Human Gene Module / Chromosome 1 / SLC45A1

SLC45A1solute carrier family 45 member 1

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
3 / 6
Rare Variants / Common Variants
8 / 0
Aliases
SLC45A1, DNB5
Associated Syndromes
-
Chromosome Band
1p36.23
Associated Disorders
ASD
Relevance to Autism

Homozygous missense variants in the SLC45A1 gene that resulted in reduced intracellular glucose transport activity were identified in two unrelated consanguineous families with affected individuals presented with moderate-to-severe intellectual disability, epilepsy, and dysmorphic features (Srour et al., 2017); one of the four affected individuals with a homozygous SLC45A1 missense variant was diagnosed with ASD, while another affected individual presented with autistic traits.

Molecular Function

Mediates glucose uptake along the pH gradient.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to SLC45A1 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield Anazi S , et al. (2016) No -
2 Primary Dysfunction of the Cerebral Glucose Transporter SLC45A1 in Individuals with Intellectual Disability and Epilepsy Srour M , et al. (2017) No ASD or autistic features
3 Support - Mir A et al. (2021) No -
4 Support - Woodbury-Smith M et al. (2022) Yes -
5 Support - Zhou X et al. (2022) Yes -
6 Support - Tamam Khalaf et al. (2024) Yes DD, epilepsy/seizures
Rare Variants   (8)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.799C>T p.Arg267Ter stop_gained De novo - - 35982159 Zhou X et al. (2022)
c.96G>A p.Ser32= synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.269T>C p.Ile90Thr missense_variant Familial Both parents - 34797406 Mir A et al. (2021)
c.1973C>T p.Ser658Leu missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.269T>C p.Ile90Thr missense_variant Familial Both parents Simplex 27431290 Anazi S , et al. (2016)
c.526C>T p.Arg176Trp missense_variant Familial Both parents Multiplex 28434495 Srour M , et al. (2017)
c.629C>T p.Ala210Val missense_variant Familial Both parents Multiplex 28434495 Srour M , et al. (2017)
c.628C>T p.Arg210Trp missense_variant Familial Both parents Multiplex 38438125 Tamam Khalaf et al. (2024)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Homozygous missense variants in the SLC45A1 gene that resulted in reduced intracellular glucose transport activity were identified in two unrelated consanguineous families with affected individuals presented with moderate-to-severe intellectual disability, epilepsy, and dysmorphic features (Srour et al., 2017); one of the four affected individuals with a homozygous SLC45A1 missense variant was diagnosed with ASD, while another affected individual presented with autistic traits.

Score Delta: Score remained at S

criteria met
See SFARI Gene'scoring criteria
S

Syndromic

See all Category S Genes

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."

10/1/2019
S
icon
S

Score remained at S

New Scoring Scheme
Description

Homozygous missense variants in the SLC45A1 gene that resulted in reduced intracellular glucose transport activity were identified in two unrelated consanguineous families with affected individuals presented with moderate-to-severe intellectual disability, epilepsy, and dysmorphic features (Srour et al., 2017); one of the four affected individuals with a homozygous SLC45A1 missense variant was diagnosed with ASD, while another affected individual presented with autistic traits.

Reports Added
[New Scoring Scheme]
Krishnan Probability Score

Score 0.49135228483169

Ranking 5627/25841 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 0.045189255890918

Ranking 8659/18225 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 0.94286203522827

Ranking 15467/18665 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 0.39278050973431

Ranking 1538/20870 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
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