KIF1Akinesin family member 1A
Autism Reports / Total Reports
8 / 16Rare Variants / Common Variants
31 / 0Aliases
KIF1A, ATSV, C2orf20, HSN2C, MRD9, NESCAVS, SPG30, UNC104Associated Syndromes
-Chromosome Band
2q37.3Associated Disorders
DD/NDD, ID, EPS, ASDRelevance to Autism
Two individuals with missense variants affecting the p.Arg13 residue of KIF1A were shown to have diagnoses of ASD and ADHD in addition to spasticity (Tomaselli et al., 2017; Kurihara et al., 2020). Phenotypic characterization of 117 individuals with KIF1A Associated Neurological Disorder (KAND) in Boyle et al., 2021 determined that autism was observed in 20% (16/80) individuals from whom information was available. A total of three de novo missense variants in KIF1A (one of which was mosaic) have been identified in ASD probands from the Simons Simplex Collection and the Autism Sequencing Consortium (Iossifov et al., 2014; Krupp et al., 2017; Satterstrom et al., 2020).
Molecular Function
The protein encoded by this gene is a member of the kinesin family and functions as an anterograde motor protein that transports membranous organelles along axonal microtubules. Mutations at this locus have been associated with spastic paraplegia-30, hereditary sensory neuropathy IIC, and NESCAV syndrome.
External Links
SFARI Genomic Platforms
Reports related to KIF1A (16 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Support | The contribution of de novo coding mutations to autism spectrum disorder | Iossifov I et al. (2014) | Yes | - |
| 2 | Primary | - | Tomaselli PJ et al. (2017) | Yes | DD |
| 3 | Support | Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder | Krupp DR , et al. (2017) | Yes | - |
| 4 | Support | - | Kurihara M et al. (2020) | Yes | ID, epilepsy/seizures |
| 5 | Support | Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism | Satterstrom FK et al. (2020) | Yes | - |
| 6 | Recent Recommendation | - | Boyle L et al. (2021) | No | ASD |
| 7 | Support | - | Valentino F et al. (2021) | No | DD, epilepsy/seizures |
| 8 | Support | - | Brea-Fernández AJ et al. (2022) | No | - |
| 9 | Support | - | Hu C et al. (2022) | Yes | - |
| 10 | Support | - | Chen Y et al. (2021) | No | - |
| 11 | Support | - | Zhou X et al. (2022) | Yes | - |
| 12 | Support | - | Chen WX et al. (2022) | Yes | - |
| 13 | Support | - | Sanchis-Juan A et al. (2023) | No | - |
| 14 | Support | - | Karthika Ajit Valaparambil et al. () | No | - |
| 15 | Support | - | Liene Thys et al. (2024) | No | ASD, ADHD, DD, ID, epilepsy/seizures |
| 16 | Support | - | Hosneara Akter et al. () | No | ASD, epilepsy/seizures |
Rare Variants (31)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.1924G>A | p.Asp642Asn | missense_variant | Unknown | - | - | 35741772 | Hu C et al. (2022) | |
| c.2231A>G | p.Glu744Gly | missense_variant | De novo | - | - | 35741772 | Hu C et al. (2022) | |
| c.31C>T | p.Arg11Trp | missense_variant | De novo | - | - | 39213953 | Liene Thys et al. (2024) | |
| c.38G>A | p.Arg13His | missense_variant | De novo | - | - | 39213953 | Liene Thys et al. (2024) | |
| c.37C>T | p.Arg13Cys | missense_variant | De novo | - | - | 34356170 | Valentino F et al. (2021) | |
| c.4716C>T | p.His1572%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.5136G>A | p.Glu1712%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.304G>A | p.Gly102Ser | missense_variant | De novo | - | - | 39213953 | Liene Thys et al. (2024) | |
| c.641G>C | p.Ser214Thr | missense_variant | De novo | - | - | 39213953 | Liene Thys et al. (2024) | |
| c.773C>T | p.Thr258Met | missense_variant | De novo | - | - | 39213953 | Liene Thys et al. (2024) | |
| c.821C>T | p.Ser274Leu | missense_variant | De novo | - | - | 39213953 | Liene Thys et al. (2024) | |
| c.1162C>T | p.Leu388Phe | missense_variant | Unknown | - | - | 39342494 | Hosneara Akter et al. () | |
| c.1250C>T | p.Thr417Met | missense_variant | Unknown | - | - | 39342494 | Hosneara Akter et al. () | |
| c.2323G>A | p.Val775Met | missense_variant | Unknown | - | - | 39342494 | Hosneara Akter et al. () | |
| c.914C>T | p.Pro305Leu | missense_variant | De novo | - | - | 34356170 | Valentino F et al. (2021) | |
