Human Gene Module / Chromosome 2 / SLC4A10

SLC4A10solute carrier family 4, sodium bicarbonate transporter-like, member 10

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 10
Rare Variants / Common Variants
23 / 0
Aliases
SLC4A10, NBCn2,  NCBE
Associated Syndromes
-
Chromosome Band
2q24.2
Associated Disorders
-
Relevance to Autism

A rare CNV in the SLC4A10 gene has been identified with autism in AGRE, NIMH and additional cohorts (Sebat et al., 2007). In addition, a rare translocation involving the SLC4A10 gene has been identified with epilepsy and cognitive impairment in a patient (Gurnett et al., 2008). More recently, biallelic variants in the SLC4A10 gene have been found to cause an autosomal recessive neurodevelopmental disorder in which a subset of affected individuals presented with autistic features or stereotypy (Fasham et al., 2023; Maroofian et al., 2024).

Molecular Function

inorganic anion exchanger activity

SFARI Genomic Platforms
Reports related to SLC4A10 (10 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited A SCL4A10 gene product maps selectively to the basolateral plasma membrane of choroid plexus epithelial cells Praetorius J , et al. (2003) No -
2 Recent Recommendation Sodium coupled bicarbonate transporters in the kidney, an update Aalkjaer C , et al. (2004) No -
3 Primary Strong association of de novo copy number mutations with autism Sebat J , et al. (2007) Yes -
4 Recent Recommendation Mice with targeted Slc4a10 gene disruption have small brain ventricles and show reduced neuronal excitability Jacobs S , et al. (2008) No -
5 Recent Recommendation Disruption of sodium bicarbonate transporter SLC4A10 in a patient with complex partial epilepsy and mental retardation Gurnett CA , et al. (2008) No MR
6 Support Whole-Genome Sequencing of Cytogenetically Balanced Chromosome Translocations Identifies Potentially Pathological Gene Disruptions and Highlights the Importance of Microhomology in the Mechanism of Formation Nilsson D , et al. (2016) Yes -
7 Support - Zhou X et al. (2022) Yes -
8 Support - et al. () No Stereotypy, epilepsy/seizures
9 Support - Cirnigliaro M et al. (2023) Yes -
10 Recent Recommendation - et al. () No Autistic features, epilepsy/seizures
Rare Variants   (23)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - translocation De novo - - 27862604 Nilsson D , et al. (2016)
- - translocation De novo - - 18413482 Gurnett CA , et al. (2008)
- - copy_number_loss De novo - Simplex 17363630 Sebat J , et al. (2007)
- - copy_number_loss Familial Both parents Multiplex 37459438 et al. ()
c.577+1G>T - splice_site_variant De novo - - 35982159 Zhou X et al. (2022)
c.1052G>C p.Arg351Thr missense_variant De novo - Simplex 38054405 et al. ()
c.1195G>T p.Val399Leu missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1366C>G p.Pro456Ala missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.81+2T>C - splice_site_variant Familial Both parents Multiplex 38054405 et al. ()
c.2269C>T p.Arg757Ter stop_gained Familial Both parents Simplex 37459438 et al. ()
c.1612C>T p.Arg538Cys missense_variant Familial Paternal Simplex 38054405 et al. ()
c.1864C>T p.Arg622Trp missense_variant Familial Maternal Simplex 38054405 et al. ()
c.2118G>T p.Leu706Phe missense_variant Familial Maternal Simplex 38054405 et al. ()
c.2863-2A>C - splice_site_variant Familial Both parents Multiplex 37459438 et al. ()
c.1570del p.Val524SerfsTer16 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.667C>T p.His223Tyr missense_variant Familial Both parents Multiplex 38054405 et al. ()
c.1730A>T p.Lys577Met missense_variant Familial Both parents Multiplex 37459438 et al. ()
c.2162A>G p.Tyr721Cys missense_variant Familial Both parents Multiplex 38054405 et al. ()
c.2894C>T p.Pro965Leu missense_variant Familial Both parents Multiplex 38054405 et al. ()
c.3308A>T p.Asn1103Ile missense_variant Familial Both parents Multiplex 37459438 et al. ()
c.2619G>A p.Trp873Ter stop_gained Familial Both parents Extended multiplex 37459438 et al. ()
c.1570del p.Val524SerfsTer16 frameshift_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.767-2A>G - splice_site_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A single individual with a deletion was reported by Sebat et al., 2007 (PMID: 17363630).

Score Delta: Score remained at 2

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
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2

Decreased from 3 to 2

Description

A single individual with a deletion was reported by Sebat et al., 2007 (PMID: 17363630).

10/1/2019
4
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3

Decreased from 4 to 3

New Scoring Scheme
Description

A single individual with a deletion was reported by Sebat et al., 2007 (PMID: 17363630).

Reports Added
[New Scoring Scheme]
1/1/2017
4
icon
4

Decreased from 4 to 4

Description

A single individual with a deletion was reported by Sebat et al., 2007 (PMID: 17363630).

7/1/2014
No data
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4

Increased from No data to 4

Description

A single individual with a deletion was reported by Sebat et al., 2007 (PMID: 17363630).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

A single individual with a deletion was reported by Sebat et al., 2007 (PMID: 17363630).

Krishnan Probability Score

Score 0.4969506655495

Ranking 2473/25841 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 0.0026355437261549

Ranking 11092/18225 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 0.9415065632116

Ranking 14958/18665 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 0.5753268837689

Ranking 151/20870 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.
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