Human Gene Module / Chromosome 9 / SLC24A2

SLC24A2solute carrier family 24 member 2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 4
Rare Variants / Common Variants
3 / 0
Aliases
SLC24A2, NCKX2
Associated Syndromes
-
Chromosome Band
9p22.1
Associated Disorders
-
Relevance to Autism

A paternally-inherited deletion disrupting an exon of the SLC24A2 gene was detected in a male ASD proband but not in an affected male sibling; this variant was not observed in controls (Prasad et al., 2012).

Molecular Function

This gene encodes a member of the calcium/cation antiporter superfamily of transport proteins. The encoded protein belongs to the SLC24 branch of exchangers, which can mediate the extrusion of one Ca2+ ion and one K+ ion in exchange for four Na+ ions. This family member is a retinal cone/brain exchanger that can mediate a light-induced decrease in free Ca2+ concentration. This protein may also play a neuroprotective role during ischemic brain injury.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to SLC24A2 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Importance of K+-dependent Na+/Ca2+-exchanger 2, NCKX2, in motor learning and memory Li XF , et al. (2006) No -
2 Primary A discovery resource of rare copy number variations in individuals with autism spectrum disorder Prasad A , et al. (2013) Yes -
3 Support Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder Takata A , et al. (2018) Yes -
4 Support - Zhou X et al. (2022) Yes -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1202G>A p.Arg401Lys missense_variant De novo - - 35982159 Zhou X et al. (2022)
- - copy_number_loss Familial Paternal Multiplex 23275889 Prasad A , et al. (2013)
c.1052T>A p.Ile351Lys missense_variant De novo - Simplex 29346770 Takata A , et al. (2018)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A paternally-inherited deletion disrupting an exon of the SLC24A2 gene was detected in a male ASD proband but not in an affected male sibling; this variant was not observed in controls (Prasad et al., 2012). A de novo missense variant in the SLC24A2 gene (c.1052T>A;p.Ile351Lys) that was predicted to be damaging by multiple in silico algorithms was identified in a Japanese ASD proband from a trio family in Takata et al., 2018. Knockout of this gene in mice revealed a significant reduction in Ca2+ flux in cortical neurons, a profound loss of long term potentiation and an increase in long term depression at hippocampal Schaffer/CA1 synapses, and clear deficits in specific tests of motor learning and spatial working memory (Li et al., 2006).

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We 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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

A paternally-inherited deletion disrupting an exon of the SLC24A2 gene was detected in a male ASD proband but not in an affected male sibling; this variant was not observed in controls (Prasad et al., 2012). A de novo missense variant in the SLC24A2 gene (c.1052T>A;p.Ile351Lys) that was predicted to be damaging by multiple in silico algorithms was identified in a Japanese ASD proband from a trio family in Takata et al., 2018. Knockout of this gene in mice revealed a significant reduction in Ca2+ flux in cortical neurons, a profound loss of long term potentiation and an increase in long term depression at hippocampal Schaffer/CA1 synapses, and clear deficits in specific tests of motor learning and spatial working memory (Li et al., 2006).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A paternally-inherited deletion disrupting an exon of the SLC24A2 gene was detected in a male ASD proband but not in an affected male sibling; this variant was not observed in controls (Prasad et al., 2012). A de novo missense variant in the SLC24A2 gene (c.1052T>A;p.Ile351Lys) that was predicted to be damaging by multiple in silico algorithms was identified in a Japanese ASD proband from a trio family in Takata et al., 2018. Knockout of this gene in mice revealed a significant reduction in Ca2+ flux in cortical neurons, a profound loss of long term potentiation and an increase in long term depression at hippocampal Schaffer/CA1 synapses, and clear deficits in specific tests of motor learning and spatial working memory (Li et al., 2006).

Reports Added
[New Scoring Scheme]
10/1/2018
icon
4

Increased from to 4

Description

A paternally-inherited deletion disrupting an exon of the SLC24A2 gene was detected in a male ASD proband but not in an affected male sibling; this variant was not observed in controls (Prasad et al., 2012). A de novo missense variant in the SLC24A2 gene (c.1052T>A;p.Ile351Lys) that was predicted to be damaging by multiple in silico algorithms was identified in a Japanese ASD proband from a trio family in Takata et al., 2018. Knockout of this gene in mice revealed a significant reduction in Ca2+ flux in cortical neurons, a profound loss of long term potentiation and an increase in long term depression at hippocampal Schaffer/CA1 synapses, and clear deficits in specific tests of motor learning and spatial working memory (Li et al., 2006).

Krishnan Probability Score

Score 0.52080500785355

Ranking 1691/25841 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.
Original Source
ExAC Score

Score 0.035059825847639

Ranking 8910/18225 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
Original Source
Sanders TADA Score

Score 0.93780519717642

Ranking 13648/18665 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).
Original Source
Zhang D Score

Score 0.33564317429341

Ranking 2201/20870 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.
Original Source
Submit New Gene

Report an Error