| c.3703G>A | p.Asp1235Asn | missense_variant | Unknown | - | - | 39342494 | Hosneara Akter et al. () | |
| c.4766G>A | p.Arg1589Gln | missense_variant | Unknown | - | - | 39342494 | Hosneara Akter et al. () | |
| c.575T>G | p.Ile192Ser | missense_variant | De novo | - | Simplex | 35873028 | Chen Y et al. (2021) | |
| c.142A>C | p.Lys48Gln | missense_variant | De novo | - | Multiplex | 35982159 | Zhou X et al. (2022) | |
| c.37C>T | p.Arg13Cys | missense_variant | De novo | - | Simplex | 31813911 | Kurihara M et al. (2020) | |
| c.5015G>A | p.Arg1672Gln | missense_variant | De novo | - | Simplex | 36320054 | Chen WX et al. (2022) | |
| c.655G>A | p.Ala219Thr | missense_variant | De novo | - | Simplex | 28867142 | Krupp DR , et al. (2017) | |
| c.4798G>T | p.Gly1600Cys | missense_variant | De novo | - | - | 31981491 | Satterstrom FK et al. (2020) | |
| c.5130C>T | p.Phe1710%3D | synonymous_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| c.38G>A | p.Arg13His | missense_variant | De novo | - | Simplex | 28834584 | Tomaselli PJ et al. (2017) | |
| c.232G>A | p.Gly78Ser | missense_variant | Familial | Paternal | - | 39213953 | Liene Thys et al. (2024) | |
| c.38G>A | p.Arg13His | missense_variant | De novo | - | - | 35322241 | Brea-Fernández AJ et al. (2022) | |
| c.3671G>A | p.Arg1224Gln | missense_variant | De novo | - | Simplex | 25363768 | Iossifov I et al. (2014) | |
| c.694G>A | p.Ala232Thr | missense_variant | Unknown | - | Simplex | 37541188 | Sanchis-Juan A et al. (2023) | |
| c.1985G>C | p.Arg662Pro | missense_variant | Unknown | - | Simplex | 37541188 | Sanchis-Juan A et al. (2023) | |
| c.3728C>T | p.Ala1243Val | missense_variant | Unknown | - | - | 37943464 | Karthika Ajit Valaparambil et al. () |
Common Variants
No common variants reported.
SFARI Gene score
2S
Strong Candidate, Syndromic
Score Delta: Score remained at 2S
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."
4/1/2022
2S
Increased from to 2S
Krishnan Probability Score
Score 0.57186991997781
Ranking 743/25841 scored genes
[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning
approach on a human brain-specific gene network. The method was first presented in Nat
Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed
in column G of supplementary table 3 (see:
http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser,
with the ability to view networks of associated ASD risk genes, can be found at
asd.princeton.edu.
ExAC Score
Score 0.99998943706213
Ranking 460/18225 scored genes
[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has
been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by
Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at
exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of-
function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of-
function mutations in autism in such a gene would be more likely to confer risk. For a full list of
pLI scores see:
ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle
aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score
Score 0.74444334022256
Ranking 1501/18665 scored genes
[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013),
and is a statistic that integrates evidence from both de novo and transmitted mutations.
It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233
(2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper
(the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Zhang D Score
Score 0.19297641512191
Ranking 4371/20870 scored genes
[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures),
or D score, was developed to combine evidence from de novo loss-of- function mutation with
evidence from cell-type- specific gene expression in the mouse brain (specifically translational
profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with
positive D scores are more likely to be associated with autism risk, with higher-confidence genes
having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204-
215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in
supplementary table 2 from that paper.