkey and Belgium .
In SPG30, homozygous missense mutations were found to cosegregate with the disease (Erlich et al., 2011 PMID: 21487076, Klebe et al., 2012 (PMID: 22258533).
There is no evidence to suggest that loss of a single copy of KIF1A causes an abnormal phenotype.
Triplosensitivity (TS) Score Details
TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
There is no evidence of triplosensitivity at the time of this review.
Genomic View
Select assembly:
(NC_000002.11)
(NC_000002.12)